RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study

International Nuclear Information System (INIS)

Beier, Christoph P; Dietmaier, Christopher; Jauch-Worley, Tanja; Kölbl, Oliver; Pietsch, Torsten; Proescholdt, Martin; Rümmele, Petra; Muigg, Armin; Stockhammer, Günther; Hegi, Monika; Bogdahn, Ulrich; Schmid, Christina; Hau, Peter; Gorlia, Thierry; Kleinletzenberger, Christine; Beier, Dagmar; Grauer, Oliver; Steinbrecher, Andreas; Hirschmann, Birgit; Brawanski, Alexander

2009-01-01

Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx™, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m 2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m 2 daily during radiotherapy (60 Gy) and 150-200 mg/m 2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data clinicaltrials.gov NCT00944801

Prolonged phone-call posture causes changes of ulnar motor nerve conduction across elbow.

Science.gov (United States)

Padua, Luca; Coraci, Daniele; Erra, Carmen; Doneddu, Pietro Emiliano; Granata, Giuseppe; Rossini, Paolo Maria

2016-08-01

Postures and work-hobby activities may play a role in the origin and progression of ulnar neuropathy at the elbow (UNE), whose occurrence appears to be increasing. The time spent on mobile-phone has increased in the last decades leading to an increased time spent with flexed elbow (prolonged-phone-posture, PPP). We aimed to assess the effect of PPP both in patients with symptoms of UNE and in symptom-free subjects. Patients with pure sensory symptoms of UNE and negative neurophysiological tests (MIN-UNE) and symptom-free subjects were enrolled. We evaluated ulnar motor nerve conduction velocity across elbow at baseline and after 6, 9, 12, 15, and 18min of PPP in both groups. Fifty-six symptom-free subjects and fifty-eight patients were enrolled. Globally 186 ulnar nerves from 114 subjects were studied. Conduction velocity of ulnar nerve across the elbow significantly changed over PPP time in patients with MIN-UNE, showing a different evolution between the two groups. PPP causes a modification of ulnar nerve functionality in patients with MIN-UNE. PPP may cause transient stress of ulnar nerve at elbow. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Histologic progression in non-hodgkin's lymphoma

International Nuclear Information System (INIS)

Hubbard, S.M.; Chabner, B.A.; DeVita, V.T. Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.

1982-01-01

The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy

Progress towards a Drag-free SmallSat

Science.gov (United States)

Saraf, Shailendhar

The net force acting on a drag-free satellite is purely gravitational as all other forces, mainly atmospheric drag and solar radiation pressure, are canceled out. In order to achieve this, a free floating reference (test mass) inside the satellite is shielded against all forces but gravity and a system of thrusters is commanded by a control algorithm such that the relative displacement between the reference and the satellite stays constant. The main input to that control algorithm is the output of a sensor which measures the relative displacement between the satellite and the test mass. Internal disturbance forces such as electrostatic or magnetic forces cannot be canceled out his way and have to be minimized by a careful design of the satellite. A drag-free technology package is under development at Stanford since 2004. It includes an optical displacement sensor to measure the relative position of the test mass inside the satellite, a caging mechanism to lock the test mass during launch, a UV LED based charge management system to minimize the effect of electrostatic forces, a thermal enclosure, and the drag-free control algorithms. Possible applications of drag-free satellites in fundamental physics (Gravity Probe B, LISA), geodesy (GOCE), and navigation (TRIAD I). In this presentation we will highlight the progress of the technology development towards a drag-free mission. The planned mission on a SaudiSat bus will demonstrate drag-free technology on a small spacecraft at a fraction of the cost of previous drag-free missions. The target acceleration noise is 10-12 m/sec2. With multiple such satellites a GRACE-like mission with improved sensitivity and potentially improved spatial and temporal resolution can be achieved.

Prolonged delirium misdiagnosed as a mood disorder.

Science.gov (United States)

Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

2017-01-01

Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study

Directory of Open Access Journals (Sweden)

Proescholdt Martin

2009-09-01

Full Text Available Abstract Background Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. Methods In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx™, PEG-Dox and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. Results The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12 was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. Conclusion Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data Trial registration clinicaltrials.gov NCT00944801.

Maximum standard uptake value on pre-chemotherapeutic FDG-PET is a significant parameter for disease progression of newly diagnosed lymphoma

International Nuclear Information System (INIS)

Eo, Jae Seon; Lee, Won Woo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

2005-01-01

F-18 FDG-PET is useful for detection and staging of lymphoma. We investigated the prognostic significance of maximum standard uptake (maxSUV) value of FDG-PET for newly diagnosed lymphoma patients before chemotherapy. Twenty-seven patients (male: female = 17: 10: age: 49±19 years) with newly diagnosed lymphoma were enrolled. Nine-teen patients suffered from B cell lymphoma, 6 Hodgkins disease and 2 T cell lymphoma. One patient was stage I, 9 stage II, 3 stage III, 1 stage IV and 13 others. All patients underwent FDG-PET before initiation of chemotherapy. MaxSUV values using lean body weight were obtained for main and largest lesion to represent maxSUV of the patients. The disease progression was defined as total change of the chemotherapeutic regimen or addition of new chemotherapeutic agent during follow up period. The observed period was 389±224 days. The value of maxSUV ranged from 3 to 18 (mean±SD = 10.6±4.4). The disease progressions occurred in 6 patients. Using Cox proportional-hazard regression analysis, maxSUV was identified as a significant parameter for the disease progression free survival (p=0.044). Kaplan-Meier survival curve analysis revealed that the group with higher maxSUV (=10.6, n=5) suffered from shorter disease progression free survival (median 299 days) than the group with lower maxSUV (<10.6, n = 22) (median 378 days, p=0.0146). We found that maxSUV on pre-chemotherapeutic F-18 FDG-PET for newly diagnosed lymphoma patients is a significant parameter for disease progression. Lymphoma patients can be stratified before initiation of chemotherapy in terms of disease progression by the value of maxSUV 10.6

The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Kwong, Dora L.W.; Sham, Jonathan S.T.; Chua, Daniel T.T.; Choy, Damon T.K.; Au, Gordon K.H.; Wu, P.M.

1997-01-01

Purpose: The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. Methods and Materials: Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment 'per schedule' were compared with those who had 'prolonged' treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. Results: Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco

Progress update of NASA's free-piston Stirling space power converter technology project

Science.gov (United States)

Dudenhoefer, James E.; Winter, Jerry M.; Alger, Donald

1992-01-01

A progress update is presented of the NASA LeRC Free-Piston Stirling Space Power Converter Technology Project. This work is being conducted under NASA's Civil Space Technology Initiative (CSTI). The goal of the CSTI High Capacity Power Element is to develop the technology base needed to meet the long duration, high capacity power requirements for future NASA space initiatives. Efforts are focused upon increasing system power output and system thermal and electric energy conversion efficiency at least five fold over current SP-100 technology, and on achieving systems that are compatible with space nuclear reactors. This paper will discuss progress toward 1050 K Stirling Space Power Converters. Fabrication is nearly completed for the 1050 K Component Test Power Converter (CTPC); results of motoring tests of the cold end (525 K), are presented. The success of these and future designs is dependent upon supporting research and technology efforts including heat pipes, bearings, superalloy joining technologies, high efficiency alternators, life and reliability testing, and predictive methodologies. This paper will compare progress in significant areas of component development from the start of the program with the Space Power Development Engine (SPDE) to the present work on CTPC.

Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

Science.gov (United States)

Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

2014-01-01

Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2– metastatic breast cancer

Directory of Open Access Journals (Sweden)

Forsythe A

2018-05-01

Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,2 Gabriel Tremblay1 1Purple Squirrel Economics, New York, NY, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Novartis Pharma GmbH, Nuremberg, Germany; 4Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada Background: Several recent randomized controlled trials (RCTs in hormone receptor-positive (HR+, human epidermal growth factor receptor 2-negative (HER2– metastatic breast cancer (MBC have demonstrated significant improvements in progression-free survival (PFS; however, few have reported improvement in overall survival (OS. The surrogacy of PFS or time to progression (TTP for OS has not been formally investigated in HR+, HER2– MBC.Methods: A systematic literature review of RCTs in HR+, HER2– MBC was conducted to identify studies that reported both median PFS/TTP and OS. The correlation between PFS/TTP and OS was evaluated using Pearson’s product–moment correlation and Spearman’s rank correlation. Subgroup analyses were performed to explore possible reasons for heterogeneity. Errors-in-variables weighted least squares regression (LSR was used to model incremental OS months as a function of incremental PFS/TTP months. An exploratory analysis investigated the impact of three covariates (chemotherapy vs hormonal/targeted therapy, PFS vs TTP, and first-line therapy vs second-line therapy or greater on OS prediction. The lower 95% prediction band was used to determine the minimum incremental PFS/TTP months required to predict OS benefit (surrogate threshold effect [STE].Results: Forty studies were identified. There was a statistically significant correlation between median PFS/TTP and OS (Pearson =0.741, P=0.000; Spearman =0.650, P=0.000. These results proved consistent for chemotherapy and hormonal/targeted therapy. Univariate LSR analysis yielded an R2 of 0.354 with 1 incremental PFS/TTP month corresponding to 1.13 incremental OS months

Progress in Electrolyte-Free Fuel Cells

International Nuclear Information System (INIS)

Lu, Yuzheng; Zhu, Bin; Cai, Yixiao; Kim, Jung-Sik; Wang, Baoyuan; Wang, Jun; Zhang, Yaoming; Li, Junjiao

2016-01-01

Solid oxide fuel cell (SOFC) represents a clean electrochemical energy conversion technology with characteristics of high conversion efficiency and low emissions. It is one of the most important new energy technologies in the future. However, the manufacture of SOFCs based on the structure of anode/electrolyte/cathode is complicated and time-consuming. Thus, the cost for the entire fabrication and technology is too high to be affordable, and challenges still hinder commercialization. Recently, a novel type of electrolyte-free fuel cell (EFFC) with single component was invented, which could be the potential candidate for the next generation of advanced fuel cells. This paper briefly introduces the EFFC, working principle, performance, and advantages with updated research progress. A number of key R&D issues about EFFCs have been addressed, and future opportunities and challenges are discussed.

Progress in Electrolyte-Free Fuel Cells

Energy Technology Data Exchange (ETDEWEB)

Lu, Yuzheng [Jiangsu Provincial Key Laboratory of Solar Energy Science and Technology, School of Energy and Environment, Southeast University, Nanjing (China); Zhu, Bin, E-mail: binzhu@kth.se [Faculty of Physics and Electronic Technology, Hubei Collaborative Innovation Center for Advanced Organic Materials, Hubei University, Wuhan (China); Department of Energy Technology, Royal Institute of Technology KTH, Stockholm (Sweden); Cai, Yixiao [Ångström Laboratory, Department of Engineering Sciences, Uppsala University, Uppsala (Sweden); Kim, Jung-Sik [Department of Aeronautical and Automotive Engineering, Loughborough University, Loughborough (United Kingdom); Wang, Baoyuan [Faculty of Physics and Electronic Technology, Hubei Collaborative Innovation Center for Advanced Organic Materials, Hubei University, Wuhan (China); Department of Energy Technology, Royal Institute of Technology KTH, Stockholm (Sweden); Wang, Jun, E-mail: binzhu@kth.se; Zhang, Yaoming [Jiangsu Provincial Key Laboratory of Solar Energy Science and Technology, School of Energy and Environment, Southeast University, Nanjing (China); Li, Junjiao [Nanjing Yunna Nano Technology Co., Ltd., Nanjing (China)

2016-05-02

Solid oxide fuel cell (SOFC) represents a clean electrochemical energy conversion technology with characteristics of high conversion efficiency and low emissions. It is one of the most important new energy technologies in the future. However, the manufacture of SOFCs based on the structure of anode/electrolyte/cathode is complicated and time-consuming. Thus, the cost for the entire fabrication and technology is too high to be affordable, and challenges still hinder commercialization. Recently, a novel type of electrolyte-free fuel cell (EFFC) with single component was invented, which could be the potential candidate for the next generation of advanced fuel cells. This paper briefly introduces the EFFC, working principle, performance, and advantages with updated research progress. A number of key R&D issues about EFFCs have been addressed, and future opportunities and challenges are discussed.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

Energy Technology Data Exchange (ETDEWEB)

Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

2016-03-15

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

International Nuclear Information System (INIS)

Ruella, Marco; Filippi, Andrea Riccardo; Bruna, Riccardo; Di Russo, Anna; Magni, Michele; Caracciolo, Daniele; Passera, Roberto; Matteucci, Paola; Di Nicola, Massimo; Corradini, Paolo; Parvis, Guido; Gini, Guido; Olivieri, Attilio; Ladetto, Marco; Ricardi, Umberto; Tarella, Corrado; Devizzi, Liliana

2016-01-01

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m"2, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Fast-Dissolving, Prolonged Release, and Antibacterial Cyclodextrin/Limonene-Inclusion Complex Nanofibrous Webs via Polymer-Free Electrospinning.

Science.gov (United States)

Aytac, Zeynep; Yildiz, Zehra Irem; Kayaci-Senirmak, Fatma; San Keskin, Nalan Oya; Kusku, Semran Ipek; Durgun, Engin; Tekinay, Turgay; Uyar, Tamer

2016-10-05

We have proposed a new strategy for preparing free-standing nanofibrous webs from an inclusion complex (IC) of a well-known flavor/fragrance compound (limonene) with three modified cyclodextrins (HPβCD, MβCD, and HPγCD) via electrospinning (CD/limonene-IC-NFs) without using a polymeric matrix. The experimental and computational modeling studies proved that the stoichiometry of the complexes was 1:1 for CD/limonene systems. MβCD/limonene-IC-NF released much more limonene at 37, 50, and 75 °C than HPβCD/limonene-IC-NF and HPγCD/limonene-IC-NF because of the greater amount of preserved limonene. Moreover, MβCD/limonene-IC-NF has released only 25% (w/w) of its limonene, whereas HPβCD/limonene-IC-NF and HPγCD/limonene-IC-NF released 51 and 88% (w/w) of their limonene in 100 days, respectively. CD/limonene-IC-NFs exhibited high antibacterial activity against E. coli and S. aureus. The water solubility of limonene increased significantly and CD/limonene-IC-NFs were dissolved in water in a few seconds. In brief, CD/limonene-IC-NFs with fast-dissolving character enhanced the thermal stability and prolonged the shelf life along with antibacterial properties could be quite applicable in food and oral care applications.

The hemodynamic effects of prolonged respiratory alkalosis in anesthetized newborn piglets.

Science.gov (United States)

Jundi, K; Barrington, K J; Henderson, C; Allen, R G; Finer, N N

2000-04-01

To test the hypothesis that prolonged alkalosis decreases cardiac output and, furthermore, exacerbates hypoxic pulmonary vasoconstriction, as respiratory alkalosis is frequently induced as a therapy for persistent pulmonary hypertension of the newborn despite a lack of controlled evidence of improved outcomes. Potential adverse effects of prolonged alkalosis have been demonstrated. Two groups (control, n = 6, and hypocapnic alkalosis, n = 6) of 1-3 day old fentanyl-anesthetized, vecuronium-paralyzed piglets were instrumented to measure cardiac index (CI) and mean systemic (MAP) and pulmonary (PAP) arterial pressures. Baseline values were recorded. Alveolar hypoxia was then induced to achieve an arterial oxygen saturation of between 50 and 60% for 15 min. Respiratory alkalosis was then induced, by increasing ventilation to achieve a pH between 7.55-7.60, and was continued for 240 min. Inspired carbon dioxide was used with hyperventilation in the control group to maintain pressure of arterial carbon dioxide (PaCO2) at 35-45 mmHg and pH of 7.35-7.45. Hypoxia was induced again at 15 and 240 min. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated. Prolonged alkalosis led to a significant and progressive fall in mean MAP from 61 (SD 7) mmHg at the start of the study falling to 50 (SD 6.9, p = 0.043), with no effect on CI. Calculated SVR decreased (0.45 SD 0.03 vs 0.36 SD 0.05). There were no statistically significant changes in any of the variables in the control group. Neither acute nor prolonged respiratory alkalosis had a significant effect on hypoxic pulmonary vasoconstriction. Prolonged hyperventilation leads to systemic hypotension, however it does not exacerbate hypoxic pulmonary vasoconstriction.

Progress in Electrolyte-Free Fuel Cells

Directory of Open Access Journals (Sweden)

Yuzheng eLu

2016-05-01

Full Text Available Solid Oxide Fuel Cell (SOFC represents a clean electrochemical energy conversion technology with characteristics of high conversion efficiency and low emissions. It is one of the most important new energy technologies in the future. However, the manufacture of SOFCs based on the structure of anode/electrolyte/cathode is complicated and time-consuming. Thus, the cost for the entire fabrication and technology is too high to be affordable and challenges still hinder commercialization. Recently, a novel type of Electrolyte -free fuel cell (EFFC with single component was invented which could be the potential candidate for the next generation of advanced fuel cells. This paper briefly introduces the EFFC, working principle, performance and advantages with updated research progress. A number of key R&D issues about EFFCs have been addressed and future opportunities and challenges are discussed.

Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

Science.gov (United States)

Regis, Lucas; Planas, Jacques; Carles, Joan; Maldonado, Xavier; Comas, Inma; Ferrer, Roser; Morote, Juan

2017-01-01

The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Progress of long coated conductors fabrication with fluorine-free CSD method at SWJTU

International Nuclear Information System (INIS)

Zhao, Y.; Wang, W.T.; Lei, M.; Pu, M.H.; Zhang, Y.; Cheng, C.H.

2013-01-01

Highlights: • Recent progress on the long coated conductors fabrication by F-free CSD method is presented. • Single buffer and partial-melting technology and slot-die coating methods have been developed. • Reel-to-reel facilities for continuous process have been achieved. -- Abstract: Recent progress on the fabrication of long high-T c superconducting coated conductors with a fluorine-free chemical solution deposition (CSD) method is presented. Developments including such novel methods as single buffer technology, partial-melting process on YBa 2 Cu 3 O 7 (YBCO), slot-die coating and drying; reel-to-reel facilities for continuous process have been achieved in the effort on high-T c superconducting coated conductors at SWJTU, which form a comprehensive technology to fabricate long coated tapes with high performances

Progress of long coated conductors fabrication with fluorine-free CSD method at SWJTU

Energy Technology Data Exchange (ETDEWEB)

Zhao, Y., E-mail: yzhao@swjtu.edu.cn [Key Lab of Advanced Materials Technologies, Key Lab of Magnetic Levitation Technologies and Maglev Trains (Ministry of Education), Superconductivity and New Energy Center (SNEC), Southwest Jiaotong University, Chengdu 610031 (China); School of Materials Science and Engineering, University of New South Wales, Sydney 2052, NSW (Australia); Wang, W.T.; Lei, M.; Pu, M.H.; Zhang, Y. [Key Lab of Advanced Materials Technologies, Key Lab of Magnetic Levitation Technologies and Maglev Trains (Ministry of Education), Superconductivity and New Energy Center (SNEC), Southwest Jiaotong University, Chengdu 610031 (China); Cheng, C.H. [School of Materials Science and Engineering, University of New South Wales, Sydney 2052, NSW (Australia)

2013-10-15

Highlights: • Recent progress on the long coated conductors fabrication by F-free CSD method is presented. • Single buffer and partial-melting technology and slot-die coating methods have been developed. • Reel-to-reel facilities for continuous process have been achieved. -- Abstract: Recent progress on the fabrication of long high-T{sub c} superconducting coated conductors with a fluorine-free chemical solution deposition (CSD) method is presented. Developments including such novel methods as single buffer technology, partial-melting process on YBa{sub 2}Cu{sub 3}O{sub 7} (YBCO), slot-die coating and drying; reel-to-reel facilities for continuous process have been achieved in the effort on high-T{sub c} superconducting coated conductors at SWJTU, which form a comprehensive technology to fabricate long coated tapes with high performances.

Prolonged jaundice in newborns is associated with low antioxidant capacity in breast milk.

Science.gov (United States)

Uras, Nurdan; Tonbul, Alpaslan; Karadag, Ahmet; Dogan, Derya G; Erel, Ozcan; Tatli, Mustafa M

2010-10-01

In breastfeeding newborns who are otherwise healthy, the mechanism of prolonged jaundice remains unclear. The aim of this study was to investigate relations between prolonged jaundice and oxidative parameters in breast milk. Full-term, otherwise healthy newborns with jaundice lasting more than 2 weeks were enrolled prospectively in the study. As a control group, newborns in the same age group but without prolonged jaundice were selected. All newborns in the study were exclusively breastfed. In the newborns with prolonged jaundice, investigations of the etiology of the jaundice included complete blood count, peripheral blood smear, blood typing, direct Coombs test, measurement of serum levels of total and direct bilirubin, tests for liver and thyroid function (TSH, free T4, total T4), urine culture and measurement of urine reducing substances, and determination of glucose 6 phosphate dehydrogenase enzyme levels. Breast milk was collected from the mothers of the newborns in both groups. The antioxidant status of the breast milk was assessed via determination of total antioxidant capacity (TAC). Oxidative stress was also assessed in breast milk by measurement of total oxidation status (TOS) and calculation of the oxidative stress index (OSI). The prolonged jaundice group differed significantly from the control group in terms of mean TAC and OSI (p antioxidant capacity was found to be decreased.

Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

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Verduyn S

2012-09-01

Full Text Available Abstract Background Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC patients with an activating mutation in the epidermal growth factor receptor (EGFR. Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+. From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis; pemetrexed/cisplatin (Pem/Cis; paclitaxel/carboplatin (Pac/Carb in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS. Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. Results The Quality Adjusted progression free survival (PFS (mean, (95% credibility interval was 5.2 months (4.5; 5.8 for Gem/Cis, 5.3 months (4.6; 6.1 for Pem/Cis; 4.9 months (4.4; 5.5 for Pac/Carb and 8

Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

DEFF Research Database (Denmark)

Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

2010-01-01

To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

DEFF Research Database (Denmark)

Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

2010-01-01

To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-a trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, ß-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

Label-free SERS in biological and biomedical applications: Recent progress, current challenges and opportunities

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Zheng, Xiao-Shan; Jahn, Izabella Jolan; Weber, Karina; Cialla-May, Dana; Popp, Jürgen

2018-05-01

To achieve an insightful look within biomolecular processes on the cellular level, the development of diseases as well as the reliable detection of metabolites and pathogens, a modern analytical tool is needed that is highly sensitive, molecular-specific and exhibits fast detection. Surface-enhanced Raman spectroscopy (SERS) is known to meet these requirements and, within this review article, the recent progress of label-free SERS in biological and biomedical applications is summarized and discussed. This includes the detection of biomolecules such as metabolites, nucleic acids and proteins. Further, the characterization and identification of microorganisms has been achieved by label-free SERS-based approaches. Eukaryotic cells can be characterized by SERS in order to gain information about the outer cell wall or to detect intracellular molecules and metabolites. The potential of SERS for medically relevant detection schemes is emphasized by the label-free detection of tissue, the investigation of body fluids as well as applications for therapeutic and illicit drug monitoring. The review article is concluded with an evaluation of the recent progress and current challenges in order to highlight the direction of label-free SERS in the future.

Expression and clinicopathological significance of Mel-18 mRNA in colorectal cancer.

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Tao, Ji; Liu, Yan-Long; Zhang, Gan; Ma, Yu-Yan; Cui, Bin-Bin; Yang, Yan-Mei

2014-10-01

Mel-18 is a member of the polycomb group (PcG) of proteins, which are chromatin regulatory factors that play an important role in oncogenesis. This study was designed to investigate the clinical and prognostic significance of Mel-18 in colorectal cancer (CRC) patients. For this purpose, expression of Mel-18 mRNA was evaluated in 82 primary CRC and paired noncancerous mucosa samples by qRT-PCR and Western blotting. We found that overall Mel-18 mRNA expression in the CRC tissue was significantly lower than in the noncancerous mucosal tissue (p = 0.007, Wilcoxon matched-pairs signed-ranks test). Mel-18 was conversely correlated with the pathological classifications (p = 0.003 for T, p Mel-18 showed prolonged disease-free survivals (DFS) (p Mel-18 expression may be a risk factor for the patients' 3-year DFS (HR = 1.895; 95 % CI 1.032, 3.477; p = 0.039). It was therefore concluded that the lower Mel-18 expression might contribute to the CRC development/progression.

Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

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Beauchemin C

2014-06-01

Full Text Available Catherine Beauchemin,1 Dan Cooper,2 Marie-Ève Lapierre,1 Louise Yelle,3 Jean Lachaine11Université de Montréal, Faculté de pharmacie, Montreal, 2Institut national d'excellence en santé et en services sociaux (INESSS, 3Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, CanadaBackground: Progression-free survival (PFS and time to progression (TTP are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS remains a matter of uncertainty in metastatic breast cancer (mBC. This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach.Methods: We conducted a systematic literature review according to the PICO method: 'Population' consisted of women with mBC; 'Interventions' and 'Comparators' were standard treatments for mBC or best supportive care; 'Outcomes' of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP.Results: A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01. Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01. The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172 + 1.753 (95% CI 1.307–2.198 × ΔPFS (R2=0.86.Conclusion: Results of

Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.

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Song, Guohong; Wang, Xiaoli; Jia, Jun; Yuan, Yanhua; Wan, Fengling; Zhou, Xinna; Yang, Huabing; Ren, Jun; Gu, Jiezhun; Lyerly, Herbert Kim

2013-06-01

Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells' growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers. This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured. Both CD8(+)CD28(-) and CD4(+)CD25(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3(+) and CD8(+)CD28(+)cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8(+)CD28(-) and CD4(+)CD25(+) cells showed increased levels of IL-6, and only patients with elevated CD8(+)CD28(-) had decreased interferon-γ. Univariate analysis indicated increased CD3(+)CD4(+) or CD8(+)CD28(+)correlated with prolonged progression-free survival (PFS), while elevated CD8(+)CD28(-)associated with shorten PFS. The percent of CD8(+)CD28(-) T lymphocytes is an independent predictor for PFS through multivariate analysis. This study suggests that progressive elevated levels of CD8(+)CD28(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.

Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIα expression in neural changes associated with a prolonged exposure therapy.

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Ogundele, Olalekan M; Ebenezer, Philip J; Lee, Charles C; Francis, Joseph

2017-06-14

Traumatic stress patients showed significant improvement in behavior after a prolonged exposure to an unrelated stimulus. This treatment method attempts to promote extinction of the fear memory associated with the initial traumatic experience. However, the subsequent prolonged exposure to such stimulus creates an additional layer of neural stress. Although the mechanism remains unclear, prolonged exposure therapy (PET) likely involves changes in synaptic plasticity, neurotransmitter function and inflammation; especially in parts of the brain concerned with the formation and retrieval of fear memory (Hippocampus and Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in danger-associated molecular pattern signaling (DAMP), we identified the significance of IGF-1/IGF-1R/CaMKIIα expression as a potential link between the concurrent progression of synaptic and inflammatory changes in stress. Thus, a comparison between IGF-1/IGF-1R/CaMKIIα, synaptic and DAMP proteins in stress and PET may highlight the significance of PET on synaptic morphology and neuronal inflammatory response. In behaviorally characterized Sprague-Dawley rats, there was a significant decline in neural IGF-1 (pIGF-1R expression. These animals showed a significant loss of presynaptic markers (synaptophysin; pIGF-1 (pIGF-1R was recorded in the Stress-PET group (pIGF-1/IGF-1R, an increase in activated hippocampal and cortical microglia was seen in stress (pIGF1/IGF-1R/CaMKIIα. Firstly, we showed a direct relationship between IGF-1/IGF-1R expression, presynaptic function (synaptophysin) and neurotransmitter activity in stress and PET. Secondly, we identified the possible role of CaMKIIα in post-synaptic function and regulation of small ion conductance channels. Lastly, we highlighted some of the possible links between IGF1/IGF-1R/CaMKIIα, the expression of DAMP proteins, Microglia activation, and its implication on synaptic plasticity during stress and PET. Copyright © 2017

Are shame and self-esteem risk factors in prolonged grief after death of a spouse?

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Dellmann, Thomas

2018-07-01

Although many single factors of prolonged grief have been identified in the literature, a comprehensive understanding of predictors is still lacking. This article argues that shame and low self-esteem, present risk factors in prolonged grief after spousal loss, based on a review of correlational studies. Using a practitioner-scientist approach, a developmental model of shame as a core factor in prolonged grief is proposed, outlining the progression from childhood relational trauma, to insecure attachment, shame, self-esteem contingent on spousal approval to eventual prolonged grief.

Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

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Hisao Imai

2015-01-01

Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

Progress towards a leprosy-free country: The experience of Oman.

Science.gov (United States)

Al Awaidy, Salah T

2017-11-01

The World Health Organization (WHO) released the Global Leprosy Strategy 2016-2020 towards a leprosy-free world. The author described the progress made towards the elimination of leprosy and suggested recommendations for the acceleration towards a Leprosy-free country according to WHO laid out criterion. Case record review of Leprosy patients managed between the years 1992 to 2015 were registered and analyzed. Data were collected from annual reports of the Ministry of Health including demographics, classification of leprosy new cases, relapse, childhood, grades of disability (GD) and multidrug therapy (MDT) completion rates. Leprosy prevalence rate declined from 1.64 to 0.09 per 10,000 population during the period 1992 and 2015 (pOman as they left the country shortly after diagnosis of leprosy due to a very short term contract, discretionary employment practices by the employers and prefer to go home to complete their treatment. Oman has met the elimination goals and made great strides towards becoming a leprosy-free country. However, challenges such as improving surveillance system efficiency and sensitivity for detecting timely leprosy cases, as well as foreign-born workers are still a major concerns.

Effect of leucine supplementation on fat free mass with prolonged hypoxic exposure during a 13-day trek to Everest Base Camp: a double-blind randomized study.

Science.gov (United States)

Wing-Gaia, Stacie L; Gershenoff, Dana C; Drummond, Micah J; Askew, E Wayne

2014-03-01

Loss of body weight and fat-free mass (FFM) are commonly noted with prolonged exposure to hypobaric hypoxia. Recent evidence suggests protein supplementation, specifically leucine, may potentially attenuate loss of FFM in subcaloric conditions during normoxia. The purpose of this study was to determine if leucine supplementation would prevent the loss of FFM in subcaloric conditions during prolonged hypoxia. Eighteen physically active male (n = 10) and female (n = 8) trekkers completed a 13-day trek in Nepal to Everest Base Camp with a mean altitude of 4140 m (range 2810-5364 m). In this double-blind study, participants were randomized to ingest either leucine (LEU) (7 g leucine, 93 kcal, 14.5 g whey-based protein) or an isocaloric isonitrogenous control (CON) (0.3 g LEU, 93 kcal, 11.3 g collagen protein) twice daily prior to meals. Body weight, body composition, and circumferences of bicep, thigh, and calf were measured pre- and post-trek. There was a significant time effect for body weight (-2.2% ± 1.7%), FFM (-1.7% ± 1.5%), fat mass (-4.0% ± 6.9%), and circumferences (p FFM (CON -2.1 ± 1.5%; LEU -1.2 ± 1.6%), fat mass (CON -2.9% ± 5.9%; LEU -5.4% ± 8.1%), or circumferences. Although a significant loss of body weight, FFM, and fat mass was noted in 13 days of high altitude exposure, FFM loss was not attenuated by leucine. Future studies are needed to determine if leucine attenuates loss of FFM with longer duration high altitude exposure.

Prolonged whole body immersion in cold water: hormonal and metabolic changes.

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Smith, D J; Deuster, P A; Ryan, C J; Doubt, T J

1990-03-01

To characterize metabolic and hormonal responses during prolonged whole body immersion, 16 divers wearing dry suits completed four immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 meters of sea water. One immersion began in the AM (1000 h) and one began in the PM (2200 h) to evaluate diurnal variations. Venous blood samples were obtained before and after completion of each immersion. Cortisol and ACTH levels demonstrated diurnal variation, with larger increases occurring after PM immersions. A greater than three-fold postimmersion increase occurred in norepinephrine (NE). There were significant increases in triiodothyronine (T3) uptake and epinephrine, but no change in T3, thyroxine, thyrotrophic hormone, and dopamine. Postimmersion free fatty acid levels increased 409% from preimmersion levels; glucose levels declined, and lactate increased significantly. Only changes in NE correlated significantly with changes in rectal temperature. In summary, when subjects are immersed in cold water for prolonged periods, with a slow rate of body cooling afforded by thermal protection and intermittent exercise, hormonal and metabolic changes occur that are similar in direction and magnitude to short-duration unprotected exposures. Except for cortisol and ACTH, none of the other measured variables exhibited diurnal alterations.

P02.03INCREASED COUNTS OF NK AND NKT CELLS ARE ASSOCIATED WITH PROLONGED SURVIVAL IN PRIMARY GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL IMMUNOTHERAPY IN COMBINATION WITH RADIO- AND CHEMO-THERAPY

Science.gov (United States)

Pellegatta, S.; Eoli, M.; Cantini, G.; Anghileri, E.; Antozzi, C.; Frigerio, S.; Bruzzone, M.; Pollo, B.; Parati, E.; Finocchiaro, G.

2014-01-01

Two clinical studies, DENDR1 and DENDR2 including, respectively, the treatment of first diagnosis and recurrent glioblastoma (GB) patients with dendritic cells (DCs) loaded with autologous tumor lysate are currently active at Istituto Neurologico Besta, Milan. Our first results obtained on a group of recurrent GB patients demonstrated that the response of NK cells correlates with significantly prolonged survival. Here we provide results of the interim analysis on 22 patients affected by primary GB. Patients with post-surgery volume ≤10 cc underwent leukapheresis before radiotherapy and chemotherapy with temozolomide (TMZ). Three intradermal injections of mature DC were done before adjuvant chemotherapy. The subsequent 4 injections were performed 17 ± 3 days after adjuvant TMZ. MRI, clinical and immunological follow-up were performed every 2 months. The median age at surgery was 54.5 years (28-69). RT-TMZ induced significant lymphopenia (1000 lymphocytes/microl (5/22) before first vaccination had shorter PFS than others (p < 0.005). Peripheral Blood Lymphocytes (PBLs) were analyzed by flow cytometry to identify CD8+ T cells, NK and NKT cells before and after DC vaccines. The ratio of vaccination/baseline frequencies and counts (V/B ratio) of all of the immunological parameters for each patient was calculated, and the median of all of the observations used as the cut off value to separate patients. V/B ratio was correlated with the progression free survival (PFS) of each patient. Increased V/B ratio for NK cells and in particular NKT cells, but not for CD8 T lymphocytes, was significantly associated with prolonged PFS (median PFS 14 vs 8.0 mo, p = 0.01; 15.0 vs 8.0 mo, respectively). Interferon (IFN)-γ in PBLs was significantly higher in patients with PFS12 (p < 0.02), increasing immediately after the second vaccination as evaluated by real time-PCR. No changes in the expression levels of IFN-γ were observed in the other patients. After a median follow up of 14

Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Farnebo, Jacob; Grybäck, Per; Harmenberg, Ulrika; Laurell, Anna; Wersäll, Peter; Blomqvist, Lennart K; Ullén, Anders; Sandström, Per

2014-01-01

To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression- free patient survival. Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression- free survival. Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression- free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression- free and overall survival in patients with mRCC

Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1-deficient colorectal cancer HCT116 cells.

Science.gov (United States)

Yan, Tao; Seo, Yuji; Kinsella, Timothy J

2009-11-15

MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged low-dose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy. An isogenic pair of MMR(+) (MLH1(+)) and MMR(-) (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting. MLH1(+) HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G(2)/M arrest) following LDR-IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels. MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51).

Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in Gastric Cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeonghun; Lim, Seok Tae; Na, Chang Ju; Han, Yeonhee; Kim, Chanyoung; Jeong, Hwanjeong; Sohn, Myunghee [Chonbuk National Univ., Jeonju (Korea, Republic of)

2014-03-15

We performed this study to evaluate the predictive value of pretreatment F-18 FDG PET/CT for progression-free survival (PFS) in patients with gastric cancer. Of 321 patients with a diagnosis of gastric cancer, we retrospectively enrolled 97 patients (men:women = 61:36, age 59.8±13.2 years), who underwent pretreatment F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) from January 2009 to December 2009. Maximum standardized uptake value (SUVmax) was measured for each case with detectable primary lesions. In the remaining non-detectable cases, SUVmax was measured from the corresponding site seen on gastroduodenoscopy for analysis. In subgroup analysis, metabolic tumor volume (MTV) was measured in 50 patients with clearly distinguishable primary lesions. SUVmax, stage, depth of tumor invasion and presence of lymph node metastasis were analyzed in terms of PFS. Receiver operating characteristic (ROC) curves were used to find optimal cutoff values of SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and PFS was analyzed using the Kaplan-Meier with log-rank test and Cox's proportional hazard regression methods. Of 97 patients, 15 (15.5 %) had disease progression. The mean follow-up duration was 29.6±10.2 months. The mean PFS of low SUVmax group (≤5.74) was significantly longer than that of the high SUVmax group (>5.74) (30.9±8.0 vs 24.3±13.6 months, p =0.008). In univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2, T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs ≤5.74) were significantly associated with recurrence. In multivariate analysis, high SUVmax (>5.74) was the only poor prognostic factor for PFS (p =0.002, HR 11.03, 95% CI 2.48.49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was the only poor prognostic factor for PFS (p =0.034, HR 3.59, 95 % CI 1.10.11.71). In gastric cancer, SUVmax measured by pretreatment F-18

Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

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Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

2009-11-30

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

Myocardial perfusion after prolonged submaximal exercise in patients with coronary artery disease

International Nuclear Information System (INIS)

Flotats, A.; Mena, E.; Camacho, V.; Tembl, A.; Hernandez, M.A.; Estorch, M.; Carrio, I.; Serra-Grima, R.

2002-01-01

Aim: Exercise training in patients with coronary artery disease (CAD) has established benefits. We assessed myocardial perfusion after submaximal but prolonged exercise in patients with CAD, who were enrolled in supervised exercise rehabilitation programs. Material and Methods: Nine patients with CAD enrolled in supervised exercise rehabilitation programs (7 men, 2 women; mean age 54±9 years), 7 with prior AMI and 2 with re-vascularized (CABG) multiple vessel disease, were encouraged to walk/run actively around the perimeter of our Hospital during the annual social sporting event organised in our Institution. Patients were studied by means of perfusion Tc-99m tetrofosmin SPECT imaging after prolonged exercise and at rest (gated SPECT), for two consecutive years. All patients remained symptom free during this interval period. Quantitative analysis was performed dividing polar map images in 13 segments. Tracer activity 9% in the resting image. The analysis was focused on those segments showing perfusion defects. Results: No symptoms other than fatigue were registered during prolonged exercise (range 1-2 hr). There were no significant differences in distance covered (7,462±3,031 m vs. 8,456±2,998 m), heart rate (92±11 bpm vs. 85±13 bpm) and rate-pressure product at the end of exercise (10,804±2,467 vs. 10,403±2,955) or gated SPECT calculated LVEF (44%±19 vs. 46%±20) between the two consecutive annual sporting events. Tracer activity in segments with perfusion defects did not significantly differ between both events. Overall agreement between both examinations regarding patient classification as having scar/ischemia was 77% (kappa=0.49). There was one patient who showed partial reversibility in three segments, consistent with mild anteroapical ischemia, only in the first examination. On the other hand, another patient showed reversibility in one segment (medium septum), only in the second examination, when he covered a distance 1.3 times superior. Conclusions

Prolonged intensive dominance behavior between gray wolves, Canis lupus

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Mech, L. David; Cluff, H. Dean

2010-01-01

Dominance is one of the most pervasive and important behaviors among wolves in a pack, yet its significance in free-ranging packs has been little studied. Insights into a behavior can often be gained by examining unusual examples of it. In the High Arctic near Eureka, Nunavut, Canada, we videotaped and described an unusually prolonged and intensive behavioral bout between an adult male Gray Wolf (Canis lupus) and a male member of his pack, thought to be a maturing son. With tail raised, the adult approached a male pack mate about 50 m from us and pinned and straddled this packmate repeatedly over 6.5 minutes, longer than we had ever seen in over 50 years of studying wolves. We interpreted this behavior as an extreme example of an adult wolf harassing a maturing offspring, perhaps in prelude to the offspring?s dispersal.

Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

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Jeonghyeon Park

Full Text Available Drug-induced torsades de pointes (TdP, a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93. From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5 were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP, deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2− metastatic breast cancer?

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Forsythe A

2018-05-01

Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,5 Anastasiya Shor,1 Gabriel Tremblay6 1Health Technology Assessment Evidence, Purple Squirrel Economics, New York, NY, USA; 2Global Value and Access, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 3German Market Access, Novartis Pharma GmbH, Nuremberg, Germany; 4Health Policy and Patient Access, Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada; 5Global Medical Affairs (Oncology Business Unit, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6Health Economics, Purple Squirrel Economics, New York, NY, USA Background: Hormone receptor-positive (HR+, human epidermal growth factor receptor 2- negative (HER2−, metastatic breast cancer (MBC accounts for 73% of all MBCs. Endocrine therapy (ET is the basis of first-line (1L therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL. Methods: The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs, observational, and retrospective studies were included. Results: Seventy-nine RCTs were identified: 58 (73% in the 1L+ setting and 21 (27% in second-line or greater settings. PFS hazard ratios (HRs were reported in 61 (77% studies; 31 (39% reported significant PFS improvements. OS was reported in 44 (41% studies; 12 (15% reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8% studies

Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model

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Lascano, Valeria; Guadagnoli, Marco; Schot, Jan G.; Luijks, Dieuwertje M.; Guikema, Jeroen E. J.; Cameron, Katherine; Hahne, Michael; Pals, Steven; Slinger, Erik; Kipps, Thomas J.; van Oers, Marinus H. J.; Eldering, Eric; Medema, Jan Paul; Kater, Arnon P.

2013-01-01

Although in vitro studies pointed to the tumor necrosis factor family member APRIL (a proliferation-inducing ligand) in mediating survival of chronic lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and progression in CLL is lacking. APRIL significantly prolonged in

PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

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Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

2018-03-01

To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

Retrospective evaluation of doxorubicin-piroxicam combination for the treatment of transitional cell carcinoma in dogs.

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Robat, C; Burton, J; Thamm, D; Vail, D

2013-02-01

To determine whether doxorubicin-piroxicam combination is safe and has activity against transitional cell carcinoma in dogs. Data was collected retrospectively from 34 dogs from two institutions over a 6-year period. Signalment, clinical presentation, treatment specifics, adverse events, response, progression-free survival and overall survival time were evaluated. Dogs received doxorubicin every 3 weeks and daily piroxicam; 17 dogs (50%) had surgery. Clinical presentations were those typically reported for transitional cell carcinoma. Mean number of doses administered was 3·5. Of the 23 dogs with measurable disease, 14 (60·5%) had stable disease, 7 (30·5%) had progressive disease and 2 (9%) a partial response. Adverse events were generally manageable, and gastrointestinal in origin; one dog died of treatment-related complications. Overall median progression-free survival and overall survival were 103 and 168 days, respectively. Cytoreductive surgery did not result in prolongation of progression-free survival, but significantly prolonged overall survival. All dogs but one died as a result of disease progression. Doxorubicin-piroxicam combination therapy is well-tolerated in dogs with transitional cell carcinoma although progression-free survival, overall survival and biological response rates appear modest. Combination with surgery appears to offer a survival advantage; however, this may reflect tumour location and volume. Prospective studies are necessary to compare activity of combination doxorubicin-piroxicam to currently applied therapies. © 2013 British Small Animal Veterinary Association.

EFFECT OF THE VOLUME OF FLUID INGESTED ON URINE CONCENTRATING ABILITY DURING PROLONGED HEAVY EXERCISE IN A HOT ENVIRONMENT

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Hidenori Otani

2013-03-01

Full Text Available This study examined the effect of the volume of fluid ingested on urine concentrating ability during prolonged heavy exercise in a hot environment at low levels of dehydration. Seven healthy males performed 105 min of intermittent cycle exercise at 70% maximum oxygen uptake (32°C, 60% relative humidity while receiving no fluid ingestion (NF, voluntary fluid ingestion (VF, partial fluid ingestion equivalent to one-half of body mass loss (PF, and full fluid ingestion equivalent to body mass loss (FF. Fluid (5°C, 3.4% carbohydrate, 10.5 mmol·L-1 sodium was ingested just before commencing exercise and at 15, 33, 51, 69, and 87 min of exercise, and the total amount of fluid ingested in PF and FF was divided into six equal volumes. During exercise, body mass loss was 2.2 ± 0.2, 1.1 ± 0.5, 1.1 ± 0.2, and 0.1 ± 0.2% in NF, VF, PF, and FF, respectively, whereas total sweat loss was about 2% of body mass in each trial. Subjects in VF ingested 719 ± 240 ml of fluid during exercise; the volume of fluid ingested was 1.1 ± 0.4% of body mass. Creatinine clearance was significantly higher and free water clearance was significantly lower in FF than in NF during exercise. Urine flow rate during exercise decreased significantly in NF. There were significant decreases in creatinine and osmolar clearance and was a significant increase in free water clearance during exercise in NF and VF. Creatinine clearance decreased significantly and free water clearance increased significantly during exercise in PF. There was no statistical change in urinary indices of renal function during exercise in FF. The findings suggest that full fluid ingestion equivalent to body mass loss has attenuated the decline in urine concentrating ability during prolonged heavy exercise in a hot environment at low levels of dehydration.

Filter testing and development for prolonged transuranic service and waste reduction

International Nuclear Information System (INIS)

Geer, J.A.; Buttedahl, O.I.; Skaats, C.D.; Terada, K.; Woodard, R.W.

1977-02-01

The life of High Efficiency Particulate Air (HEPA) filters used in transuranic service is influenced greatly by the gaseous and particulate matter to which the filters are exposed. The most severe conditions encountered at Rocky Flats are at the ventilation systems serving the plutonium recovery operations in Bldg. 771. A project of filter testing and development for prolonged transuranic service and waste reduction was formally initiated at Rocky Flats on July 1, 1975. The project is directed toward improving filtration methods which will prolong the life of HEPA filter systems without sacrificing effectiveness. Another important aspect of the project is to reduce the volume of HEPA filter waste shipped from the plant for long-term storage. Progress to September 30, 1976, is reported

Differential action of glycoprotein hormones: significance in cancer progression.

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Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

2014-02-01

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

Missing data and censoring in the analysis of progression-free survival in oncology clinical trials.

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Denne, J S; Stone, A M; Bailey-Iacona, R; Chen, T-T

2013-01-01

Progression-free survival (PFS) is increasingly used as a primary endpoint in oncology clinical trials. However, trial conduct is often such that PFS data on some patients may be partially missing either due to incomplete follow-up for progression, or due to data that may be collected but confounded by patients stopping randomized therapy or starting alternative therapy prior to progression. Regulatory guidance on how to handle these patients in the analysis and whether to censor these patients differs between agencies. We present results of a reanalysis of 28 Phase III trials from 12 companies or institutions performed by the Pharmaceutical Research and Manufacturers Association-sponsored PFS Expert Team. We show that analyses not adhering to the intention-to-treat principle tend to give hazard ratio estimates further from unity and describe several factors associated with this shift. We present illustrative simulations to support these findings and provide recommendations for the analysis of PFS.

Prolonged pain and disability are common after rib fractures.

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Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

2013-05-01

The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Progress in High Power Free-Piston Stirling Convertor Development

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Brandhorst, Henry W., Jr.; Kirby, Raymond L.; Chapman, Peter A.; Walter, Thomas J.

2008-09-01

The U.S. Space Exploration Policy has established a vision for human exploration of the moon and Mars. One option for power for future outposts on the lunar and Martian surfaces is a nuclear reactor coupled with a free-piston Stirling convertor at a power level of 30-40 kWe. A 25 kW convertor was developed in the 1990s under the SP-100 program. This system consisted of two 12.5 kWe engines connected at their hot ends and mounted in tandem to cancel vibration. Recently, NASA began a new project with Auburn University to develop a 5 kWe, single convertor for use in such a possible lunar power system. Goals of this development program include a specific power in excess of 140 We/kg at the convertor level, lifetime in excess of five years and a control system that will safely manage the convertors in case of an emergency. Foster-Miller, Inc. is developing the 5 kWe Stirling Convertor Assembly. The characteristics of the design along with progress in developing the system will be described.

Free amino acids in the shrimp crangon crangon and their osmoregulatory significance

NARCIS (Netherlands)

Weber, R.E.; Marrewijk, W.J.A. van

Measurements of the concentrations of ninhydrin positive substance () and of the individual free amino acids in muscle and haemolymph of Crangon crangon, adapted to various salinities at different temperatures, are recorded, and their significance as osmotic effectors is evaluated. The pattern of

Pretransplant portal venous administration of donor antigen and portal venous allograft drainage synergistically prolong rat cardiac allograft survival

International Nuclear Information System (INIS)

Kamei, T.; Callery, M.P.; Flye, M.W.

1990-01-01

The effect of antigen given through the portal vein (PV) before transplantation or continuous drainage of a graft into the PV results in moderate prolongation of allograft survival. This study examines these treatment modalities further. Pretransplant donor antigen as 25 x 10(6) ultraviolet B-irradiated (12,000 joules/m2) donor spleen cells was given 7 days before heart transplantation through either the PV or systemic venous (IV) routes. On day 0, Lewis-to-Buffalo rat cardiac allografts were drained either into the PV or IV. Pretransplant PV donor antigen administration (p less than 0.005), but not by IV administration, significantly prolonged cardiac allograft survival across the strong RT 1 rat histoincompatibility barrier. Similarly PV, but not IV, drainage of the graft prolonged graft survival (p less than 0.005). Pretransplant IV antigen administration had no additive effect on PV drainage graft survival. In contrast, when pretransplant PV donor antigen was combined with PV drainage, 11 of 14 allografts (p less than 0.001) continued to function, free of rejection, after 150 days. Therefore for rat cardiac transplants a clearly synergistic graft-prolonging effect results when pretransplant PV donor antigen is combined with PV drainage of the allografts. These data clarify the potent tolerogenic effects of alloantigen not only administered into the PV but also continuously shed intraportally so that it is first processed by the liver

Impact of tumour volume on prediction of progression-free survival in sinonasal cancer

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Hennersdorf, Florian; Mauz, Paul-Stefan; Adam, Patrick; Welz, Stefan; Sievert, Anne; Ernemann, Ulrike; Bisdas, Sotirios

2015-01-01

The present study aimed to analyse potential prognostic factors, with emphasis on tumour volume, in determining progression free survival (PFS) for malignancies of the nasal cavity and the paranasal sinuses. Retrospective analysis of 106 patients with primary sinonasal malignancies treated and followed-up between March 2006 and October 2012. Possible predictive parameters for PFS were entered into univariate and multivariate Cox regression analysis. Kaplan-Meier curve analysis included age, sex, baseline tumour volume (based on MR imaging), histology type, TNM stage and prognostic groups according to the American Joint Committee on Cancer (AJCC) classification. Receiver operating characteristic (ROC) curve analysis concerning the predictive value of tumour volume for recurrence was also conducted. The main histological subgroup consisted of epithelial tumours (77%). The majority of the patients (68%) showed advanced tumour burden (AJCC stage III–IV). Lymph node involvement was present in 18 cases. The mean tumour volume was 26.6 ± 21.2 cm 3 . The median PFS for all patients was 24.9 months (range: 2.5–84.5 months). The ROC curve analysis for the tumour volume showed 58.1% sensitivity and 75.4% specificity for predicting recurrence. Tumour volume, AJCC staging, T- and N- stage were significant predictors in the univariate analysis. Positive lymph node status and tumour volume remained significant and independent predictors in the multivariate analysis. Radiological tumour volume proofed to be a statistically reliable predictor of PFS. In the multivariate analysis, T-, N- and overall AJCC staging did not show significant prognostic value

Atraumatic femoral neck fracture secondary to prolonged lactation induced osteomalacia

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Dhammapal Sahebrao Bhamare

2013-01-01

Full Text Available Presenting a case of atraumatic fracture neck femur secondary to 2 years of prolonged lactation. A 26-year-old lactating mother presented with pain in left hip from last 12 months. She was apparently alright before and during pregnancy. Plain radiograph showed a complete undisplaced fracture of femoral neck. Osteomalacia was diagnosed by radiological and serological investigations. The fracture was fixed using AO type cannulated cancellous screws. The fracture showed good clinical and radiological union at 3 months. Literature review shows that this is a first case of atraumatic fracture of neck femur due to prolonged lactational osteomalacia. It showed that even apparently healthy Indians are susceptible to osteomalacia, more so during pregnancy and lactation and can be presented as atraumatic fracture. Although considered relatively stable, a compression type incomplete fracture neck femur may progress to a complete fracture if not treated in time.

Association of low baseline free thyroxin levels with progression of coronary artery calcification over 4 years in euthyroid subjects: the Kangbuk Samsung Health Study.

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Park, Hye-Jeong; Kim, Jihyun; Han, Eun Jin; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

2016-06-01

Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472-0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537-1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years. © 2015 John Wiley & Sons Ltd.

Clinical Significance of the Neutrophil-to-Lymphocyte Ratio in Endocrine Therapy for Stage IV Breast Cancer.

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Iimori, Nozomi; Kashiwagi, Shinichiro; Asano, Yuka; Goto, Wataru; Takada, Koji; Takahashi, Katsuyuki; Hatano, Takaharu; Takashima, Tsutomu; Tomita, Shuhei; Motomura, Hisashi; Hirakawa, Kosei; Ohira, Masaichi

2018-01-01

Studies have found that patients with cancer exhibit abnormal leukocyte fractions, such as elevated neutrophil count and diminished lymphocyte count, and that the neutrophil-to-lymphocyte ratio (NLR) provides a surrogate marker for prognosis and response to treatment of patients after radical surgery for several different types of cancer. However, few reports have addressed the association between the NLR and response to endocrine therapy. In this study, we carried out a clinical investigation to confirm whether or not the NLR predicted the response to endocrine therapy of stage IV breast cancer. The study subjects were 34 patients who underwent endocrine therapy as initial drug therapy for stage IV breast cancer. The correlation between NLR and prognosis, including the efficacy of endocrine therapy, was evaluated retrospectively. Among the 34 patients, the NLR was high in 10 (29.4%) and low in 24 (70.6%). In analysis of outcomes, the group with low NLR had a significant prolongation of progression-free survival (p=0.003), time to treatment failure (p=0.031), and overall survival (p=0.013) compared to the group with high NLR. Univariate analysis of progression-free survival found that responding to treatment [hazard ratio (HR)=4.310, p=0.004] and low NLR (HR=3.940, p=0.016) were factors associated with a favorable prognosis. Multivariate analysis also showed that responding to treatment (HR=4.329, p=0.006) and low NLR (HR=3.930, p=0.008) were independent factors associated with a favorable prognosis. Our results suggested that the NLR may represent a predictive marker for response to endocrine therapy in stage IV breast cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

Science.gov (United States)

2012-01-01

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

The effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation.

Science.gov (United States)

Weng, Yi-Ming; Wu, Shih-Hao; Li, Wen-Cheng; Kuo, Chan-Wei; Chen, Shou-Yen; Chen, Jih-Chang

2013-03-01

This study was performed to determine the effects of sodium bicarbonate injection during prolonged cardiopulmonary resuscitation (for >15 minutes). The retrospective cohort study consisted of adult patients who presented to the emergency department (ED) with the diagnosis of cardiac arrest in 2009. Data were retrieved from the institutional database. A total of 92 patients were enrolled in the study. Patients were divided into 2 groups based on whether they were treated (group1, n = 30) or not treated (group 2, n = 62) with sodium bicarbonate. There were no significant differences in demographic characteristics between groups. The median time interval between the administration of CPR and sodium bicarbonate injection was 36.0 minutes (IQR: 30.5-41.8 minutes). The median amount of bicarbonate injection was 100.2 mEq (IQR: 66.8-104.4). Patients who received a sodium bicarbonate injection during prolonged CPR had a higher percentage of return of spontaneous circulation, but not statistical significant (ROSC, 40.0% vs. 32.3%; P = .465). Sustained ROSC was achieved by 2 (6.7%) patients in the sodium bicarbonate treatment group, with no survival to discharge. No significant differences in vital signs after ROSC were detected between the 2 groups (heart rate, P = .124; systolic blood pressure, P = .094). Sodium bicarbonate injection during prolonged CPR was not associated with ROSC after adjust for variables by regression analysis (Table 3; P = .615; odds ratio, 1.270; 95% confidence interval: 0.501-3.219) The administration of sodium bicarbonate during prolonged CPR did not significantly improve the rate of ROSC in out-of-hospital cardiac arrest. Copyright © 2013 Elsevier Inc. All rights reserved.

Translating QT interval prolongation from conscious dogs to humans.

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Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

2017-02-01

In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

Morphology change of retained austenite during austempering of carbide-free bainitic steel

Energy Technology Data Exchange (ETDEWEB)

Hofer, Christina, E-mail: christina.hofer@unileoben.ac.at [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Franz-Josef-Straße 18, 8700 Leoben (Austria); Winkelhofer, Florian [Research and Development - Business Unit Coil, voestalpine Stahl GmbH, voestalpine‐Straße 3, A-4020 Linz (Austria); Clemens, Helmut; Primig, Sophie [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Franz-Josef-Straße 18, 8700 Leoben (Austria)

2016-05-10

A change in the mechanical properties of a carbide-free bainitic steel was observed during prolonged holding at austempering temperature after termination of the bainitic transformation. To determine the origin of the property change, the microstructure was investigated by correlative electron microscopy. Although the retained austenite content remains the same during prolonged holding, its morphology changes from thin films separating the individual bainitic sub-units to a more globular structure. Since films of austenite contain a higher C concentration, the blocky austenite becomes gradually enriched in C during this morphology change. The more homogeneous distribution of the C after prolonged austempering leads to higher deformability as a result of a more pronounced TRIP effect. - Highlights: • Higher deformability after prolonged austempering of carbide-free bainite. • Microstructure-property relationship revealed by correlative electron microscopy. • Change in austenite morphology. • Spherodization of film austenite; C enrichment & homogenization of blocky austenite.

A nuclear-free zone for the Southwest Pacific: prospects and significance

International Nuclear Information System (INIS)

Fry, G.

1983-01-01

The Australian Government is currently seeking to promote the concept of a nuclear-free zone for the Southwest Pacific. This paper explores three fundamental questions concerning the Australian proposal. Firstly, what would be the boundaries of such a zone and what does 'nuclear-free' mean in this context Secondly, what are the prospects for agreement on the establishment of a zone. Could regional states and nuclear powers agree to what is being proposed. And finally, what would be the significance, in arms control terms, were such an agreement to be signed. Would it, in fact, achieve anything. In an approach to these questions, the author surveys the strategic situation in the region, the level and pattern of nuclear involvement, past experience with zone proposals, and the current positions of various regional states and nuclear weapons powers on this question. He concludes that the necessary basis for agreement does exist and that modest arms control objectives could be served by the establishment of such a zone

Laryngotracheal Injury following Prolonged Endotracheal Intubation

Directory of Open Access Journals (Sweden)

J. Mehdizadeh

2006-07-01

Full Text Available Background: Prolonged endotracheal intubation is a growing method for supporting ventilation in patients who require intensive care. Despite considerable advancement in endotracheal intubation, this method still has some complications; the most important is laryngo-tracheal injuries. Methods: Over a 2-year period, this retrospective study was conducted on 57 patients with history of prolonged intubation who were referred to the ENT Department of Amir Alam Hospital. For each patient, a complete evaluation including history, physical examination, and direct laryngoscopy and bronchoscopy was done under general anesthesia. Results: Fifty-seven patients (44 male; mean age, 23.014.7 years were studied. Mean intubation period was 15.88 days. The most common presenting symptom was dyspnea (62%. Head trauma was responsible for most cases of intubation (72.4%. The most common types of tracheal and laryngeal lesions were tracheal (56.9% and subglottic (55.2% stenosis, respectively. Mean length of tracheal stenosis was 0.810.83 cm. There was a statistically significant relationship between length of tracheal stenosis and intubation period (P=0.0001 but no relation was observed between tracheal stenosis and age, sex, and etiology of intubation (All P=NS. Among the glottic lesions, inter- arytenoids adhesion was the most common lesion (25.9%. No statistically significant relation was found between glottic and subglottic lesions and age, sex and intubation period (all P=NS. Length of stenosis and intubation period was significantly greater in tracheal/ subglottic lesions than those in glottic/ supraglottic lesions (all P=NS. Conclusion: After prolonged endotracheal intubation, laryngo-tracheal lesions had no relation with patient’s age, sex, and cause of intubation.There was direct relation between length of tracheal stenosis and intubation period. Glottic lesions were more commonly observed in head trauma patients. Lesion length and intubation

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

DEFF Research Database (Denmark)

Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske

2014-01-01

, development of sustained side-effects, or abiraterone acetate becoming available in the respective country. The primary outcome was the number of adverse events arising during study treatment and within 30 days of discontinuation. Efficacy measures (time to prostate-specific antigen [PSA] progression and time......BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final...... analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. METHODS: We did a multicentre, open-label, early...

The incidence of hyponatremia during prolonged ultraendurance exercise.

Science.gov (United States)

Noakes, T D; Norman, R J; Buck, R H; Godlonton, J; Stevenson, K; Pittaway, D

1990-04-01

Recent studies have shown that potentially fatal hyponatremia can develop during prolonged exercise. To determine the incidence of hyponatremia in athletes competing in ultradistance events, we measured serum sodium levels in 315 of 626 (50%) runners who were treated for collapse after two 90 km ultramarathon footraces (total starters 20,335; total finishers 18,031) and in 101 of 147 (69%) finishers in a 186 km ultratriathlon. In both races the athletes drank fluids with low sodium chloride content (less than 6.8 mmol.l-1). Hyponatremia (serum sodium level less than 130 mmol.l-1) was identified in 27 of 315 (9%) collapsed runners in the 90 km races and in none of the triathletes. In response to diuretic therapy, the runner with the most severe hyponatremia (serum sodium level = 112 mmol.l-1) excreted in excess of 7.5 l dilute urine during the first 17 h of hospitalization. These data suggest that, although symptomatic hyponatremia occurs in less than 0.3% of competitors during prolonged exercise even when they ingest little sodium chloride, it is found in a significant proportion (9%) of collapsed runners. A regulated contraction of the extracellular fluid volume would explain why the majority of athletes maintain normal serum sodium levels even though they develop a significant sodium chloride deficit during prolonged exercise. Alternatively, sodium chloride losses during prolonged exercise may be substantially less than are currently believed. Physicians treating collapsed ultradistance athletes need to be aware that as many as 10% or more of such patients may be hyponatremic.

Clinical significance of adiponectin expression in colon cancer patients

Directory of Open Access Journals (Sweden)

Mustafa Canhoroz

2014-01-01

Conclusion: Adiponectin, which is secreted by adipose tissue, may have a role in the development and progression of cancer via its pro-apoptotic and/or anti-proliferative effects. Adiponectin expression in tumor tissues is likely to have a negative effect on disease - free survival in patients with stage II/III colon cancer; however, no statistically significant effect was demonstrated.

Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

LENUS (Irish Health Repository)

2012-02-01

Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

Science.gov (United States)

Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

2018-02-01

Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known

Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

International Nuclear Information System (INIS)

Vargas, H.A.; Burger, I.A.; Micco, M.; Sosa, R.E.; Weber, W.; Hricak, H.; Sala, E.; Goldman, D.A.; Chi, D.S.

2015-01-01

Our aim was to evaluate the associations between quantitative 18 F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUV max ), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUV max and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUV max was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. (orig.)

IAEA Mission Sees Significant Progress in Georgia’s Regulatory Framework, Challenges Ahead

International Nuclear Information System (INIS)

2018-01-01

An International Atomic Energy Agency (IAEA) team of experts said Georgia has made significant progress in strengthening its regulatory framework for nuclear and radiation safety. The team also pointed to challenges ahead as Georgia seeks to achieve further progress. The Integrated Regulatory Review Service (IRRS) team concluded a 10-day mission on 28 February to assess the regulatory safety framework in Georgia. The mission was conducted at the request of the Government and hosted by the Agency of Nuclear and Radiation Safety (ANRS), which is responsible for regulatory oversight in the country. IRRS missions are designed to strengthen the effectiveness of the national safety regulatory infrastructure, while recognizing the responsibility of each State to ensure nuclear and radiation safety. Georgia uses radioactive sources in medicine and industry and operates radioactive waste management facilities. It has decommissioned its only research reactor and has no nuclear power plants. In recent years, the Government and ANRS, with assistance from the IAEA, introduced new safety regulations and increased the number of regulatory inspections.

High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

Science.gov (United States)

Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

2017-06-01

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The progressive tax

OpenAIRE

Estrada, Fernando

2010-01-01

This article describes the argumentative structure of Hayek on the relationship between power to tax and the progressive tax. It is observed throughout its work giving special attention to two works: The Constitution of Liberty (1959) and Law, Legislation and Liberty, vol3; The Political Order of Free People, 1979) Hayek describes one of the arguments most complete information bout SFP progressive tax systems (progressive tax). According to the author the history of the tax progressive system...

Qt interval prolongation and ventricular arrhythmias in patients with chronic heart failure

International Nuclear Information System (INIS)

Sarwar, M.; Majeed, S.M.I.; Khan, M.A.; Majeed, S.M.

2014-01-01

To determine the association of QTc interval prolongation with ventricular arrhythmias in patients with chronic heart failure. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi, Pakistan from April 2013 to August 2013. Patients and Methods: Fifty three heart failure patients were monitored for 48 hours using ambulatory holter electrocardiography recorders. Digital ECG data was analyzed for QTc interval along with frequency and severity of arrhythmias. Association of prolonged QTc interval with ventricular arrhythmias and severity of arrhythmias was analyzed. Results: Cardiac arrhythmias were observed in 79.2% patients. QT analysis revealed that 69.8% patients had prolonged QTc interval, 86.4% patients with prolonged QTc had ventricular arrhythmias. Of these 66% patients were found to have severe ventricular arrhythmias. Comparison of mean QTc interval of our study population with a reference value showed significantly higher QTc interval of our study group than the test value. Conclusion: Arrhythmia frequency and severity significantly increases with an increase in QTc interval in heart failure demonstrating association of prolonged QTc interval with high risk of severe ventricular arrhythmias and sudden cardiac death in chronic heart failure. (author)

Progress in Developing a New 5 Kilowatt Free-Piston Stirling Space Convertor

International Nuclear Information System (INIS)

Brandhorst, Henry W. Jr.; Kirby, Raymond L.; Chapman, Peter A.

2008-01-01

The NASA Vision for Exploration of the Moon envisions a nuclear reactor coupled with a free-piston Stirling convertor at a power level of 30-40 kWe. In the 1990s, Mechanical Technology, Inc.'s Stirling Engine Systems Division (now a part of Foster-Miller, Inc.) developed a 25 kWe free piston Stirling Space Power Demonstrator Engine under the SP-100 program. This system consisted of two 12.5 kWe engines connected at their hot ends and mounted in tandem to cancel vibration. Recently, NASA and DoE have been developing dual 55 We and 80 We Stirling convertor systems for use with radioisotope heat sources. Total test times of all convertors in this effort exceed 120,000 hours. Recently, NASA began a new project with Auburn University to develop a 5 kWe, single convertor for use in the Lunar power system. Goals of this development program include a specific power in excess of 140 We/kg at the convertor level, lifetime in excess of five years and a control system that will safely manage the convertors in case of an emergency. Auburn University awarded a subcontract to Foster-Miller, Inc. to undertake development of the 5 kWe Stirling Convertor Assembly. The characteristics of the design along with progress in developing the system will be described

Progress in Developing a New 5 Kilowatt Free-Piston Stirling Space Convertor

Science.gov (United States)

Brandhorst, Henry W.; Kirby, Raymond L.; Chapman, Peter A.

2008-01-01

The NASA Vision for Exploration of the Moon envisions a nuclear reactor coupled with a free-piston Stirling convertor at a power level of 30-40 kWe. In the 1990s, Mechanical Technology, Inc.'s Stirling Engine Systems Division (now a part of Foster-Miller, Inc.) developed a 25 kWe free piston Stirling Space Power Demonstrator Engine under the SP-100 program. This system consisted of two 12.5 kWe engines connected at their hot ends and mounted in tandem to cancel vibration. Recently, NASA and DoE have been developing dual 55 We and 80 We Stirling convertor systems for use with radioisotope heat sources. Total test times of all convertors in this effort exceed 120,000 hours. Recently, NASA began a new project with Auburn University to develop a 5 kWe, single convertor for use in the Lunar power system. Goals of this development program include a specific power in excess of 140 We/kg at the convertor level, lifetime in excess of five years and a control system that will safely manage the convertors in case of an emergency. Auburn University awarded a subcontract to Foster-Miller, Inc. to undertake development of the 5 kWe Stirling Convertor Assembly. The characteristics of the design along with progress in developing the system will be described.

Licence prolongations of US nuclear power plants; Les prolongations de licence des centrales nucleaires americaines

Energy Technology Data Exchange (ETDEWEB)

NONE

2004-04-01

Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps.

Directory of Open Access Journals (Sweden)

Andreas M Fichter

Full Text Available Extracorporeal perfusion (ECP might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps.After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7.ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27% was even lower than after in vivo perfusion (49%, although not statistically significant (P = 0,083. After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%. Angiographic and histological findings confirmed these observations.Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies.

Management of prolonged pregnancy

International Nuclear Information System (INIS)

Iqbal, S.

2004-01-01

Objective: To compare two strategies for management of prolonged pregnancy (= or >294 days) i.e. induction (intervention) versus expectant management (non-intervention) and evaluate the associated feto-maternal risks. Subjects and Methods: One hundred cases of uncomplicated prolonged gestation were selected. The gestational age was confirmed by ultrasound in first trimester. One group (50 patients) was managed by intervention i.e. induction of labour (group A) and other group (50 patients) by non-intervention i.e. expectant management (group B). In group A intervention was done at 42 weeks. In expectant group, the methods of monitoring were fetal kick charting recorded daily by the patient, and ultrasound for amniotic fluid index. The biophysical profile score and NST (non stress test) were performed once a week till 42 weeks and then twice weekly. Results: The frequency of prolonged pregnancy was found to be 10.9%. There was no significant difference in the number of spontaneous vaginal deliveries between the two groups. The rate of LSCS (lower segment caesarean section) was higher in intervention group ( 30% versus 18% ). The neonatal depression at birth was more in group B ( 10% versus 4%) and at 5 minutes almost same between two groups (4% versus 2%). There were 11 cases of meconium aspiration syndrome, leading to one neonatal death. Among nine perinatal deaths two were neonatal deaths. Seven cases of intrauterine deaths in which antepartum deaths occurred because of non compliance of patients. No cause could be detected for the other three fetuses. Conclusion: There was increased LSCS rate in group A. However in expectant group B perinatal mortality was about twice more as compared to intervention group. Active early intervention at 42 weeks is warranted to reduce perinatal morbidity and mortality. (author)

Resveratrol-Loaded Albumin Nanoparticles with Prolonged Blood Circulation and Improved Biocompatibility for Highly Effective Targeted Pancreatic Tumor Therapy

Science.gov (United States)

Geng, Tao; Zhao, Xia; Ma, Meng; Zhu, Gang; Yin, Ling

2017-06-01

Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances across cell membranes. Herein, we have designed and prepared resveratrol (RV)-loaded HSA nanoparticles conjugating RGD (arginine-glycine-aspartate) via a polyethylene glycol (PEG) "bridge" (HRP-RGD NPs) for highly effective targeted pancreatic tumor therapy. HRP-RGD NPs possess an average size of 120 ± 2.6 nm with a narrow distribution, a homodisperse spherical shape, a RV encapsulation efficiency of 62.5 ± 4.21%, and a maximum RV release ratio of 58.4.2 ± 2.8% at pH 5.0 and 37 °C. In vitro biocompatibility of RV is improved after coating with HSA and PEG. Confocal fluorescence images show that HRP-RGD NPs have the highest cellular uptake ratio of 47.3 ± 4.6% compared to HRP NPs and HRP-RGD NPs with free RGD blocking, attributing to an RGD-mediated effect. A cell counting kit-8 (CCK-8) assay indicates that HRP-RGD NPs without RV (HP-RGD NPs) have nearly no cytotoxicity, but HRP-RGD NPs are significantly more cytotoxic to PANC-1 cells compared to free RV and HRP NPs in a concentration dependent manner, showing apoptotic morphology. Furthermore, with a formulated PEG and HSA coating, HRP-RGD NPs prolong the blood circulation of RV, increasing approximately 5.43-fold (t1/2). After intravenous injection into tumor-bearing mice, the content of HRP-RGD NPs in tumor tissue was proven to be approximately 3.01- and 8.1-fold higher than that of HRP NPs and free RV, respectively. Based on these results, HRP-RGD NPs were used in an in vivo anti-cancer study and demonstrated the best tumor growth suppression effect of all tested drugs with no relapse, high in vivo biocompatibility, and no significant systemic toxicity over 35 days treatment. These results demonstrate that HRP-RGD NPs with prolonged blood circulation and improved biocompatibility have high anti-cancer effects with promising future applications in cancer therapy.

Hungary making progress toward free market

International Nuclear Information System (INIS)

Anon.

1992-01-01

This paper reports that the Hungarian government made major progress in reorienting the energy sector toward a market economy in 1991. A study conducted by the International Energy Agency the progress was particularly evident in price reform and restructuring of the Hungarian energy industry. The pace of change has accelerated. Effective with fourth quarter 1991 through 1992 all the main energy enterprises will begin operating under new structures. Assuming that liberalized energy prices are set by suppliers to cover their costs and local governments do not subsidize district heating prices, all energy prices are to be at least at their economic cost level by mid-1992, IEA the. Some prices will be above this level because of sales taxes on gasoline and diesel and taxes on all imported energy. Hungary depends on imports for about half of its primary energy supply. Because domestic production has peaked, the share of imports will rise if consumption, after a likely further decline in the short term, returns to an upward trend

Quality of drug label information on QT interval prolongation

DEFF Research Database (Denmark)

Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

2014-01-01

BACKGROUND: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. OBJECTIVE: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

Energy Technology Data Exchange (ETDEWEB)

Vargas, H.A.; Burger, I.A.; Micco, M.; Sosa, R.E.; Weber, W.; Hricak, H.; Sala, E. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Goldman, D.A. [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Chi, D.S. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States)

2015-11-15

Our aim was to evaluate the associations between quantitative {sup 18}F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUV{sub max}), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUV{sub max} and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUV{sub max} was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. (orig.)

Spreading depolarizations have prolonged direct current shifts and are associated with poor outcome in brain trauma

DEFF Research Database (Denmark)

Hartings, Jed A; Watanabe, Tomas; Bullock, M Ross

2011-01-01

, although prolonged events have not been observed in animal models. To determine whether detrimental penumbral-type depolarizations occur in human brain trauma, we analysed electrocorticographic recordings obtained by subdural electrode-strip monitoring during intensive care. Of 53 patients studied, 10......Cortical spreading depolarizations occur spontaneously after ischaemic, haemorrhagic and traumatic brain injury. Their effects vary spatially and temporally as graded phenomena, from infarction to complete recovery, and are reflected in the duration of depolarization measured by the negative direct...... current shift of electrocorticographic recordings. In the focal ischaemic penumbra, peri-infarct depolarizations have prolonged direct current shifts and cause progressive recruitment of the penumbra into the core infarct. In traumatic brain injury, the effects of spreading depolarizations are unknown...

Electric power and its significance as the energy for innovation and progress

International Nuclear Information System (INIS)

Klinger, H.; Boehmer, T.

1999-01-01

The significance of electric power as the essential form of energy to support innovation and progress well into the future is explained with respect to four major domains of application: 1. Innovative activities in microelectronics and semiconductor technology, for applications such as automation and computer technology, instrumentation and control technology, facility and systems management and control. 2. Energy efficiency programmes and schemes for increasing the penetration of energiy from renewable sources in the market. Example: Heat pump technology. 3. Electric power as an energy boosting innovation in industrial production processes. Examples are given from the transportation sector. (orig./CB) [de

Coexistence of Ureaplasma and chorioamnionitis is associated with prolonged mechanical ventilation.

Science.gov (United States)

Jung, Euiseok; Choi, Chang Won; Kim, Su Yeong; Sung, Tae-Jung; Kim, Haeryoung; Park, Kyoung Un; Kim, Han-Suk; Kim, Beyong Il; Choi, Jung-Hwan

2017-01-01

Both histologic chorioamnionitis (HCAM) and Ureaplasma infection are considered important contributors to perinatal lung injury. We tested the hypothesis that coexistence of maternal HCAM and perinatal Ureaplasma exposure increases the risk of prolonged mechanical ventilation in extremely low-birthweight (ELBW) infants. A retrospective cohort study was carried out of all ELBW infants born between January 2008 and December 2013 at a single academic center. Placental pathology and gastric fluid Ureaplasma data were available for all infants. Culture and polymerase chain reaction were used to detect Ureaplasma in gastric fluid. Prolonged mechanical ventilation was defined as mechanical ventilation that began within 28 days after birth and continued. Of 111 ELBW infants enrolled, 84 survived beyond 36 weeks of postmenstrual age (PMA) and were included in the analysis. Eighteen infants (21.4%) had both HCAM and Ureaplasma exposure. Seven infants (8.3%) required mechanical ventilation beyond 36 weeks of PMA. Coexistence of HCAM and Ureaplasma in gastric fluid was significantly associated with prolonged mechanical ventilation after adjustment for gestational age, sex, mode of delivery, and use of macrolide antibiotics (OR, 8.7; 95%CI: 1.1-67.2). Coexistence of maternal HCAM and perinatal Ureaplasma exposure significantly increases the risk of prolonged mechanical ventilation in ELBW infants. © 2016 Japan Pediatric Society.

Rituximab-containing reduced-intensity conditioning improves progression-free survival following allogeneic transplantation in B cell non-Hodgkin lymphoma

Directory of Open Access Journals (Sweden)

Narendranath Epperla

2017-06-01

Full Text Available Abstract Background In B cell non-Hodgkin lymphoma (B-NHL, rituximab-containing reduced-intensity conditioning regimens (R-RIC have been shown to provide favorable outcomes in single-arm studies; however, large multicenter studies comparing R-RIC and non-rituximab-containing reduced-intensity conditioning regimens (nonR-RIC have not been performed. Using the CIBMTR database, we report the outcomes of R-RIC versus nonR-RIC regimens in B-NHL. Methods We evaluated 1401 adult B-NHL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT who received nonR-RIC (n = 1022 or R-RIC (n = 379 regimens. Graft-versus-host disease (GVHD prophylaxis was limited to calcineurin inhibitor-based approaches. Results Median follow-up of survivors in the R-RIC and nonR-RIC groups was 47 and 37 months, respectively. On multivariate analysis, no difference was seen between the R-RIC and nonR-RIC cohorts in terms of acute GVHD grade II–IV (RR = 1.14, 95%CI = 0.83–1.56, p = 0.43 or grade III–IV (RR = 1.16, 95%CI = 0.72–1.89, p = 0.54, chronic GVHD (RR = 1.15, 95%CI = 0.92–1.46, p = 0.22, non-relapse mortality (RR = 0.90; 95%CI = 0.67–1.22; p = 0.51, relapse/progression (RR = 0.79; 95%CI = 0.63–1.01; p = 0.055, and mortality (RR = 0.84, 95%CI = 0.69–1.02, p = 0.08 risk. However, R-RIC was associated with a significantly improved progression-free survival (RR = 0.76; 95%CI 0.62–0.92; p = 0.006. On subgroup analysis, mortality benefit was noted in the R-RIC group patients not receiving busulfan-based RIC (RR = 0.76; 95%CI = 0.60–0.96; p = 0.02 and with the use of a higher cumulative rituximab dose (RR = 0.43; 95%CI = 0.21–0.90; p = 0.02. Conclusion Our analysis shows that inclusion of rituximab in RIC regimens improves progression-free survival in patients with B cell NHL. These data supports the use of R-RIC in B

Prolonged pregnancy: Methods, Causal Determinants and Outcome

DEFF Research Database (Denmark)

Olesen, Annette Wind

Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1......) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... the risk of recurrence of prolonged pregnancy as a function of change in male partner and social conditions (IV). The National Birth Cohort provided data for the study on prenatal risk indicators of prolonged pregnancy in a follow-up design (V). The self-reported gestational ages from this database...

Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

DEFF Research Database (Denmark)

Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.

2016-01-01

Doppler imaging, and two-dimensional speckle tracking. Correlation between echocardiographic variables and cardiac troponin I was evaluated. Results: Early diastolic myocardial velocities decreased significantly in longitudinal (baseline: −17.4 ± 2.4cm/s; end of ride: −15.8 ± 3.2cm/s (P = .013); morning......Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...... and diastolic function in horses. Animals: Twenty-six horses competing in 120–160 km endurance rides. Methods: Cross-sectional field study. Echocardiography was performed before and after rides, and the following morning, and included two-dimensional echocardiography, anatomical M-mode, pulsed-wave tissue...

Prolonged CT urography in duplex kidney.

Science.gov (United States)

Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

2016-05-13

Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

Effect of progressive drought stress on growth, leaf gas exchange, and antioxidant production in two maize cultivars.

Science.gov (United States)

Anjum, Shakeel Ahmad; Tanveer, Mohsin; Ashraf, Umair; Hussain, Saddam; Shahzad, Babar; Khan, Imran; Wang, Longchang

2016-09-01

Drought stress is one of the major environmental factors responsible for reduction in crop productivity. In the present study, responses of two maize cultivars (Rung Nong 35 and Dong Dan 80) were examined to explicate the growth, yield, leaf gas exchange, leaf water contents, osmolyte accumulation, membrane lipid peroxidation, and antioxidant activity under progressive drought stress. Maize cultivars were subjected to varying field capacities (FC) viz., well-watered (80 % FC) and drought-stressed (35 % FC) at 45 days after sowing. The effects of drought stress were analyzed at 5, 10, 15, 20, ad 25 days after drought stress (DAS) imposition. Under prolonged drought stress, Rung Nong 35 exhibited higher reduction in growth and yield as compared to Dong Dan 80. Maize cultivar Dong Dan 80 showed higher leaf relative water content (RWC), free proline, and total carbohydrate accumulation than Run Nong 35. Malondialdehyde (MDA) and superoxide anion were increased with prolongation of drought stress, with higher rates in cultivar Run Nong 35 than cultivar Dong Dan 80. Higher production of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) and glutathione reductase (GR) resulted in improved growth and yield in Dong Dan 80. Overall, the cultivar Dong Dan 80 was better able to resist the detrimental effects of progressive drought stress as indicated by better growth and yield due to higher antioxidant enzymes, reduced lipid peroxidation, better accumulation of osmolytes, and maintenance of tissue water contents.

Progressive significance map and its application to error-resilient image transmission.

Science.gov (United States)

Hu, Yang; Pearlman, William A; Li, Xin

2012-07-01

Set partition coding (SPC) has shown tremendous success in image compression. Despite its popularity, the lack of error resilience remains a significant challenge to the transmission of images in error-prone environments. In this paper, we propose a novel data representation called the progressive significance map (prog-sig-map) for error-resilient SPC. It structures the significance map (sig-map) into two parts: a high-level summation sig-map and a low-level complementary sig-map (comp-sig-map). Such a structured representation of the sig-map allows us to improve its error-resilient property at the price of only a slight sacrifice in compression efficiency. For example, we have found that a fixed-length coding of the comp-sig-map in the prog-sig-map renders 64% of the coded bitstream insensitive to bit errors, compared with 40% with that of the conventional sig-map. Simulation results have shown that the prog-sig-map can achieve highly competitive rate-distortion performance for binary symmetric channels while maintaining low computational complexity. Moreover, we note that prog-sig-map is complementary to existing independent packetization and channel-coding-based error-resilient approaches and readily lends itself to other source coding applications such as distributed video coding.

Internalized stigma in adults with early phase versus prolonged psychosis.

Science.gov (United States)

Firmin, Ruth L; Lysaker, Paul H; Luther, Lauren; Yanos, Philip T; Leonhardt, Bethany; Breier, Alan; Vohs, Jenifer L

2018-03-30

Although internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one's illness stigma is internalized and the impact of internalization on symptoms or social functioning over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with social functioning or symptoms among those with prolonged compared to early phase psychosis. Individuals with early phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and social functioning. Controlling for education, race and sex differences, internalized stigma was significantly greater among those with prolonged psychosis compared to early phase. Internalized stigma was negatively related to social functioning and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early phase. Stereotype endorsement, discrimination experiences and social withdrawal also differentially related to symptoms and social functioning across the 2 samples. Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Furthermore, internalized stigma may be a possible treatment target among those with early phase psychosis. © 2018 John Wiley & Sons Australia, Ltd.

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

Science.gov (United States)

Brtalik, Douglas; Stopyra, Jason; Hannum, Jennifer

2017-06-01

Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. We present a case of intravenous poison hemlock injection encountered in the emergency department. We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

Progressive buckling analysis for a cylindrical shell structure with the free edge subjected to moving thermal cycles

International Nuclear Information System (INIS)

Koo, Gyeong-Hoi; Lee, Jae-Han

2004-01-01

In the KALIMER (Korea Advanced Liquid Metal Reactor) design, the reactor baffle structure is adopted to prevent the hot pool sodium from directly contacting the reactor vessel and to guide the hot sodium overflow in severe transient operating conditions. The parts in the vicinity of the hot pool free surface region could be repeatedly subjected to a moving axial temperature gradient and this might result in thermal ratcheting deformation. In this paper, the progressive thermal buckling behaviour following thermal ratcheting due to the moving axial temperature gradients in a cylindrical shell structure with an open free edge is investigated using numerical inelastic analysis with Chaboche's model. To do this, the analyses of the moving temperature distribution are carried out with a simple model and the severe moving axial temperature gradients are assumed to be sufficient for the evolution of thermal ratcheting

Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

DEFF Research Database (Denmark)

Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

2003-01-01

(HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during...... not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes....

[Brain function recovery after prolonged posttraumatic coma].

Science.gov (United States)

Klimash, A V; Zhanaidarov, Z S

2016-01-01

To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

[Pathophysiology of prolonged hypokinesia].

Science.gov (United States)

Kovalenko, E A

1976-01-01

Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

QM/MM free energy simulations: recent progress and challenges

Science.gov (United States)

Lu, Xiya; Fang, Dong; Ito, Shingo; Okamoto, Yuko; Ovchinnikov, Victor

2016-01-01

Due to the higher computational cost relative to pure molecular mechanical (MM) simulations, hybrid quantum mechanical/molecular mechanical (QM/MM) free energy simulations particularly require a careful consideration of balancing computational cost and accuracy. Here we review several recent developments in free energy methods most relevant to QM/MM simulations and discuss several topics motivated by these developments using simple but informative examples that involve processes in water. For chemical reactions, we highlight the value of invoking enhanced sampling technique (e.g., replica-exchange) in umbrella sampling calculations and the value of including collective environmental variables (e.g., hydration level) in metadynamics simulations; we also illustrate the sensitivity of string calculations, especially free energy along the path, to various parameters in the computation. Alchemical free energy simulations with a specific thermodynamic cycle are used to probe the effect of including the first solvation shell into the QM region when computing solvation free energies. For cases where high-level QM/MM potential functions are needed, we analyze two different approaches: the QM/MM-MFEP method of Yang and co-workers and perturbative correction to low-level QM/MM free energy results. For the examples analyzed here, both approaches seem productive although care needs to be exercised when analyzing the perturbative corrections. PMID:27563170

Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

Directory of Open Access Journals (Sweden)

Singh S

2014-08-01

Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome.

Science.gov (United States)

Gavali, H; Mani, K; Tegler, G; Kawati, R; Covaciu, L; Wanhainen, A

2017-08-01

The aim of the study was to investigate the frequency and outcome of prolonged intensive care unit (ICU) length of stay (LOS) after abdominal aortic aneurysm (AAA) repair in the endovascular era. All patients operated on for AAA between 1999 and 2013 at Uppsala University hospital were identified. Data were retrieved from the Swedish Vascular registry, the Swedish Intensive Care registry, the National Population registry, and case records. Prolonged ICU LOS was defined as ≥ 48 h during the primary hospital stay. Patients surviving ≥ 48 h after AAA surgery were included in the analysis. A total of 725 patients were identified, of whom 707 (97.5%) survived ≥ 48 h; 563 (79.6%) underwent intact AAA repair and 144 (20.4%) ruptured AAA repair. A total of 548 patients (77.5%) required AAA repairs in 1999 to 7.3% in 2013 (p < .001) whereas the use of endovascular aortic repair (EVAR) increased from 6.9% in 1999 to 78.0% in 2013 (p < .001). The 30 day survival rate was 98.2% for those with < 48 h ICU stay versus 93.0% for 2-6 days versus 81.8% for ≥ 7 days (p < .001); the corresponding 90 day survival was 97.1% versus 86.1% versus 63.6% (p < .001) respectively. For patients surviving 90 days after repair, there was no difference in long-term survival between the groups. During the period of progressively increasing use of EVAR, a simultaneous significant reduction in frequency of prolonged ICU LOS occurred. Although prolonged ICU LOS was associated with a high short-term mortality, long-term outcome among those surviving the initial 90 days was less affected. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

[The significance of free radicals and antioxidants due to the load induced by sport activity].

Science.gov (United States)

Holecek, V; Liska, J; Racek, J; Rokyta, R

2004-01-01

Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable.

QT Prolongation due to Graves’ Disease

Directory of Open Access Journals (Sweden)

Zain Kulairi

2017-01-01

Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

Feasibility of proton pencil beam scanning treatment of free-breathing lung cancer patients

NARCIS (Netherlands)

Jakobi, Annika; Perrin, Rosalind; Knopf, Antje; Richter, Christian

BACKGROUND: The interplay effect might degrade the dose of pencil beam scanning proton therapy to a degree that free-breathing treatment might be impossible without further motion mitigation techniques, which complicate and prolong the treatment. We assessed whether treatment of free-breathing

Prognostic significance of macrophage invasion in hilar cholangiocarcinoma

International Nuclear Information System (INIS)

Atanasov, Georgi; Hau, Hans-Michael; Dietel, Corinna; Benzing, Christian; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Matia, Ivan; Prager, Isabel; Schierle, Katrin; Robson, Simon C.; Reutzel-Selke, Anja; Pratschke, Johann; Schmelzle, Moritz; Jonas, Sven

2015-01-01

Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients’ survival. Statistical analysis was performed using SPSS software. Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6 % vs. 75.1 %; three-year 61.3 % vs. 42.4 %; both ρ < 0.05) and recurrence-free survival (one-year 93.9 % vs. 57.4 %; three-year 59.8 % vs. 26.2 %; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs

Exhaustion from prolonged gambling

Directory of Open Access Journals (Sweden)

Fatimah Lateef

2013-01-01

Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

Demonstrating the benefits of fuel cells: further significant progress towards commercialisation

Energy Technology Data Exchange (ETDEWEB)

Anon,

1995-01-01

The fourteenth Fuel Cell Seminar held in San Diego, California in 1994 is reported. The phosphoric acid fuel cell (PAFC) is the closest to widespread commercialization. PAFC cogeneration plants have to be shown to compare favourable in reliability with current mature natural gas-fuelled engine and turbine technologies. Although highly efficient, further development is necessary to produce cost effective generators. Progress is being made on proton exchange membrane fuel cell (PEMFC) stationary power plants, too, which may prove to be cost effective. In view of its lower operating temperature, at below 100[sup o]C compared with about 200[sup o]C for the PAFC, the principal use of the PEMFC has been identified as powering vehicles. Fuel cells have significant environmental advantages but further capital cost reductions are necessary if they are to compete with established technologies. (UK)

9. Nuclear power plant service life prolongation

International Nuclear Information System (INIS)

Evropin, S.V.

1998-01-01

The problem of prolongation of nuclear power plant service life duration is discussed. A schematic diagram of the program developed in the course of activities dealing with NPP service time prolongation is shown and analyzed in details. It is shown that the basic moment when determining the strategy for NPP service time prolongation is the positive confirmation of the agreement between the NPP safety provisions and modern safety requirements. The other very important aspect of the problem is engineering substantiation of the measures assuring the reactor operation prolongation. The conclusion is made that available methods of recovering reactor materials properties, main components repair and replacement, the modern techniques for nondestructive testing of metals and NPP pipelines, as well as the developed approaches to reactor facility safety improvements make the prolongation of the Russian NPP service lifetimes possible from engineering viewpoint and economically desirable

Study progress on free radicals and graves disease

International Nuclear Information System (INIS)

Zhang Ruiguo; Jin Jianhua

2009-01-01

Free radical-mediated oxidative injury has been closely implicated in the occurrence and development of many diseases. Graves disease was also accompanied by changes of the free radicals, especially for reactive oxygen species and reactive nitrogen, et al, and the oxidative stress can cause a certain degree of injury on the thyroid and other human important organs. Antithyroid drug and 131 I treatment of Graves disease, the oxidative and antioxidative parameters can also be changed. (authors)

Therapeutic advancements in multiple myeloma

Directory of Open Access Journals (Sweden)

Alessandro eGozzetti

2014-09-01

Full Text Available Multiple myeloma survival has significantly improved in latest years, due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib and lenalidomide together with autologous stem cell transplantation has dramatically prolonged complete remissions rate, progression free survivals resulting ultimately in prolonged survivals in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to implement responses. A number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, and new kids on the block are entering, making the future of myeloma patients brighter.

Hydroelectrolytic and hormonal modifications related to prolonged bedrest in antiorthostatic position

Science.gov (United States)

Güell, A.; Dupui, Ph.; Fanjaud, G.; Bes, A.; Moatti, J. P.; Gharrib, Cl.

The effects of prolonged bedrest in antiorthostatic position (-4° head down) on electrolyte balance were studied in 4 young volunteers. An increase was noted in sodium excretion during the first 4 days. Plasma renin activity and plasma aldosterone varied in parallel manner during the same period. Potassium balance and creatinine clearance were not significantly modified. In light of these data we feel that prolonged bedrest in antiorthostatic position constitutes an effective way to simulate on earth metabolic and hormonal modifications occurring in man under weightlessness conditions.

Safety information on QT-interval prolongation

DEFF Research Database (Denmark)

Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

2014-01-01

Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve...

Dynamics of the Intratumoral Immune Response during Progression of High-Grade Serous Ovarian Cancer

Directory of Open Access Journals (Sweden)

Mandy Stanske

2018-03-01

Full Text Available PURPOSE: Tumor-infiltrating lymphocytes (TILs have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC, however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2 expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each. Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018. There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026 and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031. High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012. CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.

Celecoxib and GABA cooperatively prevent the progression of pancreatic cancer in vitro and in xenograft models of stress-free and stress-exposed mice.

Directory of Open Access Journals (Sweden)

Hussein A N Al-Wadei

Full Text Available Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis and is associated with high levels of psychological distress. We have shown that beta-adrenergic receptors (β-ARs, which are activated by stress neurotransmitters, regulate PDAC cells via cyclic AMP (cAMP-dependent signaling in vitro, that social stress promotes PDAC progression in mouse xenografts and that γ-aminobutyric acid (GABA inhibits these responses in vitro and in vivo. The targeted inhibition of stress-induced regulatory pathways may abolish the potentially negative impact of psychological stress on clinical outcomes. Our current data show that chronic exposure of PDAC cell lines Panc-1 (activating point mutations in K-ras and BXPC-3 (no mutations in K-ras in vitro to the stress neurotransmitter epinephrine at the concentration (15 nM previously measured in the serum of mice exposed to social stress significantly increased proliferation and migration. These responses were inhibited in a concentration-dependent manner by celecoxib. The effects of celecoxib alone and in combination with γ-aminobutyric acid (GABA on the progression of subcutaneous mouse xenografts from the cell line (BXPC-3 most responsive to epinephrine were then investigated in the presence and absence of social stress. Cancer-stimulating factors (VEGF & prostaglandin E(2 [PGE(2] and levels of cAMP were measured by immunoassays in blood and xenograft tissue. Phosphorylation of the signaling proteins ERK, CREB, Src, and AKT was assessed by ELISA assays and Western blotting. Expression of COX-2, 5-lipoxygenase, and p-5-LOX were determined by semi-quantitative Western blotting. Celecoxib alone significantly inhibited xenograft progression and decreased systemic and tumor VEGF, PGE2, and cAMP as well as phosphorylated signaling proteins in stress-exposed and stress-free mice. These responses were significantly enhanced by co-treatment with GABA. The celecoxib-induced downregulation of COX-2 protein and p-5-LOX

Genetic influence on prolonged gestation

DEFF Research Database (Denmark)

Laursen, Maja; Bille, Camilla; Olesen, Annette Wind

2004-01-01

OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the D...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....

Progress in engineering high strain lead-free piezoelectric ceramics

International Nuclear Information System (INIS)

Leontsev, Serhiy O; Eitel, Richard E

2010-01-01

Environmental concerns are strongly driving the need to replace the lead-based piezoelectric materials currently employed as multilayer actuators. The current review describes both compositional and structural engineering approaches to achieve enhanced piezoelectric properties in lead-free materials. The review of the compositional engineering approach focuses on compositional tuning of the properties and phase behavior in three promising families of lead-free perovskite ferroelectrics: the titanate, alkaline niobate and bismuth perovskites and their solid solutions. The 'structural engineering' approaches focus instead on optimization of microstructural features including grain size, grain orientation or texture, ferroelectric domain size and electrical bias field as potential paths to induce large piezoelectric properties in lead-free piezoceramics. It is suggested that a combination of both compositional and novel structural engineering approaches will be required in order to realize viable lead-free alternatives to current lead-based materials for piezoelectric actuator applications. (topical review)

Progress in engineering high strain lead-free piezoelectric ceramics

Science.gov (United States)

Leontsev, Serhiy O; Eitel, Richard E

2010-01-01

Environmental concerns are strongly driving the need to replace the lead-based piezoelectric materials currently employed as multilayer actuators. The current review describes both compositional and structural engineering approaches to achieve enhanced piezoelectric properties in lead-free materials. The review of the compositional engineering approach focuses on compositional tuning of the properties and phase behavior in three promising families of lead-free perovskite ferroelectrics: the titanate, alkaline niobate and bismuth perovskites and their solid solutions. The ‘structural engineering’ approaches focus instead on optimization of microstructural features including grain size, grain orientation or texture, ferroelectric domain size and electrical bias field as potential paths to induce large piezoelectric properties in lead-free piezoceramics. It is suggested that a combination of both compositional and novel structural engineering approaches will be required in order to realize viable lead-free alternatives to current lead-based materials for piezoelectric actuator applications. PMID:27877343

The research progress of several kinds of free radical scavengers

International Nuclear Information System (INIS)

Qian Liren; Huang Yuecheng; Cai Jianming

2009-01-01

Ionization radiation can generate free radicals in biological system, which could induce lipid peroxi-dation, biomacromolecule and biomembrane damage, lost of cell function, cell cycle disturbance, genetic mutation and so on. The scavenging free radicals can protect organism from radiation damage. Many radio-protective agents, such as amylase, hydroxyl-benzene derivatives, hormone, vitamin, have great abilities to protect organism from radiation via scavenging free radicals. In this paper, we mainly review the free radical scavenging effects of several kinds of radio-protective agents. (authors)

Intrinsic motivation and amotivation in first episode and prolonged psychosis.

Science.gov (United States)

Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L

2015-12-01

The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services. Copyright © 2015 Elsevier B.V. All rights reserved.

Risk factors for QTc interval prolongation

NARCIS (Netherlands)

Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

2018-01-01

Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

Clinical significance of the measurements of serum free thyroxine and free triiodothyronine concentrations

International Nuclear Information System (INIS)

Kubota, Ken; Sasaki, Norio; Takaku, Fumimaro; Uchimura, Hidemasa

1988-01-01

A commercially available ''DPC'' radioimmunoassay kit was used to study the serum concentrations of free triiodothyronine (FT3) and free thyroxine (FT4) in a series of 189 patients with various thyroid diseases and 120 healthy controls. The basal serum concentrations of FT3 and FT4 in normal controls ranged from 0.98 to 2.04 ng/dl and from 1.43 to 3.66 pg/ml, respectively. All untreated patients with Graves' disease had abnormally high FT3 and FT4 values, indicating the discrimination between hyperthyroid and normal subjects. A decreased ratio of FT4 to FT3 was observed in patients managed with antithyroid drugs. In diagnosing hypothyroidism, ''DPC'' FT4 kits were more sensitive than ''DPC'' TT4 and ''Amerlex'' FT4 kits. In the case of non-thyroid diseases, FT4 and FT3 values, as well as total T4 and total T3, were normal or decreased, with the exception of occasionally unknown high values. The interference of thyroxine binding globulin abnormablity was successfully eliminated by using new versions of ''DPC'' kits. (Namekawa, K.)

Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

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Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László

2012-01-01

Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901

Changes in myonuclear domain size do not precede muscle hypertrophy during prolonged resistance-type exercise training.

Science.gov (United States)

Snijders, T; Smeets, J S J; van Kranenburg, J; Kies, A K; van Loon, L J C; Verdijk, L B

2016-02-01

Muscle fibre hypertrophy is accompanied by an increase in myonuclear number, an increase in myonuclear domain size or both. It has been suggested that increases in myonuclear domain size precede myonuclear accretion and subsequent muscle fibre hypertrophy during prolonged exercise training. In this study, we assessed the changes in muscle fibre size, myonuclear and satellite cell content throughout 12 weeks of resistance-type exercise training in young men. Twenty-two young men (23 ± 1 year) were assigned to a progressive, 12-weeks resistance-type exercise training programme (3 sessions per week). Muscle biopsies from the vastus lateralis muscle were taken before and after 2, 4, 8 and 12 weeks of exercise training. Muscle fibre size, myonuclear content, myonuclear domain size and satellite cell content were assessed by immunohistochemistry. Type I and type II muscle fibre size increased gradually throughout the 12 weeks of training (type I: 18 ± 5%, type II: 41 ± 6%, P muscle fibres. No changes in type I and type II myonuclear domain size were observed at any time point throughout the intervention. Satellite cell content increased significantly over time in both type I and type II muscle fibres (P muscle fibre hypertrophy during prolonged resistance-type exercise training in vivo in humans. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Scaling of the critical free length for progressive unfolding of self-bonded graphene

Energy Technology Data Exchange (ETDEWEB)

Kwan, Kenny; Cranford, Steven W., E-mail: s.cranford@neu.edu [Laboratory of Nanotechnology in Civil Engineering (NICE), Department of Civil and Environmental Engineering, Northeastern University, 400 Snell Engineering, 360 Huntington Avenue, Boston, Massachusetts 02115 (United States)

2014-05-19

Like filled pasta, rolled or folded graphene can form a large nanocapsule surrounding a hollow interior. Use as a molecular carrier, however, requires understanding of the opening of such vessels. Here, we investigate a monolayer sheet of graphene as a theoretical trial platform for such a nanocapsule. The graphene is bonded to itself via aligned disulfide (S-S) bonds. Through theoretical analysis and atomistic modeling, we probe the critical nonbonded length (free length, L{sub crit}) that induces fracture-like progressive unfolding as a function of folding radius (R{sub i}). We show a clear linear scaling relationship between the length and radius, which can be used to determine the necessary bond density to predict mechanical opening/closing. However, stochastic dissipated energy limits any exact elastic formulation, and the required energy far exceeds the dissociation energy of the S-S bond. We account for the necessary dissipated kinetic energy through a simple scaling factor (Ω), which agrees well with computational results.

The Prolonged Neonatal Admission: Implications for our National Children's Hospital

LENUS (Irish Health Repository)

McGlacken-Byrne, SM

2016-06-01

A significant number of neonates are admitted to tertiary paediatric units for prolonged stays annually, despite limited availability of neonatal beds. As the three Dublin paediatric hospitals merge, this pressure will be transferred to our new National Children’s Hospital.\\r\

The efficacy of antipsychotics for prolonged delirium with renal dysfunction

Directory of Open Access Journals (Sweden)

Asano S

2017-11-01

Full Text Available Satoko Asano, Yasuto Kunii, Hiroshi Hoshino, Yusuke Osakabe, Tetsuya Shiga, Shuntaro Itagaki, Itaru Miura, Hirooki Yabe Department of Neuropsychiatry, School of Medicine Fukushima Medical University, Fukushima, Japan Aim: Delirium is commonly encountered in daily clinical practice. To identify predictors influencing outcomes, we retrospectively examined the characteristics of inpatients with delirium who required psychiatric medication during hospitalization.Methods: We extracted all new inpatients (n=523 consulted for psychiatric symptoms at Fukushima Medical University Hospital between October 2011 and September 2013. We selected 203 inpatients with delirium diagnosed by psychiatrists. We analyzed data from 177 inpatients with delirium who received psychiatric medication. We defined an “early improvement group” in which delirium resolved in ≤3 days after starting psychiatric medication, and a “prolonged group” with delirium lasting for >3 days. Among the 83 inpatients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2, we defined an “early improvement group with renal dysfunction” in which delirium resolved in ≤3 days after starting psychiatric medication and a “prolonged group with renal dysfunction” with delirium lasting for >3 days. We then examined differences between groups for different categorical variables.Results: Dose of antipsychotic medication at end point was significantly lower in the prolonged group with renal dysfunction than in the early improvement group with renal dysfunction.Conclusion: The results suggest that maintaining a sufficient dose of antipsychotics from an early stage may prevent prolongation of delirium even in inpatients with renal dysfunction. Keywords: antipsychotic, prolonged delirium, chronic kidney disease, pharmacokinetics 

The impact of prolonged violent video-gaming on adolescent sleep: an experimental study.

Science.gov (United States)

King, Daniel L; Gradisar, Michael; Drummond, Aaron; Lovato, Nicole; Wessel, Jason; Micic, Gorica; Douglas, Paul; Delfabbro, Paul

2013-04-01

Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep. © 2012 European Sleep Research Society.

Effects of hydrogen rich water on prolonged intermittent exercise.

Science.gov (United States)

Da Ponte, Alessandro; Giovanelli, Nicola; Nigris, Daniele; Lazzer, Stefano

2018-05-01

Recent studies showed a positive effect of hydrogen rich water (HRW) intake on acid-base homeostasis at rest. We investigated 2-weeks of HRW intake on repeated sprint performance and acid-base status during prolonged intermittent cycling exercise. In a cross over single-blind protocol, 8 trained male cyclists (age [mean±SD] 41±7 years, body mass 72.3±4.4 kg, height 1.77±0.04 m, maximal oxygen uptake [V̇O2max] 52.6±4.4 mL·kg-1·min-1) were provided daily with 2 liters of placebo normal water (PLA, pH 7.6, oxidation/reduction potential [ORP] +230 mV, free hydrogen content 0 ppb) or HRW (pH 9.8, ORP -180 mV, free Hydrogen 450 ppb). Tests were performed at baseline and after each period of 2 weeks of treatment. The treatments were counter-balanced and the sequence randomized. The 30-minute intermittent cycling trial consisted in 10 3-minute blocks, each one composed by 90 seconds at 40% V̇O2max, 60 seconds at 60% V̇O2max, 16 seconds all out sprint, and 14 seconds active recovery. Oxygen uptake (V̇O2), heart rate and power output were measured during the whole test, while mean and peak power output (PPO), time to peak power and Fatigue Index (FI) were determined during all the 16 seconds sprints. Lactate, pH and bicarbonate (HCO3-) concentrations were determined at rest and after each sprint on blood obtained by an antecubital vein indwelling catheter. In the PLA group, PPO in absolute values decreased significantly at the 8th and 9th of 10 sprints and in relative values, ΔPPO, decreased significantly at 6th, 8th and 9th of 10 sprints (by mean: -12±5%, Pmay help to maintain PPO in repetitive sprints to exhaustion over 30 minutes.

Prolongation of islet allograft survival

International Nuclear Information System (INIS)

Lacy, P.E.; Davie, J.M.; Finke, E.H.; Scharp, D.W.

1979-01-01

Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if hand-picked, clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier

Features of History, Anthropometric Data and Individual Functions of the Liver in Children with Prolonged Jaundice

Directory of Open Access Journals (Sweden)

O.V. Tyajka

2016-11-01

Full Text Available Background. Neonatal jaundice is one of the urgent problems in neonatology. There is a tendency to increase the incidence of prolonged jaundice. The aim of our study was to explore the features of history, anthropometric data and some liver functions in children with prolonged jaundice. Materials and methods. The study involved 111 children with prolonged jaundice aged from 3 weeks to 3 months. In all children with prolonged jaundice, we have examined complete blood count, urinalysis, blood chemistry (determination of total bilirubin and fractions, total protein, albumin, glucose and used instrumental methods of examination — ultrasound of the abdominal cavity and cranial ultrasonography, electrocardiography. Most children with prolonged jaundice were breastfed and were term infants. Results. Indicators of physical development at birth (body weight, body length, head circumference, chest circumference in children with prolonged jaundice and in healthy children had not statistically significant differences. Neonatal jaundice was prolonged in children, who were born from the first pregnancy, — 60 children (54.1 %. A high level of total and indirect bilirubin was accompanied by a low level of albumin in the blood serum of children with prolonged jaundice. Protein-synthesis function of the liver was reduced in children with prolonged jaundice.

Effects on respiratory homeostasis of prolonged, continuous hyperoxia at 1.5 to 3.0 ATA in man in Predictive Studies V

Science.gov (United States)

Gelfand, R.; Clark, J. M.; Lambertsen, C. J.; Pisarello, J. B.

1987-01-01

Prolonged exposures of men to continuous hyperoxia at 3.0, 2.5, 2.0, and 1.5 ATA were conducted to define CNS oxygen tolerance and to investigate the effects of prolonged hyperoxia on CNS and other organ functions. Altered respiratory homeostasis was evident during exposures of men to 2.5 and 3.0 ATA O2 as nonprogressive increment in ventilation and reciprocal decrement in PET(CO2). These changes were progressive during exposure at 1.5 ATA O2. Mean values of respiratory reactivity at CO2 were somewhat increased following prolonged hyperoxia at 1.5 and 2.5 ATA, compared to preexposure mean values. Hypoxic ventilatory response was unchanged or enhanced after oxygen exposures at 1.5 and 2.5 ATA. Observed respiratory and body temperature changes were not of sufficient magnitude to impair function.

Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Gogna, Nirdosh Kumar, E-mail: kumar_gogna@health.qld.gov.au [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Burmeister, Elizabeth [Princess Alexandra Hospital, Brisbane, Queensland (Australia); Holt, Tanya [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia)

2012-06-01

Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

Does significant renal ablation truly and invariably lead to hyperfiltration and progressive chronic kidney disease?

Science.gov (United States)

Wang, Andrew; Sam, Ramin

2017-06-01

It is generally believed that significant renal ablation leads to hyperfiltration and eventually progressively worsening chronic kidney disease. The data behind this belief have not been scrutinized intensively. More importantly, the above belief leads many physicians to manage patients differently than they otherwise would manage. Here, we examine the data behind whether hyperfiltration occurs when patients lose kidney mass (by excision or by disease) and whether the hyperfiltration is uniformly injurious.

High frequency components of tracheal sound are emphasized during prolonged flow limitation

International Nuclear Information System (INIS)

Tenhunen, M; Huupponen, E; Saastamoinen, A; Kulkas, A; Himanen, S-L; Rauhala, E

2009-01-01

A nasal pressure transducer, which is used to study nocturnal airflow, also provides information about the inspiratory flow waveform. A round flow shape is presented during normal breathing. A flattened, non-round shape is found during hypopneas and it can also appear in prolonged episodes. The significance of this prolonged flow limitation is still not established. A tracheal sound spectrum has been analyzed further in order to achieve additional information about breathing during sleep. Increased sound frequencies over 500 Hz have been connected to obstruction of the upper airway. The aim of the present study was to examine the tracheal sound signal content of prolonged flow limitation and to find out whether prolonged flow limitation would consist of abundant high frequency activity. Sleep recordings of 36 consecutive patients were examined. The tracheal sound spectral analysis was performed on 10 min episodes of prolonged flow limitation, normal breathing and periodic apnea-hypopnea breathing. The highest total spectral amplitude, implicating loudest sounds, occurred during flow-limited breathing which also presented loudest sounds in all frequency bands above 100 Hz. In addition, the tracheal sound signal during flow-limited breathing constituted proportionally more high frequency activities compared to normal breathing and even periodic apnea-hypopnea breathing

Attachment style dimensions can affect prolonged grief risk in caregivers of terminally ill patients with cancer.

Science.gov (United States)

Lai, Carlo; Luciani, Massimiliano; Galli, Federico; Morelli, Emanuela; Cappelluti, Roberta; Penco, Italo; Aceto, Paola; Lombardo, Luigi

2015-12-01

The aim of the present study was to evaluate the predictive role of attachment dimensions on the risk of prolonged grief. Sixty caregivers of 51 terminally ill patients with cancer who had been admitted in a hospice were selected. Caregivers were interviewed using Attachment Scale Questionnaire, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Prolonged Grief Disorder 12 (PG-12). The consort caregivers showed higher PG-12 level compared to the sibling caregivers. Anxiety, depression, need for approval, and preoccupation with relationships levels were significantly correlated with PG-12 scores. Female gender, high levels of depression, and preoccupation with relationships significantly predicted higher levels of prolonged grief risk. © The Author(s) 2014.

Prolonged preconditioning with natural honey against myocardial infarction injuries.

Science.gov (United States)

Eteraf-Oskouei, Tahereh; Shaseb, Elnaz; Ghaffary, Saba; Najafi, Moslem

2013-07-01

Potential protective effects of prolonged preconditioning with natural honey against myocardial infarction were investigated. Male Wistar rats were pre-treated with honey (1%, 2% and 4%) for 45 days then their hearts were isolated and mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during 30 min regional ischemia fallowed by 120 min reperfusion. Two important indexes of ischemia-induced damage (infarction size and arrhythmias) were determined by computerized planimetry and ECG analysis, respectively. Honey (1% and 2%) reduced infarct size from 23±3.1% (control) to 9.7±2.4 and 9.5±2.3%, respectively (Phoney (1%) significantly reduced (PHoney (1% and 2%) also significantly decreased number of ventricular ectopic beats (VEBs). In addition, incidence and duration of reversible ventricular fibrillation (Rev VF) were lowered by honey 2% (Phoney produced significant reduction in the incidences of VT, total and Rev VF, duration and number of VT. The results showed cardioprotective effects of prolonged pre-treatment of rats with honey following myocardial infarction. Maybe, the existence of antioxidants and energy sources (glucose and fructose) in honey composition and improvement of hemodynamic functions may involve in those protective effects.

Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Rolf Warta

Full Text Available Drug transporters such as P-glycoprotein (ABCB1 have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR or protein expression by tissue microarray (TMA in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC (qRT-PCR, n = 40; TMA, n = 61, this in situ study re-examined the significance of transporter expression for progression-free survival (PFS and overall survival (OS. Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317. In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357 and overall survival (OS, p = 0.0535. Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038. In contrast, protein expression of ATP7b (copper transporter ATP7b, mRNA expression of ABCG2 (BCRP, breast cancer resistance protein, ABCC2 (MRP2, and SLC31A1 (hCTR1, human copper transporter 1 did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC.

Extrinsic factors significantly affect patterns of disease in free-ranging and captive cheetah (Acinonyx jubatus) populations.

Science.gov (United States)

Munson, Linda; Terio, Karen A; Worley, Michael; Jago, Mark; Bagot-Smith, Arthur; Marker, Laurie

2005-07-01

The cheetah (Acinonyx jubatus) has been considered a paradigm for disease vulnerability due to loss of genetic diversity. This species monomorphism has been suspected to be the basis for their general poor health and dwindling populations in captivity. North American and South African captive populations have high prevalences of hepatic veno-occlusive disease, glomerulosclerosis, gastritis, and systemic amyloidosis, diseases that are rare in other species. Unusually severe inflammatory reactions to common infectious agents have also been documented in captive cheetahs. The current study compared disease prevalences in free-ranging Namibian cheetahs with those in two captive populations of similar ages. The occurrence of diseases in the free-ranging population was determined from 49 necropsies and 27 gastric biopsies obtained between 1986 and 2003 and compared with prevalences in 147 North American and 80 South African captive cheetahs. Except for two cheetahs, the free-ranging population was in robust health with only mild lesions present, in contrast with significantly higher prevalences in the captive populations. Despite widespread heavy Helicobacter colonization in wild cheetahs, only 3% of the free-ranging population had moderate to severe gastritis, in contrast with 64% of captive cheetahs. No severe inflammatory reactions to viral infections were detected in the free-ranging animals. Because free-ranging Namibian cheetahs are as genetically impoverished as captive cheetahs, these findings caution against attributing loss of fitness solely to genetic factors and attest to the fundamental importance of extrinsic factors in wildlife health.

Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy

DEFF Research Database (Denmark)

Mollerup, Hannah Malthe; Gätke, M R

2011-01-01

patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim...... of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT....

QT interval prolongation associated with sibutramine treatment

Science.gov (United States)

Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

2006-01-01

Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

Influence of a prolonged fasting and mild activity on routine laboratory tests.

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Šupak-Smolčić, Vesna; Antončić, Dragana; Ožanić, Doris; Vladilo, Ivana; Bilić-Zulle, Lidija

2015-01-01

Despite the standardization of the phlebotomy procedure, blood analysis is occasionally requested after recommended hours with the excuse that the patient is still fasting. We aimed to examine the influence of prolonged fasting and mild physical activity on routine laboratory tests. The study was conducted on 30 volunteers (27 female) median age 40y (20-59). Blood samples were taken in the morning (7:00-8:00a.m.) and early afternoon (1:00-2:00p.m.) after prolonged fasting and usual daily activities. Serum glucose (GLU), urea, creatinine, triglyceride, uric acid (UA), iron and electrolytes were analyzed on Roche cobas 6000 c501 and complete blood count on Siemens ADVIA 2120i. Statistical significance between the two measurements was tested using paired t-test or Wilcoxon test according to data distribution. Clinical significance was judged against calculated reference change values (RCV). A statistically significant decrease was found for red blood cell count, hemoglobin, hematocrit, mean corpuscular volume (MCV), GLU, urea, creatinine, triglycerides and electrolytes, whereas white blood cell count and iron were significantly increased. Judging against desirable bias derived from biological variation, a significant change was found for all the analytes except MCV, platelet count, UA and triglycerides. A clinically significant change was not found for any of the tested analytes when compared to RCV. Prolonged fasting and mild activity will not influence the medical decision for healthy subjects with normal results. Despite the present statistically significant change, the clinically significant change was not shown. However, the study did not include pathological results which have to be interpreted more carefully. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Electrocardiographic PR prolongation and atrial fibrillation risk: a meta-analysis of prospective cohort studies.

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Cheng, Min; Lu, Xiangfeng; Huang, Jianfeng; Zhang, Shu; Gu, Dongfeng

2015-01-01

Electrocardiographic PR interval prolongation is considered a benign condition, but recent studies have challenged the notion by demonstrating that prolonged PR interval is associated with an increased risk of atrial fibrillation (AF). The purpose of this study was to perform a meta-analysis of prospective cohort studies to evaluate the evidence supporting an association of prolonged PR interval with AF incidence. We searched the MEDLINE and EMBASE database (from inception to May 2014) supplemented by manual searches of references of relevant retrieved articles. Prospective cohort studies were included with hazard ratio (HR) of prolonged PR interval for incident AF. The search strategy yielded 6 cohort studies meeting eligibility criteria. A total of 328,932 participants were included, with 14,191 participants suffering from AF during follow-up. Pooled HRs of prolonged PR interval for incident AF was 1.30 (95% CI: 1.13 to 1.49) using random-effect model (I(2) = 30%). There was a significant difference of combined HRs between studies with and without adjustment for taking of AV nodal blocking agents in subgroup analysis. Sensitivity analysis supported the robustness of the results. Prolonged PR interval is not a totally benign condition but an independent risk factor for AF incidence. The mechanisms underlying the association of prolonged PR interval with AF incidence need further research. © 2014 Wiley Periodicals, Inc.

Licence prolongations of US nuclear power plants

International Nuclear Information System (INIS)

2004-04-01

Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

Free-Floating Iris Cyst in a Patient with Recurrent Iritis

Directory of Open Access Journals (Sweden)

Joanne M.Y. Teong

2015-06-01

Full Text Available Purpose: We describe an unusual clinical finding of a free-floating iris cyst in a patient with recurrent iritis. Method: The clinical finding of a free-floating iris cyst was recorded using slit-lamp photography. Results: A 39-year-old male with a 5-year history of recurrent right iritis was found to have a small mobile iris cyst within his right anterior chamber, first identified 3 years ago. The patient did not experience any discomfort or visual symptoms resulting from the cyst. Conclusion: Surgical removal is not indicated for asymptomatic non-progressive free-floating iris cysts. The significance of a free-floating iris cyst in the setting of recurrent iritis remains unknown.

Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

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Attila Kristóf

Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

Spin-trappers and vitamin E prolong endurance to muscle fatigue in mice

Energy Technology Data Exchange (ETDEWEB)

Novelli, G.P.; Bracciotti, G.; Falsini, S. (Univ. of Florence (Italy))

1990-01-01

The involvement of free radicals in endurance to muscle effort is suggested by experimental and clinical data. Therefore, experiments have been performed to observe the effect of trapping free radicals on endurance to swimming in mice. Animals were injected intraperitoneally with each of three spin-trappers (N-tert-Butyl-alpha-Phenyl-Nitrone (PBN),alpha-4-Pyridyil-1-Oxide-N-tert-Butyl-Nitrone (POBN) and 5,5-Dimethyl-1-Pirrolyn-N-Oxide (DMPO): 0.2 ml of 10(-1) molar solution). Each mouse was submitted to a swimming test to control resistance to exhaustion (a) without any treatment, (b) after administration of each spin-trapper in a random order (c) after saline. Control experiments were performed with saline and with vitamin E. Endurance to swimming was greatly prolonged by pretreatment with all the spin-trappers (DMPO less than 0.0001; POBN less than 0.0001; PBN less than 0.001) and with Vitamin E. Experiments state that compared to treatment with spin-trappers or Vitamin E, administration of saline alone did not enhance time to exhaustion so that the increase in time to exhaustion with the various free radical scavengers was not the effect of training. Therefore, free radicals could be considered as one of the factors terminating muscle effort in mice.

Prolonged Intermittent Renal Replacement Therapy.

Science.gov (United States)

Edrees, Fahad; Li, Tingting; Vijayan, Anitha

2016-05-01

Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Clinical significance of pretreatment FDG PET/CT IN MOBG-avid pediatric neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Kang, Seo Young; Kim, Yong Il; Cheon, Gi Jeong; Kang, Keon Wook; Chung, June Key; Lee, Dong Soo; Kang, Hyoung Jin; Shin, Hee Young [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Seoul National University, Seoul (Korea, Republic of); Rahim, Muhammad Kashif [Nishtar Medical College and Hospital, Multan (Pakistan)

2017-06-15

{sup 18}F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in 123I- or 131I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information—including histopathology, and serum markers—and several PET parameters—including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)—were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS). Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023). FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.

Grading of Emphysema Is Indispensable for Predicting Prolonged Air Leak After Lung Lobectomy.

Science.gov (United States)

Murakami, Junichi; Ueda, Kazuhiro; Tanaka, Toshiki; Kobayashi, Taiga; Hamano, Kimikazu

2018-04-01

The aim of this study was to assess the utility of quantitative computed tomography-based grading of emphysema for predicting prolonged air leak after thoracoscopic lobectomy. A consecutive series of 284 patients undergoing thoracoscopic lobectomy for lung cancer was retrospectively reviewed. Prolonged air leak was defined as air leaks lasting 7 days or longer. The grade of emphysema (emphysema index) was defined by the proportion of the emphysematous lung volume (less than -910 HU) to the total lung volume (-600 to -1,024 HU) by a computer-assisted histogram analysis of whole-lung computed tomography scans. The mean length of chest tube drainage was 1.5 days. Fifteen patients (5.3%) presented with prolonged air leak. According to a receiver-operating characteristics curve analysis, the emphysema index was the best predictor of prolonged air leak, with an area under the curve of 0.85 (95% confidence interval: 0.73 to 0.98). An emphysema index of 35% or greater was the best cutoff value for predicting prolonged air leak, with a negative predictive value of 0.99. The emphysema index was the only significant predictor for the length of postoperative chest tube drainage among conventional variables, including the pulmonary function and resected lobe, in both univariate and multivariate analyses. Prolonged air leak resulted in an increased duration of hospitalization (p leak that adversely influences early postoperative outcomes. We must take new measures against prolonged air leak in quantitative computed tomography-based high-risk patients. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

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Tulay Akman

2014-11-01

Full Text Available Background: Pazopanib (PZP may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6. The first group (normal group received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP, to the normal group and to the second group (control-PZP+SP group; 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca, to the third group (PZP+metoprolol group; and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat, to the fourth group (PZP+diltiazem group. One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001. Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

Effectiveness of Cognitive Processing Therapy and Prolonged Exposure in the Department of Veterans Affairs.

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Rutt, Benjamin T; Oehlert, Mary E; Krieshok, Thomas S; Lichtenberg, James W

2018-04-01

Objective This study evaluated the effectiveness of cognitive processing therapy and prolonged exposure in conditions reflective of current clinical practice within the Veterans Health Administration. Method This study involved a retrospective review of 2030 charts. A total of 750 veterans from 10 U.S. states who received cognitive processing therapy or prolonged exposure in individual psychotherapy were included in the study (participants in cognitive processing therapy, N = 376; participants in prolonged exposure, N = 374). The main dependent variable was self-reported posttraumatic stress disorder symptoms as measured by total scores on the Posttraumatic Stress Disorder Checklist. The study used multilevel modeling to evaluate the absolute and relative effectiveness of both treatments and determine the relationship between patient-level variables and total Posttraumatic Stress Disorder Checklist scores during treatment. Results Cognitive processing therapy and prolonged exposure were equally effective at reducing total Posttraumatic Stress Disorder Checklist scores. Veterans who completed therapy reported significantly larger reductions in the Posttraumatic Stress Disorder Checklist than patients who did not complete therapy. There were no significant differences in the improvement of posttraumatic stress disorder symptoms with respect to age and three racial/ethnic groups (Caucasian, African American, and Hispanic). Conclusions Cognitive processing therapy and prolonged exposure were shown to be effective in conditions highly reflective of clinical practice and with a highly diverse sample of veterans. Challenges related to dropout from trauma focused therapy should continue to be researched.

Past, Recent Progresses and Future Perspectives of Nanotechnology Applied to Antifungal Agents.

Science.gov (United States)

Roque, Luis; Molpeceres, Jesus; Reis, Claudia; Rijo, Patrícia; Reis, Catarina Pinto

2017-01-01

Candida species remain a significant cause of nosocomial bloodstream infections, associated with prolonged hospital stay in the ICU and high healthcare cost. The incidence of Candida is very high in certain risk groups of patients (AIDS, diabetes, cancer, etc.). Recent developments of nanotechnology have strongly contributed to the design of new multifunctional drug carriers that improve drug bioavailability through a controlled and prolonged release profile or even through a more specific targeted delivery of the antifungal agent. Those types of systems have strongly increased with a progressive generation of new structures, permitting the conjunction of new materials, biomolecules, physical and chemical techniques, for better outcomes. Nanotechnology shows expanded possibilities within the medical field and in the case of the yeast infections it may overcome several issues related with the fungal proliferation or higher inhibition of the pathogen causing the infection. This review covers a period of the most representative research of Candidiasis since 1993 to the present. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Progress of new label-free techniques for biosensors: a review.

Science.gov (United States)

Sang, Shengbo; Wang, Yajun; Feng, Qiliang; Wei, Ye; Ji, Jianlong; Zhang, Wendong

2016-01-01

The detection techniques used in biosensors can be broadly classified into label-based and label-free. Label-based detection relies on the specific properties of labels for detecting a particular target. In contrast, label-free detection is suitable for the target molecules that are not labeled or the screening of analytes which are not easy to tag. Also, more types of label-free biosensors have emerged with developments in biotechnology. The latest developed techniques in label-free biosensors, such as field-effect transistors-based biosensors including carbon nanotube field-effect transistor biosensors, graphene field-effect transistor biosensors and silicon nanowire field-effect transistor biosensors, magnetoelastic biosensors, optical-based biosensors, surface stress-based biosensors and other type of biosensors based on the nanotechnology are discussed. The sensing principles, configurations, sensing performance, applications, advantages and restriction of different label-free based biosensors are considered and discussed in this review. Most concepts included in this survey could certainly be applied to the development of this kind of biosensor in the future.

Screening for older emergency department inpatients at risk of prolonged hospital stay: the brief geriatric assessment tool.

Directory of Open Access Journals (Sweden)

Cyrille P Launay

Full Text Available The aims of this study were 1 to confirm that combinations of brief geriatric assessment (BGA items were significant risk factors for prolonged LHS among geriatric patients hospitalized in acute care medical units after their admission to the emergency department (ED; and 2 to determine whether these combinations of BGA items could be used as a prognostic tool of prolonged LHS.Based on a prospective observational cohort design, 1254 inpatients (mean age ± standard deviation, 84.9±5.9 years; 59.3% female recruited upon their admission to ED and discharged in acute care medical units of Angers University Hospital, France, were selected in this study. At baseline assessment, a BGA was performed and included the following 6 items: age ≥85years, male gender, polypharmacy (i.e., ≥5 drugs per day, use of home-help services, history of falls in previous 6 months and temporal disorientation (i.e., inability to give the month and/or year. The LHS in acute care medical units was prospectively calculated in number of days using the hospital registry.Area under receiver operating characteristic (ROC curves of prolonged LHS of different combinations of BGA items ranged from 0.50 to 0.57. Cox regression models revealed that combinations defining a high risk of prolonged LHS, identified from ROC curves, were significant risk factors for prolonged LHS (hazard ratio >1.16 with P>0.010. Kaplan-Meier distributions of discharge showed that inpatients classified in high-risk group of prolonged LHS were discharged later than those in low-risk group (P<0.003. Prognostic value for prolonged LHS of all combinations was poor with sensitivity under 77%, a high variation of specificity (from 26.6 to 97.4 and a low likelihood ratio of positive test under 5.6.Combinations of 6-item BGA tool were significant risk factors for prolonged LHS but their prognostic value was poor in the studied sample of older inpatients.

[Research progress in hirudin fusion protein--review].

Science.gov (United States)

Zhang, Chuan-Ling; Yu, Ai-Ping; Jin, Ji-De; Wu, Chu-Tse

2007-02-01

Natural hirudin extracted from the secretion of medical leech salivary gland is a single-chain peptide containing 65 aminoacid residues with molecular weight of 7000 D, and exists in three isomers of HV1, HV2 and HV3. Hirudin possesses three disulfide bridges forming the structure of core cyclic peptides, which binds to the catalytic site of thrombin so as to inhibit the catalysis of thrombin. Its c-terminus rich in acidic aminoacid residues possesses hydrophilicity, and is free on the molecular surface, and can bind with fibrin recognition site of hirudin. The minimal segment of 12 - 16 C-terminal acidic residues keeps the minimal activity of anti-thrombosis. Thus, hirudin, as a potent and specific inhibitor of thrombin, can be used to protect from and to treat clinically thrombosis. As it has some disadvantages such as short half-life, bleeding side-effect and mono-function, and so on, hirudin has been fused with some other functional proteins in recent years. The obtained fusion proteins can prolong the half life of hirudin, or relieve it bleeding side effect, or bring new functions, such as thrombolysis, inhibiting the platelet aggregation, targeting specifically. The research progress in hirudin fusion protein was summarized in this review.

Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

Science.gov (United States)

Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

2010-01-01

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

Science.gov (United States)

Payancé, Audrey; Scotto, Béatrice; Perarnau, Jean-Marc; de Muret, Anne; Bacq, Yannick

2013-11-01

Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Prenatal risk indicators of a prolonged pregnancy

DEFF Research Database (Denmark)

Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn

2006-01-01

BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from...

Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures.

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Zilony, Neta; Rosenberg, Michal; Holtzman, Liran; Schori, Hadas; Shefi, Orit; Segal, Ester

2017-07-10

Although nerve growth factor (NGF) is beneficial for the treatment of numerous neurological and non-neurological diseases, its therapeutic administration represents a significant challenge, due to the difficulty to locally deliver relevant doses in a safe and non-invasive manner. In this work, we employ degradable nanostructured porous silicon (PSi) films as carriers for NGF, allowing its continuous and prolonged release, while retaining its bioactivity. The PSi carriers exhibit high loading efficacy (up to 90%) of NGF and a continuous release, with no burst, over a period of>26days. The released NGF bioactivity is compared to that of free NGF in both PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the NGF has retained its bioactivity and induces neurite outgrowth and profound differentiation (of >50% for PC12 cells) throughout the period of release within a single administration. Thus, this proof-of-concept study demonstrates the immense therapeutic potential of these tunable carriers as long-term implants of NGF reservoirs and paves the way for new localized treatment strategies of neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Free will and psychiatric assessments of criminal responsibility: a parallel with informed consent.

Science.gov (United States)

Meynen, Gerben

2010-11-01

In some criminal cases a forensic psychiatrist is asked to make an assessment of the state of mind of the defendant at the time of the legally relevant act. A considerable number of people seem to hold that the basis for this assessment is that free will is required for legal responsibility, and that mental disorders can compromise free will. In fact, because of the alleged relationship between the forensic assessment and free will, researchers in forensic psychiatry also consider the complicated metaphysical discussions on free will relevant to the assessment. At the same time, there is concern about the lack of advancement with respect to clarifying the nature of the forensic assessment. In this paper I argue that, even if free will is considered relevant, there may be no need for forensic researchers to engage into metaphysical discussions on free will in order to make significant progress. I will do so, drawing a parallel between the assessment of criminal responsibility on the one hand, and the medical practice of obtaining informed consent on the other. I argue that also with respect to informed consent, free will is considered relevant, or even crucial. This is the parallel. Yet, researchers on informed consent have not entered into metaphysical debates on free will. Meanwhile, research on informed consent has made significant progress. Based on the parallel with respect to free will, and the differences with respect to research, I conclude that researchers on forensic assessment may not have to engage into metaphysical discussions on free will in order to advance our understanding of this psychiatric practice.

Assigning Significance in Label-Free Quantitative Proteomics to Include Single-Peptide-Hit Proteins with Low Replicates

OpenAIRE

Li, Qingbo

2010-01-01

When sample replicates are limited in a label-free proteomics experiment, selecting differentially regulated proteins with an assignment of statistical significance remains difficult for proteins with a single-peptide hit or a small fold-change. This paper aims to address this issue. An important component of the approach employed here is to utilize the rule of Minimum number of Permuted Significant Pairings (MPSP) to reduce false positives. The MPSP rule generates permuted sample pairings fr...

Correlation of prolonged QT interval and severity of cirrhosis of liver

International Nuclear Information System (INIS)

Tarique, S.; Sarwar, S.

2011-01-01

To determine correlation between prolonged QT interval and severity of disease in patients of cirrhosis of liver. Study Design: Descriptive cross sectional study. Patients and Methods: One hundred and seventeen patients of cirrhosis were included. Baseline haematological and biochemical parameters were determined. Model for end stage liver disease (MELD) score was determined for all patients to document stage of liver disease. Corrected QT interval was determined from electrocardiography of each patient using QT cirrhosis formula. Correlation between QT interval and MELD score was determined using Pearson correlation and Receiver Operating Characteristic (ROC) curve. Results: One hundred and seventeen included patients had mean age of 53.58 (+- 12.11) while male to female ratio was 1.78/1 (75 / 42). Mean MELD score was 17.08 (+- 6.54) in study patients varying between 6 and 37 while mean corrected QT interval was 0.44 seconds (+- 0.06). Pearson correlation revealed no significant relation between severity of liver disease as determined with MELD score and prolonged QT interval (p value 0.18) Area under curve with ROC curve for correlation between prolonged QT interval and severity of liver disease was 0.42. Conclusion: Prolonged QT interval is not an indicator of severity of disease in cirrhosis of liver. (author)

Randomized controlled trial of a protein substitute with prolonged release on the protein status of children with phenylketonuria.

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Giovannini, Marcello; Riva, Enrica; Salvatici, Elisabetta; Cefalo, Graziella; Radaelli, Giovanni

2014-01-01

To examine whether a phenylalanine-free protein substitute with prolonged release may be beneficial to the protein status of children with phenylketonuria (PKU) compared to conventional substitutes. Sixty children with PKU, 7 to 16 years of age, were randomly allocated to receive either a prolonged-release (test) or the current conventional protein substitute for 30 days. Subjects were additionally sex and age matched with 60 subjects with mild hyperphenylalaninemia and 60 unaffected subjects. The protein status in children with PKU was assessed by albumin, transthyretin, and retinol-binding protein (RBP), and changes throughout the trial period were the primary outcome measures. Children with PKU did not differ in anthropometry from children with mild hyperphenylalaninemia or unaffected children but they ingested lower amounts of proteins (p phenylketonuria.

Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue

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Malmström Anders

2006-05-01

Full Text Available Abstract Background Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods Uterine isthmic biopsies were collected from non-pregnant (n = 7, term pregnant women not in labour (n = 14, in normal labour (n = 7 and in prolonged labour (n = 7. mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p Conclusion The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

Does UTI cause prolonged jaundice in otherwise well infants?

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Chowdhury, Tanzila; Kisat, Hamudi; Tullus, Kjell

2015-07-01

The symptoms of urinary tract infections in infants are very non-specific and have historically included prolonged hyperbilirubinaemia. We studied the results of routine urine samples in 319 infants with prolonged jaundice. Convincing findings of UTI was not found in any of these children even if one of them was treated with antibiotics after four consecutive urine cultures with different bacteria. A urine culture might thus not be an appropriate investigation in a child with prolonged jaundice without any other symptoms of UTI. • The symptoms of UTI in infancy are very non-specific. • Old studies suggest that prolonged hyperbilirubinaemia is one such symptom; more modern studies give more conflicting results. What is New: • Our study could not confirm that children with prolonged jaundice have an increased risk of UTI. • Routine urine testing is thus not needed in otherwise healthy infants with prolonged jaundice.

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort.

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Abdul-Aziz, Mohd H; Lipman, Jeffrey; Akova, Murat; Bassetti, Matteo; De Waele, Jan J; Dimopoulos, George; Dulhunty, Joel; Kaukonen, Kirsi-Maija; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C; Roberts, Jason A

2016-01-01

We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT>MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P = 0.012]. Additionally, in patients with a SOFA score of ≥9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P = 0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P = 0.025]. Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e

Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid Bioadhesive Nanoparticles

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J. Varshosaz

2014-01-01

Full Text Available The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT. Therefore, poly(methyl vinyl ether maleic acid [P(MVEMA] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1, iv solution of sCT (5 μg·kg−1, and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly.

How to Deal with Interval-Censored Data Practically while Assessing the Progression-Free Survival: A Step-by-Step Guide Using SAS and R Software.

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Dugué, Audrey Emmanuelle; Pulido, Marina; Chabaud, Sylvie; Belin, Lisa; Gal, Jocelyn

2016-12-01

We describe how to estimate progression-free survival while dealing with interval-censored data in the setting of clinical trials in oncology. Three procedures with SAS and R statistical software are described: one allowing for a nonparametric maximum likelihood estimation of the survival curve using the EM-ICM (Expectation and Maximization-Iterative Convex Minorant) algorithm as described by Wellner and Zhan in 1997; a sensitivity analysis procedure in which the progression time is assigned (i) at the midpoint, (ii) at the upper limit (reflecting the standard analysis when the progression time is assigned at the first radiologic exam showing progressive disease), or (iii) at the lower limit of the censoring interval; and finally, two multiple imputations are described considering a uniform or the nonparametric maximum likelihood estimation (NPMLE) distribution. Clin Cancer Res; 22(23); 5629-35. ©2016 AACR. ©2016 American Association for Cancer Research.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

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Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

Muscle Shear Moduli Changes and Frequency of Alternate Muscle Activity of Plantar Flexor Synergists Induced by Prolonged Low-Level Contraction

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Ryota Akagi

2017-09-01

Full Text Available During prolonged low-level contractions, synergist muscles are activated in an alternating pattern of activity and silence called as alternate muscle activity. Resting muscle stiffness is considered to increase due to muscle fatigue. Thus, we investigated whether the difference in the extent of fatigue of each plantar flexor synergist corresponded to the difference in the frequency of alternate muscle activity between the synergists using muscle shear modulus as an index of muscle stiffness. Nineteen young men voluntarily participated in this study. The shear moduli of the resting medial and lateral gastrocnemius muscles (MG and LG and soleus muscle (SOL were measured using shear wave ultrasound elastography before and after a 1-h sustained contraction at 10% peak torque during maximal voluntary contraction of isometric plantar flexion. One subject did not accomplish the task and the alternate muscle activity for MG was not found in 2 subjects; therefore, data for 16 subjects were used for further analyses. The magnitude of muscle activation during the fatiguing task was similar in MG and SOL. The percent change in shear modulus before and after the fatiguing task (MG: 16.7 ± 12.0%, SOL: −4.1 ± 13.9%; mean ± standard deviation and the alternate muscle activity during the fatiguing task (MG: 33 [20–51] times, SOL: 30 [17–36] times; median [25th–75th percentile] were significantly higher in MG than in SOL. The contraction-induced change in shear modulus (7.4 ± 20.3% and the alternate muscle activity (37 [20–45] times of LG with the lowest magnitude of muscle activation during the fatiguing task among the plantar flexors were not significantly different from those of the other muscles. These results suggest that the degree of increase in muscle shear modulus induced by prolonged contraction corresponds to the frequency of alternate muscle activity between MG and SOL during prolonged contraction. Thus, it is likely that, compared with

Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

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Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

2018-05-01

Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0

High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

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Bjartell Anders

2011-09-01

Full Text Available Abstract Background High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer. Findings Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR (HR 0.56, 95% CI: 0.34-0.93, p = 0.024 and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021. These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression. Conclusion Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

Stuck in Neutral: Stalled Progress in Statewide Comprehensive Smoke-Free Laws and Cigarette Excise Taxes, United States, 2000–2014

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King, Brian A.; Babb, Stephen D.

2016-01-01

Introduction Increasing tobacco excise taxes and implementing comprehensive smoke-free laws are two of the most effective population-level strategies to reduce tobacco use, prevent tobacco use initiation, and protect nonsmokers from secondhand smoke. We examined state laws related to smoke-free buildings and to cigarette excise taxes from 2000 through 2014 to see how implementation of these laws from 2000 through 2009 differs from implementation in more recent years (2010–2014). Methods We used legislative data from LexisNexis, an online legal research database, to examine changes in statewide smoke-free laws and cigarette excise taxes in effect from January 1, 2000, through December 31, 2014. A comprehensive smoke-free law was defined as a statewide law prohibiting smoking in all indoor areas of private work sites, restaurants, and bars. Results From 2000 through 2009, 21 states and the District of Columbia implemented comprehensive smoke-free laws prohibiting smoking in work sites, restaurants, and bars. In 2010, 4 states implemented comprehensive smoke-free laws. The last state to implement a comprehensive smoke-free law was North Dakota in 2012, bringing the total number to 26 states and the District of Columbia. From 2000 through 2009, 46 states and the District of Columbia implemented laws increasing their cigarette excise tax, which increased the national average state excise tax rate by $0.92. However, from 2010 through 2014, only 14 states and the District of Columbia increased their excise tax, which increased the national average state excise tax rate by $0.20. Conclusion The recent stall in progress in enacting and implementing statewide comprehensive smoke-free laws and increasing cigarette excise taxes may undermine tobacco prevention and control efforts in the United States, undercutting efforts to reduce tobacco use, exposure to secondhand smoke, health disparities, and tobacco-related illness and death. PMID:27309417

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

International Nuclear Information System (INIS)

Chen, James X.; Rose, Steven; White, Sarah B.; El-Haddad, Ghassan; Fidelman, Nicholas; Yarmohammadi, Hooman; Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita; Stashek, Kristen; Wileyto, E. Paul; Salem, Riad; Metz, David C.; Soulen, Michael C.

2017-01-01

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p  50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

Energy Technology Data Exchange (ETDEWEB)

Chen, James X. [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Rose, Steven [University of San Diego Medical Center, Division of Interventional Radiology, Department of Radiology (United States); White, Sarah B. [Medical College of Wisconsin, Division of Interventional Radiology, Department of Radiology (United States); El-Haddad, Ghassan [Moffitt Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Fidelman, Nicholas [University of San Francisco Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Yarmohammadi, Hooman [Memorial Sloan Kettering Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita [Stanford University Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Stashek, Kristen [Hospital of the University of Pennsylvania, Department of Pathology (United States); Wileyto, E. Paul [University of Pennsylvania, Department of Biostatistics and Epidemiology (United States); Salem, Riad [Northwestern Memorial Hospital, Division of Interventional Radiology, Department of Radiology (United States); Metz, David C. [Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine (United States); Soulen, Michael C., E-mail: michael.soulen@uphs.upenn.edu [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States)

2017-01-15

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

The Association between Job-Related Psychosocial Factors and Prolonged Fatigue among Industrial Employees in Taiwan.

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Feng-Cheng Tang

Full Text Available Prolonged fatigue is common among employees, but the relationship between prolonged fatigue and job-related psychosocial factors is seldom studied. This study aimed (1 to assess the individual relations of physical condition, psychological condition, and job-related psychosocial factors to prolonged fatigue among employees, and (2 to clarify the associations between job-related psychosocial factors and prolonged fatigue using hierarchical regression when demographic characteristics, physical condition, and psychological condition were controlled.A cross-sectional study was employed. A questionnaire was used to obtain information pertaining to demographic characteristics, physical condition (perceived physical health and exercise routine, psychological condition (perceived mental health and psychological distress, job-related psychosocial factors (job demand, job control, and workplace social support, and prolonged fatigue.A total of 3,109 employees were recruited. Using multiple regression with controlled demographic characteristics, psychological condition explained 52.0% of the variance in prolonged fatigue. Physical condition and job-related psychosocial factors had an adjusted R2 of 0.370 and 0.251, respectively. Hierarchical multiple regression revealed that, among job-related psychosocial factors, job demand and job control showed significant associations with fatigue.Our findings highlight the role of job demand and job control, in addition to the role of perceived physical health, perceived mental health, and psychological distress, in workers' prolonged fatigue. However, more research is required to verify the causation among all the variables.

Prolonged labour as indication for emergency caesarean section

DEFF Research Database (Denmark)

Maaløe, Nanna; Sorensen, B L; Onesmo, R

2012-01-01

To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

Prolonged Pregnancy: Methods, Causal Determinants and Outcome

DEFF Research Database (Denmark)

Olesen, Annette Wind

) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... an ultrasound scan in the first or second trimester, or menstrual history was best at predicting the day of delivery; 5) to study the risk of recurrence of prolonged pregnancy as a function of change in male partner, social status and municipality; and 6) to detect prenatal risk indicators of prolonged...... of perinatal and obstetrical complications was high in post-term delivery compared to term delivery (OR between 1.2 and 3.1). The risk of perinatal death (OR=1.36 (1.08-1.72)) was also higher in the post-term group (I). The self-reported gestational ages in the National Birth Cohort correlated well with data...

SU119. Internalized Stigma in Adults With Early-Phase vs Prolonged Psychosis

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Firmin, Ruth; Vohs, Jenifer; Luther, Lauren; Yanos, Philip; Leonhardt, Bethany; Lysaker, Paul

2017-01-01

Abstract Background: While internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one’s illness stigma is internalized and the impact of internalization on symptoms or quality of life over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with quality of life or symptoms among those with prolonged compared to early-phase psychosis. Methods: Individuals with early-phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and quality of life. Results: Controlling for education, race, and sex differences, internalized stigma was significantly greater among those with prolonged compared to early-phase psychosis. Internalized stigma was negatively related to quality of life and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early-phase psychosis. Stereotype endorsement, discrimination experiences, and social withdrawal also deferentially related to symptoms and quality of life across the 2 samples. Conclusion: Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Further, internalized stigma may be a possible treatment target among those in their early phase of psychosis.

Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium.

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Vandael, Eline; Vandenberk, Bert; Vandenberghe, Joris; Spriet, Isabel; Willems, Rik; Foulon, Veerle

2016-04-01

Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. Management of the risk of QTc-prolongation. Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

Adapting to warmer climate through prolonged maize grain filling period in the US Midwest

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Zhu, P.; Zhuang, Q.; Jin, Z.

2017-12-01

Climate warming is expected to negatively impact the US food productivity. How to adapt to the future warmer environment and meet the rising food requirement becomes unprecedented urgent. Continuous satellite observational data provides an opportunity to examine the historic responses of crop plants to climate variation. Here 16 years crop growing phases information across US Midwest is generated based on satellite observations. We found a prolonged grain-filling period during 2000-2015, which could partly explain the increasing trend in Midwest maize yield. This longer grain-filling period might be resulted from the adoption of longer maturity group varieties or more resistant varieties to temperature variation. Other management practice changes like advance in planting date could be also an effective way of adapting future warmer climate through lowering the possibility of exposure to heat and drought stresses. If the progress in breeding technology enables the maize grain-filling period to prolong with the current rate, the maize grain filling length could be longer and maize yield in Midwest could adapt to future climate despite of the warming.

Prolonged QRS Widening After Aripiprazole Overdose.

Science.gov (United States)

Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

2018-05-05

Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

Prolonged ultraviolet light-induced erythema and the cutaneous carcinoma phenotype

International Nuclear Information System (INIS)

Tanenbaum, L.; Parrish, J.A.; Haynes, H.A.; Fitzpatrick, T.B.; Pathak, M.A.

1976-01-01

A considerable amount of evidence exists in support of the role of ultraviolet radiation as a major etiologic factor in human skin cancer, both melanoma and carcinoma types. On the basis of epidemiologic studies a phenotype has been described which helps to identify the persons who are more susceptible to skin cancer. In an attempt to further define this population, patients with cutaneous carcinoma and a normal control group were exposed to artificial ultraviolet light (UVL) and the erythema and tanning responses of each group were measured over a 21-day period. UVL-induced erythema was prolonged in a significantly higher percentage of patients with skin cancer than in control patients, lasting two to three weeks after single exposures to 6 and 8 times the patient's minimal erythema dose. The presence of prolonged erythema correlated with this history of previous skin cancer but did not correlate with other established risk factors for cutaneous carcinoma, i.e., fair skin, light hair and light eyes, easy sunburning and poor tanning, and Celtic ancestry. Prolonged erythema following UVL radiation may therefore represent an additional risk factor and help to identify the skin cancer-susceptible population

Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli.

Science.gov (United States)

Kim, Hee Kee; Schattschneider, Jörn; Lee, Inhyung; Chung, Kyungsoon; Baron, Ralf; Chung, Jin Mo

2007-05-01

This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-s stimulation repeated every 30s for 30 min. Foot withdrawal thresholds to von Frey stimuli applied to the paw were measured once a day for 4 weeks. The capsaicin-only group (control rats without daily stimulation) showed hyperalgesia lasting for 3 days. In contrast, hyperalgesia persisted for 2 weeks in the group that received vibration stimulation. Neither the soft brush nor the pressure group showed a significant difference in mechanical threshold from the control group (capsaicin only). The vibration-induced prolonged hyperalgesia was significantly reduced by systemic injection of ifenprodil, an NMDA-receptor antagonist, but it was not influenced by either an AMPA-receptor blocker or a reactive oxygen species (ROS) scavenger. Furthermore, a dorsal column lesion did not interfere with the prolongation of hyperalgesia. Data suggest that vibration-induced prolongation of hyperalgesia is mediated by spinal NMDA-receptors, and a similar mechanism may underlie some forms of chronic pain with no obvious causes, such as complex regional pain syndrome type 1 (CRPS-1).

Software-assisted small bowel motility analysis using free-breathing MRI: feasibility study.

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Bickelhaupt, Sebastian; Froehlich, Johannes M; Cattin, Roger; Raible, Stephan; Bouquet, Hanspeter; Bill, Urs; Patak, Michael A

2014-01-01

To validate a software prototype allowing for small bowel motility analysis in free breathing by comparing it to manual measurements. In all, 25 patients (15 male, 10 female; mean age 39 years) were included in this Institutional Review Board-approved, retrospective study. Magnetic resonance imaging (MRI) was performed on a 1.5T system after standardized preparation acquiring motility sequences in free breathing over 69-84 seconds. Small bowel motility was analyzed manually and with the software. Functional parameters, measurement time, and reproducibility were compared using the coefficient of variance and paired Student's t-test. Correlation was analyzed using Pearson's correlation coefficient and linear regression. The 25 segments were analyzed twice both by hand and using the software with automatic breathing correction. All assessed parameters significantly correlated between the methods (P software (3.90%, standard deviation [SD] ± 5.69) than manual examinations (9.77%, SD ± 11.08). The time needed was significantly less (P software (4.52 minutes, SD ± 1.58) compared to manual measurement, lasting 17.48 minutes for manual (SD ± 1.75 minutes). The use of the software proves reliable and faster small bowel motility measurements in free-breathing MRI compared to manual analyses. The new technique allows for analyses of prolonged sequences acquired in free breathing, improving the informative value of the examinations by amplifying the evaluable data. Copyright © 2013 Wiley Periodicals, Inc.

Prolonged Exposure Therapy For Post Traumatic Stress Disorder

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Levent SÜTÇİGİL

2012-07-01

Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma

International Nuclear Information System (INIS)

Wang, Maomao; Deng, Xiaodong; Ying, Qi; Jin, Tingyan; Li, Ming; Liang, Chong

2015-01-01

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan–Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan–Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. - Highlights: • MiR-224 expression is correlates with prognosis in meningioma patients. • ERG2 is a novel downstream target of miR-224. • MiR-224 suppressed cell growth and enhanced apoptosis in IOMM-Lee and CH157 cells. • MiR-224 is an upstream regulator of the ERG2

[Diagnostic significance of serum free DNA human telomerase reverse transcriptase quantitative determination on spinal cord injury].

Science.gov (United States)

Yang, M K; Tang, J; Xiang, Z; Zhang, X; Wang, J; Li, Z; Li, Y; Sheng, W B

2018-02-06

Objective: To investigate the relationship between the content of human telomerase reverse transcriptase (hTERT) and its clinical features in serum free DNA in patients with different degree of spinal cord injury. Methods: From December 2013 to December 2016, inpatients of the Central Hospital of Bazhong, Sichuan Province were enrolledand divided into the experimental group, the disease control group and the negative control group. For the experimental group: 46 patients with spinal cord injury were graded according to the criteria of the American Association of Spinal Cord Injury (ASIA), including 12 cases of grade A, 10 cases of grade B, 10 cases of grade C, 7 cases of grade D and 7 cases of grade E; for the disease control group: 15 patients with spinal fractures (without spinal cord injury) at the same period were included; and for the negative control group: 20 healthy adult volunteers aged 18-50 years were selected.Real-time fluorescence quantitative PCR and immunoblotting were performed to detect the content of hTERT in serum free DNA both in patients and healthy controls and to compare the difference between them. The results of the somatosensory evoked potential (SEP) of all patients were compared and analyzed.The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of hTERT content in serum free DNA in patients with spinal cord injury. Results: Comparison of serum free DNA hTERT content: in the experimental group, the serum free DNA hTERT content of grade A, B, C, D, E was (99.63±8.23), (76.24±4.37), (46.07±5.43), (16.30±0.95) and (15.74±1.12)μg/L, respectively.While it was (15.01±1.39)μg/L in the disease control group and (14.54±1.03)μg/L in the negative control group. The total difference was statistically significant between patients of each group and the control group ( F =857.917, P spinal cord injury has a certain guiding significance for the diagnosis of spinal cord injury and the degree of injury.

Flexible, cathodoluminescent and free standing mesoporous silica films with entrapped quasi-2D perovskites

Science.gov (United States)

Vassilakopoulou, Anastasia; Papadatos, Dionysios; Koutselas, Ioannis

2017-04-01

The effective entrapment of hybrid organic-inorganic semiconductors (HOIS) into mesoporous polymer-silica hybrid matrices, formed as free standing flexible films, is presented for the first time. A blend of quasi-2D HOIS, simply synthesized by mixing two-dimensional (2D) and three dimensional (3D) HOIS, exhibiting strong photoluminescence, is embedded into porous silica matrices during the sol-gel synthesis, using tetraethylorthosilicate as precursor and Pluronic F-127 triblock copolymer as structure directing agent, under acidic conditions. The final nanostructure hybrid forms flexible, free standing films, presenting high cathodoluminescence and long stable excitonic luminescence, indicating the protective character of the hybrid matrix towards the entrapped perovskite. A significant result is that the photoluminescence of the entrapped HOIS is not affected even after films' prolonged exposure to water.

Screening for older emergency department inpatients at risk of prolonged hospital stay: the brief geriatric assessment tool.

Science.gov (United States)

Launay, Cyrille P; de Decker, Laure; Kabeshova, Anastasiia; Annweiler, Cédric; Beauchet, Olivier

2014-01-01

The aims of this study were 1) to confirm that combinations of brief geriatric assessment (BGA) items were significant risk factors for prolonged LHS among geriatric patients hospitalized in acute care medical units after their admission to the emergency department (ED); and 2) to determine whether these combinations of BGA items could be used as a prognostic tool of prolonged LHS. Based on a prospective observational cohort design, 1254 inpatients (mean age ± standard deviation, 84.9±5.9 years; 59.3% female) recruited upon their admission to ED and discharged in acute care medical units of Angers University Hospital, France, were selected in this study. At baseline assessment, a BGA was performed and included the following 6 items: age ≥85years, male gender, polypharmacy (i.e., ≥5 drugs per day), use of home-help services, history of falls in previous 6 months and temporal disorientation (i.e., inability to give the month and/or year). The LHS in acute care medical units was prospectively calculated in number of days using the hospital registry. Area under receiver operating characteristic (ROC) curves of prolonged LHS of different combinations of BGA items ranged from 0.50 to 0.57. Cox regression models revealed that combinations defining a high risk of prolonged LHS, identified from ROC curves, were significant risk factors for prolonged LHS (hazard ratio >1.16 with P>0.010). Kaplan-Meier distributions of discharge showed that inpatients classified in high-risk group of prolonged LHS were discharged later than those in low-risk group (PLHS of all combinations was poor with sensitivity under 77%, a high variation of specificity (from 26.6 to 97.4) and a low likelihood ratio of positive test under 5.6. Combinations of 6-item BGA tool were significant risk factors for prolonged LHS but their prognostic value was poor in the studied sample of older inpatients.

The Association between Job-Related Psychosocial Factors and Prolonged Fatigue among Industrial Employees in Taiwan

Science.gov (United States)

Tang, Feng-Cheng; Li, Ren-Hau; Huang, Shu-Ling

2016-01-01

Background and Objectives Prolonged fatigue is common among employees, but the relationship between prolonged fatigue and job-related psychosocial factors is seldom studied. This study aimed (1) to assess the individual relations of physical condition, psychological condition, and job-related psychosocial factors to prolonged fatigue among employees, and (2) to clarify the associations between job-related psychosocial factors and prolonged fatigue using hierarchical regression when demographic characteristics, physical condition, and psychological condition were controlled. Methods A cross-sectional study was employed. A questionnaire was used to obtain information pertaining to demographic characteristics, physical condition (perceived physical health and exercise routine), psychological condition (perceived mental health and psychological distress), job-related psychosocial factors (job demand, job control, and workplace social support), and prolonged fatigue. Results A total of 3,109 employees were recruited. Using multiple regression with controlled demographic characteristics, psychological condition explained 52.0% of the variance in prolonged fatigue. Physical condition and job-related psychosocial factors had an adjusted R2 of 0.370 and 0.251, respectively. Hierarchical multiple regression revealed that, among job-related psychosocial factors, job demand and job control showed significant associations with fatigue. Conclusion Our findings highlight the role of job demand and job control, in addition to the role of perceived physical health, perceived mental health, and psychological distress, in workers’ prolonged fatigue. However, more research is required to verify the causation among all the variables. PMID:26930064

FUNCTIONAL OUTCOMES OF HIP ARTHROSCOPY IN AN ACTIVE DUTY MILITARY POPULATION UTILIZING A CRITERION-BASED EARLY WEIGHT BEARING PROGRESSION.

Science.gov (United States)

Shaw, K Aaron; Jacobs, Jeremy M; Evanson, J Richard; Pniewski, Josh; Dickston, Michelle L; Mueller, Terry; Bojescul, John A

2017-10-01

Hip arthroscopy allows surgeons to address intra-articular pathology of the hip while avoiding more invasive open surgical dislocation. However the post-operative rehabilitation protocols have varied greatly in the literature, with many having prolonged periods of limited motion and weight bearing. The purpose of this study was to describe a criterion-based early weight bearing protocol following hip arthroscopy and investigate functional outcomes in the subjects who were active duty military. Active duty personnel undergoing hip arthroscopy for symptomatic femoroacetabular impingement were prospectively assessed in a controlled environment for the ability to incorporate early postoperative weight-bearing with the following criteria: no increased pain complaint with weight bearing and normalized gait pattern. Modified Harris Hip (HHS) and Hip Outcome score (HOS) were performed preoperatively and at six months post-op. Participants were progressed with a standard hip arthroscopy protocol. Hip flexion was limited to not exceed 90 degrees for the first three weeks post-op, with progression back to running beginning at three months. Final discharge was dependent upon the ability to run two miles at military specified pace and do a single leg broad jump within six inches of the contralateral leg without an increase in pain. Eleven participants met inclusion criteria over the study period. Crutch use was discontinued at an average of five days following surgery based on established weight bearing criteria. Only one participant required continued crutch use at 15 days. Participants' functional outcome was improved postoperatively, as demonstrated by significant increases in HOS and HHS. At the six month follow up, eight of 11 participants were able to take and complete a full Army Physical Fitness Test. Following completion of the early weight bearing rehabilitation protocol, 81% of participants were able to progress to full weight bearing by four days post

All delays before radiotherapy risk progression of Merkel cell carcinoma

International Nuclear Information System (INIS)

Tsang, G.; O'Brien, P.; Robertson, R.; Hamilton, C.; Wratten, C.; Denham, J.

2004-01-01

Prolonged waiting times for radiotherapy have resulted in many centres assigning priorities to various patient or diagnostic groups. A high risk of progression on a waiting list is one factor that would reasonably influence the priority. The present descriptive study of 27 patients with Merkel cell carcinoma (MCC) found that a median wait of 24 days for radiotherapy is associated with a high risk of progression. Eleven (41%) of 27 patients developed progressive disease, including five (45%) of 11 patients waiting for adjuvant radiotherapy. Patients treated adjuvantly also had longer waiting times prior to their initial radiotherapy consultation (median 41 days), which may have contributed to the rate of progression. Merkel cell carcinoma is an aggressive but curable malignancy and appropriate management should include efforts to minimize all potential delays prior to the commencement of radiotherapy. Copyright (2004) Blackwell Science Pty Ltd

Effect of prolonging radiation delivery time on retention of gammaH2AX

International Nuclear Information System (INIS)

Moiseenko, Vitali; Banáth, Judit P; Duzenli, Cheryl; Olive, Peggy L

2008-01-01

Compared to conventional external beam radiotherapy, IMRT requires significantly more time to deliver the dose. Prolonging dose delivery potentially increases DNA repair which would reduce the biological effect. We questioned whether retention of γH2AX, a measure of lack of repair of DNA damage, would decrease when dose delivery was protracted. Exponentially growing SiHa cervical carinoma cells were irradiated with 6 MV photons in a water tank using a VarianEX linear accelerator. Cells held at 37°C received 2 Gy in 0.5 min and 4 Gy in 1 min. To evaluate effect of dose delivery prolongation, 2 and 4 Gy were delivered in 30 and 60 min. After 24 h recovery, cells were analyzed for clonogenic survival and for residual γH2AX as measured using flow cytometry. Increasing the dose delivery time from 0.5 or 1 min to 30 or 60 min produced a signficant increase in cell survival from 0.45 to 0.48 after 2 Gy, and from 0.17 to 0.20 after 4 Gy. Expression of residual γH2AX decreased from 1.27 to 1.22 relative to background after 2 Gy and 1.46 to 1.39 relative to background after 4 Gy, but differences were not statistically significant. The relative differences in the slopes of residual γH2AX versus dose for acute versus prolonged irradiation bordered on significant (p = 0.055), and the magnitude of the change was consistent with the observed increase in surviving fraction. These results support the concept that DNA repair underlies the increase in survival observed when dose delivery is prolonged. They also help to establish the limits of sensitivity of residual γH2AX, as measured using flow cytometry, for detecting differences in response to irradiation

Progress in scaffold-free bioprinting for cardiovascular medicine.

Science.gov (United States)

Moldovan, Nicanor I

2018-06-01

Biofabrication of tissue analogues is aspiring to become a disruptive technology capable to solve standing biomedical problems, from generation of improved tissue models for drug testing to alleviation of the shortage of organs for transplantation. Arguably, the most powerful tool of this revolution is bioprinting, understood as the assembling of cells with biomaterials in three-dimensional structures. It is less appreciated, however, that bioprinting is not a uniform methodology, but comprises a variety of approaches. These can be broadly classified in two categories, based on the use or not of supporting biomaterials (known as "scaffolds," usually printable hydrogels also called "bioinks"). Importantly, several limitations of scaffold-dependent bioprinting can be avoided by the "scaffold-free" methods. In this overview, we comparatively present these approaches and highlight the rapidly evolving scaffold-free bioprinting, as applied to cardiovascular tissue engineering. © 2018 The Author. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Effect of prolonged stress on the adrenal hormones of individuals with irritable bowel syndrome.

Science.gov (United States)

Sugaya, Nagisa; Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Nomura, Shinobu; Shimada, Hironori

2015-01-01

The purpose of this study was to investigate the effect of prolonged stress on the salivary adrenal hormones (cortisol, dehydroepiandrosterone [DHEA], DHEA-sulfate [DHEA-S]) of individuals with irritable bowel syndrome (IBS). The participants were female college students, including 10 with IBS and 16 without IBS (control group), who were scheduled for a 2-week teaching practice at a kindergarten. Participants were asked to collect saliva for determining adrenal hormones immediately and 30 min after awakening and before sleep, 2 weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. Regarding cortisol/DHEA ratio, significantly increased levels were found during the first week of the practice, and a significant interaction between group and time was found; the ratio at 30 min after awakening in the IBS group was higher than that in the control group. For the other adrenal hormone indexes, no significant differences due to the presence of IBS were found. Individuals with IBS showed an elevated cortisol/DHEA ratio after awakening compared with individuals without IBS, and the elevated ratio peaked under the prolonged stress. The present study suggests that the cortisol effect is dominant in individuals with IBS under prolonged stress.

Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine

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John P. O’Laughlin

2016-01-01

Full Text Available We present a case of a syncopal episode resulting from significant QT interval prolongation in a patient on hydroxychloroquine for the treatment of systemic lupus erythematosus and end stage renal disease. The patient had been treated with hydroxychloroquine for two years prior to presentation. After thorough workup for secondary causes of QT interval prolongation hydroxychloroquine was discontinued and the patient’s QT interval shortened. The patient was treated with mexiletine to prevent sudden ventricular arrhythmias, which was unique compared to other documented cases in which lidocaine was used. The patient was noted to have mild prolongation of the QT interval on electrocardiogram prior to initiation of hydroxychloroquine therapy which was exacerbated by its use and may have been caused due to toxicity from underlying renal failure.

Marked QTc prolongation and Torsades de Pointes in patients with chronic inflammatory arthritis

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Pietro Enea Lazzerini

2016-09-01

Full Text Available Mounting evidence indicates that in chronic inflammatory arthritis (CIA, QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration (APD, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in RA patients the risk of SCD is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about Torsades de Pointes (TdP prevalence in CIA, and the few case reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development.We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24h from TdP/marked QTc prolongation occurrence and levels of IL-6, TNF-alpha and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNF-alpha and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other classical risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This observation should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required.

Progressively unstable c2 spondylolysis requiring spinal fusion: case report.

Science.gov (United States)

Nishimura, Yusuke; Ellis, Michael John; Anderson, Jennifer; Hara, Masahito; Natsume, Atsushi; Ginsberg, Howard Joeseph

2014-01-01

Cervical spondylolysis is a rare condition defined as a corticated cleft at the pars interarticularis in the cervical spine. This is the case of C2 spondylolysis demonstrating progressive significant instability, which was successfully treated by anterior cervical discectomy and fusion (ACDF) with cervical anterior plate. We describe a 20-year-old female with C2 spondylolysis presenting with progressive worsening of neck pain associated with progressive instability at the C2/3 segment. The progression of instability was well-documented on flexion-extension cervical spine x-rays. She was successfully treated by C2/3 ACDF with anterior cervical plate. Her preoperative significant neck pain resolved immediately after the surgical intervention. She was completely free from neurological symptoms at 1-year postoperative follow-up. We also review the literature and discuss 24 reported cases with C2 spondylolysis. When planning treatment, we should make sure to differentiate this pathology from acute traumatic fracture, which is a hangman's fracture. Assessment of C2/3 instability associated with neurological deficits is extremely important to consider management properly. C2/3 ACDF with cervical plate is biomechanically viable, less invasive, and provides adequate surgical stabilization for unstable C2 spondylolysis.

Screening for Older Emergency Department Inpatients at Risk of Prolonged Hospital Stay: The Brief Geriatric Assessment Tool

Science.gov (United States)

Launay, Cyrille P.; de Decker, Laure; Kabeshova, Anastasiia; Annweiler, Cédric; Beauchet, Olivier

2014-01-01

Background The aims of this study were 1) to confirm that combinations of brief geriatric assessment (BGA) items were significant risk factors for prolonged LHS among geriatric patients hospitalized in acute care medical units after their admission to the emergency department (ED); and 2) to determine whether these combinations of BGA items could be used as a prognostic tool of prolonged LHS. Methods Based on a prospective observational cohort design, 1254 inpatients (mean age ± standard deviation, 84.9±5.9 years; 59.3% female) recruited upon their admission to ED and discharged in acute care medical units of Angers University Hospital, France, were selected in this study. At baseline assessment, a BGA was performed and included the following 6 items: age ≥85years, male gender, polypharmacy (i.e., ≥5 drugs per day), use of home-help services, history of falls in previous 6 months and temporal disorientation (i.e., inability to give the month and/or year). The LHS in acute care medical units was prospectively calculated in number of days using the hospital registry. Results Area under receiver operating characteristic (ROC) curves of prolonged LHS of different combinations of BGA items ranged from 0.50 to 0.57. Cox regression models revealed that combinations defining a high risk of prolonged LHS, identified from ROC curves, were significant risk factors for prolonged LHS (hazard ratio >1.16 with P>0.010). Kaplan-Meier distributions of discharge showed that inpatients classified in high-risk group of prolonged LHS were discharged later than those in low-risk group (Prisk factors for prolonged LHS but their prognostic value was poor in the studied sample of older inpatients. PMID:25333271

Prolonged Exposure Therapy For Post Traumatic Stress Disorder

Directory of Open Access Journals (Sweden)

Levent SÜTÇÝGÝL

2012-08-01

Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies. [JCBPR 2012; 1(2.000: 98-104

Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

DEFF Research Database (Denmark)

Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

2003-01-01

not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.......We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...

QTc interval prolongation in HIV-infected patients: a case–control study by 24-hour Holter ECG recording

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Fiorentini Alessandra

2012-12-01

Full Text Available Abstract Background Aim of the study was to assess QTc interval by a 24-hour ECG recording in a group of HIV-infected individuals with a basal prolonged QTc. The risk factors associated with QTc prolongation and the indices of cardiovascular autonomic control were also evaluated. Methods A case–control study was performed using as cases 32 HIV-infected patients with prolonged (>440 msec QTc interval as assessed by Holter ECG, and as controls 64 HIV-infected subjects with normal QTc interval. Autonomic function was evaluated by heart rate variability analysis during 24-hour recording. Results Duration of HIV disease was significantly longer among cases than among controls (p=0.04. Waist/hip ratio was also higher among cases than among controls (p=0.05. Frequency domain analysis showed the absence of physiologic decrease of low frequency (LF in the night period in both cases and controls. The LF night in cases showed a statistically significant reduction when compared with controls (p=0.007. Conclusions In our study group, QTc interval prolongation was associated with a longer duration of HIV infection and with a greater waist/hip ratio. HIV patients with QTc interval prolongation and with a longer duration of HIV infection were more likely to have an impairment of parasympathetic and sympathetic cardiac component.

Comparison of Ocular Pulse Amplitude Lowering Effects of Preservative-Free Tafluprost and Preservative-Free Dorzolamide-Timolol Fixed Combination Eyedrops.

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Seo, Du Ri; Ha, Seung Joo

2015-01-01

To compare the ocular pulse amplitude (OPA) lowering effects of preservative-free tafluprost and dorzolamide-timolol fixed combination (DTFC) using dynamic contour tonometry. In total, 66 eyes of 66 patients with normal tension glaucoma (NTG) (n = 34) or primary open angle glaucoma (POAG) (n = 32) were included. Patients were divided into two groups: the preservative-free tafluprost-treated group (n = 33) and the preservative-free DTFC-treated group (n = 33). Intraocular pressure (IOP) was measured using Goldmann applanation tonometry (GAT). OPA was measured using dynamic contour tonometry; corrected OPA (cOPA) was calculated at baseline and at 1 week and 1, 3, and 6 months after treatment. After 6 months of treatment, tafluprost significantly reduced IOP (P < 0.001). The OPA lowering effects differed significantly between the two treatment groups (P = 0.003). The cOPA-lowering effect of tafluprost (1.09 mmHg) was significantly greater than that of DTFC (0.36 mmHg) after 6 months of treatment (P = 0.01). Tafluprost and DTFC glaucoma treatments provided marked OPA and IOP lowering effects. Tafluprost had a greater effect than DTFC; thus, this drug is recommended for patients at risk of glaucoma progression, due to the high OPA caused by large fluctuations in IOP.

Serial CT scans of cerebral hypoxia due to prolonged status epilepticus

Energy Technology Data Exchange (ETDEWEB)

Saiwai, Shigeo; Matsumura, Yasumasa; Tamaoka, Koichi; Fukuda, Teruo; Miyamoto, Takeshi [Kobe Central Municipal Hospital, Kobe (Japan)

1983-04-01

Serial computed tomography (CT) scans of 5 infants with status epilepticus were reviewed. Four out of the 5 infants fortunately had CT scans before status epilepticus because of a convulsion. There was a diffuse and mild low density in the hemisphere, with small ventricles and tight sulci (brain swelling) at 1 to 2 days after ictus. Thereafter, a diffuse low density became apparent except for the cerebellum, the brain stem, the thalamus, and the basal ganglia. Two to 4 weeks after ictus, a localized, mottled low density was demonstrated on the cerebral mantle and atrophic changes became progressively clear. In 3 cases, no abnormal enhancement was elicited on contrast CT scans performed between 5 to 16 days after status epilepticus. We discussed the possible pathophysiological aspects of the brain damage due to ''prolonged status epilepticus.''

A Continuous-Exchange Cell-Free Protein Synthesis System Based on Extracts from Cultured Insect Cells

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Stech, Marlitt; Quast, Robert B.; Sachse, Rita; Schulze, Corina; Wüstenhagen, Doreen A.; Kubick, Stefan

2014-01-01

In this study, we present a novel technique for the synthesis of complex prokaryotic and eukaryotic proteins by using a continuous-exchange cell-free (CECF) protein synthesis system based on extracts from cultured insect cells. Our approach consists of two basic elements: First, protein synthesis is performed in insect cell lysates which harbor endogenous microsomal vesicles, enabling a translocation of de novo synthesized target proteins into the lumen of the insect vesicles or, in the case of membrane proteins, their embedding into a natural membrane scaffold. Second, cell-free reactions are performed in a two chamber dialysis device for 48 h. The combination of the eukaryotic cell-free translation system based on insect cell extracts and the CECF translation system results in significantly prolonged reaction life times and increased protein yields compared to conventional batch reactions. In this context, we demonstrate the synthesis of various representative model proteins, among them cytosolic proteins, pharmacological relevant membrane proteins and glycosylated proteins in an endotoxin-free environment. Furthermore, the cell-free system used in this study is well-suited for the synthesis of biologically active tissue-type-plasminogen activator, a complex eukaryotic protein harboring multiple disulfide bonds. PMID:24804975

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States.

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Thomas, Zachariah; Bandali, Farooq; Sankaranarayanan, Jayashri; Reardon, Tom; Olsen, Keith M

2015-12-01

The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. Multicenter, prospective, observational, 72-hour snapshot study. Sixty-seven ICUs from 32 hospitals in the United States. Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. None. Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate. Half of all

The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.

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Chun-Xia Yi

Full Text Available Ghrelin acylation by ghrelin O-acyltransferase (GOAT has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation.Male and female knockout (KO mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO were subjected to prolonged calorie restriction (40% of ad libitum chow intake. Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin.Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes.The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction.

Studies of free radicals by ultraviolet excimer laser photolysis. Progress report, 1 April 1980-1 November 1980

International Nuclear Information System (INIS)

Leone, S.R.

1980-01-01

An experimental technique has been developed to produce and directly study vibrationally excited free radicals. Pulses of light from an ultraviolet excimer laser are used to photodissociate small molecules to generate free radicals with high internal excitation. The radicals are detected directly by the technique of time and wavelength-resolved infrared emission spectroscopy using a background-limited copper-doped germanium infrared detector. New results have been obtained on the CH 3 radical. A complete spectrum of the CH 3 umbrella band reveals for the first time accurate positions of the vibrational progression in this band. Photofragmentation of (CH 3 ) 2 Hg has yielded detailed information on the vibrational distribution, rotational temperature, and deactivation rates of the CH 3 stretch mode. A technique to study chemical chain reactions using low power, radical-specific, laser initiation and realtime kinetics detection had previously been demonstrated. The results provide a general method to study a large number of chain reaction combustion systems in greater detail. New results on more complex chain reactions such as Cl 2 /butane reveal that highly detailed infrared emission spectra of various products of the chain and their time evolution is possible. Partitioning of energy between vibrational degrees of freedom and translational heating is obtained over the course of the combustion

[Prolonged desensitization pretreatment for in vitro fertilization in women with polycystic ovary].

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Kuczyński, W; Czech, R; Redźko, S; Wasilewski, T; Mrugacz, G; Wołczyński, S; Pietrewicz, P; Grochowski, D; Szamatowicz, M

2000-09-01

To analyse the outcome of intracytoplasmic sperm injection (ICSI) in women with severe polycystic ovary disease (PCD), stimulated after prolonged pituitary desensitization in comparison with regular long protocol therapy. The results of controlled ovarian hyperstimulation (COH), fertilization rate, early embryo development parameters and clinical pregnancy rates were compared depending on the duration of pituitary desensitization before gonadotropin administration. A total of 60 patients with severe PCOD were desensitized with GnRH agonist up to 30 days before COH. The results were compared with the group of 213 patients with mild PCOD treated with regular long protocol (control). We observed a slightly higher rate of mature oocytes MII as well as the number of embryos obtained in the control group, however the pregnancy rate in the group with prolonged desensitization was significantly higher (50%) in comparison to the control group (33.8%). The prolonged pituitary desensitization before controlled ovarian hyperstimulation gives better chance for obtaining pregnancy in patients with severe PCOD. It could be recommended facing previous treatment failure.

Topical Drug Formulations for Prolonged Corneal Anesthesia

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Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

2013-01-01

Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis.

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Jiajie Zang

Full Text Available Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4% and 3.7% (8.1-30.4%, respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6% and 12.0% (4.5-28.0%, respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71, than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09 and 5.70 (3.09-10.53 among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation.

Secondary bacteraemia in adult patients with prolonged dengue fever.

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Premaratna, R; Dissanayake, D; Silva, F H D S; Dassanayake, M; de Silva, H J

2015-03-01

Although dengue management guidelines do not advice on use of antibiotics in dengue shock syndrome, unrecognised bactraemia is likely to contribute to morbidity and mortality. To assess the occurance of secondary bacteraemia in adult patients with prolonged dengue fever. A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days). Two sets of blood cultures were taken in such patients prior to institution of antibiotic therapy. Demographic, clinical, haematological and biochemical parameters were recorded. Development of ascites and pleural effusions were detected using ultrasonography. Fourty patients (52.5% males) with a mean age of 29.8 years (SD 13.6) were studied. The average duration of fever was 7.9 days (SD 1.8). Ten patients (25%) had bacterial isolates in their blood cultures; Staphylococcus aureus (n=2), coliforms (n=3), pseudomonas (n=1) and 4 had mixed growths. The culture positive group had severe body aches at admission and higher fever, third space fluid accumulation, a significant drop in platelets and a higher CRP. A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture positive patients appeared more ill with body aches and had higher degrees of fever during the latter part of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia, low platelet count and elevation of CRP seem to be helpful.

Prolonged Response and Restoration of Functional Independence with Bevacizumab plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal Metastases

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Emilie Le Rhun

2015-02-01

Full Text Available Background: Survival of patients with leptomeningeal metastases (LM and impaired functional status is limited to several months, and rarely does neurological function improve with treatment. Case Report: A 34-year-old female with hormone-negative and HER2-positive metastatic breast cancer was diagnosed with bulky radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer progressed 8 months after the diagnosis of LM. At the time of the third LM progression, the patient presented with a cauda equina syndrome and cerebellar impairment resulting in an inability to walk. She was treated with CNS-directed radiotherapy (lumbosacral and cerebellar and bevacizumab plus vinorelbine. Rapid functional improvement occurred, and the patient regained the ability to walk and independently manage her daily activities. Twelve months later, she presented with rapid progression of the LM resulting in death within several weeks. Conclusion: In radiographically defined bulky LM, the combination of systemic therapy and CNS-directed radiotherapy likely is more active than intra-CSF therapy only. In lieu of the rapid and significant improvement in neurological function combined with the prolonged response, bevacizumab alone or in combination with chemotherapy and CNS-directed radiotherapy may be considered in select patients with radiographically bulky breast cancer-related LM.

TOPICAL REVIEW: Progress in engineering high strain lead-free piezoelectric ceramics

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Leontsev, Serhiy O.; Eitel, Richard E.

2010-08-01

Environmental concerns are strongly driving the need to replace the lead-based piezoelectric materials currently employed as multilayer actuators. The current review describes both compositional and structural engineering approaches to achieve enhanced piezoelectric properties in lead-free materials. The review of the compositional engineering approach focuses on compositional tuning of the properties and phase behavior in three promising families of lead-free perovskite ferroelectrics: the titanate, alkaline niobate and bismuth perovskites and their solid solutions. The 'structural engineering' approaches focus instead on optimization of microstructural features including grain size, grain orientation or texture, ferroelectric domain size and electrical bias field as potential paths to induce large piezoelectric properties in lead-free piezoceramics. It is suggested that a combination of both compositional and novel structural engineering approaches will be required in order to realize viable lead-free alternatives to current lead-based materials for piezoelectric actuator applications.

Cryogen free low temperature sample environment for neutron scattering experiments

International Nuclear Information System (INIS)

Kirichek, O; Evans, B E; Down, R B E; Bowden, Z A

2009-01-01

Recent increase in liquid helium cost caused by global helium supply problems rose significant concern about affordability of conventional cryogenic equipment. Luckily the progress in cryo-cooler technology offers a new generation of cryogenic systems with significantly reduced consumption and in some cases nearly complete elimination of cryogens. These cryogen-free systems also offer the advantage of operational simplicity and require less space than conventional cryogen-cooled systems. The ISIS facility carries on an internal development program intended to substitute gradually all conventional cryogenic systems with cryogen free systems preferably based on pulse tube refrigerators. A unique feature of this cryo-cooler is the absence of cold moving parts. This considerably reduces vibrations and increases the reliability of the cold head. The program includes few development projects which are aiming to deliver range of cryogen free equipment including top-loading cryostat, superconducting magnets and dilution refrigerators. Here we are going to describe the design of these systems and discuss the results of prototypes testing.

RD50 Prolongation Request 2018

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Casse, Gianluigi

2018-01-01

With this document, we request the prolongation of the CERN RD50 research program for 5 years. A very brief historical review of the RD50 research program since the RD50 project approval by the Research Board in the year 2002 is presented and the biggest RD50 achievements are highlighted. The present composition of the collaboration, its organizational structure, and the research methodology are described. The role of RD50 in the present various upgrade and research programs of the LHC Experiments community is given and the overall work plan explained. Finally, a detailed 5-years work program with precise milestones and deliverables for the various research activities is presented. We conclude with our prolongation request towards the LHCC.

Reduced estimated glomerular filtration rate (eGFR 73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

Science.gov (United States)

Blute, Michael L; Kucherov, Victor; Rushmer, Timothy J; Damodaran, Shivashankar; Shi, Fangfang; Abel, E Jason; Jarrard, David F; Richards, Kyle A; Messing, Edward M; Downs, Tracy M

2017-09-01

To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) 73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of 73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of 73 m 2 (P 73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of 73 m 2 (P = 0.01). Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

The effect of medial arch support over the plantar pressure and triceps surae muscle strength after prolonged standing

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Hindun Saadah

2015-11-01

Full Text Available Background: The activity with prolonged standing position is one of the causes of abnormalities in the lower leg and foot. The aim of this study is to discover the effect of medial arch support over the distribution of plantar pressure when standing and walking.Methods: This was an experimental study with pre- and post-design the strength of triceps surae muscle after prolonged standing, was also evaluated in an experimental study with pre- and post-design. Variables of plantar pressure measurement are the contact area and pressure peak were measured by using the Mat-scan tool. The measurement of the triceps surae muscle strength was done with a hand-held dynamometer, before and after using the medial arch support. Measurement was performed before and after working with prolonged standing position which took place about seven hours using the medial arch support inserted in the shoes. Data was analyzed using paired T-test.Results: There was a significant difference of peak pressure between standing (p = 0.041 and walking (p = 0.001. Whereas the contact area showed a significant decrease in the width of the contact area when standing (104.12 ± 12.42 vs 99.08 ± 10.21 p = 0.023. Whereas, the triceps surae muscle strength pre- and post-standing prolonged did not indicate a significant difference.Conclusion: There was decrease in peak pressure when standing and walking and decrease in contact area when standing on plantar after used of the medial arch support after prolonged standing.

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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Piccinelli Marco

2005-01-01

Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

Fermionic covariant prolongation structure theory for supernonlinear evolution equation

International Nuclear Information System (INIS)

Cheng Jipeng; Wang Shikun; Wu Ke; Zhao Weizhong

2010-01-01

We investigate the superprincipal bundle and its associated superbundle. The super(nonlinear)connection on the superfiber bundle is constructed. Then by means of the connection theory, we establish the fermionic covariant prolongation structure theory of the supernonlinear evolution equation. In this geometry theory, the fermionic covariant fundamental equations determining the prolongation structure are presented. As an example, the supernonlinear Schroedinger equation is analyzed in the framework of this fermionic covariant prolongation structure theory. We obtain its Lax pairs and Baecklund transformation.

Review of progress in superconducting high-beta structures

International Nuclear Information System (INIS)

Sundelin, R.M.

1992-01-01

During the past two years, there has been substantial progress in superconducting high-beta cavities in a number of areas. Understanding of the Q-disease, which occurs when a cavity is held for prolonged periods near 100 K, has advanced, and techniques for mitigating this problem have improved. Progress has been made in the use of high peak power processing to suppress field emission. Cell geometries have improved to reduce the ratio of peak surface electric field to accelerating field, and trapped mode behavior has been found to permit use of nine cells for some applications. The operating experience base for cavities installed in accelerators has increased substantially, as has the performance experience base for industrially manufactured cavities, including both solid niobium and sputter-coated copper. Additional applications for superconducting cavities have been identified. Progress has been made toward the design and construction of a Tera-Electron-Volt Superconducting Linear Accelerator (TESLA) test bed. (author). 25 refs., 1 fig

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

Science.gov (United States)

Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

2016-01-01

The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

PR interval prolongation in coronary patients or risk equivalent: excess risk of ischemic stroke and vascular pathophysiological insights.

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Chan, Yap-Hang; Hai, Jo Jo; Lau, Kui-Kai; Li, Sheung-Wai; Lau, Chu-Pak; Siu, Chung-Wah; Yiu, Kai-Hang; Tse, Hung-Fat

2017-08-24

Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P 200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.

Zoledronic acid enhances the effect of radiotherapy for bone metastases from renal cell carcinomas. More than a 24-month median follow-up

International Nuclear Information System (INIS)

Takeda, Naoki; Isu, Kazuo; Hiraga, Hiroaki; Shinohara, Nobuo; Minami, Akio; Kamata, Hajime

2012-01-01

Renal cell carcinoma (RCC) is thought to respond unreliably to radiotherapy (RT). Zoledronic acid significantly reduces the risk of skeletal complications. This study investigated whether RT with zoledronic acid prolonged the time to bone-lesion progression in comparison with RT alone. Twenty-seven patients (34 lesions) with bone metastases secondary to RCC undergoing treatment with RT with or without zoledronic acid were retrospectively evaluated at two institutions between 1999 and 2009. Twelve patients were treated with RT alone from 1999 to 2008 (RT group). Fifteen patients were treated with RT and zoledronic acid from 2006 to 2009 (RT+Z group). The time to skeletal-related events and pain progression were assessed from patients' medical records. The median (range) follow-up was 26 (3-75) and 24 (3-55) months in the RT and RT+Z groups, respectively. Three patients (three lesions) in the RT+Z group had skeletal-related events (SREs). In contrast, six patients (eight lesions) in the RT group had SREs. SREs comprised pathological fractures in five, additional surgeries in three, spinal cord or cauda equine compression in two, and repeat RT in one. There was a significant difference in SRE-free survival time and duration of site-specific pain response between groups. RT combined with zoledronic acid significantly prolonged SRE-free survival and duration of pain response compared with RT alone in the treatment of osseous metastases from RCC. (author)

Prolonged episodes of hypoglycaemia in HNF4A-MODY mutation carriers with IGT. Evidence of persistent hyperinsulinism into early adulthood.

Science.gov (United States)

Bacon, S; Kyithar, M P; Condron, E M; Vizzard, N; Burke, M; Byrne, M M

2016-12-01

HNF4A is an established cause of maturity onset diabetes of the young (MODY). Congenital hyperinsulinism can also be associated with mutations in the HNF4A gene. A dual phenotype is observed in HNF4A-MODY with hyperinsulinaemic hypoglycaemia in the neonatal period progressing to diabetes in adulthood. The nature and timing of the transition remain poorly defined. We performed an observational study to establish changes in glycaemia and insulin secretion over a 6-year period. We investigated glycaemic variability and hypoglycaemia in HNF4A-MODY using a continuous glucose monitoring system (CGMS). An OGTT with measurement of glucose, insulin and C-peptide was performed in HNF4A participants with diabetes mellitus (DM) (n = 14), HNF4A-IGT (n = 7) and age- and BMI-matched MODY negative family members (n = 10). Serial assessment was performed in the HNF4A-IGT cohort. In a subset of HNF4A-MODY mutation carriers (n = 10), CGMS was applied over a 72-h period. There was no deterioration in glycaemic control in the HNF4A-IGT cohort. The fasting glucose-to-insulin ratio was significantly lower in the HNF4A-IGT cohort when compared to the normal control group (0.13 vs. 0.24, p = 0.03). CGMS profiling demonstrated prolonged periods of hypoglycaemia in the HNF4A-IGT group when compared to the HNF4A-DM group (432 vs. 138 min p = 0.04). In a young adult HNF4A-IGT cohort, we demonstrate preserved glucose, insulin and C-peptide secretory responses to oral glucose. Utilising CGMS, prolonged periods of hypoglycaemia are evident despite a median age of 21 years. We propose a prolonged hyperinsulinaemic phase into adulthood is responsible for the notable hypoglycaemic episodes.

Brain mapping after prolonged cycling and during recovery in the heat.

Science.gov (United States)

De Pauw, Kevin; Roelands, Bart; Marusic, Uros; Tellez, Helio Fernandez; Knaepen, Kristel; Meeusen, Romain

2013-11-01

The aim of this study was to determine the effect of prolonged intensive cycling and postexercise recovery in the heat on brain sources of altered brain oscillations. After a max test and familiarization trial, nine trained male subjects (23 ± 3 yr; maximal oxygen uptake = 62.1 ± 5.3 ml·min(-1)·kg(-1)) performed three experimental trials in the heat (30°C; relative humidity 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1 h. The first was a 60-min constant-load trial, followed by a 30-min simulated time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, active recovery (AR), passive rest (PR), or cold water immersion (CWI) was applied for 15 min. Electroencephalography was measured at baseline and during postexercise recovery. Standardized low-resolution brain electromagnetic tomography was applied to accurately pinpoint and localize altered electrical neuronal activity. After CWI, PR and AR subjects completed TT2 in 761 ± 42, 791 ± 76, and 794 ± 62 s, respectively. A prolonged intensive cycling performance in the heat decreased β activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in Brodmann areas (BA) 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Postexercise CWI increased β3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.

Nuclear energy as a 'golden bridge'? Constitutional legal problems of the negotiation of the prolongation of the running time against skimming of profits

International Nuclear Information System (INIS)

Waldhoff, Christian; Aswege, Hanka von

2010-01-01

The coalition agreement of Christian Demographic Union (CDU), Christian Social Union (CSU) and Free Democratic Party (FDP) from 26th October, 2009 characterizes the nuclear energy as a bridge technology. The coalition parties explain to prolong the running times of German nuclear power stations up to a reliable replacement by renewable energies. The conditions for the prolongation of the running times are to be regulated in agreement with energy supply companies. In the contribution under consideration, the authors report on the fiscal legal problems of the skimming of profits. Constitutional legal problems of the earmaking of a skimming of profits as well as a consensual agreement are discussed in this contribution. In the result, a financial constitutionally reliable way for the skimming of added profits due to prolongation of the running time is not evident. The legal earmaking of the duty advent for the promotion of renewable energies increases the constitutional doubts.

AVS-1357 inhibits melanogenesis via prolonged ERK activation.

Science.gov (United States)

Kim, Dong-Seok; Lee, Hyun-Kyung; Park, Seo-Hyoung; Chae, Chong Hak; Park, Kyoung-Chan

2009-08-01

In this study, we demonstrated that a derivative of imidazole, AVS-1357, is a novel skin-whitening compound. AVS-1357 was found to significantly inhibit melanin production in a dose-dependent manner; however, it did not directly inhibit tyrosinase. Furthermore, we found that AVS-1357 induced prolonged activation of extracellular signal-regulated kinase (ERK) and Akt, while it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase. It has been reported that the activation of ERK and/or Akt is involved in melanogenesis. Therefore, we examined the effects of AVS-1357 on melanogenesis in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway) and/or LY294002 (a specific inhibitor of the Akt pathway). PD98059 dramatically increased melanogenesis, whereas LY294002 had no effect. Furthermore, PD98059 attenuated AVS-1357 induced ERK activation, as well as the downregulation of MITF and tyrosinase. These findings suggest that the effects of AVS-1357 occur via downregulation of MITF and tyrosinase, which is caused by AVS-1357-induced prolonged ERK activation. Taken together, our results indicate that AVS-1357 has the potential as a new skin whitening agent.

Effect of prolonged exposure to low antigen concentration for sensitization

International Nuclear Information System (INIS)

Och, Francois M.M. van; Vandebriel, Rob J.; Jong, Wim H. de; Loveren, Henk van

2003-01-01

The local lymph node assay (LLNA) is an assay in mice to identify potential allergens. Compounds that do not induce a stimulation index (SI)≥3 are not considered sensitizers. Of the chemicals that do, the SI of 3 is used as a benchmark, and indicates the sensitizing potency of a chemical. Compared to the exposure duration of the LLNA (3 days), real life exposure often lasts for months or years. We therefore investigated whether prolonged exposure to sensitizers at concentrations that do not induce a SI≥3 in the LLNA, were able to surpass this threshold. Mice were treated for 2 months at 7-day intervals with a range of concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both proliferative activity and cytokine production were established at day 60. Neither BENZ nor TMTD showed a significant increase in the proliferation rate compared to vehicle controls. Only DNCB at concentrations originally above the EC 3 a significant increase in proliferation was seen after prolonged exposure. No significant effect on IFN-γ and IL-4 production was observed for all three compounds compared. These findings indicate that for classification of sensitizers the shorter exposure period employed in the standard LLNA is sufficient, and longer periods of exposure have no bearing on this classification

Fasting and prolonged exercise increase vasoactive intestinal polypeptide (VIP) in plasma

DEFF Research Database (Denmark)

Galbo, H; Hilsted, J; Fahrenkrug, J

1979-01-01

and maximal exercise. During 59 h of fasting, VIP increased from 3.6 (0.6--6.6) to 10.2 (6.6--13.8) pmol.1(-1) (p less than 0.05). The concentration of glucose in plasma decreased significantly during the prolonged exercise as well as during fasting. The known metabolic actions of VIP and the demonstrated...

The shape of uterine contractions and labor progress in the spontaneous active labor.

Science.gov (United States)

Ebrahimzadeh Zagami, Samira; Golmakani, Nahid; Saadatjoo, Seyyed Ali-Reza; Ghomian, Nayyereh; Baghbani, Behjat

2015-03-01

Dystocia is the most common indication of primary cesarean section. The most common cause of dystocia is uterine dysfunction. In prolonged labor, more attention is usually paid to the fetus and pelvis rather than to the role of uterine contractions in a delivery. Therefore, we decided to determine the relationship between the labor progress and uterine contractions shapes. In this cross-sectional study, 200 primiparous women participated having a single pregnancy and cephalic presentation. Uterus contractions were recorded using electronic fetal monitoring at the beginning of the active phase of labor (dilatation 3-5 cm) for 30 min. Fall to rise (F:R) ratio was calculated by determining the duration of returning from a contraction peak to its baseline (fall) and the duration of the rise time from baseline to peak (rise) in two groups. The data were analyzed using t-test and Chi-square test. In this study, 162 women had a normal delivery and 38 women had a cesarean (CS) delivery due to the lack of labor progress. The average F:R ratio was 1.13±0.193 seconds in the vaginal delivery group and 1.64±0.301 seconds in the CS group. This difference was statistically significant (PR ratio was higher in the group that lacked labor progress. Therefore, contraction shapes can be used to predict the labor progress.

Serial CT scans of cerebral hypoxia due to prolonged status epilepticus

Energy Technology Data Exchange (ETDEWEB)

Saiwai, Shigeo; Matsumura, Yasumasa; Tamaoka, Koichi; Fukuda, Teruo; Miyamoto, Takeshi (Kobe Central Municipal Hospital, Kobe (Japan))

1983-04-01

Serial computed tomography (CT) scans of 5 infants with status epilepticus were reviewed. Four out of the 5 infants fortunately had CT scans before status epilepticus because of a convulsion. There was a diffuse and mild low density in the hemisphere, with small ventricles and tight sulci (brain swelling) at 1 to 2 days after ictus. Thereafter, a diffuse low density became apparent except for the cerebellum, the brain stem, the thalamus, and the basal ganglia. Two to 4 weeks after ictus, a localized, mottled low density was demonstrated on the cerebral mantle and atrophic changes became progressively clear. In 3 cases, no abnormal enhancement was elicited on contrast CT scans performed between 5 to 16 days after status epilepticus. We discussed the possible pathophysiological aspects of the brain damage due to ''prolonged status epilepticus.''

Serial CT scans of cerebral hypoxia due to prolonged status epilepticus

International Nuclear Information System (INIS)

Saiwai, Shigeo; Matsumura, Yasumasa; Tamaoka, Koichi; Fukuda, Teruo; Miyamoto, Takeshi

1983-01-01

Serial computed tomography (CT) scans of 5 infants with status epilepticus were reviewed. Four out of the 5 infants fortunately had CT scans before status epilepticus because of a convulsion. There was a diffuse and mild low density in the hemisphere, with small ventricles and tight sulci (brain swelling) at 1 to 2 days after ictus. Thereafter, a diffuse low density became apparent except for the cerebellum, the brain stem, the thalamus, and the basal ganglia. Two to 4 weeks after ictus, a localized, mottled low density was demonstrated on the cerebral mantle and atrophic changes became progressively clear. In 3 cases, no abnormal enhancement was elicited on contrast CT scans performed between 5 to 16 days after status epilepticus. We discussed the possible pathophysiological aspects of the brain damage due to ''prolonged status epilepticus.'' (author)

Progress toward the Wisconsin Free Electron Laser

International Nuclear Information System (INIS)

Bisognano, Joseph; Bosch, R.A.; Eisert, D.; Fisher, M.V.; Green, M.A.; Jacobs, K.; Kleman, K.J.; Kulpin, J.; Rogers, G.C.; Lawler, J.E.; Yavuz, D.; Legg, R.

2011-01-01

The University of Wisconsin-Madison/Synchrotron Radiation Center is advancing its design for a seeded VUV/soft X-ray Free Electron Laser facility called WiFEL. To support this vision of an ultimate light source, we are pursuing a program of strategic R and D addressing several crucial elements. This includes development of a high repetition rate, VHF superconducting RF electron gun, R and D on photocathode materials by ARPES studies, and evaluation of FEL facility architectures (e.g., recirculation, compressor scenarios, CSR dechirping, undulator technologies) with the specific goal of cost containment. Studies of high harmonic generation for laser seeding are also planned.

Weight preserving image registration for monitoring disease progression in lung CT.

Science.gov (United States)

Gorbunova, Vladlena; Lol, Pechin; Ashraf, Haseem; Dirksen, Asger; Nielsen, Mads; de Bruijne, Marleen

2008-01-01

We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan compared with intensities in the deformed baseline image indicate local loss of lung tissue that is associated with progression of emphysema. To account for differences in lung intensity owing to differences in the inspiration level in the two scans rather than disease progression, we propose to adjust the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans and may result in a more sensitive measure of disease progression than standard quantitative CT measures.

Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France

OpenAIRE

Huguet, Marius; Perrier, Lionel; Bally, Olivia; Benayoun, David; De Saint Hilaire, Pierre; Beal Ardisson, Dominique; Morelle, Magali; Havet, Nathalie; Joutard, Xavier; Meeus, Pierre; Gabelle, Philippe; Provençal, Jocelyne; Chauleur, Céline; Glehen, Olivier; Charreton, Amandine

2018-01-01

Background To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. Methods This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/...

Edaravone, a Free Radical Scavenger, Delayed Symptomatic and Pathological Progression of Motor Neuron Disease in the Wobbler Mouse.

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Ken Ikeda

Full Text Available Edaravone, a free radical scavenger is used widely in Japanese patients with acute cerebral infarction. This antioxidant could have therapeutic potentials for other neurological diseases. Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease that affects the upper and the lower motor neuron, leading to death within 3-5 years after onset. A phase III clinical trial of edaravone suggested no significant effects in ALS patients. However, recent 2nd double-blind trial has demonstrated therapeutic benefits of edaravone in definite patients diagnosed by revised El Escorial diagnostic criteria of ALS. Two previous studies showed that edaravone attenuated motor symptoms or motor neuron degeneration in mutant superoxide dismutase 1-transgenic mice or rats, animal models of familial ALS. Herein we examined whether this radical scavenger can retard progression of motor dysfunction and neuropathological changes in wobbler mice, sporadic ALS-like model. After diagnosis of the disease onset at the postnatal age of 3-4 weeks, wobbler mice received edaravone (1 or 10 mg/kg, n = 10/group or vehicle (n = 10, daily for 4 weeks by intraperitoneal administration. Motor symptoms and neuropathological changes were compared among three groups. Higher dose (10 mg/kg of edaravone treatment significantly attenuated muscle weakness and contracture in the forelimbs, and suppressed denervation atrophy in the biceps muscle and degeneration in the cervical motor neurons compared to vehicle. Previous and the present studies indicated neuroprotective effects of edaravone in three rodent ALS-like models. This drug seems to be worth performing the clinical trial in ALS patients in the United States of American and Europe, in addition to Japan.

Edaravone, a Free Radical Scavenger, Delayed Symptomatic and Pathological Progression of Motor Neuron Disease in the Wobbler Mouse.

Science.gov (United States)

Ikeda, Ken; Iwasaki, Yasuo

2015-01-01

Edaravone, a free radical scavenger is used widely in Japanese patients with acute cerebral infarction. This antioxidant could have therapeutic potentials for other neurological diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the upper and the lower motor neuron, leading to death within 3-5 years after onset. A phase III clinical trial of edaravone suggested no significant effects in ALS patients. However, recent 2nd double-blind trial has demonstrated therapeutic benefits of edaravone in definite patients diagnosed by revised El Escorial diagnostic criteria of ALS. Two previous studies showed that edaravone attenuated motor symptoms or motor neuron degeneration in mutant superoxide dismutase 1-transgenic mice or rats, animal models of familial ALS. Herein we examined whether this radical scavenger can retard progression of motor dysfunction and neuropathological changes in wobbler mice, sporadic ALS-like model. After diagnosis of the disease onset at the postnatal age of 3-4 weeks, wobbler mice received edaravone (1 or 10 mg/kg, n = 10/group) or vehicle (n = 10), daily for 4 weeks by intraperitoneal administration. Motor symptoms and neuropathological changes were compared among three groups. Higher dose (10 mg/kg) of edaravone treatment significantly attenuated muscle weakness and contracture in the forelimbs, and suppressed denervation atrophy in the biceps muscle and degeneration in the cervical motor neurons compared to vehicle. Previous and the present studies indicated neuroprotective effects of edaravone in three rodent ALS-like models. This drug seems to be worth performing the clinical trial in ALS patients in the United States of American and Europe, in addition to Japan.

Muscular soreness following prolonged intermittent high-intensity shuttle running.

Science.gov (United States)

Thompson, D; Nicholas, C W; Williams, C

1999-05-01

The aim of this study was to examine the impact of prolonged intermittent high-intensity shuttle running on soreness and markers of muscle damage. Sixteen males took part in the study, half of whom were assigned to a running group and half to a resting control group. The exercise protocol involved 90 min of intermittent shuttle running and walking (Loughborough Intermittent Shuttle Test: LIST), reflecting the activity pattern found in multiple-sprint sports such as soccer. Immediately after exercise, there was a significant increase (P < 0.05) in serum activities of creatine kinase and aspartate aminotransferase, and values remained above baseline for 48 h (P < 0.05). Median peak activities of creatine kinase and aspartate aminotransferase occurred 24 h post-exercise and were 774 and 43 U x l(-1), respectively. The intensity of general muscle soreness, and in the specific muscles investigated, was greater than baseline for 72 h after the shuttle test (P < 0.05), peaking 24-48 h post-exercise (P < 0.05). Muscle soreness was not correlated with either creatine kinase or aspartate aminotransferase activity. Soreness was most frequently reported in the hamstrings. Neither soreness nor serum enzyme activity changed in the controls over the 4 day observation period. It appears that unaccustomed performance of prolonged intermittent shuttle running produces a significant increase in both soreness and markers of muscle damage.

Evolution of perceived footwear comfort over a prolonged running session.

Science.gov (United States)

Hintzy, F; Cavagna, J; Horvais, N

2015-12-01

The purpose of this study was to investigate the subjective perception of overall footwear comfort over a prolonged running session. Ten runners performed two similar sessions consisting of a 13-km trail run (5 laps of 2.6 km) as fast as possible. The overall footwear comfort was evaluated before running and at the end of each lap with a 150-mm visual analogic scale, as well as speed, heart rate and rate of perceived exertion. The results showed that both overall footwear comfort and speed decreased consistently during the run session, and significantly after 44 min of running (i.e. the 3rd lap). It could be hypothesized that the deterioration of overall footwear comfort was explained by mechanical and energetical parameter changes with time and/or fatigue occurring at the whole body, foot and footwear levels. These results justify the use of a prolonged running test for running footwear comfort evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical significance of two-step magnetic radioimmunoassay for determining serum free T3 and free T4

International Nuclear Information System (INIS)

Chen Bing

1996-01-01

The concentrations of the serum free T 3 (FT 3 ), free T 4 (FT 4 ), total triodothyronine (TT 3 ), total thyroxine (TT 4 ) and thyrotropin (TSH) are determined for 355 cases of normal persons, pregnant women and various thyropathetic patients. The normal values of FT 3 and FT 4 are 2.0-8.5 pmol/l, and 9.5-26.5 pmol/l, respectively. Neither FT 3 nor FT 4 is affected by the thyroxine combined with globulin (TBG), which is of unique diagnostic value for those with variable TBG (such as pregnant women hyperthyroidism, hypothyroidism, etc.), FT 3 and FT 4 are the most sensitive indices for diagnosis of hyperthyroidism, and hypothyroidism, respectively. In addition, FT 3 and FT 4 can greatly contribute to the observation of curative effectiveness under treatment

Significance of focal relaxation times in head injury

Energy Technology Data Exchange (ETDEWEB)

Inao, Suguru; Furuse, Masahiro; Saso, Katsuyoshi; Yoshida, Kazuo; Motegi, Yoshimasa; Kaneoke, Yoshiki; Izawa, Akira

1987-11-01

Serial examinations by nuclear magnetic resonance-computed tomography were carried out in 35 head-injured patients aged 7 to 77 years. The injuries were classified as cerebral contusion (nine cases), acute epidural hematoma (eight cases), acute cerebral swelling (two cases), and chronic subdural hematoma (16 cases). The results of 92 measurements were divided into two groups: acute stage (within 3 days of injury) and chronic stage (2 weeks or longer after injury). The spin-lattice relaxation times (T/sub 1/) of brain tissue adjacent to chronic subdural hematoma were evaluated pre- and postoperatively. A Fonar QED 80-alpha system was used for magnetic resonance imaging and measurement of focal T/sub 1/. The T/sub 1/ values at the region of interest were measured 3 to 5 times by the field focusing technique (468 gauss in the focused spot), and the mean value was used for evaluation. The standard T/sub 1/ values obtained from healthy subjects were 290 +- 41 msec in the cerebral cortex and 230 +- 34 msec in the white matter. Prolongation of T/sub 1/ in perifocal brain gradually shortened over time and normalized in the chronic stage. The degree of contusional edema may have been reflected in alterations in T/sub 1/. In contrast, parenchymal injury resulted in a progressive T/sub 1/ elevation, which far exceeded 500 msec in the chronic stage. Such time courses of T/sub 1/ may indicate irreversible tissue damage. There were no noticeable changes in tissue T/sub 1/ over time in patients with acute diffuse cerebral swelling or those who underwent evacuation of acute epidural or chronic subdural hematomas. The underlying pathophysiology in such situations seems to be not brain edema but cerebral hyperemia. In the presence of ischemia, the T/sub 1/ value was prolonged in the early stage, reflecting progression of is chemic edema. (Abstract Truncated)

The effects of prolonged oral administration of the disinfectant calcium hypochlorite in Nigerian commercial cockerels

Directory of Open Access Journals (Sweden)

Temitayo O. Iji

2013-11-01

Full Text Available This study was designed to investigate the effects of prolonged oral administration of calcium hypochlorite in the drinking water of commercial cockerels. It was carried out in order to ascertain probable toxicity associated with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were used; they were grouped into four groups of eight. Group 1, which served as the control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4 received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of drinking water for six weeks respectively. Six weeks after the administration of calcium hypochlorite, blood was collected from the jugular vein to assess liver function, lipid profiles and for markers of oxidative stress. The results revealed a significant (p < 0.05 increase in alanine aminotransferase activity in a dose-dependent manner when compared with the control. Also, there was a significant (p < 0.05 increase in aspartate aminotransferase and alkaline phosphatase activity. Similarly, there was a significant (p < 0.05 increase in total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein levels compared with the control. There was a significant increase in malondialdehyde and hydrogen peroxide generation with a concomitant significant (p < 0.05 decrease in serum glutathione level in a dose-dependent manner when compared with the control. In this study, calcium hypochloriteinduced hepatic damage via oxidative stress and decrease in antioxidant defense system was found. Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially harmful.

Prolonged ventilation post cardiac surgery - tips and pitfalls of the prediction game

Directory of Open Access Journals (Sweden)

Knapik Piotr

2011-11-01

Full Text Available Abstract Background Few available models aim to identify patients at risk of prolonged ventilation after cardiac surgery. We compared prediction models developed in ICU in two adjacent periods of time, when significant changes were observed both in population characteristics and the perioperative management. Methods We performed a retrospective review of two cohorts of patients in our department in two subsequent time periods (July 2007 - December 2008, n = 2165; January 2009 - July 2010, n = 2192. The study was approved by the Institutional Ethics Committee and the individual patient consent was not required. Patients were divided with regard to ventilation time of more or less than 48 hours. Preoperative and procedure-related variables for prolonged ventilation were identified and multivariate logistic regression analysis was performed separately for each cohort. Results Most recent patients were older, with more co-morbidities, more frequently undergoing off-pump surgery. At the beginning of 2009 we also changed the technique of postoperative ventilation. Percentage of patients with prolonged ventilation decreased from 5.7% to 2.4% (p Conclusions Prediction models for postoperative ventilation should be regularly updated, particularly when major changes are noted in patients' demographics and surgical or anaesthetic technique.

Does bariatric surgery prevent progression of diabetic retinopathy?

Science.gov (United States)

Chen, Y; Laybourne, J P; Sandinha, M T; de Alwis, N M W; Avery, P; Steel, D H

2017-08-01

PurposeTo assess the changes in diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients post bariatric surgery and report on the risk factors that may be associated with it.Patients and methodsRetrospective observational study of T2DM patients who underwent bariatric surgery in a UK specialist bariatric unit between 2009 and 2015. Preoperative and postoperative weight, HbA1c, and annual DR screening results were collected from medical records. Patients with preoperative retinal screening and at least one postoperative retinal screening were eligible for analysis. Multivariate analysis was used to explore significant clinical predictors on postoperative worsening in DR.ResultsA total of 102 patients were eligible for analysis and were followed up for 4 years. Preoperatively, 68% of patients had no DR compared to 30% with background retinopathy, 1% pre-proliferative retinopathy, and 1% proliferative retinopathy. In the first postoperative visit, 19% of patients developed new DR compared to 70% stable and 11% improved. These proportions remained similar for each postoperative visit over time. Young age, male gender, high preoperative HbA1c, and presence of preoperative retinopathy were the significant predictors of worsening postoperatively.ConclusionBariatric surgery does not prevent progression of DR. Young male patients with pre-existing DR and poor preoperative glycaemic control are most at risk of progression. All diabetic patients should attend regular DR screening post bariatric surgery to allow early detection of potentially sight-threatening changes, particularly among those with identifiable risk factors. Future prospective studies with prolonged follow-up are required to clarify the duration of risk.

Media Impacts on Women's Fertility Desires: A Prolonged Exposure Experiment.

Science.gov (United States)

Knobloch-Westerwick, Silvia; Willis, Laura E; Kennard, Ashley R

2016-06-01

Media exposure may have implications for family planning, a public health issue of key importance. Drawing on social comparison theory and social identity theory, a prolonged exposure experiment examined whether media portrayals of women's social roles affect fertility desires among 166 American, nonstudent, never married, childless women ages 21-35 years old. After sign-up and baseline sessions, participants viewed magazine pages five days in a row. Stimuli presented women in either mother/homemaker roles, beauty ideal roles, or professional roles. Three days later, participants again indicated their number of desired children and time planned until first birth. Exposure to mother/homemaker and beauty ideal portrayals increased the number of desired children across time. Exposure to professional portrayals increased the time planned until 1st birth compared to beauty ideal portrayals-this impact was partially mediated by a shift toward more progressive gender norms (per social identity theory) and assimilation (per social comparison theory).

Impact of ALSO training on the management of prolonged labor and neonatal care at Kagera Regional Hospital, Tanzania

DEFF Research Database (Denmark)

Sorensen, Bjarke Lund; Rasch, Vibeke; Massawe, Siriel

2010-01-01

OBJECTIVE: To evaluate the management of prolonged labor and neonatal care before and after Advanced Life Support in Obstetrics (ALSO) training. METHODS: Staff involved in childbirth at Kagera Regional Hospital, Tanzania, attended a 2-day ALSO provider course. In this prospective intervention study...... conducted between July and November 2008, the management and outcomes of 558 deliveries before and 550 after the training were observed. RESULTS: There was no significant difference in the rate of cesarean deliveries owing to prolonged labor, and vacuum delivery was not practiced after the intervention...... 5.6% to 71.5% (RR 12.71; 95% CI, 9.04-17.88). There was a significant decrease from 6 to 0 neonatal deaths before discharge among those born with an Apgar score after 1minute of 4 or more (P=0.03). CONCLUSION: ALSO training had no effect on the management of prolonged labor. Early contact between...

A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

International Nuclear Information System (INIS)

Gonçalves, Anthony; Turrini, Olivier; Lelong, Bernard; Viens, Patrice; Borg, Jean-Paul; Birnbaum, Daniel; Olschwang, Sylviane; Viret, Frédéric; Esteyries, Séverine; Taylor-Smedra, Brynn; Lagarde, Arnaud; Ayadi, Mounay; Monges, Geneviève; Bertucci, François; Esterni, Benjamin; Delpero, Jean-Robert

2008-01-01

Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity. We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced. Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients. This preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit

Smoke-free Workplace Rules and Laws | Cancer Trends Progress Report

Science.gov (United States)

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

International Nuclear Information System (INIS)

Hao, Hui-fang; Takaoka, Munenori; Bao, Xiao-hong; Wang, Zhi-gang; Tomono, Yasuko; Sakurama, Kazufumi; Ohara, Toshiaki; Fukazawa, Takuya; Yamatsuji, Tomoki; Fujiwara, Toshiyoshi; Naomoto, Yoshio

2012-01-01

Highlights: ► A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. ► TAE226 suppressed proliferation and migration, with a modest effect on adhesion. ► Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. ► TAE226 treatment suppressed the progression of peritoneal dissemination. ► Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken together, a possible strategy for inhibiting peritoneal dissemination by targeting FAK with TAE226 appears to be applicable

Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

Energy Technology Data Exchange (ETDEWEB)

Hao, Hui-fang [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Takaoka, Munenori [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Bao, Xiao-hong [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Wang, Zhi-gang [College of Life Science, Inner Mongolia University, The Key Laboratory of Mammal Reproductive Biology and Biotechnology, Ministry of Education, Hohhot 010021 (China); Tomono, Yasuko [Division of Molecular and Cell Biology, Shigei Medical Research Institute, 2117 Yamada, Okayama 700-0202 (Japan); Sakurama, Kazufumi; Ohara, Toshiaki [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Fukazawa, Takuya; Yamatsuji, Tomoki [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan); Fujiwara, Toshiyoshi [Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558 (Japan); Naomoto, Yoshio, E-mail: ynaomoto@med.kawasaki-m.ac.jp [Department of General Surgery, Kawasaki Medical School, 2-1-80 Nakasange, Kita-ku, Okayama 700-8505 (Japan)

2012-07-13

Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all of which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG.

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Dalla Pozza, Robert; Bechtold, Susanne; Urschel, Simon; Netz, Heinrich; Schwarz, Hans-Peter

2009-01-01

Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, pinformation about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy

International Nuclear Information System (INIS)

Yokota, Tomoya; Onozawa, Yusuke; Boku, Narikazu

2011-01-01

Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m 2 /day) for 28 days followed by a 14-day rest. The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n=7) was significantly longer than for other cancers (n=32) (14.9 vs. 4.7 months, P=0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval 6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P=0.045). The frequency of Grade 3/4 toxicities was less than 10%. S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population. (author)

SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

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Suzanne Schneider

2013-01-01

Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

The Impact of Blue Light Cystoscopy with Hexaminolevulinate (HAL) on Progression of Bladder Cancer - A New Analysis.

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Kamat, Ashish M; Cookson, Michael; Witjes, J Alfred; Stenzl, Arnulf; Grossman, H Barton

2016-04-27

Background: The International Bladder Cancer Group (IBCG) recently proposed a new definition of disease progression in non-muscle invasive bladder cancer (NMIBC), including change in T-stage, change to T2 or higher or change from low to high grade. Objective: To establish whether blue light cystoscopy with hexaminolevulinate (HAL) impacts the rate of progression and time to progression using the revised definition. Methods: An earlier long-term follow-up of a controlled Phase III study reported outcomes following blue light cystoscopy with HAL (255 patients) or white light (WL) cystoscopy (261 patients) in NMIBC patients. The data was re-analysed according to the new definition. Results: In the original analysis, after 4.5 years (median), eight HAL and 16 WL patients were deemed to have progressed (transition from NMIBC to muscle invasive bladder cancer, (T2-4)). According to the new definition, additional patients in both groups were found to have progressed: 31 (12.2%) HAL vs 46 (17.6%) WL ( p  = 0.085) with four (1.6%) HAL and 11 (4.2%) WL patients progressing from Ta to CIS. Time to progression was longer in the HAL group ( p  = 0.05). Conclusions: Applying the new IBCG definition there was a trend towards a lower rate of progression in HAL patients, particularly in those progressing from Ta to CIS. Time to progression was significantly prolonged. This suggests that patients should receive blue light cystoscopy with HAL rather than WL at resection. Adoption of the new definition could allow more patients at risk of progression to be treated appropriately earlier.

Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

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Rushaidhi, M; Zhang, H; Liu, P

2013-03-27

Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Neonatal survival after prolonged preterm premature rupture of membranes before 24 weeks of gestation.

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Brumbaugh, Jane E; Colaizy, Tarah T; Nuangchamnong, Nina; O'Brien, Emily A; Fleener, Diedre K; Rijhsinghani, Asha; Klein, Jonathan M

2014-11-01

To evaluate neonatal survival after prolonged preterm premature rupture of membranes (PROM) in the era of antenatal corticosteroids, surfactant, and inhaled nitric oxide. A single-center retrospective cohort study of neonates born from 2002-2011 after prolonged (1 week or more) preterm (less than 24 weeks of gestation) rupture of membranes was performed. The primary outcome was survival to discharge. Neonates whose membranes ruptured less than 24 hours before delivery (n=116) were matched (2:1) on gestational age at birth, sex, and antenatal corticosteroid exposure with neonates whose membranes ruptured 1 week or more before delivery (n=58). Analysis used conditional logistic regression for categorical data and Wilcoxon signed rank test for continuous data. The prolonged preterm PROM exposed and unexposed cohorts had survival rates of 90% and 95%, respectively, although underpowered to assess the statistical significance (P=.313). Exposed neonates were more likely have pulmonary hypoplasia (26/58 exposed, 1/114 unexposed, Prupture (20.4 weeks exposed, 22.3 weeks unexposed, P=.189), length of rupture (3.7 weeks exposed, 6.4 weeks unexposed, P=.717), and lowest maximal vertical pocket before 24 weeks of gestation (0 cm exposed, 1.4 cm unexposed, P=.114) did not discriminate between survivors and nonsurvivors after exposure to prolonged preterm PROM. With antenatal steroid exposure and aggressive pulmonary management, survival to discharge after prolonged preterm PROM was 90%. Pulmonary morbidities were common. Of note, the data were limited to women who remained pregnant 1 week or longer after rupture of membranes.

Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective.

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Pollard, C E; Valentin, J-P; Hammond, T G

2008-08-01

Drug-induced prolongation of the QT interval is having a significant impact on the ability of the pharmaceutical industry to develop new drugs. The development implications for a compound causing a significant effect in the 'Thorough QT/QTc Study' -- as defined in the clinical regulatory guidance (ICH E14) -- are substantial. In view of this, and the fact that QT interval prolongation is linked to direct inhibition of the hERG channel, in the early stages of drug discovery the focus is on testing for and screening out hERG activity. This has led to understanding of how to produce low potency hERG blockers whilst retaining desirable properties. Despite this, a number of factors mean that when an integrated risk assessment is generated towards the end of the discovery phase (by conducting at least an in vivo QT assessment) a QT interval prolongation risk is still often apparent; inhibition of hERG channel trafficking and partitioning into cardiac tissue are just two confounding factors. However, emerging information suggests that hERG safety margins have high predictive value and that when hERG and in vivo non-clinical data are combined, their predictive value to man, whilst not perfect, is >80%. Although understanding the anomalies is important and is being addressed, of greater importance is developing a better understanding of TdP, with the aim of being able to predict TdP rather than using an imperfect surrogate marker (QT interval prolongation). Without an understanding of how to predict TdP risk, high-benefit drugs for serious indications may never be marketed.

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

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Daniel eGorovets

2015-05-01

Full Text Available Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT in patients with brain metastases treated with stereotactic radiosurgery (SRS as their initial radiotherapy approach. Material and Methods: Patients with brain metastases treated with SRS from 2001-2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky Performance Status ≥70, and life expectancy ≥3 mo. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-yr WBRT-free survival (N=104, and those who died or required salvage WBRT within 3 mo of SRS (N=56. Differences between these groups were assessed by univariate and multivariate analyses.Results: Median survival for all patients was 11 mo. Among patients with ≥1-yr WBRT-free survival, median survival was 33 mo [12-107 mo] with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p<0.05 included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions. After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival.Conclusions: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation

International Nuclear Information System (INIS)

Fernandez, Carlos; Lobo, Maria del Val T.; Gomez-Coronado, Diego; Lasuncion, Miguel A.

2004-01-01

As an essential component of mammalian cell membranes, cells require cholesterol for proliferation, which is either obtained from plasma lipoproteins or synthesized intracellularly from acetyl-CoA. In addition to cholesterol, other non-sterol mevalonate derivatives are necessary for DNA synthesis, such as the phosphorylated forms of isopentane, farnesol, geranylgeraniol, and dolichol. The aim of the present study was to elucidate the role of cholesterol in mitosis. For this, human leukemia cells (HL-60) were incubated in a cholesterol-free medium and treated with SKF 104976, which inhibits cholesterol biosynthesis by blocking sterol 14α-demethylase, and the expression of relevant cyclins in the different phases of the cell cycle was analyzed by flow cytometry. Prolonged cholesterol starvation induced the inhibition of cytokinesis and the formation of polyploid cells, which were multinucleated and had mitotic aberrations. Supplementing the medium with cholesterol completely abolished these effects, demonstrating they were specifically due to cholesterol deficiency. This is the first evidence that cholesterol is essential for mitosis completion and that, in the absence of cholesterol, the cells fail to undergo cytokinesis, entered G1 phase at higher DNA ploidy (tetraploidy), and then progressed through S (rereplication) into G2, generating polyploid cells

Prolonged action potential duration in cardiac ablation of PDK1 mice.

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Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

Prolonged sedation and/or analgesia and 5-year neurodevelopment outcome in very preterm infants: results from the EPIPAGE cohort.

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Rozé, Jean-Christophe; Denizot, Sophie; Carbajal, Ricardo; Ancel, Pierre-Yves; Kaminski, Monique; Arnaud, Catherine; Truffert, Patrick; Marret, Stéphane; Matis, Jaqueline; Thiriez, Gérard; Cambonie, Gilles; André, Monique; Larroque, Béatrice; Bréart, Gérard

2008-08-01

To describe the long-term outcome of very preterm infants receiving prolonged sedation and/or analgesia and examine the relationship between prolonged sedation and/or analgesia and this long-term outcome. A prospective population-based study (Etude EPIdémiologique sur les Petits Ages GEstationnels [EPIPAGE]). To reduce bias, the propensity score method was used. Nine regions of France. The study population included very preterm infants of fewer than 33 weeks' gestational age, born in 1997, who received mechanical ventilation and/or surgery. Main Exposure Prolonged exposure to sedative and/or analgesic drugs in the neonatal period, defined as exposure of more than 7 days to sedative and/or opioid drugs. Presence of moderate or severe disability at 5 years of age. The analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and/or analgesia in the neonatal period was available. A total of 115 were exposed and 1457 were not exposed. There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and/or analgesia and the group who were not. Exposed very preterm infants had severe or moderate disability at 5 years (41/97; 42%) more often than those who were not exposed (324/1248; 26%). After adjustment for gestational age and propensity score, this association was no longer statistically significant (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.2). Prolonged sedation and/or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score.

Oxidative stress: development and progression of breast cancer:review article

Directory of Open Access Journals (Sweden)

Arash Salmaninejad

2017-04-01

Full Text Available Breast cancer is the most commonly diagnosed cancer in women worldwide. Enormous advancement has been made over the last decades in understanding the biology of breast cancer. Nevertheless, the molecular mechanisms regulating progression, gaining of invasive and metastatic phenotypes, and therapeutic resistance are still not completely understood. Oxidative stress initiate by disbalance in redox status of body. In this case, increase of free radicals in body cause tissue damage. One of the significant species of free radicals is reactive oxygen species (ROS that produced by various metabolic pathways, comprising aerobic metabolism in the mitochondrial respiratory chain. They play a serious role in cellular physiology and pathophysiology likewise beginning and evolution of numerous types of cancers. ROS overproduction is deleterious to cells, and considered key-factors for the development of numerous diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer. Cancer cells are commonly submitted to upper ROS levels that further incite malignant phenotype through motivation to preserved proliferation, angiogenesis, death evasion, invasiveness, and metastasis. ROS impress various signaling pathways, comprising mitogenic pathways and growth factors, and also controls numerous cellular processes, containing cell proliferation, thus stimulates the undisciplined growth of cells which inspires the development of tumors and initiates the progression of carcinogenesis. The importance of ROS on breast cancer development and etiology is being increasingly clarified. Nevertheless, fewer consideration has been given to the progress of redox system-targeted strategies for breast cancer treatment. Augmented oxidative stress caused by reactive species can diminish the body’s antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are core factors in the development of cancer. Bimolecular reactions cause

Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With Posttraumatic Stress Disorder.

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Stock, Eileen M; Zeber, John E; McNeal, Catherine J; Banchs, Javier E; Copeland, Laurel A

2018-04-01

In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880). Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, prisks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44). Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

Characterizing prolonged heat effects on mortality in a sub-tropical high-density city, Hong Kong

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Ho, Hung Chak; Lau, Kevin Ka-Lun; Ren, Chao; Ng, Edward

2017-11-01

Extreme hot weather events are likely to increase under future climate change, and it is exacerbated in urban areas due to the complex urban settings. It causes excess mortality due to prolonged exposure to such extreme heat. However, there is lack of universal definition of prolonged heat or heat wave, which leads to inadequacies of associated risk preparedness. Previous studies focused on estimating temperature-mortality relationship based on temperature thresholds for assessing heat-related health risks but only several studies investigated the association between types of prolonged heat and excess mortality. However, most studies focused on one or a few isolated heat waves, which cannot demonstrate typical scenarios that population has experienced. In addition, there are limited studies on the difference between daytime and nighttime temperature, resulting in insufficiency to conclude the effect of prolonged heat. In sub-tropical high-density cities where prolonged heat is common in summer, it is important to obtain a comprehensive understanding of prolonged heat for a complete assessment of heat-related health risks. In this study, six types of prolonged heat were examined by using a time-stratified analysis. We found that more consecutive hot nights contribute to higher mortality risk while the number of consecutive hot days does not have significant association with excess mortality. For a day after five consecutive hot nights, there were 7.99% [7.64%, 8.35%], 7.74% [6.93%, 8.55%], and 8.14% [7.38%, 8.88%] increases in all-cause, cardiovascular, and respiratory mortality, respectively. Non-consecutive hot days or nights are also found to contribute to short-term mortality risk. For a 7-day-period with at least five non-consecutive hot days and nights, there was 15.61% [14.52%, 16.70%] increase in all-cause mortality at lag 0-1, but only -2.00% [-2.83%, -1.17%] at lag 2-3. Differences in the temperature-mortality relationship caused by hot days and hot nights

Historical space weather monitoring of prolonged aurora activities in Japan and in China

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Kataoka, Ryuho; Isobe, Hiroaki; Hayakawa, Hisashi; Tamazawa, Harufumi; Kawamura, Akito Davis; Miyahara, Hiroko; Iwahashi, Kiyomi; Yamamoto, Kazuaki; Takei, Masako; Terashima, Tsuneyo; Suzuki, Hidehiko; Fujiwara, Yasunori; Nakamura, Takuji

2017-02-01

Great magnetic storms are recorded as aurora sightings in historical documents. The earliest known example of "prolonged" aurora sightings, with aurora persistent for two or more nights within a 7 day interval at low latitudes, in Japan was documented on 21-23 February 1204 in Meigetsuki, when a big sunspot was also recorded in China. We have searched for prolonged events over the 600 year interval since 620 in Japan based on the catalogue of Kanda and over the 700 year interval since 581 in China based on the catalogues of Tamazawa et al. (2017) and Hayakawa et al. (2015). Before the Meigetsuki event, a significant fraction of the 200 possible aurora sightings in Sòng dynasty (960-1279) of China was detected at least twice within a 7 day interval and sometimes recurred with approximately the solar rotation period of 27 days. The majority of prolonged aurora activity events occurred around the maximum phase of solar cycles rather than around the minimum, as estimated from the 14C analysis of tree rings. They were not reported during the Oort Minimum (1010-1050). We hypothesize that the prolonged aurora sightings are associated with great magnetic storms resulting from multiple coronal mass ejections from the same active region. The historical documents therefore provide useful information to support estimation of great magnetic storm frequency, which are often associated with power outages and other societal concerns.

Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential.

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Galat, Yekaterina; Dambaeva, Svetlana; Elcheva, Irina; Khanolkar, Aaruni; Beaman, Kenneth; Iannaccone, Philip M; Galat, Vasiliy

2017-03-17

The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification. Thus, it has been shown that variations in cytokine and inhibitory molecule treatments in the first few days of hematopoietic differentiation define primitive versus definitive potential of produced hematopoietic progenitor cells. The majority of current feeder-free, defined systems for hematopoietic induction from pluripotent stem cells include prolonged incubations with various cytokines that make the differentiation process complex and time consuming. We established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. The hemogenic endothelium differentiation was accomplished in an adherent, serum-free culture system by applying CHIR99021. Hemogenic endothelium progenitor cells were isolated on day 5 of differentiation and evaluated for their endothelial, myeloid, and lymphoid potential. Monolayer induction based on GSK3 inhibition, described here, yielded a large number of CD31 + CD34 + hemogenic endothelium cells. When isolated and propagated in adherent conditions, these progenitors gave rise to mature endothelium. When further cocultured with OP9 mouse stromal cells, these progenitors gave rise to various cells of myeloid lineages as well as natural killer lymphoid, T

Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers

DEFF Research Database (Denmark)

Holte, Kathrine; Werner, Mads U; Lacouture, Peter G

2002-01-01

BACKGROUND: The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available. METHODS: In a double-blinded study, 12 healthy male volunteers were...... randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection...... curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection. RESULTS: The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence...

[Representation of Internal Medicine in G-DRG System - Analysis of Reasons for Prolonged Length of Stay].

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Siam, Kristina; Roeder, Norbert; Fölsch, Ulrich R; Spies, Hans-Friedrich

2017-08-01

Background  There is an ongoing discussion within the German Society of Internal Medicine (DGIM) and the Professional Association of German Internists (BDI) about the appropriate depiction and remuneration of internal medicine in the G-DRG. Method  Therefore, cases with a significantly prolonged length of stay were analyzed in a multicenter study. 124 cases from 6 hospitals were collected for evaluation. Results  The results show that the observed prolongation of hospitalization was mainly due to medical reasons. Discussion  Thus, patients with unclear symptoms and consequently need for a thorough workup could not be identified to cause longer inpatient stay. Instead, treatment complications and comorbidities led to extended hospitalization. The results also reveal prolonged hospitalization as a consequence of unsettled or delayed postdischarge care e. g. in rehabilitation facilities. © Georg Thieme Verlag KG Stuttgart · New York.

Prolonged Hypocalcemia Following a Single Dose of Denosumab for Diffuse Bone Metastasis of Gastric Cancer after Total Gastrectomy.

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Iizumi, Sakura; Shimoi, Tatsunori; Nishikawa, Tadaaki; Kitano, Atsuko; Sasada, Shinsuke; Shimomura, Akihiko; Noguchi, Emi; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Fujiwara, Yasuhiro; Tamura, Kenji

2017-11-01

Hypocalcemia is a significant adverse effect of denosumab. We herein report a case of prolonged hypocalcemia in a patient with multiple risk factors for hypocalcemia, including gastrectomy, increased bone turnover, and a poor performance status. Hypocalcemia developed after denosumab treatment for diffuse bone metastasis of gastric cancer, despite oral supplementation with vitamin D and calcium. To avoid serious prolonged hypocalcemia, a thorough assessment of the bone calcium metabolism is required before initiating denosumab treatment.

Prognostic significance of IDH 1 mutation in patients with glioblastoma multiforme.

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Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

2017-05-01

Focus of brain tumour research is shifting towards tumour genesis and genetics, and possible development of individualized treatment plans. Genetic analysis shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic significance of IDH 1 mutation on the basis of published evidence. Multiple retrospective clinical analyses correlate the presence of IDH1 mutation in GBM with good prognostic outcomes compared to wild-type IDH1. A systematic review reported similar results. Based on the review of current literature IDH1 mutation is an independent factor for longer overall survival (OS) and progression free survival (PFS) in GBM patients when compared to wild-type IDH1. The prognostic significance opens up new avenues for treatment.

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

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Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

2015-10-01

To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

Brains with sporadic Creutzfeldt-Jakob disease and copathology showed a prolonged end-stage of disease.

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Miguelez-Rodriguez, Aitzol; Santos-Juanes, Jorge; Vicente-Etxenausia, Ikerne; Perez de Heredia-Goñi, Katty; Garcia, Beatriz; Quiros, Luis M; Lorente-Gea, Laura; Guerra-Merino, Isabel; Aguirre, Jose J; Fernandez-Vega, Ivan

2018-05-01

To investigate the expression of major proteins related to primary neurodegenerative diseases and their prognostic significance in brains with Creutzfeldt-Jakob disease (CJD). Thirty consecutive cases of confirmed CJD during the period 2010-2015 at Basque Brain bank were retrospectively reviewed. Moreover, major neurodegenerative-associated proteins (phosphorylated Tau, 4R tau, 3R tau, alpha-synuclein, TDP43, amyloid beta) were tested. Clinical data were reviewed. Cases were divided according to the presence or absence of copathology. Survival curves were also determined. Copathology was significantly associated with survival in brains with CJD (4.2±1.2 vs 9.2±1.9; P=0.019) and in brains with MM1/MV1 CJD (2.1±1.0 vs 6.7±2.8; P=0.012). Besides, the presence of more than one major neurodegenerative-associated protein was significantly associated with survival (4.2±1.2 vs 10.7±2.6; P=0.017). Thus, univariate analyses further pointed out variables significantly associated with better survival: copathology in CJD (HR=0.430; P=0.033); more than one neurodegenerative-associated protein in CJD (HR=0.369; P=0.036) and copathology in MM1/MV1 CJD (HR=0.525; P=0.032). The existence of copathology significantly prolongs survival in patients with rapidly progressive dementia due to CJD. The study of major neurodegenerative-associated proteins in brains with CJD could allow us to further understand the molecular mechanisms behind prion diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Management plan for deep sternal wound infection targeting to survival free of recurrence: A prospective evaluation study

Directory of Open Access Journals (Sweden)

Ibrahim Kasb

2016-10-01

Conclusion: Management of DSWI is tedious, has prolonged hospital stay and is associated with high morbidity and mortality rates. Management of DSWI must be personalized according to findings on exploration of the sternal wound and flap coverage must be initiated only when the patient is bacteriologically free. Both PMF and/or VOF provided high acceptable success rate defined as survival free of DSWI recurrence.

Prolonged social withdrawal disorder: a hikikomori case in Spain.

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Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

2014-09-01

The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.

Science.gov (United States)

Han, MeiLan K; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Noth, Imre; Lama, Vibha N; Moore, Bethany B; White, Eric S; Flaherty, Kevin R; Huffnagle, Gary B; Martinez, Fernando J

2014-07-01

The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic pulmonary fibrosis. Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a pidiopathic pulmonary fibrosis is associated with the presence of specific members within the Staphylococcus and Streptococcus genera. Additional research will be needed to identify the specific bacterial species and to ascertain whether this is a causal association. National Institutes of Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characteristics of Prolonged Concussion Recovery in a Pediatric Subspecialty Referral Population

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Corwin, Daniel J.; Zonfrillo, Mark R.; Master, Christina L.; Arbogast, Kristy B.; Grady, Matthew F.; Robinson, Roni L.; Goodman, Arlene M.; Wiebe, Douglas J.

2014-01-01

Objective To identify pre-existing characteristics associated with prolonged recovery from concussion in a sample of patients referred to a pediatric sports medicine clinic. Study design This was a retrospective, exploratory cohort study of 247 patients age 5-18 years old with concussion referred to a tertiary pediatric hospital-affiliated sports medicine clinic from July 1, 2010, through December 31, 2011. A random sample of all eligible patient visits (3740) was chosen for further review and abstraction. Statistical comparisons between subsets of patients were conducted using exact chi-square tests, logistic regression, quantile regression, and Kaplan Meier survival curves. Results The median time until returning to school part-time was 12 days (interquartile range (IQR) 6-21); until returning to school full-time without accommodations was 35 days (IQR 11-105); until becoming symptom-free was 64 days (IQR 18-119); and until being fully cleared to return to sports was 75 days (IQR 30-153). 73% of all patients were symptomatic for >4 weeks, 73% were prescribed some form of school accommodation, and 61% reported a decline in grades. Characteristics associated with a prolonged recovery included a history of depression or anxiety; an initial complaint of dizziness; abnormal convergence or symptom provocation following oculomotor examination on physical examination; and history of prior concussion. Conclusion Pediatric and adolescent patients with concussion may experience cognitive and emotional morbidity that can last for several months following injury. Clinicians should consider specific pre-existing characteristics and presenting symptoms that may be associated with a more complicated recovery for concussion patients. PMID:25262302

Defining futile life-prolonging treatments through Neo-Socratic Dialogue.

Science.gov (United States)

Aizawa, Kuniko; Asai, Atsushi; Bito, Seiji

2013-12-09

In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: "What is a life-prolonging treatment?" A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient's lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the objective of treatment, its effects

A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

NARCIS (Netherlands)

Bui-Nguyen, B.; Butrynski, J.E.; Penel, N.; Blay, J.Y.; Isambert, N.; Milhem, M.; Kerst, J.M.; Reyners, A.K.; Litiere, S.; Marreaud, S.; Collin, F.; Graaf, W.T.A. van der

2015-01-01

PURPOSE: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour

Introduction to oncology

DEFF Research Database (Denmark)

Pfeiffer, Per

2015-01-01

Over the past decade, the effi cacy of modern chemotherapy, with or without targeted therapy, has been markedly improved. Systemic therapy generates substantial tumour regression in around 50 % of patients with metastatic colorectal cancer, median progression-free survival is prolonged to around ...

Free-electron lasers with magnetized ion-wiggler

International Nuclear Information System (INIS)

Mehdian, H.; Jafari, S.; Hasanbeigi, A.; Ebrahimi, F.

2009-01-01

Significant progress has been made using laser ionized channels to guide electron beams in the ion focus regime in a free-electron laser. Propagation of an electron beam in the ion focusing regime (IFR) allows the beam to propagate without expanding from space-charge repulsion. The ninth-degree polynomial dispersion relation for electromagnetic and space-charge waves is derived analytically by solving the electron momentum transfer and wave equations. The variation of resonant frequencies and peak growth rates with axial magnetic field strength has been demonstrated. Substantial enhancement in peak growth rate is obtained as the axial field frequency approaches the gyroresonance frequency.

Modulation of internal estimates of gravity during and after prolonged roll-tilts.

Directory of Open Access Journals (Sweden)

Alexander A Tarnutzer

Full Text Available Perceived direction of gravity, as assessed by the subjective visual vertical (SVV, shows roll-angle dependent errors that drift over time and a bias upon return to upright. According to Bayesian observer theory, the estimated direction of gravity is derived from the posterior probability distribution by combining sensory input and prior knowledge about earth-vertical in a statistically optimal fashion. Here we aimed to further characterize the stability of SVV during and after prolonged roll-tilts. Specifically we asked whether the post-tilt bias is related to the drift pattern while roll-tilted. Twenty-nine healthy human subjects (23-56 yo repetitively adjusted a luminous arrow to the SVV over periods of 5 min while upright, roll-tilted (± 45°, ± 90°, and immediately after returning to upright. Significant (p<0.05 drifts (median absolute drift-amplitude: 10°/5 min were found in 71% (± 45° and 78% (± 90° of runs. At ± 90° roll-tilt significant increases in absolute adjustment errors were more likely (76%, whereas significant increases (56% and decreases (44% were about equally frequent at ± 45°. When returning to upright, an initial bias towards the previous roll-position followed by significant exponential decay (median time-constant: 71 sec was noted in 47% of all runs (all subjects pooled. No significant correlations were found between the drift pattern during and immediately after prolonged roll-tilt. We conclude that the SVV is not stable during and after prolonged roll-tilt and that the direction and magnitude of drift are individually distinct and roll-angle-dependent. Likely sensory and central adaptation and random-walk processes contribute to drift while roll-tilted. Lack of correlation between the drift and the post-tilt bias suggests that it is not the inaccuracy of the SVV estimate while tilted that determines post-tilt bias, but rather the previous head-roll orientation relative to gravity. We therefore favor central

Ventricular Cycle Length Characteristics Estimative of Prolonged RR Interval during Atrial Fibrillation

Science.gov (United States)

CIACCIO, EDWARD J.; BIVIANO, ANGELO B.; GAMBHIR, ALOK; EINSTEIN, ANDREW J.; GARAN, HASAN

2014-01-01

Background When atrial fibrillation (AF) is incessant, imaging during a prolonged ventricular RR interval may improve image quality. It was hypothesized that long RR intervals could be predicted from preceding RR values. Methods From the PhysioNet database, electrocardiogram RR intervals were obtained from 74 persistent AF patients. An RR interval lengthened by at least 250 ms beyond the immediately preceding RR interval (termed T0 and T1, respectively) was considered prolonged. A two-parameter scatterplot was used to predict the occurrence of a prolonged interval T0. The scatterplot parameters were: (1) RR variability (RRv) estimated as the average second derivative from 10 previous pairs of RR differences, T13–T2, and (2) Tm–T1, the difference between Tm, the mean from T13 to T2, and T1. For each patient, scatterplots were constructed using preliminary data from the first hour. The ranges of parameters 1 and 2 were adjusted to maximize the proportion of prolonged RR intervals within range. These constraints were used for prediction of prolonged RR in test data collected during the second hour. Results The mean prolonged event was 1.0 seconds in duration. Actual prolonged events were identified with a mean positive predictive value (PPV) of 80% in the test set. PPV was >80% in 36 of 74 patients. An average of 10.8 prolonged RR intervals per 60 minutes was correctly identified. Conclusions A method was developed to predict prolonged RR intervals using two parameters and prior statistical sampling for each patient. This or similar methodology may help improve cardiac imaging in many longstanding persistent AF patients. PMID:23998759

Heart Rate Variability Frequency Domain Alterations among Healthy Nurses Exposed to Prolonged Work Stress.

Science.gov (United States)

Borchini, Rossana; Veronesi, Giovanni; Bonzini, Matteo; Gianfagna, Francesco; Dashi, Oriana; Ferrario, Marco Mario

2018-01-11

The deregulation of the autonomic nervous system assessed through the heart rate variability (HRV) analysis is a promising pathway linking work stress and cardiovascular diseases. We aim to investigate the associations between HRV High Frequency (HF) and Low Frequency (LF) powers and work stress in a sample of 36 healthy nurses. Perceived work stress was assessed twice one year apart, using the Job Content and Effort Reward Imbalance questionnaires. This allows to classify nurses in three exposure groups: "prolonged high stress" (PHS), "recent high stress" (RHS) and "stable low stress" (SLS). A 24-h ECG monitoring was later performed during a working day (WD) and a subsequent resting day (RD). Statistically significantly lower ( p working periods. In the subsequent resting periods, HF means showed increases over time in the RHS (beta = +0.41, p working and resting periods. Our study evidences that both prolonged and recent perceived high work stress were associated with a reduction of HF and LF powers during work. In addition, prolonged stress was associated with a lack of recovery during not-working and resting periods.

A retrospective analysis of the results of p(65) + Be neutron therapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: survival and progression-free survival

International Nuclear Information System (INIS)

Scalliet, P.G.M.; Remouchamps, V.; Wambersie, A.; Richard, F.; Lhoas, F.; Van Glabbeke, M.; Curran, D.; Van Cangh, P.; Ledent, T.

2001-01-01

Purpose. -To retrospectively evaluate survival, progression free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. Patients and methods. - Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neo-adjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neo-adjuvant hormonotherapy; seven patients only had an initial PSA S 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). Results. -The median follow-up was 2.8 years (0-7.8). Five year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% Cl: 54-74%) for the entire series. PFS in patients with an initial PSA >- 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age

Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

International Nuclear Information System (INIS)

Dakhel, Yaman; Jamali, Fakhreddin

2006-01-01

Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists

Causes of Death Associated With Prolonged TV Viewing

Science.gov (United States)

Keadle, Sarah K.; Moore, Steven C.; Sampson, Joshua N.; Xiao, Qian; Albanes, Demetrius; Matthews, Charles E.

2015-01-01

Introduction TV viewing is the most prevalent sedentary behavior and is associated with increased risk of cardiovascular disease and cancer mortality, but the association with other leading causes of death is unknown. This study examined the association between TV viewing and leading causes of death in the U.S. Methods A prospective cohort of 221,426 individuals (57% male) aged 50–71 years who were free of chronic disease at baseline (1995–1996), 93% white, with an average BMI of 26.7 (SD=4.4) kg/m2 were included. Participants self-reported TV viewing at baseline and were followed until death or December 31, 2011. Hazard ratios (HRs) and 95% CIs for TV viewing and cause-specific mortality were estimated using Cox proportional hazards regression. Analyses were conducted in 2014–2015. Results After an average follow-up of 14.1 years, adjusted mortality risk for a 2-hour/day increase in TV viewing was significantly higher for the following causes of death (HR [95% CI]): cancer (1.07 [1.03, 1.11); heart disease (1.23 [1.17, 1.29]); chronic obstructive pulmonary disease (1.28 [1.14, 1.43]); diabetes (1.56 [1.33, 1.83]); influenza/pneumonia (1.24 [1.02, 1.50]); Parkinson disease (1.35 [1.11, 1.65]); liver disease (1.33 [1.05, 1.67]); and suicide (1.43 [1.10, 1.85]. Mortality associations persisted in stratified analyses with important potential confounders, reducing causation concerns. Conclusions This study shows the breadth of mortality outcomes associated with prolonged TV viewing, and identifies novel associations for several leading causes of death. TV viewing is a prevalent discretionary behavior that may be a more important target for public health intervention than previously recognized. Trial Registration ClinicalTrials.gov number, NCT00340015 PMID:26215832

Women's experiences of becoming a mother after prolonged labour.

Science.gov (United States)

Nystedt, Astrid; Högberg, Ulf; Lundman, Berit

2008-08-01

This paper is a report of a study to explore women's experiences of becoming a mother after prolonged labour. The negativity associated with a complicated labour such as prolonged labour can lead to a struggle to become a healthy mother and could restrict the process of becoming a mother. Interviews were conducted in 2004 with 10 mothers who had been through a prolonged labour with assisted vaginal or caesarean delivery 1-3 months previously. Thematic content analysis was used. Three themes were formulated, describing women's experiences as fumbling in the dark, struggling for motherhood and achieving confidence in being a mother. The difficulties and suffering involved in becoming a mother after a prolonged labour were interpreted to be like 'fumbling in the dark'. Women experienced bodily fatigue, accompanied by feelings of illness and detachment from the child. Having the child when in this condition entailed a struggle to become a mother. In spite of these experiences and the desire to achieve confidence in being a mother, the reassurance of these women regarding their capacity for motherhood was crucial: it was central to their happiness as mothers, encouraged interaction and relationship with the child, and contributed to their adaptation to motherhood. Women experiencing prolonged labour may be comparable with the experience of and recovery from illness, which could contribute to difficulties transitioning to motherhood and limit a woman's ability to be emotionally available for the child.

Prolonged unexplained fatigue in paediatrics

NARCIS (Netherlands)

Bakker, R.J.

2010-01-01

Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of

Significant progress towards development of the low-level radioactive waste disposal facility in Illinois

International Nuclear Information System (INIS)

Klebe, M.; Henry, T.L.; Corpstein, P.

1996-01-01

Development of disposal sites for low-level radioactive waste is a complicated legal, regulatory and public sector process. Development of the low-level radioactive waste disposal facility to support generators in Illinois and Kentucky is well under way. Significant progress has been made to re-engineer the siting development process capitalizing on prior lessons learned and a recommitment from Illinois state leadership assuring the future success of the program. Comparisons of why this new process will succeed are the major focus of this paper. Specific changes in approach from the previous process including changes in the Illinois Management Act (Management Act), creation of the Illinois Low-Level Radioactive Waste Siting Task Group (Task Group), new roles for the Illinois State Geologic Survey and Illinois State Water Survey (Scientific Surveys) and the Illinois Department of Nuclear Safety (IDNS), a new contractor reliance approach and increased confidence on the open-quote science close-quote are the major contrasts between the previous process and the new process currently underway

Birth outcomes for women using free-standing birth centers in South Auckland, New Zealand.

Science.gov (United States)

Bailey, David John

2017-09-01

This study investigates maternal and perinatal outcomes for women with low-risk pregnancies laboring in free-standing birth centers compared with laboring in a hospital maternity unit in a large New Zealand health district. The study used observational data from 47 381 births to women with low-risk pregnancies in South Auckland maternity facilities 2003-2010. Adjusted odds ratios with 95% confidence intervals were calculated for instrumental delivery, cesarean section, blood transfusion, neonatal unit admission, and perinatal mortality. Labor in birth centers was associated with significantly lower rates of instrumental delivery, cesarean section and blood transfusion compared with labor in hospital. Neonatal unit admission rates were lower for infants of nulliparous women laboring in birth centers. Intrapartum and neonatal mortality rates for birth centers were low and were not significantly different from the hospital population. Transfers to hospital for labor and postnatal complications occurred in 39% of nulliparous and 9% of multiparous labors. Risk factors identified for transfer were nulliparity, advanced maternal age, and prolonged pregnancy ≥41 weeks' gestation. Labor in South Auckland free-standing birth centers was associated with significantly lower maternal intervention and complication rates than labor in the hospital maternity unit and was not associated with increased perinatal morbidity. © 2017 Wiley Periodicals, Inc.

Has the time to come leave the “watch-and-wait” strategy in newly diagnosed asymptomatic follicular lymphoma patients?

International Nuclear Information System (INIS)

Rueda, Antonio; Casanova, María; Redondo, Maximino; Pérez-Ruiz, Elisabeth; Medina-Pérez, Ángeles

2012-01-01

Historically, the median overall survival for follicular lymphoma (FL) has been considered to be 9-10 years, and no treatment had ever prolonged this time period. Studies conducted more than 20 years ago demonstrated that treating patients with asymptomatic FL at the onset of the disease did not increase their survival, and that almost 20% of these patients did not need any treatment in the first 10 years of follow-up. Based on these facts, most clinical practice guidelines recommend active surveillance policies for patients with asymptomatic FL. The introduction of antiCD-20 monoclonal antibodies, over the last 15 years, has significantly increased the median survival rate to above 14 years. This improvement was achieved before the combination of rituximab and chemotherapy regimens became extensively used in patients with symptomatic disease. Therefore, this increase in survival may currently be more significant. At present, several clinical trials have evaluated low-toxicity therapies that prolong progression-free periods, among which rituximab monotherapy, radioimmunotherapy or the combination of rituximab with bendamustine are the most relevant. Unfortunately, these clinical trials have included only patients with symptomatic FL. The results of a recently reported clinical trial show that treatment with single-agent rituximab prolongs progression-free survival rates, time to new treatment and the quality of life of asymptomatic patients, as compared with the active surveillance strategy. Longer follow-up of these results and data regarding overall survival are awaited before this treatment can be recommended as the standard initial therapy. There are different therapeutic possibilities for asymptomatic FL patients, but no data are currently available to indicate which option is the best. Patients need to understand the risks and benefits of observation versus treatment before a final decision can be made. For patients who want active treatment the

Has the time to come leave the "watch-and-wait" strategy in newly diagnosed asymptomatic follicular lymphoma patients?

Science.gov (United States)

Rueda, Antonio; Casanova, María; Redondo, Maximino; Pérez-Ruiz, Elisabeth; Medina-Pérez, Angeles

2012-05-31

Historically, the median overall survival for follicular lymphoma (FL) has been considered to be 9-10 years, and no treatment had ever prolonged this time period. Studies conducted more than 20 years ago demonstrated that treating patients with asymptomatic FL at the onset of the disease did not increase their survival, and that almost 20% of these patients did not need any treatment in the first 10 years of follow-up. Based on these facts, most clinical practice guidelines recommend active surveillance policies for patients with asymptomatic FL. The introduction of antiCD-20 monoclonal antibodies, over the last 15 years, has significantly increased the median survival rate to above 14 years. This improvement was achieved before the combination of rituximab and chemotherapy regimens became extensively used in patients with symptomatic disease. Therefore, this increase in survival may currently be more significant. At present, several clinical trials have evaluated low-toxicity therapies that prolong progression-free periods, among which rituximab monotherapy, radioimmunotherapy or the combination of rituximab with bendamustine are the most relevant. Unfortunately, these clinical trials have included only patients with symptomatic FL. The results of a recently reported clinical trial show that treatment with single-agent rituximab prolongs progression-free survival rates, time to new treatment and the quality of life of asymptomatic patients, as compared with the active surveillance strategy. Longer follow-up of these results and data regarding overall survival are awaited before this treatment can be recommended as the standard initial therapy. There are different therapeutic possibilities for asymptomatic FL patients, but no data are currently available to indicate which option is the best. Patients need to understand the risks and benefits of observation versus treatment before a final decision can be made. For patients who want active treatment the

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

International Nuclear Information System (INIS)

Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

2010-01-01

Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

Does a 'tight' hamstring predict low back pain reporting during prolonged standing?

Science.gov (United States)

Raftry, Sean M; Marshall, Paul W M

2012-06-01

The purpose of this study was to investigate the relationship between hamstring passive stiffness and extensibility in asymptomatic individuals with the reporting of low back pain during 2-h prolonged standing. Twenty healthy participants with no history of low back pain (mean±SD, age 22.6±2.7 years, height 1.74±0.09 m, weight 76.2±14.8 kg). Low back pain (VAS score; mm) was continuously monitored during 2-h prolonged standing. Hamstring extensibility, passive stiffness, and stretch tolerance were measured before and after prolonged standing using an instrumented straight leg raise (iSLR). Ten participants reported a clinically relevant increase (Δ VAS>10mm) in low back pain during prolonged standing. Hamstring extensiblity (leg°(max)), passive stiffness (Nm.°(-1)), and stretch tolerance (VAS; mm) were no different between pain developers and non-pain developers. No changes in hamstring measures were observed following 2-h prolonged standing. No relationship was observed in this study between measures of hamstring extensibility and the reporting of low back pain during prolonged standing. There is no evidence to recommend hamstring extensibility interventions (i.e. passive stretching) as a means of reducing pain reporting in occupations requiring prolonged standing. Copyright © 2012 Elsevier Ltd. All rights reserved.

Do Partial Home Smoking Bans Signal Progress toward a Smoke-Free Home?

Science.gov (United States)

Kegler, Michelle C.; Haardörfer, Regine; Bundy, Lucja T.; Escoffery, Cam; Berg, Carla J.; Fernandez, Maria; Williams, Rebecca; Hovell, Mel

2016-01-01

Understanding who establishes partial home smoking bans, what these bans cover, and whether they are an intermediate step in going smoke-free would help to inform smoke-free home interventions. Participants were recruited from United Way of Greater Atlanta's 2-1-1 contact center. Data were collected at baseline, 3 and 6 months via telephone…

The Extent of Myocardial Injury During Prolonged Targeted Temperature Management After Out-of-Hospital Cardiac Arrest

DEFF Research Database (Denmark)

Grejs, Anders Morten; Gjedsted, Jakob; Thygesen, Kristian

2017-01-01

AIM: The aim of this study is to evaluate the extent of myocardial injury by cardiac biomarkers during prolonged targeted temperature management of 24 hours vs 48 hours after out-of-hospital cardiac arrest. METHODS: This randomized Scandinavian multicenter study compares the extent of myocardial...... injury estimated by hs-cTnTAUC of prolonged targeted temperature management of 48 hours vs 24 hours, although the CK-MBAUC was significantly higher during 48 hours vs 24 hours. Hence, it seems unlikely that the duration of targeted temperature management has a beneficial effect on the extent...... injury quantified by area under the curve (AUC) of cardiac biomarkers during prolonged targeted temperature management at 33°C ± 1°C of 24 hours and 48 hours, respectively. Through a period of 2.5 years, 161 comatose out-of-hospital cardiac arrest patients were randomized to targeted temperature...

Erotic Utopia - Free Upbringing, Free Sex and Socialism

DEFF Research Database (Denmark)

Paldam, Camilla Skovbjerg

2015-01-01

and open-mindedness. Common to both theorists and artists of the period was a focus on liberation; this, however, could be understood in many ways and to different extents. German psychoanalyst Wilhelm Reich held one of the most radical beliefs, that a sexually free upbringing would ultimately lead...... Wolffheim as a way to understand how radical Reich’s theories were in comparison to the more pragmatic approaches suggested by other – otherwise progressive – thinkers of the time....

The Free Senior High Policy: An Appropriate Replacement to the Progressive Free Senior High Policy

Science.gov (United States)

Abdul-Rahaman, Nurudeen; Rahaman, Abdul Basit Abdul; Ming, Wan; Ahmed, Abdul-Rahim; Salma, Abdul-Rahaman S.

2018-01-01

Governments all over the world have been improving their educational sector through funding programs aimed at reducing the financial burden on parents, increasing access and quality to education. The government of Ghana in 2017 switched policy to a free senior high school policy to reduce poverty by finally eliminating the financial burdens…

Predictive factors for oropharyngeal dysphagia after prolonged orotracheal intubation.

Science.gov (United States)

Oliveira, Ana Carolina Martins de; Friche, Amélia Augusta de Lima; Salomão, Marina Silva; Bougo, Graziela Chamarelli; Vicente, Laélia Cristina Caseiro

2017-09-13

Lesions in the oral cavity, pharynx and larynx due to endotracheal intubation can cause reduction in the local motility and sensitivity, impairing the swallowing process, resulting in oropharyngeal dysphagia. To verify the predictive factors for the development of oropharyngeal dysphagia and the risk of aspiration in patients with prolonged orotracheal intubation admitted to an intensive care unit. This is an observational, analytical, cross-sectional and retrospective data collection study of 181 electronic medical records of patients submitted to prolonged orotracheal intubation. Data on age; gender; underlying disease; associated comorbidities; time and reason for orotracheal intubation; Glasgow scale on the day of the Speech Therapist assessment; comprehension; vocal quality; presence and severity of dysphagia; risk of bronchoaspiration; and the suggested oral route were collected. The data were analyzed through logistic regression. The level of significance was set at 5%, with a 95% Confidence Interval. The prevalence of dysphagia in this study was 35.9% and the risk of aspiration was 24.9%. As the age increased, the altered vocal quality and the degree of voice impairment increased the risk of the presence of dysphagia by 5-; 45.4- and 6.7-fold, respectively, and of aspiration by 6-; 36.4- and 4.8-fold. The increase in the time of orotracheal intubation increased the risk of aspiration by 5.5-fold. Patients submitted to prolonged intubation who have risk factors associated with dysphagia and aspiration should be submitted to an early speech-language/audiology assessment and receive appropriate and timely treatment. The recognition of these predictive factors by the entire multidisciplinary team can minimize the possibility of clinical complications inherent to the risk of dysphagia and aspiration in extubated patients. Copyright © 2017. Published by Elsevier Editora Ltda.

Effects of specific and prolonged expression of zebrafish growth factors, Fgf2 and Lif in primordial germ cells in vivo

Energy Technology Data Exchange (ETDEWEB)

Wong, Ten-Tsao, E-mail: wong20@purdue.edu [Department of Animal Sciences, Purdue University, 901 W. State Street, West Lafayette, IN 47907 (United States); Collodi, Paul [Department of Animal Sciences, Purdue University, 901 W. State Street, West Lafayette, IN 47907 (United States)

2013-01-04

Highlights: Black-Right-Pointing-Pointer We discovered that nanos3 3 Prime UTR prolonged PGC-specific protein expression up to 26 days. Black-Right-Pointing-Pointer Expression of Fgf2 in PGCs significantly increased PGC number at later developmental stages. Black-Right-Pointing-Pointer Expression of Lif in PGCs resulted in a significant disruption of PGC migration. Black-Right-Pointing-Pointer Lif illicited its effect on PGC migration through Lif receptor a. Black-Right-Pointing-Pointer Our approach could be used to achieve prolonged PGC-specific expression of other proteins. -- Abstract: Primordial germ cells (PGCs), specified early in development, proliferate and migrate to the developing gonad before sexual differentiation occurs in the embryo and eventually give rise to spermatogonia or oogonia. In this study, we discovered that nanos3 3 Prime UTR, a common method used to label PGCs, not only directed PGC-specific expression of DsRed but also prolonged this expression up to 26 days post fertilization (dpf) when DsRed-nanos3 3 Prime UTR hybrid mRNAs were introduced into 1- to 2-cell-stage embryos. As such, we employed this knowledge to express zebrafish leukemia inhibitory factor (Lif), basic fibroblast growth factor (Fgf2) and bone morphogenetic protein 4 (Bmp4) in the PGCs and evaluate their effects on PGC development in vivo for over a period of 3 weeks. The results show that expression of Fgf2 significantly increased PGC number at 14- and 21-dpf while Bmp4 resulted in severe ventralization and death of the embryos by 3 days. Expression of Lif resulted in a significant disruption of PGC migration. Mopholino knockdown experiments indicated that Lif illicited its effect on PGC migration through Lif receptor a (Lifra) but not Lifrb. The general approach described in this study could be used to achieve prolonged PGC-specific expression of other proteins to investigate their roles in germ cell and gonad development. The results also indicate that zebrafish PGCs

African Journal of Oral Health is making progress | Ogunbodede ...

African Journals Online (AJOL)

African Journal of Oral Health is making progress. Professor Eyitope O. Ogunbodede. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

Science.gov (United States)

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

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

DEFF Research Database (Denmark)

Albert, Nikolai; Melau, Marianne; Jensen, Heidi

2017-01-01

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......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...

Selective lymphoid irradiation: III. Prolongation of cardiac xenografts and allografts in presensitized rats

International Nuclear Information System (INIS)

Hardy, M.A.; Oluwole, S.; Fawwaz, R.; Satake, K.; Nowygrod, R.; Reemtsma, K.

1982-01-01

Selective lymphoid irradiation (SLI) with palladium-109-hematoporphyrin (Pd-H) combined with antilymphocyte globulin (ALG) induces either donor-specific permanent rat heart allograft acceptance or significant allograft prolongation depending on the degree of donor-recipient matching. The purpose of this study was to determine if SLI combined with ALG can affect ACI heart allograft survival in Lewis recipients presensitized to ACI, and of hamster heart xenografts of Lewis rats. SLI combined with ALG delays allograft and xenograft rejection in the presence of induced or preformed antidonor antibodies, and converts primarily a humoral rejection into a cellular rejection by mechanisms as yet uncertain. Such peritransplant treatment had significant effect on the levels of antidonor complement-dependent cytotoxic antibody titers but did not correlate directly with graft survival. Histological analysis of rejected hearts in all groups demonstrated primarily a humoral hyperacute rejection in control animals and in recipients treated with ALG alone, while peritransplant treatment with Pd-H and ALG resulted not only in prolonged graft survival but histologically, primarily a cellular rejection of the graft

Recent progress in orbital-free density functional theory (recent advances in computational chemistry)

CERN Document Server

Wesolowski, Tomasz A

2013-01-01

This is a comprehensive overview of state-of-the-art computational methods based on orbital-free formulation of density functional theory completed by the most recent developments concerning the exact properties, approximations, and interpretations of the relevant quantities in density functional theory. The book is a compilation of contributions stemming from a series of workshops which had been taking place since 2002. It not only chronicles many of the latest developments but also summarises some of the more significant ones. The chapters are mainly reviews of sub-domains but also include original research. Readership: Graduate students, academics and researchers in computational chemistry. Atomic & molecular physicists, theoretical physicists, theoretical chemists, physical chemists and chemical physicists.

What prolongs a butterfly's life?: Trade-offs between dormancy, fecundity and body size.

Directory of Open Access Journals (Sweden)

Elena Haeler

Full Text Available In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies' life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h, thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13. Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels.

Prolonged fatigue is associated with sickness absence in men but not in women: prospective study with 1-year follow-up of white-collar employees.

Science.gov (United States)

Roelen, Corné A M; van Rhenen, Willem; Groothoff, Johan W; van der Klink, Jac J L; Bültmann, Ute

2014-04-01

Prolonged fatigue adversely affects an individual's performance and functioning. The present study investigated the prospective associations between prolonged fatigue and sickness absence (SA) during 1-year follow-up. At baseline, a convenience sample of white-collar employees received the 20-item Checklist Individual Strength (CIS), which measures prolonged fatigue by covering the dimensions fatigue severity, reduced concentration, reduced motivation, and reduced physical activity. SA episodes were registered during the 1-year follow-up distinguishing between short-term (1-7 days) and long-term ( 7 days) SA episodes. Baseline CIS scores were linked to SA during follow-up by negative binomial regression models in which age, gender, job grade, and prior SA were controlled for. Six hundred and thirty-three (56 %) employees participated in the study of which 598 had complete data and were eligible for analysis. Gender was a significant effect modifier of the relationship between prolonged fatigue and SA. Therefore, the results were stratified for men (N = 365) and women (N = 233). In white-collar men, fatigue severity and reduced concentration were positively associated with the number of long-term SA episodes, while other fatigue dimensions were not significantly related to SA. In white-collar women, prolonged fatigue was not associated with SA during 1-year follow-up. The results of this study warrant more attention for prolonged fatigue in occupational healthcare practice and research. Early identification of and treatment for prolonged fatigue might prevent future health problems and SA, especially in white-collar men.

Evaluation of a digital method to assess evening meal intake in a free-living

DEFF Research Database (Denmark)

Lassen, Anne Dahl; Poulsen, Sanne; Andersen, Lotte Ernst

2010-01-01

Background: In recent years new applications of technologies, including digital images, to capture dietary behaviour in real time have been explored. Objectives: To validate a digital method for estimating evening meal intake in a free-living adult population, and to examine the feasibility...... of the method for recording evening meal intake over a prolonged period of time. Design: The digital method was compared against weighed records of 19 participants’ usual evening meals for five consecutive days. Two trained image analysts independently estimated the weight of individual foods within the meals...... estimation in real-time where a prolonged recording period of participants’ meals is needed....

IINFLUENCE OF FREEZING AND PROLONGED STORAGE OF EXPRESSED BREAST MILK ON ITS NUTRITIVE, BIOLOGICAL VALUES AND MICROBIOLOGICAL SAFETY

Directory of Open Access Journals (Sweden)

O. L. Lukoyanova

2011-01-01

Full Text Available Evaluation of prolonged storage of breast milk safety for nutrition of newborns remains actual problem of modern nutritiology. Objectives: to evaluate an influence of freezing and prolonged storage of expressed breast milk on its nutritive, biological values and microbiological safety. Methods: samples of expressed breast milk (native samples and after 1 and 3 months of storage in containers Philips AVENT in t -18°С were analyzed; levels of secretory IgA, lysozyme, transforming growth factor (TGF β1, potassium, calcium, magnesium, pH, buffer capacity and bacterial cells were detected. Results: there is no statistically significant influence of low temperature and prolonged storage of expressed breast milk on levels of secretory IgA, lysozyme, TGF β1 and bacterial cells. Potassium and calcium levels significantly decreased (on about 10% and 20% accordingly, pH increased, and buffer capacity of milk lowered after freezing during 3 months. Conclusion: children’s feeding with native and expressed breast milk defrosted after 3 months of storage is equal in nutritive and biological values and microbiological safety.

Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

Science.gov (United States)

Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

2015-11-01

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . Copyright © 2015 the American Physiological Society.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

DEFF Research Database (Denmark)

Rasmussen, Morten Schnack; Jørgensen, Lars Nannestad; Wille-Jørgensen, Peer

2009-01-01

BACKGROUND: Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular weight heparin (LMWH) administered during the in-hospital period is well documented, but the optimal duration of thromboprophylaxis after surgery...... evaluating prolonged thromboprophylaxis with LMWH as compared to control or placebo. 133 studies were found in the searches, of which only 4 were found eligible for inclusion, and 129 were excluded. The incidence of overall VTE after major abdominal or pelvic surgery was 14.3% (95% confidence interval 11...... significant reduction of even the incidence of symptomatic VTE from 1.7% (95% CI 0.8% - 3.4%) in the control group to 0.2 % (95% CI 0.0% - 1.2%) in patients receiving prolonged thromboprophylaxis, Peto Odds ratio 0.22 (95% CI 0.06 -0.80), P = 0.02. The respective incidence of bleeding in the control and LMWH...

Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

Science.gov (United States)

2014-01-01

Background Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women’s experiences of prolonged and normal labour. Method Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic and obstetric background, birth outcome and women’s feelings and experiences of birth. The prevalence of prolonged labour, as defined by a documented ICD-code and inspection of partogram was calculated. Four groups were identified; women with prolonged labour as identified by documented ICD-codes or by partogram inspection but no ICD-code; women with normal labour augmented with oxytocin or not. Results Every fifth woman experienced a prolonged labour. The prevalence with the documented ICD-code was (13%) and without ICD-code but positive partogram was (8%). Seven percent of women with prolonged labour were not treated with oxytocin. Approximately one in three women (28%) received oxytocin augmentation despite having no evidence of prolonged labour. The length of labour differed between the four groups of women, from 7 to 23 hours. Women with a prolonged labour had a negative birth experience more often (13%) than did women who had a normal labour (3%) (P women with prolonged labour were emergency Caesarean section (OR 9.0, 95% CI 1.2-3.0) and to strongly agree with the following statement ‘My birth experience made me decide not to have any more children’ (OR 41.3, 95% CI 4.9-349.6). The factors that contributed most strongly to a negative birth experience in women with normal labour were less agreement with the statement ‘It was exiting to give birth’ (OR 0.13, 95% CI 0.34-0.5). Conclusions There is need for increased clinical skill in identification and classification

The cumulative effect of small dietary changes may significantly improve nutritional intakes in free-living children and adults

OpenAIRE

Bornet , Francis; Paineau , Damien; Beaufils , François; Boulier , Alain; Cassuto , Dominique-Adèle; Chwalow , Judith; Combris , Pierre; Couet , Charles; Jouret , Béatrice; Lafay , Lionel; Laville , Martine; Mahé , Sylvain; Ricour , Claude; Romon , Monique; Simon , Chantal

2010-01-01

Abstract Background/Objectives: The ELPAS study was an 8-month randomized controlled dietary modification trial designed to test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in 2026 free-living children and parents (Paineau et al., 2008). It resulted in significant nutritional changes, with beneficial effects on body mass index in adults. In these ancillary analyses, we investigated dietary changes throughout the intervention. ...

Prolonged fasting activates Nrf2 in post-weaned elephant seals.

Science.gov (United States)

Vázquez-Medina, José Pablo; Soñanez-Organis, José G; Rodriguez, Ruben; Viscarra, Jose A; Nishiyama, Akira; Crocker, Daniel E; Ortiz, Rudy M

2013-08-01

Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin-angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 167% at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 5000% and 250% higher at week 7 than at week 1. Phosphorylation of Smad2, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 430% at week 7, while Nox4 protein expression, which can activate Nrf2, was 170% higher at week 7 than at week 1. These results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. The results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals.

AORN Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings.

Science.gov (United States)

Hughes, Nancy L; Nelson, Audrey; Matz, Mary W; Lloyd, John

2011-06-01

Prolonged standing during surgical procedures poses a high risk of causing musculoskeletal disorders, including back, leg, and foot pain, which can be chronic or acute in nature. Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings provides recommendations for relieving the strain of prolonged standing, including the use of antifatigue mats, supportive footwear, and sit/stand stools, that are based on well-accepted ergonomic safety concepts, current research, and access to new and emerging technology. Published by Elsevier Inc.

Diagnostic utility of fractional exhaled nitric oxide in prolonged and chronic cough according to atopic status

Directory of Open Access Journals (Sweden)

Takamitsu Asano

2017-04-01

Conclusions: Although high FeNO levels suggested the existence of AC, lower FeNO levels had limited diagnostic significance. Atopic status affects the utility of FeNO levels in the differential diagnosis of prolonged and chronic cough.

Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

Directory of Open Access Journals (Sweden)

Christina Bognet

2011-12-01

Full Text Available Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL solutions, with or without epinephrine 5 µg/mL (1:200,000 in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001 or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001. Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

MRI findings of prolonged post-traumatic sternal pain

International Nuclear Information System (INIS)

Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne; Steinbach, Lynne

2007-01-01

The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

Impaired Neonatal Outcome after Emergency Cerclage Adds Controversy to Prolongation of Pregnancy.

Directory of Open Access Journals (Sweden)

Ruben-J Kuon

Full Text Available Emergency cervical cerclage is one of the treatment options for the reduction of preterm birth. The aim of this study is to assess neonatal outcome after cerclage with special focus on adverse effects in very low birth weight infants.Retrospective cohort study. Classification of cerclages in history-indicated (HIC, n = 38, ultrasound-indicated (UIC, n = 29 and emergency/ physical examination-indicated (PEIC, n = 33 cerclage. Descriptive analysis of pregnancy and neonatal outcome (admission to NICU, duration of hospitalization, respiratory outcome (intubation, CPAP, FiO2max, neonatal complications (ROP, IVH. Statistical comparison of perinatal parameters and outcome of neonates <1500 g after cerclage with a birth weight matched control group.Neonates <1500 g after PEIC show significantly impaired outcome, i.e. prolonged respiratory support (total ventilation in days, CPAP, FiO2max and higher rates of neonatal complications (IVH ≥ II, ROP ≥ 2. Placental pathologic evaluation revealed a significantly higher rate of chorioamnionitis (CAM after PEIC. Neonates <1500 g after UIC or HIC show no significant difference in neonatal complications or CAM.In our study PEIC is associated with adverse neonatal outcome in infants <1500 g. The high incidence of CAM indicates a potential inflammatory factor in the pathogenesis. Large well-designed RCTs are required to give conclusive answers to the question whether to prolong or to deliver.

Physiology Of Prolonged Bed Rest

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Greenleaf, John E.

1991-01-01

Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

PR Interval Prolongation and Cryptogenic Stroke: A Multicenter Retrospective Study.

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Montalvo, Mayra; Tadi, Prasanna; Merkler, Alexander; Gialdini, Gino; Martin-Schild, Sheryl; Navalkele, Digvijaya; Samai, Alyana; Nouh, Amre; Hussain, Mohammad; Goldblatt, Steven; Hemendinger, Morgan; Chu, Antony; Song, Christopher; Kamel, Hooman; Furie, Karen L; Yaghi, Shadi

2017-10-01

Atrial dysfunction or "cardiopathy" has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared with known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes. We used prospective ischemic stroke databases of 3 comprehensive stroke centers to identify patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke between December 1, 2013 and August 31, 2015. The main outcome was ischemic stroke subtype (CS versus NCNCS). We compared PR intervals as a continuous and categorical variable (PR interval prolongation and CS. We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). Patients with CS were more likely to have a PR of 200 milliseconds or greater when compared with those with NCNCS (23.2% versus 13.8%, P = .009). After adjusting for factors that were significant in univariate analyses, a PR of 200 milliseconds or greater was independently associated with CS (odds ratio [OR] 1.70, 95% CI 1.08-2.70). The association was more pronounced when excluding patients on atrioventricular nodal blocking agents (OR 2.64, 95% CI 1.44-4.83). A PR of 200 milliseconds or greater is associated with CS and may be a biomarker of atrial cardiopathy in the absence of atrial fibrillation. Prospective studies are needed to confirm this association. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Prolonged peritoneal gene expression using a helper-dependent adenovirus.

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Liu, Limin; Shi, Chang-Xin; Ghayur, Ayesha; Zhang, Claire; Su, Je Yen; Hoff, Catherine M; Margetts, Peter J

2009-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS. We developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-beta1; HDAdTGF-beta1). Mice were administered HDAdTGF-beta1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-beta1 (AdTGF-beta1) or control adenovirus (AdGFP). HDAdTGF-beta1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-beta1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-beta1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-beta1 compared to both the control-treated animals and the AdTGF-beta1-treated animals. Inflammation was not a major component of the fibroproliferative response. Peritoneal administration of a first-generation AdTGF-beta1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-beta1 expression induced by the helper-dependent HDAdTGF-beta1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-beta1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

Metabolic responses to prolonged work during treadmill and water immersion running.

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Frangolias, D D; Rhodes, E C; Taunton, J E; Belcastro, A N; Coutts, K D

2000-12-01

The primary aim of this study was to compare the physiological responses to prolonged treadmill (TM) and water immersion to the neck (WI) running at threshold intensity. Ten endurance runners performed TM and WI running VO2max tests. Subjects completed submaximal performance tests at ventilatory threshold (Tvent) intensities under TM and WI conditions and responses at 15 and 42 minutes examined. VO2 was lower in WI (p<0.05) at maximal effort and Tvent. The Tvent VO2 intensities interpolated from the TM and WI VO2max tests were performed in both TM (i.e., TM@TM(tvent),TM@WI(tvent), corresponding to 77.6 and 71.3% respectively of TM VO2max) and WI conditions (i.e., WI@TM(tvent), WI@WI(tvent), corresponding to 85.5% and 78.2% respectively of WI VO2max). Each of the dependent variables was analyzed using a 3-way repeated measures ANOVA (2 conditions X 2 exercise intensities X 7 time points during exercise). VO2max values were significantly lower in the WI (52.4(5.1) ml.kg(-1) min(-1)) versus TM (59.7(6.5) ml.kg(-1) min(-1)) condition. VO2 during submaximal tests were similar during the TM and WI conditions. HR and [BLa] responses to exercise at and above WI(tvent) were similar during short-term exercise, but values tended to be lower during prolonged exercise in the WI condition. There were no statistical differences in VE responses in the 2 conditions, however as with HR and [BLa] an upward trend was noted with TM exercise over the 42 minute duration of the tests. RPE at WI(tvent) was similar for TM and WI exercise sessions, however, RPE at TM(tvent) was higher during WI compared to TM running. Cardiovascular drift was observed during prolonged TM but not WI running. Results suggest differences in metabolic responses to prolonged submaximal exercise in WI, however it can be used effectively for cross training.

Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.

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Advani, Ranjana H; Buggy, Joseph J; Sharman, Jeff P; Smith, Sonali M; Boyd, Thomas E; Grant, Barbara; Kolibaba, Kathryn S; Furman, Richard R; Rodriguez, Sara; Chang, Betty Y; Sukbuntherng, Juthamas; Izumi, Raquel; Hamdy, Ahmed; Hedrick, Eric; Fowler, Nathan H

2013-01-01

Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.

The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

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Wang, Xin; Xiong, Xiao-Peng; Lu, Jiade; Zhu, Guo-Pei; He, Shao-Qin; Hu, Chao-Su; Ying, Hong-Mei

2011-01-01

High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time

Cardiovascular drugs inducing QT prolongation: facts and evidence.

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Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

2010-01-01

Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

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Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

2017-07-01

An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

Prolonged continuous exposure to high fine particulate matter associated with cardiovascular and respiratory disease mortality in Beijing, China

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Wang, Jinfeng; Yin, Qian; Tong, Shilu; Ren, Zhoupeng; Hu, Maogui; Zhang, Hongrui

2017-11-01

Although many studies examined the effects of fine particulate matter (PM2.5) on the deaths of cardiovascular disease (CVD) and respiratory disease (RD), few research has paid attention to the effects of prolonged continuous exposure to high PM2.5 pollution. This study estimated the excess risks (ER) of CVD and RD mortalities associated with prolonged continuous exposure to high PM2.5 pollution for the whole population and specific subsociodemographic groups in Beijing, which is the capital city of China with over 20 million residents and having severe PM2.5 pollution problems. Our results suggested that when high PM2.5 pollution occurred continuously, at various thresholds and durations, the adverse effects on CVD and RD mortalities varied significantly. The CVD mortality risks in association with prolonged continuous high PM2.5 pollution exposure were more serious for single individuals (including unmarried, divorced, and widowed), illiterate and outdoor workers than for other specific subsociodemographic groups. When the daily PM2.5 concentration higher than 105 μg/m3 consecutively occurs, at the ninth day, the ERs of CVD death for single individuals, illiterate and outdoor workers groups reached to 45% (95% CI: 22, 71), 51% (95% CI: 28, 79) and 53% (95% CI: 29, 82) respectively. On the other hand, prolonged continuous high PM2.5 pollution level appeared to contribute a higher proportion of RD deaths among illiterate and outdoor workers, but less significant for the other specific subsociodemographic groups. When the duration with daily PM2.5 pollution higher than 115 μg/m3 reached to six days, the ERs for outdoor workers and illiterate attributed to prolonged continuous PM2.5 pollution exposure increased 36% (95% CI: 5, 76) and 49% (95% CI: 16, 91) respectively.

Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

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Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

2016-01-06

Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of Muscle Fatigue Associated with Prolonged Standing in the Workplace

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Omar, Abdul Rahman; Saman, Alias Mohd; Othman, Ibrahim

2012-01-01

Objectives The objectives of this study were to determine the psychological fatigue and analyze muscle activity of production workers who are performing processes jobs while standing for prolonged time periods. Methods The psychological fatigue experienced by the workers was obtained through questionnaire surveys. Meanwhile, muscle activity has been analyzed using surface electromyography (sEMG) measurement. Lower extremities muscles include: erector spinae, tibialis anterior, and gastrocnemius were concurrently measured for more than five hours of standing. Twenty male production workers in a metal stamping company participated as subjects in this study. The subjects were required to undergo questionnaire surveys and sEMG measurement. Results Results of the questionnaire surveys found that all subjects experienced psychological fatigue due to prolonged standing jobs. Similarly, muscle fatigue has been identified through sEMG measurement. Based on the non-parametric statistical test using the Spearman's rank order correlation, the left erector spinae obtained a moderate positive correlation and statistically significant (rs = 0.552, p fatigue and to muscle fatigue among the production workers. PMID:22953228

MRI findings of prolonged post-traumatic sternal pain

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Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne [University Hospital of Berne, Department of Diagnostic, Pediatric and Interventional Radiology, Berne (Switzerland); Steinbach, Lynne [University of California San Francisco, Department of Radiology, San Francisco, CA (United States)

2007-05-15

The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

Prolonged sitting in cars: prevalence, socio-demographic variations, and trends.

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Sugiyama, Takemi; Merom, Dafna; van der Ploeg, Hidde P; Corpuz, Grace; Bauman, Adrian; Owen, Neville

2012-10-01

Prolonged sitting is detrimentally associated with health outcomes. However, the prevalence and characteristics of those who sit in cars for long periods are not well understood. This study examined the population prevalence, socio-demographic variations, and trends for prolonged sitting in cars among adults. Using the Sydney Greater Metropolitan Area Household Travel Survey, the prevalence of prolonged sitting time in cars (≥2 h/day) was calculated for four 3-year periods (1997-99, 2000-02, 2003-05, and 2006-08) for each population subgroup. Trends were calculated as the mean change in prevalence between adjacent survey periods. Cars were used for 66% of the total trips recorded (n=336,505). The prevalence of prolonged sitting time in cars was 16-18% in men, and 10-12% in women. Relatively higher prevalence rates were found among middle-age groups (men: 20-22%, women: 12-15%), full-time workers (men: 21-24%, women: 14-15%), those with higher income (men: 21-25%, women: 14-16%), couples with children (men: 20-21%, women: 12-14%), and those living in outer suburbs (men: 20-23%, women: 12-13%). Trends were stable in men, but increasing in women. Several subgroups (older age; living in regional suburbs) also showed increasing trends. These findings provide evidence to inform integrated approaches to measurement and policy development on prolonged car use among the public health, urban planning, and transport sectors. Copyright © 2012 Elsevier Inc. All rights reserved.

Free probability and random matrices

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Mingo, James A

2017-01-01

This volume opens the world of free probability to a wide variety of readers. From its roots in the theory of operator algebras, free probability has intertwined with non-crossing partitions, random matrices, applications in wireless communications, representation theory of large groups, quantum groups, the invariant subspace problem, large deviations, subfactors, and beyond. This book puts a special emphasis on the relation of free probability to random matrices, but also touches upon the operator algebraic, combinatorial, and analytic aspects of the theory. The book serves as a combination textbook/research monograph, with self-contained chapters, exercises scattered throughout the text, and coverage of important ongoing progress of the theory. It will appeal to graduate students and all mathematicians interested in random matrices and free probability from the point of view of operator algebras, combinatorics, analytic functions, or applications in engineering and statistical physics.

PATHOGENETIC VALIDATION OF ADDITIONAL OBJECTIVE CRITERIA FOR POSSIBLE EFFECTIVE PREGNANCY PROLONGATION AFTER PREMATURE MEMBRANE RUPTURE

Directory of Open Access Journals (Sweden)

L. I. Dyatlova

2015-01-01

, when adequate and comprehensive therapy was applied. In the course of pregnancy prolongation, we found a progressive increase in pro-inflammatory cytokine levels (IL-2, IL-6, IL-8, TNFα, a steady decrease in CD19+ B cell counts, CD3+СD4+ helpers, natural killer cells, increased levels of cytotoxic CD3+CD8+ T cells .The pathogenesis-based criteria for necessary termination of the pregnancy for women with PROM are identified, including an increase in acute-phase proteins levels in blood, development of neutrophilic leukocytosis, lymphopenia, increase of pro-inflammatory cytokine levels in blood (IL-1β, IL-6, IL-8, TNFα, along with progressive reduction of CD3+СD4+ lymphocytes, CD16+CD56+ and CD19+ В lymphocytes.  

Management of children with prolonged diarrhea [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Antonietta Giannattasio

2016-02-01

Full Text Available Prolonged diarrhea is usually defined as acute-onset diarrhea lasting 7 days or more, but less than 14 days. Its trend has been declining in recent years because of improvement in the management of acute diarrhea, which represents the ideal strategy to prevent prolonged diarrhea. The pathogenesis of prolonged diarrhea is multifactorial and essentially based on persistent mucosal damage due to specific infections or sequential infections with different pathogens, host-related factors including micronutrient and/or vitamin deficiency, undernutrition and immunodeficiency, high mucosal permeability due to previous infectious processes and nutrient deficiency with consequential malabsorption, and microbiota disruption. Infections seem to play a major role in causing prolonged diarrhea in both developing and developed areas. However, single etiologic pathogens have not been identified, and the pattern of agents varies according to settings, host risk factors, and previous use of antibiotics and other drugs. The management of prolonged diarrhea is complex. Because of the wide etiologic spectrum, diagnostic algorithms should take into consideration the age of the patient, clinical and epidemiological factors, and the nutritional status and should always include a search for enteric pathogens. Often, expensive laboratory evaluations are of little benefit in guiding therapy, and an empirical approach may be effective in the majority of cases. The presence or absence of weight loss is crucial for driving the initial management of prolonged diarrhea. If there is no weight loss, generally there is no need for further evaluation. If weight loss is present, empiric anti-infectious therapy or elimination diet may be considered once specific etiologies have been excluded.

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

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Xin Qiao

2017-09-01

Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration

NARCIS (Netherlands)

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, Imc; Danhof, M; Meijer, J H; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in

Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

Science.gov (United States)

Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

2013-10-01

We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal.

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Martinez, Bridget; Soñanez-Organis, José G; Vázquez-Medina, José Pablo; Viscarra, Jose A; MacKenzie, Duncan S; Crocker, Daniel E; Ortiz, Rudy M

2013-12-15

Food deprivation in mammals is typically associated with reduced thyroid hormone (TH) concentrations and deiodinase content and activity to suppress metabolism. However, in prolonged-fasted, metabolically active elephant seal pups, TH levels are maintained, if not elevated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food-deprived mammals. To address our hypothesis that cellular TH-mediated activity is upregulated with fasting duration, we quantified the mRNA expression and protein content of adipose and muscle deiodinase type I (DI1) and type II (DI2), and TH receptor beta-1 (THrβ-1) after 1, 3 and 7 weeks of fasting in northern elephant seal pups (N=5-7 per week). Fasting did not decrease the concentrations of plasma thyroid stimulating hormone, total triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting that the hypothalamic-pituitary-thyroid axis is not suppressed, but rather maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased threefold and fourfold, respectively, and 20- and 30-fold, respectively, in muscle. With the exception of adipose DI1, protein expression of adipose DI2 and muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose (fivefold) and muscle (fourfold) THrβ-1 mRNA expression, suggesting that the mechanisms mediating cellular TH activity are upregulated with prolonged fasting. The data demonstrate a unique, atypical mechanism of TH activity and regulation in mammals adapted to prolonged food deprivation in which the potential responsiveness of peripheral tissues and cellular TH activity are increased, which may contribute to their lipid-based metabolism.

Progressive multiple cranial neuropathies presenting as a delayed complication of radiotherapy in infancy.

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Pall, H. S.; Nightingale, S.; Clough, C. G.; Spooner, D.

1988-01-01

A 38 year old woman who had undergone irradiation during infancy for a left facial cutaneous arteriovenous malformation sequentially developed complete palsies of the ipsilateral VII, V, XI, IX, X, XII and VI cranial nerves. Apart from optic and olfactory nerve damage there are few reports of radiotherapy causing cranial nerve injury. We link the unusually extensive and progressive neural damage and the prolonged latency to the patient's age at time of irradiation.

Low-intensity pulsed ultrasound is effective for progressive-stage lumbar spondylolysis with MRI high-signal change.

Science.gov (United States)

Arima, Hideyuki; Suzuki, Yoshiji; Togawa, Daisuke; Mihara, Yuki; Murata, Hideyuki; Matsuyama, Yukihiro

2017-12-01

This study aimed to investigate the treatment effects of low-intensity pulsed ultrasound (LIPUS) on progressive-stage spondylolysis. Spondylolysis is a stress fracture of the pars interarticularis. Based on the results of computed tomography, spondylolysis was classified into three categories: early, progressive, and terminal. Bone healing was prolonged or not obtained in progressive-stage spondylolysis. The progression of spondylolysis to nonunion has been associated with an increased incidence of spondylolisthesis. To prevent these clinical conditions, achieving bony healing of the spondylolysis site should be the goal of treatment. 15 consecutive pediatric patients with progressive-stage spondylolysis (defects) with MRI high-signal change were analyzed. Nine patients were treated conservative treatment including avoidance of any sport activity and the use of a brace during treatment (conventional). Six patients were treated using LIPUS everyday during treatment in addition to conservative treatment. Approximately every 1.5 months, bone healing was evaluated via CT. Cases that retained defects after 4.5 months were defined as nonunion. Two patients dropped out during the study period. A total of 13 patients (mean 14.6 ± 2.5 years) from the database met with 19 interarticularis defects. The bone union rate in LIPUS group was significantly higher than that in conventional group (66.7 vs. 10.0%, p = 0.020). The treatment period to bone union was 3.8 months and 2.7 ± 0.3 months in conventional and LIPUS groups. This study revealed that LIPUS treatment might be effective for bone union in patients with progressive-stage spondylolysis with MRI high-signal change. 4.

Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder

DEFF Research Database (Denmark)

Baandrup, Lone; Lindschou, Jane; Winkel, Per

2016-01-01

OBJECTIVES: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. METHODS: Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised...... to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine...... cessation proportion, and benzodiazepine withdrawal symptoms. RESULTS: In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group...

Influence of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing.

Science.gov (United States)

Karimi, Zanyar; Allahyari, Teimour; Azghani, Mahmood Reza; Khalkhali, Hamidreza

2016-03-01

The present study was an attempt to investigate the effect of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing. Ten healthy subjects were recruited to stand for 2 h in three footwear conditions: barefoot, flat-bottomed shoe and unstable shoe. During standing, lower leg discomfort and EMG activity of medial gastrocnemius (MG) and tibialis anterior (TA) muscles were continuously monitored. Changes in lower leg volume over standing time also were measured. Lower leg discomfort rating reduced significantly while subjects standing on unstable shoe compared to the flat-bottomed shoe and barefoot condition. For lower leg volume, less changes also were observed with unstable shoe. The activity level and variation of right MG muscle was greater with unstable shoe compared to the other footwear conditions; however regarding the left MG muscle, significant difference was found between unstable shoe and flat-bottomed shoe only for activity level. Furthermore no significant differences were observed for the activity level and variation of TA muscles (right/left) among all footwear conditions. The findings suggested that prolonged standing with unstable footwear produces changes in lower leg muscles activity and leads to less volume changes. Perceived discomfort also was lower for this type of footwear and this might mean that unstable footwear can be used as ergonomic solution for employees whose work requires prolonged standing. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Ethograms indicate stable well-being during prolonged training phases in rhesus monkeys used in neurophysiological research.

Science.gov (United States)

Hage, Steffen R; Ott, Torben; Eiselt, Anne-Kathrin; Jacob, Simon N; Nieder, Andreas

2014-01-01

Awake, behaving rhesus monkeys are widely used in neurophysiological research. Neural signals are typically measured from monkeys trained with operant conditioning techniques to perform a variety of behavioral tasks in exchange for rewards. Over the past years, monkeys' psychological well-being during experimentation has become an increasingly important concern. We suggest objective criteria to explore whether training sessions during which the monkeys work under controlled water intake over many days might affect their behavior. With that aim, we analyzed a broad range of species-specific behaviors over several months ('ethogram') and used these ethograms as a proxy for the monkeys' well-being. Our results show that monkeys' behavior during training sessions is unaffected by the duration of training-free days in-between. Independently of the number of training-free days (two or nine days) with ad libitum food and water supply, the monkeys were equally active and alert in their home group cages during training phases. This indicates that the monkeys were well habituated to prolonged working schedules and that their well-being was stably ensured during the training sessions.

Acute physiological changes in elite free-style wrestlers during a one-day tournament.

Science.gov (United States)

Kafkas, Muhammed E; Taşkiran, Celal; Şahin Kafkas, Armağan; Özen, Gökmen; Taşkapan, Çağatay; Özyalin, Fatma; Skarpańska-Stejnborn, Anna

2016-10-01

The purpose of this study was to examine free radical production, muscle damage and inflammation responses of well-trained wrestlers to a simulated one-day tournament of free-style wrestling. Twelve elite competitive wrestlers with mean age (±SD) of 24.09±6.20 years, body mass 74.09±11.50 kg, and body height 174.90±8.8 cm and who had competed for national teams completed five matches according to the official Olympic wrestling tournament regulations. Blood sampling was collected before and after fifth match. Baseline blood testing was measured at 10:00 a.m. and then matches started at 12:00. Each match was implemented within one hour. Also, the resting time was 45 minutes following each match. The measurements were analyzed by Wilcoxon Signed Ranks Test, which is used to test for significant differences between pre- and post-test. The post-match lactate dehydrogenase (LDH), creatine kinase (CK), and interleukin (IL)-6 levels were significantly increased compared with the baseline status. However, baseline malondialdehyde levels were not found significantly different compared with post-match. The current study ensured that one-day Free-Style wrestling tournament brings about significantly increasing on CK, LDH of muscle damage markers. Also, inflammatory status showed a progressive worsening during the course of one-day tournament. The study showed enhanced muscle damage markers and inflammatory status after one-day Free-Style wrestling tournament. Therefore, it appears that one-day free-style wrestling tournament imposes significant physiological demands on wrestlers that may adversely affect their performance and inflammatory status, thereby putting the athletes in a greater risk for injury.

Use of a sealant to prevent prolonged air leaks after lung resection: a prospective randomized study.

Science.gov (United States)

Lequaglie, Cosimo; Giudice, Gabriella; Marasco, Rita; Morte, Aniello Della; Gallo, Massimiliano

2012-10-08

Pulmonary air leaks are common complications of lung resection and result in prolonged hospital stays and increased costs. The purpose of this study was to investigate whether, compared with standard care, the use of a synthetic polyethylene glycol matrix (CoSeal®) could reduce air leaks detected by means of a digital chest drain system (DigiVent™), in patients undergoing lung resection (sutures and/or staples alone). Patients who intraoperatively showed moderate or severe air leaks (evaluated by water submersion tests) were intraoperatively randomized to receive just sutures/staples (control group) or sutures/staples plus CoSeal® (sealant group). Differences among the groups in terms of air leaks, prolonged air leaks, time to chest tube removal, length of hospital stay and related costs were assessed. In total, 216 lung resection patients completed the study. Nineteen patients (18.1%) in the control group and 12 (10.8%) patients in the sealant group experienced postoperative air leaks, while a prolonged air leak was recorded in 11.4% (n=12) of patients in the control group and 2.7% (n=3) of patients in the sealant group. The difference in the incidence of air leaks and prolonged air leaks between the two groups was statistically significant (p=0.0002 and p=0.0013). The mean length of hospital stay was significantly shorter in the sealant group (4 days) than the control group (8 days) (p=0.0001). We also observed lower costs in the sealant group than the control group. The use of CoSeal® may decrease the occurrence and severity of postoperative air leaks after lung resection and is associated with shorter hospital stay. Not registered. The trial was approved by the Institutional Review Board of the IRCCS-CROB Basilicata Regional Cancer Institute, Rionero in Vulture, Italy.

Levo-α-acetylmethadol (LAAM induced QTc-prolongation - results from a controlled clinical trial

Directory of Open Access Journals (Sweden)

Wieneke H

2009-01-01

Full Text Available Abstract Background Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. Methods ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1 during a run-in period with all patients on methadone and 2 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. Results Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group. No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046, whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1. Conclusions In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended

Variation in Definition of Prolonged Mechanical Ventilation.

Science.gov (United States)

Rose, Louise; McGinlay, Michael; Amin, Reshma; Burns, Karen Ea; Connolly, Bronwen; Hart, Nicholas; Jouvet, Philippe; Katz, Sherri; Leasa, David; Mawdsley, Cathy; McAuley, Danny F; Schultz, Marcus J; Blackwood, Bronagh

2017-10-01

Consistency of definitional criteria for terminology applied to describe subject cohorts receiving mechanical ventilation within ICU and post-acute care settings is important for understanding prevalence, risk stratification, effectiveness of interventions, and projections for resource allocation. Our objective was to quantify the application and definition of terms for prolonged mechanical ventilation. We conducted a scoping review of studies (all designs except single-case study) reporting a study population (adult and pediatric) using the term prolonged mechanical ventilation or a synonym. We screened 5,331 references, reviewed 539 full-text references, and excluded 120. Of the 419 studies (representing 38 countries) meeting inclusion criteria, 297 (71%) reported data on a heterogeneous subject cohort, and 66 (16%) included surgical subjects only (46 of those 66, 70% cardiac surgery). Other studies described COPD (16, 4%), trauma (22, 5%), neuromuscular (17, 4%), and sepsis (1, 0.2%) cohorts. A total of 741 terms were used to refer to the 419 study cohorts. The most common terms were: prolonged mechanical ventilation (253, 60%), admission to specialized unit (107, 26%), and long-term mechanical ventilation (79, 19%). Some authors (282, 67%) defined their cohorts based on duration of mechanical ventilation, with 154 studies (55%) using this as the sole criterion. We identified 37 different durations of ventilation ranging from 5 h to 1 y, with > 21 d being the most common (28 of 282, 7%). For studies describing a surgical cohort, minimum ventilation duration required for inclusion was ≥ 24 h for 20 of 66 studies (30%). More than half of all studies (237, 57%) did not provide a reason/rationale for definitional criteria used, with only 28 studies (7%) referring to a consensus definition. We conclude that substantial variation exists in the terminology and definitional criteria for cohorts of subjects receiving prolonged mechanical ventilation. Standardization of

Acute Right Ventricular Dysfunction Complicating Prolonged ...

African Journals Online (AJOL)

We report a case of transient right ventricular dysfunction associated with prolonged cardiac tamponade, an unusual complication of uncertain etiology. We believe that in this case dynamic coronary flow restriction resulted in ischemic injury and stunning of the right ventricle. Other possible causes are briefly reviewed. Right ...

Dynamics of heterogeneous liners with prolonged plasma creation

International Nuclear Information System (INIS)

Aleksandrov, V.V.; Branitskii, A.V.; Volkov, G.S.; Grabovskii, E.V.; Zurin, M.V.; Nedoseev, S.L.; Oleinik, G.M.; Samokhin, A.A.; Smirnov, V.P.; Fedulov, M.V.; Frolov, I.N.; Sasorov, P.V.

2001-01-01

Prolonged plasma creation in heterogeneous liners, in which the liner substance is separated into two phase states (a hot plasma and a cold skeleton), is investigated both experimentally and theoretically. This situation is typical of multiwire, foam, and even gas liners in high-current high-voltage facilities. The main mechanisms governing the rate at which the plasma is created are investigated, and the simplest estimates of the creation rate are presented. It is found that, during prolonged plasma creation, the electric current flows through the entire cross section of the produced plasma shell, whose thickness is comparable with the liner radius; in other words, a current skin layer does not form. During compression, such a shell is fairly stable because of its relatively high resilience. It is shown that, under certain conditions, even a thick plasma shell can be highly compressed toward the discharge axis. A simplified numerical simulation of the compression of a plasma shell in a liner with prolonged plasma creation is employed in order to determine the conditions for achieving regimes of fairly compact and relatively stable radial compression of the shell

Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

Energy Technology Data Exchange (ETDEWEB)

Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

2016-07-15

The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

Severe bradycardia and prolonged hypotension in ciguatera.

Science.gov (United States)

Chan, Thomas Yan Keung

2013-06-01

Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

The application of Gadopentate-Dimeneglumin has no impact on progression free and overall survival as well as renal function in patients with monoclonal plasma cell disorders if general precautions are taken

Energy Technology Data Exchange (ETDEWEB)

Hillengass, J. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany); Stoll, J.; Wagner, B.; Goldschmidt, H. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Zechmann, C.M. [Rinecker Proton Therapy Center, Munich (Germany); Kunz, C.; Heiss, C. [German Cancer Research Center Heidelberg, Department of Biostatistics, Heidelberg (Germany); Sumkauskaite, M. [University of Heidelberg, Department of Radiology, Heidelberg (Germany); Moehler, T.M. [InVentiv Health Clinical, Wiesbaden (Germany); Schlemmer, H.P.; Delorme, S. [German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany)

2014-10-31

The current analysis investigated the prognostic significance of gadopentetate dimeglumine on survival and renal function in patients with monoclonal plasma cell disorders. In this study 263 patients who had received gadopentetate dimeglumine within a prospective trial investigating dynamic contrast-enhanced magnetic resonance imaging (MRI) were compared with 335 patients who had undergone routine, unenhanced MRI. We found no significant prognostic impact of the application of contrast agent on progression-free survival in patients with either monoclonal gammopathy of undetermined significance, smouldering or symptomatic myeloma and no significant prognostic impact on overall survival in patients with symptomatic myeloma. Since renal impairment is a frequent complication of myeloma, and decreased renal function is associated with a higher risk of complications in patients receiving contrast agents, we evaluated the impact of contrast agent on renal function after 1 year. In the present analysis the only significant adverse impact on kidney function occurred in symptomatic myeloma patients who already had impaired renal parameters at baseline. Here, the renal function did not recover during therapy, whereas it did so in patients with normal or only slightly impaired renal function. If general recommendations are adhered to, gadopentetate dimeglumine can be safely applied in patients with monoclonal plasma cell disease. (orig.)

Prolonged infusion versus intermittent boluses of β-lactam antibiotics for treatment of acute infections: a meta-analysis.

Science.gov (United States)

Teo, Jocelyn; Liew, Yixin; Lee, Winnie; Kwa, Andrea Lay-Hoon

2014-05-01

The clinical advantages of prolonged (extended/continuous) infusion remain controversial. Previous studies and reviews have failed to show consistent clinical benefits of extending the infusion time. This meta-analysis sought to determine whether prolonged β-lactam infusions were associated with a reduction in mortality and improvement in clinical success. A search of PubMed, EMBASE and The Cochrane Library for randomised controlled trials (RCTs) and observational studies comparing prolonged infusion with intermittent bolus administration of the same antibiotic in hospitalised adult patients was conducted. Primary outcomes evaluated were mortality and clinical success. A total of 29 studies with 2206 patients (18 RCTs and 11 observational studies) were included in the meta-analysis. Compared with intermittent boluses, use of prolonged infusion appeared to be associated with a significant reduction in mortality [pooled relative risk (RR) = 0.66, 95% confidence interval (CI) 0.53-0.83] and improvement in clinical success (RR = 1.12, 95% CI 1.03-1.21). Statistically significant benefit was supported by non-randomised studies (mortality, RR = 0.57, 95% CI 0.43-0.76; clinical success, RR = 1.34, 95% CI 1.02-1.76) but not by RCTs (mortality, RR = 0.83, 95% CI 0.57-1.21; clinical success, RR = 1.05, 95% CI 0.99-1.12). The positive results from observational studies, especially in the face of increasing antibiotic resistance, serve to justify the imperative need to conduct a large-scale, well-designed, multicentre RCT involving critically ill patients infected with high minimum inhibitory concentration pathogens to clearly substantiate this benefit. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Prolonged whole-body cold water immersion: fluid and ion shifts.

Science.gov (United States)

Deuster, P A; Smith, D J; Smoak, B L; Montgomery, L C; Singh, A; Doubt, T J

1989-01-01

To characterize fluid and ion shifts during prolonged whole-body immersion, 16 divers wearing dry suits completed four whole-body immersions in 5 degrees C water during each of two 5-day air saturation dives at 6.1 msw. One immersion was conducted at 1000 (AM) and one at 2200 (PM) so that diurnal variations could be evaluated. Fifty-four hours separated the immersions, which lasted up to 6 h; 9 days separated each air saturation dive. Blood was collected before and after immersion; urine was collected for 12 h before, during, and after immersion for a total of 24 h. Plasma volume decreased significantly and to the same extent (approximately 17%) during both AM and PM immersions. Urine flow increased by 236.1 +/- 38.7 and 296.3 +/- 52.0%, urinary excretion of Na increased by 290.4 +/- 89.0 and 329.5 +/- 77.0%, K by 245.0 +/- 73.4 and 215.5 +/- 44.6%, Ca by 211.0 +/- 31.4 and 241.1 +/- 50.4%, Mg by 201.4 +/- 45.9 and 165.3 +/- 287%, and Zn by 427.8 +/- 93.7 and 301.9 +/- 75.4% during AM and PM immersions, respectively, compared with preimmersion. Urine flow and K excretion were significantly higher during the AM than PM. In summary, when subjects are immersed in cold water for prolonged periods, combined with a slow rate of body cooling afforded by thermal protection and enforced intermittent exercise, there is diuresis, decreased plasma volume, and increased excretions of Na, K, Ca, Mg, and Zn.

Vision and Vestibular System Dysfunction Predicts Prolonged Concussion Recovery in Children.

Science.gov (United States)

Master, Christina L; Master, Stephen R; Wiebe, Douglas J; Storey, Eileen P; Lockyer, Julia E; Podolak, Olivia E; Grady, Matthew F

2018-03-01

Up to one-third of children with concussion have prolonged symptoms lasting beyond 4 weeks. Vision and vestibular dysfunction is common after concussion. It is unknown whether such dysfunction predicts prolonged recovery. We sought to determine which vision or vestibular problems predict prolonged recovery in children. A retrospective cohort of pediatric patients with concussion. A subspecialty pediatric concussion program. Four hundred thirty-two patient records were abstracted. Presence of vision or vestibular dysfunction upon presentation to the subspecialty concussion program. The main outcome of interest was time to clinical recovery, defined by discharge from clinical follow-up, including resolution of acute symptoms, resumption of normal physical and cognitive activity, and normalization of physical examination findings to functional levels. Study subjects were 5 to 18 years (median = 14). A total of 378 of 432 subjects (88%) presented with vision or vestibular problems. A history of motion sickness was associated with vestibular dysfunction. Younger age, public insurance, and presence of headache were associated with later presentation for subspecialty concussion care. Vision and vestibular problems were associated within distinct clusters. Provocable symptoms with vestibulo-ocular reflex (VOR) and smooth pursuits and abnormal balance and accommodative amplitude (AA) predicted prolonged recovery time. Vision and vestibular problems predict prolonged concussion recovery in children. A history of motion sickness may be an important premorbid factor. Public insurance status may represent problems with disparities in access to concussion care. Vision assessments in concussion must include smooth pursuits, saccades, near point of convergence (NPC), and accommodative amplitude (AA). A comprehensive, multidomain assessment is essential to predict prolonged recovery time and enable active intervention with specific school accommodations and targeted rehabilitation.

QTc Prolongation in Veterans With Heroin Dependence on Methadone Maintenance Treatment.

Science.gov (United States)

Hassamal, Sameer; Fernandez, Antony; Moradi Rekabdarkolaee, Hossein; Pandurangi, Ananda

2015-06-01

QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance. In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared. ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. Data and risk factors were retrospectively collected from the medical records. The mean QTc at baseline (pre-methadone) was 426 ± 34 msec and after being on methadone for an average of 8.72 ± 4.50 years was significantly higher at 450 ± 35 msec. No significant relationships were found between QTc prolongation and risk factors except for calcium. The methadone dosage was significantly higher in veterans with a QTc change above the mean change of ≥ 24 msec (88.48 ± 27.20 mg v.s 68.96 ± 19.84 mg). None of the veterans experienced cardiac arrhythmias. The low complexity of medical co-morbidities may explain the lack of a significant correlation between any risk factor with the QTc except calcium and methadone dosage. The absence of TdP may be explained by the low prevalence of QTc values > 500 msec as well as the retrospective design of the study. During long-term methadone treatment, there was a slight increase in the QTc interval but we did not find evidence of increased cardiac toxicity as a reason for treatment termination.

Smoking prolongs the infectivity of patients with tuberculosis.

LENUS (Irish Health Repository)

Siddiqui, U A

2010-10-01

We sought to establish if smokers on anti-tuberculosis treatment are more likely to have a prolonged period of infectivity, compared to non-smoking tuberculosis patients, in a low tuberculosis prevalence country. We conducted a cross-sectional, retrospective study in Ireland that recruited 53 microbiologically confirmed cases of pulmonary tuberculosis (PTB). The age-sex adjusted odds ratios (AOR) suggest that the infectivity status of PTB on treatment was four times more likely to be prolonged beyond 6-8 weeks, if the cases had a smoking history (AOR: 4.42; 95% CI: 1.23; 15.9). Smoking was associated with delayed sputum smear conversion in PTB patients on treatment.

Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin

Directory of Open Access Journals (Sweden)

Hui Ming Chua

2016-01-01

Full Text Available Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used “off-label” to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58, whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

Science.gov (United States)

San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

2015-01-01

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

Central aortic systolic blood pressure can predict prolonged QTc duration better than brachial artery systolic blood pressure in rural community residents.

Science.gov (United States)

Huang, Yuqing; Tang, Songtao; Chen, Ji-Yan; Huang, Cheng; Li, Jie; Cai, An-Ping; Feng, Yingqing

2018-01-01

Previous studies have suggested that prolonged electrocardiogram QTc duration was independent risk factor for both increased cardiovascular and all-cause mortality, but there was no dating about the relationship between central aortic systolic blood pressure (CASP) and QTc duration. The aim of this study was to analyze the relationship between CASP and QTc duration, and assess whether CASP can predict prolonged QTc duration more than BSBP. A total of 500 patients were enrolled in this study, central and brachial aortic blood pressure and electrocardiogram QTc duration were measured. Pearson correlation was assessed for determining the associations of QTc duration with clinical conditions. Multivariate logistic regression analyses were performed to determine the independent predictor of prolonged QTc duration. Receiver operating characteristic (ROC) curve was used to evaluate the utility of blood pressure for prolonged QTc duration. We found QTc durations were significantly positive with CASP (r = 0.308, p AUC: 0.771 vs. 0.646, p < 0.001) BSBP. Our results suggested that the non-invasive CASP is independently correlated with QTc duration, and CASP can predict prolonged QTc duration more than BSBP.

Clinical significance of determination of GFR, urinary albumin and UAlb/UCr in patients with type 2 diabetes

International Nuclear Information System (INIS)

Zhang Li; Li Sumei; Zhang Rong; Zhai Fei

2010-01-01

Objective: To study the diagnostic value of determination of glomerular filtration rate (GFR), Urinary albumin (UAlb) and UAlb/UCr for early diabetic nephropathy in patients with type 2 Diabetes. Methods: UAlb, UAlb/UCr were measured with radioimmunoassay (RIA) and GFR measured with Tcm DTPA dynamic renal imaging in 102 DM2 patients with diabetic nephropathy (DN) and 23 DM2 patients without nephropathy. Results: In diabetics with nephropathy with a disease course of less than five years (n=38), the GFR, UAlb/UCr were significantly higher than those in diabetics without nephropathy. With prolongation of the disease, GFR gradually declined and UAlb/UCr rose further and in patients with nephropathy with disease courses over 10 years, the GFR was significantly lower and UAlb/UCr significantly higher than those in diabetics without nephropathy (all P<0.05). The GFR was negatively correlated with course of disease, BMI and UAlb/UCr (r=-0.691, -0.631, -0.698, respectively, P<0.01). Conclusion: GFR can reflect the degree of renal damage of diabetic patients,and may be helpful for evaluation of progression of DN when combined with assay of albuminuria. (authors)

Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

Science.gov (United States)

Khan, Tapan K; Wender, Paul A; Alkon, Daniel L

2018-02-01

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis

DEFF Research Database (Denmark)

Ytting, Henriette; Henriksen, Jens Henrik; Fuglsang, Stefan

2005-01-01

BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic...... venous pressure gradient (HVPG) portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS......), values which are significantly above that of the controls (0.410 s(1/2), P portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P

Three year progress report

International Nuclear Information System (INIS)

1977-07-01

Progress is reported on the following studies: x-ray and uv effects in photosynthetic organisms; effects of alcohols and oxygen concentration on transforming DNA; free radical studies; sensitization by metal ions; role of the solvated electron in radiation damage to cells; effectiveness of organic and inorganic compounds in sensitizing bacterial spores to high energy radiation; oxygen effects; radiosensitivity of enzyme systems in Chlorella; and effects of pre-irradiation of solutions on spores

Peculiarities of prolonged neonatal jaundice and possibility of their pharmacological correction

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Yablon O.

2017-03-01

Full Text Available Purpose: to study of peculiarities of prolonged neonatal jaundice and the possibility of pharmacological correction based on ursodeoxycholic acid. Patients and methods. Were examined 42 children (29 boys and 13 girls with prolonged neonatal jaundice. The study group included 22 children, who in complex of pharmacological treatment received the ursodeoxycholic acid, the comparison group comprised 20 children who received only basic treatment such as phototherapy. The effectiveness of the treatment was evaluated by biochemical parameters of blood (bilirubin and its fractions, liver transaminase, the level of serum alpha&fetoprotein, epidermal growth factor were determined by ELISA. Results. All children were full term. The mean age of children in the study group was 20.8±1.9 days in the control group and 22±1.5 days. In the main group indirect bilirubin was above on 35 μmol/l, but significant differences in the level of indirect bilirubin were absent at the beginning of treatment in both groups of children included in the study, respectively, 286±14,3 μmol/l and 250±16.4 μmol/l (p>0.05. The average indirect bilirubin after treatment significantly decreased in both groups but in the main group, a decline of 49% in the comparison group decrease of bilirubin was on 30%. It was also noted signs of neonatal cholestasis: every fifth child had the increased level of direct bilirubin, every third child had elevated liver transaminase. Also, there were no significant differenses in the mean levels of serum AFP and EGF, there were higher in children of both study groups, respectively, mean level of serum AFP in the main group was 834±28 ng/ml in the comparison group — 809±26 ng/ml(p>0.05; mean level of serum EGF in the main group 651±57,2 ng/ml in the comparison group — 714±27 ng/ml(p>0.05. However, in children who were treated with ursodeoxycholic acid (UkrlivR suspension the levels of serum AFP and EGF were significantly decreased, in

Is There a Fiscal Free Lunch in a Liquidity Trap?

OpenAIRE

Jesper Linde; Christopher J. Erceg

2010-01-01

This paper uses a DSGE model to examine the effects of an expansion in government spending in a liquidity trap. If the liquidity trap is very prolonged, the spending multiplier can be much larger than in normal circumstances, and the budgetary costs minimal. But given this "fiscal free lunch," it is unclear why policymakers would want to limit the size of fiscal expansion. Our paper addresses this question in a model environment in which the duration of the liquidity trap is determined endoge...

Diet-consumer nitrogen isotope fractionation for prolonged fasting arthropods.

Science.gov (United States)

Mizota, Chitoshi; Yamanaka, Toshiro

2011-12-01

Nitrogen acquisition for cellular metabolism during diapause is a primary concern for herbivorous arthropods. Analyses of naturally occurring stable isotopes of nitrogen help elucidate the mechanism. Relevant articles have cited (58 times up to mid-June 2011) anomalously elevated δ(15)N (per mil deviation of (15)N/(14)N, relative to atmospheric nitrogen=0 ‰) values (diet-consumer nitrogen isotope fractionation; up to 12 ‰) for a prolonged fasting raspberry beetle (Byturus tomentosus Degeer (Coleoptera: Byturidae)), which feeds on red raspberries (Rubus idaeus: δ(15)N= ~ +2 ‰). Biologists have hypothesised that extensive recycling of amino acid nitrogen is responsible for the prolonged fasting. Since this hypothesis was proposed in 1995, scientists have integrated biochemical and molecular knowledge to support the mechanism of prolonged diapausing of animals. To test the validity of the recycling hypothesis, we analysed tissue nitrogen isotope ratios for four Japanese arthropods: the shield bug Parastrachia japonensis Scott (Hemiptera: Cydnidae), the burrower bug Canthophorus niveimarginatus Scott (Hemiptera: Cydnidae), leaf beetle Gastrophysa atrocyanea Motschulsky (Coleoptera: Chrysomelidae) and the Japanese oak silkworm Antheraea yamamai (Lepidoptera: Saturniidae), all of which fast for more than 6 months as part of their life-history strategy. Resulting diet-consumer nitrogen isotope discrimination during fasting ranged from 0 to 7‰, as in many commonly known terrestrial arthropods. We conclude that prolonged fasting of arthropods does not always result in anomalous diet-consumer nitrogen isotope fractionation, since the recycling process is closed or nearly closed with respect to nitrogen isotopes.

Prolonged methylprednisolone therapy after the pulse treatment for patients with moderate-to-severe paraquat poisoning: A retrospective analysis.

Science.gov (United States)

Gao, Jie; Feng, ShunYi; Wang, Jian; Yang, SiYuan; Li, Yong

2017-06-01

This retrospective study aims to evaluate the effect of prolonged methylprednisolone (MP) therapy on the mortality of patients with moderate-to-severe paraquat (PQ) poisoning after the pulse treatment.We performed a retrospective analysis of patients with acute moderate-to-severe PQ poisoning that were admitted to the emergency department from May 2012 to August 2016. Out of 138 patients, 60 were treated with pulse treatment (15 mg kg day MP for 3 days) and 78 were treated with prolonged MP therapy after pulse treatment (15 mg kg day MP for 3 days; afterward, the dosage was reduced in half every 2 days, and the MP therapy was terminated until 0.47 mg kg day). Kaplan-Meier method was used to compare the mortality between the 2 groups. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI).The mortality of the prolonged MP therapy after pulse treatment group was lower than that of the pulse group (47.4% vs 63.3%; log-rank tests, P  =  .003). According to the multivariate Cox analysis, the prolonged MP therapy after pulse treatment was significantly associated with a lower mortality risk (HR: 0.31, 95% CI: 0.19-0.52, P treatment caused more incidences of leucopenia than the pulse treatment alone (25.6% vs 11.7%, P  =  .04).The prolonged MP therapy after pulse treatment can reduce the mortality of moderate-to-severe PQ poisoning patients.

Prolonged job strain and subsequent risk of cancer in women–a longitudinal study, based on the Danish Nurse Cohort

DEFF Research Database (Denmark)

Vesterlund, Gitte K.; Høeg, Beverley L.; Johansen, Christoffer

2017-01-01

Background: The role of psychological stress in cancer risk is continuously debated. Stress at work is the most common form of stress and previous studies have shown inconsistent results regarding cancer risk. In this longitudinal study, we examined the association between prolonged job strain......-related, digestive and lung cancers according to level of prolonged job strain. The women were followed from 1 January 2000 until cancer diagnosis, emigration, death or 31 December 2013 (mean follow-up 13 years) and models were adjusted for potential confounders. Effect modification was examined according to working...... nightshifts and full time. Results: No significant differences in the risk of overall cancer or any of the cancer subgroups were identified in relation to prolonged busyness, speed, influence, or overall job strain. Effect modification by working full time was observed when examining job influence in relation...

Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

Science.gov (United States)

Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

2017-01-01

A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m 2 ) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of prolonged antimicrobial chemotherapy for brucellar spondylodiscitis.

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Ioannou, S; Karadima, D; Pneumaticos, S; Athanasiou, H; Pontikis, J; Zormpala, A; Sipsas, N V

2011-05-01

The standard treatment of brucellar spondylitis with a combination of two antibiotics for 6-12 weeks is associated with high rates of treatment failure and relapse. The present study aimed to assess the safety and efficacy of a treatment strategy based on the prolonged administration of a triple combination of suitable antibiotics. Eighteen patients with brucellar spondylitis were treated with a combination of at least three suitable antibiotics (doxycycline, rifampin, plus intramuscular streptomycin or cotrimoxazole or ciprofloxacin) until the completion of at least 6 months of treatment, when clinical, radiological and serology re-evaluation was performed. If necessary, the treatment was continued with additional 6-month cycles, until resolution or significant improvement of clinical and radiological findings, or for a maximum of 18 months. At presentation, the median age was 66 years (range, 42-85 years) with male predominance. The median duration of therapy was 48 weeks (range 24-72 weeks). Treatment was discontinued early because of side-effects in only one patient. Surgical intervention was required for three patients. At the end of treatment all patients had a complete response. After completion of treatment, all patients were followed up with regular visits. During the follow-up period (duration 1-96 months, median 36.5 months), no relapses were observed. In conclusion, prolonged (at least 6 months) administration of a triple combination of suitable antibiotics appears to be an effective treatment for brucellar spondylitis. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.

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Hui Qun Fu

Full Text Available Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001 and up to 6 hours (p<0.001 following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG, IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.

Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.

Science.gov (United States)

Imamura, Naoko; Horikoshi, Yosuke; Matsuzaki, Tomohiko; Toriumi, Kentaro; Kitatani, Kanae; Ogura, Go; Masuda, Ryota; Nakamura, Naoya; Takekoshi, Susumu; Iwazaki, Masayuki

2013-12-20

Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.

Prolonged parenteral nutrition after neonatal gastrointestinal surgery

DEFF Research Database (Denmark)

Estmann, Anne; Qvist, Niels; Husby, Steffen

2002-01-01

to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

Effects of drought and prolonged winter on Townsend's ground squirrel demography in shrubsteppe habitats

Science.gov (United States)

Van Horne, Beatrice; Olson, Gail S.; Schooley, Robert L.; Corn, Janelle G.; Burnham, Kenneth P.

1997-01-01

in persistence and density and produced more young per female during the next active season following the drought (1993) than did ground squirrels in grassland habitat, where densities had been significantly higher prior to the drought and prolonged winter.Studies involving habitat comparisons of animal demography should always be placed in the context of long-term weather patterns, because habitat quality rankings based on density, reproduction, and survival may differ with environmental conditions. Physiological effects of environmental “crunches” on consumers may persist beyond the period of influence on food resources, reducing reproductive success and growth rates of future offspring.

Management of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).

Science.gov (United States)

Kyle, Robert A; Rajkumar, S Vincent

2011-06-01

Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk continues even after more than 25 years of observation. Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is characterized by the presence of an M protein level of 3 g/dL or higher and/or 10% or more monoclonal plasma cells in the bone marrow but no evidence of end-organ damage. The overall risk of progression to a malignant condition is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% to 2% per year for the following 10 years. Patients with both MGUS and SMM must be followed up for their lifetime.

Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

Science.gov (United States)

Kucuk, Mehmet; Karadeniz, Cem; Ozdemir, Rahmi; Meşe, Timur

2018-03-25

Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

NARCIS (Netherlands)

Birjmohun, R. S.; Kastelein, J. J. P.; Poldermans, D.; Stroes, E. S. G.; Hostalek, U.; Assmann, G.

2007-01-01

Objective: To evaluate the safety and tolerability of prolonged -release nicotinic acid (Niaspan*) added to statin therapy in patients at increased cardiovascular risk. Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid

Mesenteric venous thrombosis after prolonged air travel-a case report

Directory of Open Access Journals (Sweden)

Joaquín Salas-Coronas

2014-07-01

Full Text Available We present a case of acute mesenteric venous thrombosis after a long distance flight in a traveller presenting with abdominal pain, diarrhoea and vomiting within 48 h of prolonged immobility situation. Venous thrombosis in the lower limbs and venous thromboembolism has been clearly associated with prolonged air travel (economy class syndrome. Thrombosis was diagnosed by computed tomography of the abdomen, and after starting anticoagulant therapy with acenocumarol, symptoms yielded completely in a few weeks. The study of thrombophilia was negative, although the existence of two first-degree relatives (mother and grandmother with a history of venous thrombosis with a history of venous thrombosis makes it likely a situation of inherited thrombophilia. Although exceptional, mesenteric venous thrombosis should be considered in travellers with acute abdominal pain after prolonged air travel when there are thrombophilic conditions.

A randomized clinical trial of chlorhexidine in the maintenance of oral candidiasis-free period in HIV infection

Science.gov (United States)

Nittayananta, W; DeRouen, TA; Arirachakaran, P; Laothumthut, T; Pangsomboon, K; Petsantad, S; Vuddhakul, V; Sriplung, H; Jaruratanasirikul, S; Martin, MD

2011-01-01

OBJECTIVE To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis. SUBJECTS AND METHODS A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22–52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22–55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed. RESULTS The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034). CONCLUSIONS Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings. PMID:18627504

Detecting free-living steps and walking bouts: validating an algorithm for macro gait analysis.

Science.gov (United States)

Hickey, Aodhán; Del Din, Silvia; Rochester, Lynn; Godfrey, Alan

2017-01-01

Research suggests wearables and not instrumented walkways are better suited to quantify gait outcomes in clinic and free-living environments, providing a more comprehensive overview of walking due to continuous monitoring. Numerous validation studies in controlled settings exist, but few have examined the validity of wearables and associated algorithms for identifying and quantifying step counts and walking bouts in uncontrolled (free-living) environments. Studies which have examined free-living step and bout count validity found limited agreement due to variations in walking speed, changing terrain or task. Here we present a gait segmentation algorithm to define free-living step count and walking bouts from an open-source, high-resolution, accelerometer-based wearable (AX3, Axivity). Ten healthy participants (20-33 years) wore two portable gait measurement systems; a wearable accelerometer on the lower-back and a wearable body-mounted camera (GoPro HERO) on the chest, for 1 h on two separate occasions (24 h apart) during free-living activities. Step count and walking bouts were derived for both measurement systems and compared. For all participants during a total of almost 20 h of uncontrolled and unscripted free-living activity data, excellent relative (rho  ⩾  0.941) and absolute (ICC (2,1)   ⩾  0.975) agreement with no presence of bias were identified for step count compared to the camera (gold standard reference). Walking bout identification showed excellent relative (rho  ⩾  0.909) and absolute agreement (ICC (2,1)   ⩾  0.941) but demonstrated significant bias. The algorithm employed for identifying and quantifying steps and bouts from a single wearable accelerometer worn on the lower-back has been demonstrated to be valid and could be used for pragmatic gait analysis in prolonged uncontrolled free-living environments.

Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

Science.gov (United States)

McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

2013-01-01

We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

OpenAIRE

Nystedt, Astrid; Hildingsson, Ingegerd

2014-01-01

Background: Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women's experiences of prolonged and normal labour. Method: Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic an...

The Limit of Free Magnetic Energy in Active Regions

Science.gov (United States)

Moore, Ron; Falconer, David; Sterling, Alphonse

2012-01-01

By measuring from active-region magnetograms a proxy of the free energy in the active region fs magnetic field, it has been found previously that (1) there is an abrupt upper limit to the free energy the field can hold that increases with the amount of magnetic field in the active region, the active region fs magnetic flux content, and (2) the free energy is usually near its limit when the field explodes in a CME/flare eruption. That is, explosive active regions are concentrated in a main-sequence path bordering the free-energy ]limit line in (flux content, free-energy proxy) phase space. Here, from measurement of Marshall Space Flight Center vector magnetograms, we find the magnetic condition that underlies the free ]energy limit and the accompanying main sequence of explosive active regions. Using a suitable free ]energy proxy measured from vector magnetograms of 44 active regions, we find that (1) in active regions at and near their free ]energy limit, the ratio of magnetic-shear free energy to the non ]free magnetic energy the potential field would have is approximately 1 in the core field, the field rooted along the neutral line, and (2) this ratio is progressively less in active regions progressively farther below their free ]energy limit. This shows that most active regions in which this core-field energy ratio is much less than 1 cannot be triggered to explode; as this ratio approaches 1, most active regions become capable of exploding; and when this ratio is 1 or greater, most active regions are compelled to explode. From these results we surmise the magnetic condition that determines the free ]energy limit is the ratio of the free magnetic energy to the non-free energy the active region fs field would have were it completely relaxed to its potential ]field configuration, and that this ratio is approximately 1 at the free-energy limit and in the main sequence of explosive active regions.

SECONDARY BACTERIAL INFECTION IN ADULT PATIENTS WITH PROLONGED AND SEVERE DENGUE FEVER

Directory of Open Access Journals (Sweden)

Anil Kumar

2016-05-01

Full Text Available INTRODUCTION Generally, in dengue shock syndrome antibiotics are not advised. But unrecognised bacterial infection is likely to contribute to morbidity and mortality, probably because of increased vascular permeability. OBJECTIVES To assess the incidence of secondary bacterial infection in adult patients with prolonged and severe dengue fever. METHODS A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days. Prior to institution of antibiotic therapy, two sets of blood cultures were taken from patients. Demographic, clinical, haematological and biochemical parameters were recorded. Severity of fever & associated symptoms assessed. Ultrasonography done to find out development of ascites and pleural effusions. RESULTS Sixty patients (60.0% males with a mean age of 33.5 years (SD 12.1 were studied. The average duration of fever was 6.9 days (SD 1.6. Fifteen patients (25% had bacterial isolates in their blood cultures; Staphylococcus aureus (n=3, coliforms (n=7, pseudomonas (n=2 and 3 had mixed growths. The culture positive group had severe body aches and joints paint at admission and high grade fever, third space fluid accumulation and significant drop in platelets compared to culture-negative group. CONCLUSIONS A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture-positive patients appeared more ill with body aches and had higher degrees of fever during the course of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia in dengue fever, low platelet count and severe symptoms at presentation may be helpful.

Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.

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Katakawa, Mayumi; Fukuda, Noboru; Tsunemi, Akiko; Mori, Mari; Maruyama, Takashi; Matsumoto, Taro; Abe, Masanori; Yamori, Yukio

2016-12-01

Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

Current concepts on burn wound conversion – a review of recent advances in understanding the secondary progressions of burns

Science.gov (United States)

Salibian, Ara A.; Del Rosario, Angelica Tan; De Almeida Moura Severo, Lucio; Nguyen, Long; Banyard, Derek A.; Toranto, Jason D.; Evans, Gregory R.D.; Widgerow, Alan D.

2016-01-01

Burn wound conversion describes the process by which superficial partial thickness burns convert into deeper burns necessitating surgical intervention. Fully understanding and thus controlling this phenomenon continues to defy burn surgeons. However, potentially guiding burn wound progression so as to obviate the need for surgery while still bringing about healing with limited scarring is the major unmet challenge. Comprehending the pathophysiologic background contributing to deeper progression of these burns is an essential prerequisite to planning any intervention. In this study, a review of articles examining burn wound progression over the last five years was conducted to analyze trends in recent burn progression research, determine changes in understanding of the pathogenesis of burn conversion, and subsequently examine the direction for future research in developing therapies. The majority of recent research focuses on applying therapies from other disease processes to common underlying pathogenic mechanisms in burn conversion. While ischemia, inflammation, and free oxygen radicals continue to demonstrate a critical role in secondary necrosis, novel mechanisms such as autophagy have also been shown to contribute affect significantly burn progression significantly. Further research will have to determine whether multiple mechanisms should be targeted when developing clinical therapies. PMID:26787127

PROLONGED MULTIPLE SPASMS OF SMOOTH CORONARY ARTERIES PRESENTING AS ACUTE MIOCARDIAL INFARCTION, COMPLETE AV BLOCK AND SYNCOPE

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Franci Cesar

2004-11-01

Full Text Available Background. A variant form of angina pectoris (VAP is caused by coronary vessel spasm and occures in patients with and without varying degrees of obstructive coronary artery disease. Although the prognosis of VAP without significant organic stenosis is generally good, multivessel spasm is associated with a high risk of life-threatening abnormalities of rhythm and conduction.Patient and methods. We describe a patient who presented with prolonged chest pain, associated with hypotension, lost of consciousness, complete AV block and widespread ST segment elevations consistent with inferoanterior acute myocardial infarction. Urgent selective coronary angiography revealed spasms in right coronary artery and in left circumflex artery that were relieved by intracoronary injection of nitroglycerin. All coronary arteries were otherwise patient, without signs of atherosclerosis. The patient was treated with diltiazem and nitrates. She made a complete recovery and resumed her normal activities.Conclusions. Simultaneous multiple spasms of native coronary arteries represent a rare syndrome characterized by significantly higher incidence of potentially life-threatening arrhythmia. Less commonly, prolonged coronary spasm may mimic acute myocardial infarction. Modern management of acute coronary syndromes, including urgent coronarography, enables a prompt differentiation between prolonged coronary spasm and atherosclerotic coronary disease, warranting different treatment strategies. Medical treatment with nitrates and calcium channel blockers in most cases prevents recurrence of vasospasms and arrhythmias.

An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

Science.gov (United States)

Aleksandrova, I. V.; Bazdenkov, S. V.; Chtcherbakov, V. I.; Gromov, A. I.; Koresheva, E. R.; Koshelev, E. A.; Osipov, I. E.; Yaguzinskiy, L. S.

2004-04-01

Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets.

An efficient method of fuel ice formation in moving free-standing ICF/IFE targets

International Nuclear Information System (INIS)

Aleksandrova, I V; Bazdenkov, S V; Chtcherbakov, V I; Gromov, A I; Koresheva, E R; Koshelev, E A; Osipov, I E; Yaguzinskiy, L S

2004-01-01

Currently, research fields related to the elaboration of efficient layering methods for ICF/IFE applications are rapidly expanding. Significant progress has been made in the technology development based on rapid fuel layering inside moving free-standing targets (FST) which is referred to as the FST layering method. This paper presents our new results obtained in this area and describes technologically elegant solutions towards demonstrating a credible pathway for mass production of IFE cryogenic targets

Prolonged Mechanical Ventilation as a Predictor of Mortality After Cardiac Surgery.

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Fernandez-Zamora, Maria Dolores; Gordillo-Brenes, Antonio; Banderas-Bravo, Esther; Arboleda-Sánchez, José Andrés; Hinojosa-Pérez, Rafael; Aguilar-Alonso, Eduardo; Herruzo-Aviles, Ángel; Curiel-Balsera, Emilio; Sánchez-Rodríguez, Ángel; Rivera-Fernández, Ricardo

2018-05-01

Mortality among the small percentage of cardiac surgery patients receiving prolonged mechanical ventilation is high, but this issue appears to be inadequately addressed in guidelines. This study is a retrospective analysis of prospective, multi-center, and observational study in Spain including all adults undergoing cardiac surgery in 3 Andalusian hospitals between June 2008 and December 2012. The study included 3,588 adults with mean ± SD age of 63.5 ± 12.8 y and with median (interquartile range) EuroSCORE of 5 (3-7) points. Prolonged mechanical ventilation (> 24 h) was required by 415 subjects (11.6%), with ICU mortality of 44.3% (184 subjects), and was not required by 3,173 subjects (88.4%), with ICU mortality of 3.1% (99 subjects, P mechanical ventilation was associated with more complications and was required by 4.5% of subjects with a EuroSCORE 10. In the multivariable analysis, ICU mortality was associated with illness severity, duration of bypass surgery, surgery type, and prolonged mechanical ventilation (odds ratio 15.19, 95% CI 11.56-22.09). The main cause of death was multiple organ failure and sepsis in subjects who required prolonged mechanical ventilation (50.3%) and cardiogenic shock in those who did not (59.2%). Prolonged postoperative mechanical ventilation was required by 10-20% of cardiac surgery subjects, who constitute a specific group that represents most of the postoperative mortality, which is associated with multiple organ failure and sepsis. Copyright © 2018 by Daedalus Enterprises.

Prolonged exposure of colon cancer cells to 5-fluorouracil nanoparticles improves its anticancer activity

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Essam Tawfik

2017-02-01

Full Text Available In this study, we aimed to improve the anticancer effect of 5-FU on human colon cancer cell lines by incorporating in poly(d,l lactic-co-glycolic acid (PLGA nanoparticles (NPs. The 5-FU-PLGA NPs were prepared by nanoprecipitation technique. Prepared NPs were moderately dispersed with an average diameter of 133 ± 25.19 nm. Scanning Electron Microscope (SEM images revealed spherical structures with subtle surface irregularity. Free 5-FU dose–response curves were constructed (12.5–2000 μM using MTT assay on HCT 116 and HT-29 cell lines for 1, 3, and 5 days. The calculated IC50 on HCT 116 were 185 μM after 1 day, 11.3 μM after 3 days, and 1.48 μM after 5 days. On HT-29, IC50 was only reached after 5 days of 5-FU treatment (11.25 μM. The HCT 116 viability following treatment with 100 μM 5-FU in free or NPs forms for 3 days was 38.8% and 18.6%, respectively. Similarly, when 250 μM was applied, HCT 116 viability was 17.03% and 14.6% after treatment with free and NPs forms of 5-FU, respectively. Moreover, HT-29 cell viability after 250 μM 5-FU treatment in free or NPs forms was 55.45% and 34.01%, respectively. We also noticed that HCT 116 cells were more sensitive to 5-FU-PLGA NPs as compared to HT-29 cells. Overall, our data indicate that 5-FU activity is time dependent and the prolonged effects created by PLGA NPs may contribute, at least in part, to the noticed enhancement of the anticancer activity of 5-FU drug.

Prebiotics enhance survival and prolong the retention period of specific probiotic inocula in an in vivo murine model.

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Su, P; Henriksson, A; Mitchell, H

2007-12-01

To identify novel prebiotics that could be used to maintain persistence of three representative probiotic strains in vivo. Test mice were treated with prebiotics soybean oligosaccharide (SOS), fructooligosaccharide (FOS) or inulin, followed by probiotics Lactobacillus acidophilus LAFTI L10 (L10), Bifidobacterium lactis LAFTI B94 (B94) or Lactobacillus casei L26 LAFTI (L26). Faecal samples were then collected and analysed using selective medium and PCR analysis to determine the presence of the probiotic strains. In contrast to the control groups, in mice fed prebiotics, the survival and retention time of the test probiotics was increased extensively. SOS and FOS prolonged the retention period of L10 from 24 to 30 h. Of the three prebiotics, FOS gave the best result with B94, prolonging the retention period from 3 to > or =10 days. Of the three prebiotics, inulin gave the best result for L26, prolonging the retention period from 2 to > or =6 days. The prebiotics SOS, FOS and inulin significantly enhance survival and prolong the retention period of L10, B94 and L26 in vivo. Our results demonstrate the potential use of FOS, inulin and SOS as prebiotics in conjunction with the probiotic strains L10, B94 and L26 for new synbiotic products.

Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

Science.gov (United States)

Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

2014-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. © The Author(s) 2013.

Free piston space Stirling technology program

Science.gov (United States)

Dochat, G. R.; Dhar, M.

1989-01-01

MTI recently completed an initial technology feasibility program for NASA by designing, fabricating and testing a space power demonstrator engine (SPDE). This program, which confirms the potential of free-piston Stirling engines, provided the major impetus to initiate a free-piston Stirling space engine (SSE) technology program. The accomplishments of the SPDE program are reviewed, and an overview of the SSE technology program and technical status to date is provided. It is shown that progress in both programs continues to justify its potential for either nuclear or solar space power missions.

Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure.

Science.gov (United States)

Freeman, G L; Colston, J T; Miller, D D

1994-01-01

The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane. Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([123I]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment. The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [123I]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure. This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.

[Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia].

Science.gov (United States)

Braslavsky, D; Keselman, A; Chiesa, A; Bergadá, I

2012-03-01

The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Atypical squamous cells of undetermined significance in patients with HPV positive DNA testing and correlation with disease progression by age group: an institutional experience.

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Rodriguez, Erika F; Reynolds, Jordan P; Jenkins, Sarah M; Winter, Stephanie M; Henry, Michael R; Nassar, Aziza

2012-01-01

Atypical squamous cells of undetermined significance (ASC-US) is a broad diagnostic category that could be attributed to human papillomavirus infection (HPV), malignant neoplasia and reactive conditions. We evaluated our institutional experience with ASC-US in women who are positive for high risk HPV (HRHPV+) by the Digene hybrid capture method from 2005-2009 to identify the risk of progression to squamous intraepithelial lesion (SIL) and cervical intraepithelial neoplasia (CIN) in association with age. We reviewed cytologic and follow-up surgical pathology reports for all specimens available. Progression was defined as a diagnosis of at least CINI on follow-up biopsy or resection or SIL on cytology. We identified 2613 cases and follow-up was available in 1839 (70.4%). Of these 74.2% had just one follow-up, 16.2% had a total of 2 follow-ups, 5.3% had a total of 3 follow-ups, and the remaining had as many as 6 follow-ups. Among the 1839 patients, 69.4% were age 30 or younger, 16.0% were between 31 to 40, 9.0% were between 41 to 50, and 5.6% were 51 or older. Among these, 25-30% progressed to dysplasia. The risk of progression varied by age (p=0.04) and was lowest among women between the ages of 41-50. Our findings highlight the importance of continued cytologic follow-up in women with HRHPV+ ASC-US in order to detect progression of disease, although the risk of progression is age dependent.

Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

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Motoh Iwasa

Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

Single-prolonged stress induces endoplasmic reticulum-dependent apoptosis in the hippocampus in a rat model of post-traumatic stress disorder.

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Fang Han

Full Text Available BACKGROUND: Our previous research indicated that apoptosis induced atrophy in the hippocampus of post-traumatic stress disorder (PTSD rats. Endoplasmic reticulum (ER stress-induced apoptosis has been implicated in the development of several disorder diseases. The aim of this study was to investigate whether endoplasmic reticulum-related pathway is involved in single-prolonged stress (SPS induces apoptosis in the hippocampus of PTSD rats by examining the expression levels of three important indicators in the ER-related apoptotic pathway: Glucose-regulated protein (GRP 78, caspase-12 and Ca(2+/CaM/CaMkinaseIIα (CaMkIIα. METHODS: Wistar rats were sacrificed at 1, 4 and 7 days after SPS. SPS is a reliable animal model of PTSD. The apoptotic cells in the hippocampus were assessed by TUNEL method and transmission electron microscopy (TEM. Free intracellular Ca(2+ concentration was measured. GRP78 expression was examined by immunohistochemistry, western blotting and RT-PCR. mRNA of caspase-12 and CaM/CaMkIIα were determined by RT-PCR. RESULTS: Our results showed that apoptotic cells were increased in the SPS rats. TEM analysis revealed characteristic morphological changes of apoptosis in these cells. We observed that GRP78 was significantly up-regulated during early PTSD, and then recovered at 7 days after SPS. By RT-PCR, we observed that the change in caspase-12 expression level was similar to that in GRP78. Moreover, the free intracellular Ca(2+ concentration was significantly higher at 1 day after SPS and decreased in 7 days. CaM expression increased significantly, while CaMKIIα expression decreased significantly in the hippocampus at 1 day after SPS. CONCLUSION: SPS induced change in the expression levels of GRP78, caspase-12 and Ca(2+/CaM/CaMkIIα in the hippocampus of PTSD rats indicated that the endoplasmic reticulum pathway may be involved in PTSD-induced apoptosis.

Prolonged displacement may compromise resilience in Eritrean ...

African Journals Online (AJOL)

Objective: to assess the impact of prolonged displacement on the resilience of Eritrean mothers. Methods: an adapted SOC scale (short form) was administered. Complementary qualitative data were gathered from study participants' spontaneous reactions to and commentaries on the SOC scale. Results: Displaced ...

Weight preserving image registration for monitoring disease progression in lung CT

DEFF Research Database (Denmark)

Gorbunova, Vladlena; Lo, Pechin Chien Pau; Haseem, Ashraf

2008-01-01

We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan...... the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans...

Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

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Chen XR

2016-09-01

Full Text Available Xin-Ru Chen,1,* Jian-Zhong Liang,2,* Shu-Xiang Ma,1 Wen-Feng Fang,1 Ning-Ning Zhou,1 Hai Liao,1 De-Lan Li,1 Li-Kun Chen1 1Department of Medical Oncology, 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Concurrent chemoradiotherapy (CCRT is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC. However, the efficacy of consolidation chemotherapy (CCT in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods: This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC. Overall survival (OS and progression-free survival (PFS were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results: Among the 177 patients, 72 (41% received CCT and 105 (59% did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031, whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118. The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035, having undergone prophylactic cranial irradiation (P<0.001, and having received CCT (P=0.002 could serve as favorable independent prognostic factors

Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

Science.gov (United States)

Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

2012-01-01

Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: A five-year follow-up

Energy Technology Data Exchange (ETDEWEB)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com [Department of Community and Social Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Limpatanachote, Pisit [Department of Internal Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Mahasakpan, Pranee [Department of Community and Social Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Krintratun, Somyot [Department of Internal Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Punta, Boonyarat; Funkhiew, Thippawan [Department of Community and Social Medicine, Mae Sot General Hospital, Tak 63110 (Thailand)

2012-01-15

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels {>=}5 {mu}g/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of {beta}{sub 2}-microglobulin ({beta}{sub 2}-MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmium statistically significantly reduced from 9.5{+-}1.6 {mu}g/g creatinine in 2005 to 8.8{+-}1.6 {mu}g/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary {beta}{sub 2}-MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy.

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: A five-year follow-up

International Nuclear Information System (INIS)

Swaddiwudhipong, Witaya; Limpatanachote, Pisit; Mahasakpan, Pranee; Krintratun, Somyot; Punta, Boonyarat; Funkhiew, Thippawan

2012-01-01

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels ≥5 μg/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of β 2 -microglobulin (β 2 -MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmium statistically significantly reduced from 9.5±1.6 μg/g creatinine in 2005 to 8.8±1.6 μg/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary β 2 -MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy.

Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation

International Nuclear Information System (INIS)

Oluwole, S.F.; Iga, C.; Lau, H.; Hardy, M.A.

1985-01-01

The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators

P6 Electroacupuncture Improved QTc Interval Prolongation by Upregulation of Connexin43 in Droperidol Treated Rats

Directory of Open Access Journals (Sweden)

Feng Zhao

2014-01-01

Full Text Available Aim. This study investigated the effect of P6 EA on droperidol-induced QTc interval prolongation and Cx43 expression in ventricular muscle of rats. Methods. Twenty-four rats were randomly divided into control group (C, droperidol group (D, or EA group (E. C group rats were injected with normal saline. D group rats were injected with droperidol 0.13 mg/kg. E group rats were pretreated with EA at left P6 acupoint for 30 min and then injected with droperidol (0.13 mg/kg. QTc intervals were recorded at lead II in ECG within 120 min. Cx43 expression was measured by RT-PCR and western blotting. Result. Droperidol significantly prolonged QTc intervals compared with controls at 5 min, 10 min, 15 min, and 30 min (P0.05. Conclusion. P6 EA could improve QTc interval prolongation induced by droperidol, which may relate to upregulation of Cx43 mRNA and protein. Antiemetic dose of droperidol had minor effects on Cx43 mRNA and protein expression at 120 min.

Materials towards carbon-free, emission-free and oil-free mobility: hydrogen fuel-cell vehicles--now and in the future.

Science.gov (United States)

Hirose, Katsuhiko

2010-07-28

In the past, material innovation has changed society through new material-induced technologies, adding a new value to society. In the present world, engineers and scientists are expected to invent new materials to solve the global problem of climate change. For the transport sector, the challenge for material engineers is to change the oil-based world into a sustainable world. After witnessing the recent high oil price and its adverse impact on the global economy, it is time to accelerate our efforts towards this change. Industries are tackling global energy issues such as oil and CO2, as well as local environmental problems, such as NO(x) and particulate matter. Hydrogen is the most promising candidate to provide carbon-free, emission-free and oil-free mobility. As such, engineers are working very hard to bring this technology into the real society. This paper describes recent progress of vehicle technologies, as well as hydrogen-storage technologies to extend the cruise range and ensure the easiness of refuelling and requesting material scientists to collaborate with industry to fight against global warming.

High frequency of pertussis in older children and adolescents with prolonged cough in Turkey.

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Aslan, Aslı; Kurugöl, Zafer; Aydemir, Şöhret; Gürsel, Derya; Koturoğlu, Güldane

2016-01-01

This study aimed to determine the frequency of B. pertussis infection among Turkish children with prolonged cough. Nasopharyngeal specimens were collected from 7-18 year old children, presenting with prolonged cough of two to four weeks' duration. Specimens were examined for B. pertussis by PCR. Of 101 children with prolonged cough, 20 (19.8%) had a positive PCR testing for B. pertussis. Children who were vaccinated ≥5 years previously had a 6.13-fold higher risk of PCR-confirmed pertussis than those who were vaccinated pertussis (paroxysmal cough, whooping and post-tussive vomiting) were seen in 30%, 15% and 25% of the patients with positive PCR, respectively; 55% of them had only a prolonged cough without any classic symptoms. Pertussis is common among Turkish children with prolonged cough, even after implementation of a fifth dose of pertussis vaccination and despite high vaccination coverage.

In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

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Liu, Y H; Hawk, R M; Ramaprasad, S

1995-01-01

RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

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O.G. Shadrin

2015-09-01

Full Text Available The article is devoted to the optimization of the treatment of prolonged conjugation jaundice. Inclusion of ursodeoxycholic acid in the treatment of neonatal prolonged conjugation jaundice in a dose of 15–20 mg/kg of body mass per day increases the terms of regression of clinical and paraclinical signs of jaundice as much as 2 times and leads to cytolysis normalization. The preparation has a sufficient level of safety, there were not revealed side effects whilst its application.

Hippocampal Abnormalities after Prolonged Febrile Convulsions

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J Gordon Millichap

2003-11-01

Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

Intrathecal tramadol as and adjuvant in subrachnoid block to prolong the duration of analgesia

International Nuclear Information System (INIS)

Zahid, F.; Tarar, H. M.; Tariq, M.; Nazir, H.; Zafar, I.; Munir, S.

2017-01-01

Objective: To assess the effect of intrathecal tramadol added to bupivacaine to prolong the duration of analgesia in subarachnoid block for lower limb orthopedic surgeries. Study Design: Randomized controlled trial. Place and Duration of Study: Anesthesia department of Combined Military Hospital Sialkot, from Nov 2015 to Apr 2016. Material and Methods: Patients were selected by non-probability consecutive sampling. One hundred and fifty patients from American Society of Anesthesiologists (ASA) I, II and III category fulfilling inclusion criteria undergoing various lower limb orthopedic surgeries were divided into two groups by lottery system. Group tramadol bupivacaine (TB) received 25mg (1 ml) of tramadol plus 2ml (10mg) of 0.5 percent bupivacaine while group bupivacaine alone (SB) received 1 ml normal saline plus 2ml (10mg) of 0.5 percent bupivacaine. Time to first analgesia request was noted as a measure of duration of analgesia. Time of onset of sensory block level and peak sensory block level and time to reach the peak sensory block level were also noted. Quality of anesthesia was compared among two groups. Data were analyzed by using SPSS version 22. Results: Four patients were excluded from the study. The duration of anesthesia was effectively prolonged in group TB 181.56 ± 12.42 mins as compared to group SB 120.93 ± 15.54 mins. VAS score was significantly lower in group TB. Higher peak sensory block levels (T6) were achieved in group TB as compared to group SB. However time to reach the peak sensory block levels were significantly longer in group TB. (4.5 ± 0.47mins vs 3.09 ± 0.54 mins). Conclusion: This study showed that intrathecal tramadol (25mg) can safely be used along with bupivacaine in subarachnoid blockade to prolong the duration of analgesia and improve the quality of anesthesia as well. (author)

Ultraviolet light immunomodulation of canine islets for prolongation of allograft survival

International Nuclear Information System (INIS)

Kenyon, N.S.; Strasser, S.; Alejandro, R.

1990-01-01

Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100

Use of a sealant to prevent prolonged air leaks after lung resection: a prospective randomized study

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Lequaglie Cosimo

2012-10-01

Full Text Available Abstract Background Pulmonary air leaks are common complications of lung resection and result in prolonged hospital stays and increased costs. The purpose of this study was to investigate whether, compared with standard care, the use of a synthetic polyethylene glycol matrix (CoSeal® could reduce air leaks detected by means of a digital chest drain system (DigiVent™, in patients undergoing lung resection (sutures and/or staples alone. Methods Patients who intraoperatively showed moderate or severe air leaks (evaluated by water submersion tests were intraoperatively randomized to receive just sutures/staples (control group or sutures/staples plus CoSeal® (sealant group. Differences among the groups in terms of air leaks, prolonged air leaks, time to chest tube removal, length of hospital stay and related costs were assessed. Results In total, 216 lung resection patients completed the study. Nineteen patients (18.1% in the control group and 12 (10.8% patients in the sealant group experienced postoperative air leaks, while a prolonged air leak was recorded in 11.4% (n = 12 of patients in the control group and 2.7% (n = 3 of patients in the sealant group. The difference in the incidence of air leaks and prolonged air leaks between the two groups was statistically significant (p = 0.0002 and p = 0.0013. The mean length of hospital stay was significantly shorter in the sealant group (4 days than the control group (8 days (p = 0.0001. We also observed lower costs in the sealant group than the control group. Conclusion The use of CoSeal® may decrease the occurrence and severity of postoperative air leaks after lung resection and is associated with shorter hospital stay. Trial registration Not registered. The trial was approved by the Institutional Review Board of the IRCCS-CROB Basilicata Regional Cancer Institute, Rionero in Vulture, Italy.

Duration of IOP reduction with travoprost BAK-free solution.

Science.gov (United States)

Gross, Ronald L; Peace, James H; Smith, Stephen E; Walters, Thomas R; Dubiner, Harvey B; Weiss, Mark J; Ochsner, Katherine I

2008-01-01

To compare the duration of action of travoprost ophthalmic solution 0.004% (Travatan Z) formulated without benzalkonium chloride (BAK) to travoprost ophthalmic solution 0.004% formulated with BAK (Travatan). This was a prospective, randomized, double-masked study. Patients with open-angle glaucoma or ocular hypertension were randomized to receive 2 weeks of once-daily therapy with travoprost BAK-free or travoprost with BAK. Patients received the last dose of medication on day 13 and then intraocular pressure (IOP) was assessed every 12 hours for 60 hours. Statistical analysis included change in IOP from baseline for each group and comparison of mean IOP between groups. Of the 109 patients enrolled, 106 patients completed the study. Untreated mean baseline IOP at 8 AM was 26.9 mm Hg in the travoprost BAK-free group and 27.1 mm Hg in the travoprost with BAK group. At 12, 24, 36, 48, and 60 hours after the last dose, mean IOP in the travoprost BAK-free group was 18.7, 17.2, 19.5, 18.7, and 20.8 mm Hg, respectively; whereas mean IOP in the travoprost with BAK group was 18.5, 16.8, 19.7, 18.0, and 20.8 mm Hg, respectively. Mean IOP at all time points after the last dose of medication was >6 mm Hg lower than the 8 AM baseline in both groups. Between-group differences were within +/-0.6 mm Hg at all postdose time points. There were no statistically significant differences between the 2 treatment groups at baseline or at any postdose time point. Drug-related side effects were uncommon, mild in intensity, and comparable between groups. Travoprost without BAK has similar IOP-lowering efficacy and safety compared with travoprost preserved with BAK. Both formulations of travoprost have a prolonged duration of action, with statistically and clinically significant reductions from baseline persisting up to 60 hours after the last dose.

Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy.

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Verstappen, Ralph; Djedovic, Gabriel; Morandi, Evi Maria; Heiser, Dietmar; Rieger, Ulrich Michael; Bauer, Thomas

2018-03-01

A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

Has the time to come leave the “watch-and-wait” strategy in newly diagnosed asymptomatic follicular lymphoma patients?

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Rueda Antonio

2012-05-01

Full Text Available Abstract Background Historically, the median overall survival for follicular lymphoma (FL has been considered to be 9-10 years, and no treatment had ever prolonged this time period. Studies conducted more than 20 years ago demonstrated that treating patients with asymptomatic FL at the onset of the disease did not increase their survival, and that almost 20% of these patients did not need any treatment in the first 10 years of follow-up. Based on these facts, most clinical practice guidelines recommend active surveillance policies for patients with asymptomatic FL. Discussion The introduction of antiCD-20 monoclonal antibodies, over the last 15 years, has significantly increased the median survival rate to above 14 years. This improvement was achieved before the combination of rituximab and chemotherapy regimens became extensively used in patients with symptomatic disease. Therefore, this increase in survival may currently be more significant. At present, several clinical trials have evaluated low-toxicity therapies that prolong progression-free periods, among which rituximab monotherapy, radioimmunotherapy or the combination of rituximab with bendamustine are the most relevant. Unfortunately, these clinical trials have included only patients with symptomatic FL. The results of a recently reported clinical trial show that treatment with single-agent rituximab prolongs progression-free survival rates, time to new treatment and the quality of life of asymptomatic patients, as compared with the active surveillance strategy. Longer follow-up of these results and data regarding overall survival are awaited before this treatment can be recommended as the standard initial therapy. Summary There are different therapeutic possibilities for asymptomatic FL patients, but no data are currently available to indicate which option is the best. Patients need to understand the risks and benefits of observation versus treatment before a final decision

Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis

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Fanming Meng

2018-01-01

Full Text Available Background Long non-coding RNAs (lncRNAs have been reported to modulate cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream were proposed to be potential biomarkers for clinical diagnosis. However, few cardiovascular diseases-related circulating lncRNAs were identified and their prediction power has not been investigated in depth. Here we report a new circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript (APPAT, and evaluated its role and predicting ability in atherosclerotic development. Methods APPAT was analyzed and screened by high-throughput sequencing, and then detected in vitro and in vivo. Immunofluorescence-fluorescence in situ hybridization (IF-FISH was utilized to explore distribution and subcellular location of APPAT. The expressing alteration of APPAT in samples of healthy and pathological coronary artery was explored further. We also assessed the level of circulating APPAT in blood samples from healthy individuals, and patients with angina pectoris (AP or myocardial infarction (MI. Additionally, we predicted and validated microRNA targets of APPAT, then showed the expression level of a candidate target which was primarily measured in human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined the potential indicating ability of APPAT for the risk of AP or MI. Results APPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It enriched in contractile VSMCs of artery tunica media and mainly existed in cytoplasm. Significant down-regulation of APPAT was found in coronary artery samples with severe stenosis. More importantly, we observed decreased expression of APPAT in blood samples accompanying disease progression. ROC and correlation analyses further verified the relatively high predicting ability of APPAT. We also observed the predicted miRNA exhibited opposite expression direction to that of APPAT. Conclusions This study revealed that

A tumor-targeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme.

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Kim, Sang-Soo; Rait, Antonina; Kim, Eric; Pirollo, Kathleen F; Chang, Esther H

2015-02-01

Development of temozolomide (TMZ) resistance contributes to the poor prognosis for glioblastoma multiforme (GBM) patients. It was previously demonstrated that delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex (SGT-53) which crosses the blood-brain barrier could sensitize highly TMZ-resistant GBM tumors to TMZ. Here we assessed whether SGT-53 could inhibit development of TMZ resistance. SGT-53 significantly chemosensitized TMZ-sensitive human GBM cell lines (U87 and U251), in vitro and in vivo. Furthermore, in an intracranial GBM tumor model, two cycles of concurrent treatment with systemically administered SGT-53 and TMZ inhibited tumor growth, increased apoptosis and most importantly, significantly prolonged median survival. In contrast TMZ alone had no significant effect on median survival compared to a single cycle of TMZ. These results suggest that combining SGT-53 with TMZ appears to limit development of TMZ resistance, prolonging its anti-tumor effect and could be a more effective therapy for GBM. Using human glioblastoma multiforma cell lines, this research team demonstrated that the delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex limited the development of temozolomide resistance and prolonged its anti-tumor effect, which may enable future human application of this or similar techniques. Copyright © 2015 Elsevier Inc. All rights reserved.

[The value of serum free light chain in differential diagnosis of monoclonal gammopathy of renal significance].

Science.gov (United States)

Li, C; Wen, Y B; Li, H; Su, W; Li, J; Cai, J F; Chen, L M; Li, X M; Li, X W

2017-08-08

Objective: To investigate the value of serum free light chain (FLC) in differential diagnosis of monoclonal gammopathy of renal significance (MGRS). Methods: Forty-nine hospitalized patients who underwent renal biopsy in Peking Union Medical College Hospital between January 2013 and December 2015 were included. Monoclonal gammopathy was detected by serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE), urine IFE and serum FLC. All patients were classified as MGRS ( n =32) and monoclonal gammopathy of undetermined significance (MGUS) ( n =17). Results: Renal lesions in MGRS subgroup included light chain amyloidosis ( n =24, 75.0%), light chain deposition disease ( n =7, 21.9%), and fibrillary glomerulopathy ( n =1, 3.1%). Renal diseases in MGUS subgroup included membranous nephropathy ( n =10), focal segmental glomerulosclerosi (FSGS) ( n =3), diabetic glomerulopathy ( n =1), Henoch-Schonlein purpura nephritis ( n =1), anti-GBM disease concurrent with membranous nephropathy ( n =1) and glomerulomegaly ( n =1). Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGRS subgroup were 12, 16, 23 and 30, respectively. Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGUS subgroup were 11, 17, 6 and 3, respectively. MGRS and MGUS subgroups differed significantly in positive rate of serum IFE ( P value for MGRS, which was helpful for differential diagnosis of patients who had contraindication to renal biopsy.

Model-Free Trajectory Optimisation for Unmanned Aircraft Serving as Data Ferries for Widespread Sensors

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Ben Pearre

2012-10-01

Full Text Available Given multiple widespread stationary data sources such as ground-based sensors, an unmanned aircraft can fly over the sensors and gather the data via a wireless link. Performance criteria for such a network may incorporate costs such as trajectory length for the aircraft or the energy required by the sensors for radio transmission. Planning is hampered by the complex vehicle and communication dynamics and by uncertainty in the locations of sensors, so we develop a technique based on model-free learning. We present a stochastic optimisation method that allows the data-ferrying aircraft to optimise data collection trajectories through an unknown environment in situ, obviating the need for system identification. We compare two trajectory representations, one that learns near-optimal trajectories at low data requirements but that fails at high requirements, and one that gives up some performance in exchange for a data collection guarantee. With either encoding the ferry is able to learn significantly improved trajectories compared with alternative heuristics. To demonstrate the versatility of the model-free learning approach, we also learn a policy to minimise the radio transmission energy required by the sensor nodes, allowing prolonged network lifetime.

Ageing is associated with a prolonged fever response in human endotoxemia

DEFF Research Database (Denmark)

Krabbe, Karen S.; Kemp Bruunsgaard, Helle; Hansen, Christian Muff

2017-01-01

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2......-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein...... levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response....

Primiparous women's preferences for care during a prolonged latent phase of labour.

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Ängeby, Karin; Wilde-Larsson, Bodil; Hildingsson, Ingegerd; Sandin-Bojö, Ann-Kristin

2015-10-01

To investigate primiparous women's preferences for care during a prolonged latent phase of labour. A qualitative study based on focus groups and individual interviews and analysed with inductive content analysis. Sixteen primiparous women with a prolonged latent phase of labour >18 hours were interviewed in five focus groups (n = 11) or individually (n = 5). One main category emerged "Beyond normality - a need of individual adapted guidance in order to understand and manage an extended latent phase of labour" which covers the women's preferences during the prolonged latent phase. Five categories were generated from the data: "A welcoming manner and not being rejected", "Individually adapted care", "Important information which prepares for reality and coping", "Participation and need for feedback" and "Staying nearby the labour ward or being admitted for midwifery support". Women with a prolonged latent phase of labour sought to use their own resources, but their needs for professional support increased as time passed. A welcoming attitude from an available midwife during the latent phase created a feeling of security, and personally adapted care was perceived positively. Women with a prolonged latent phase of labour preferred woman-centred care. Midwives play an important role in supporting these women. Women's need for midwifery-support increases as the time spent in latent phase increases. Copyright © 2015 Elsevier B.V. All rights reserved.

THE ROLE OF WORK AND LABOUR MARKET FLEXIBILITY IN WORKING LIFE PROLONGATION: CASE SLOVENIA

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Klemen, SIROK

2014-11-01

Full Text Available Building upon the premise that the prolongation of working life presents an adequate approach to address the fast approaching challenges of population ageing, the paper presents labour market outcomes of older workers in Slovenia in order to explore the role of social system and labour market flexibility in retirement behaviour. By applying bivariate graphic analysis and series of logistic models, paper finds that decisions of older workers (aged 50 - 69 of whether to retire or to continue working up to legal retirement age is being predominately shaped by the pension system parameters. Economic activity beyond this age (or when retired on the other hand predominately correlates with flexible work arrangements and work motivation. Thus, the future policies in Slovenia aiming to prolong working careers within formal or informal sector should simultaneously do both; change pension system parameters and significantly expand the system flexibility stimulating willing and capable elderly to continue working within the formal sector.

Free will and paranormal beliefs.

Science.gov (United States)

Mogi, Ken

2014-01-01

Free will is one of the fundamental aspects of human cognition. In the context of cognitive neuroscience, various experiments on time perception, sensorimotor coordination, and agency suggest the possibility that it is a robust illusion (a feeling independent of actual causal relationship with actions) constructed by neural mechanisms. Humans are known to suffer from various cognitive biases and failures, and the sense of free will might be one of them. Here I report a positive correlation between the belief in free will and paranormal beliefs (UFO, reincarnation, astrology, and psi). Web questionnaires involving 2076 subjects (978 males, 1087 females, and 11 other genders) were conducted, which revealed significant positive correlations between belief in free will (theory and practice) and paranormal beliefs. There was no significant correlation between belief in free will and knowledge in paranormal phenomena. Paranormal belief scores for females were significantly higher than those for males, with corresponding significant (albeit weaker) difference in belief in free will. These results are consistent with the view that free will is an illusion which shares common cognitive elements with paranormal beliefs.

Free will and paranormal beliefs

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Ken eMogi

2014-04-01

Full Text Available Free will is one of the fundamental aspects of human cognition. In the context of cognitive neuroscience, various experiments on time perception, sensorimotor coordination, and agency suggest the possibility that it is a robust illusion (a feeling independent of actual causal relationship with actions constructed by neural mechanisms. Humans are known to suffer from various cognitive biases and failures, and the sense of free will might be one of them. Here I report a positive correlation between the belief in free will and paranormal beliefs (UFO, reincarnation, astrology, and psi. Web questionnaires involving 2076 subjects (978 males, 1087 females, and 11 other genders were conducted, which revealed significant positive correlations between belief in free will (theory and practice and paranormal beliefs. There was no significant correlation between belief in free will and knowledge in paranormal phenomena. Paranormal belief scores for females were significantly higher than those for males, with corresponding significant (albeit weaker difference in belief in free will. These results are consistent with the view that free will is an illusion which shares common cognitive elements with paranormal beliefs.

Free will and paranormal beliefs

Science.gov (United States)

Mogi, Ken

2014-01-01

Free will is one of the fundamental aspects of human cognition. In the context of cognitive neuroscience, various experiments on time perception, sensorimotor coordination, and agency suggest the possibility that it is a robust illusion (a feeling independent of actual causal relationship with actions) constructed by neural mechanisms. Humans are known to suffer from various cognitive biases and failures, and the sense of free will might be one of them. Here I report a positive correlation between the belief in free will and paranormal beliefs (UFO, reincarnation, astrology, and psi). Web questionnaires involving 2076 subjects (978 males, 1087 females, and 11 other genders) were conducted, which revealed significant positive correlations between belief in free will (theory and practice) and paranormal beliefs. There was no significant correlation between belief in free will and knowledge in paranormal phenomena. Paranormal belief scores for females were significantly higher than those for males, with corresponding significant (albeit weaker) difference in belief in free will. These results are consistent with the view that free will is an illusion which shares common cognitive elements with paranormal beliefs. PMID:24765084

Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression

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Hua Chen

2016-12-01

Full Text Available Early detection is critical in prevention and treatment of kidney disease. However currently clinical laboratory and histopathological tests do not provide region-specific and accurate biomarkers for early detection of kidney disease. The present study was conducted to identify sensitive biomarkers for early detection and progression of tubulo-interstitial nephropathy in aristolochic acid I-induced rats at weeks 4, 8 and 12. Biomarkers were validated using aristolochic acid nephropathy (AAN rats at week 24, adenine-induced chronic kidney disease (CKD rats and CKD patients. Compared with control rats, AAN rats showed anemia, increased serum urea and creatinine, progressive renal interstitial fibrosis, activation of nuclear factor-kappa B, and up-regulation of pro-inflammatory, pro-oxidant, and pro-fibrotic proteins at weeks 8 and 12. However, no significant difference was found at week 4. Metabolomics identified 12-ketodeoxycholic acid, taurochenodesoxycholic acid, LPC(15:0 and docosahexaenoic acid as biomarkers for early detection of tubulo-interstitial nephropathy. With prolonging aristolochic acid I exposure, LPE(20:2, cholic acid, chenodeoxycholic acid and LPC(17:0 were identified as biomarkers for progression from early to advanced AAN and lysoPE(22:5, indoxyl sulfate, uric acid and creatinine as biomarkers of advanced AAN. These biomarkers were reversed by treatment of irbesartan and ergone in AAN rats at week 24 and adenine-induced CKD rats. In addition, these biomarkers were also reversed by irbesartan treatment in CKD patients.

Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.

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Wei-Hua Tang

Full Text Available Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD. In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes

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Tadahiro Shinozawa

2017-02-01

Full Text Available To predict drug-induced serious adverse events (SAE in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects. Here, we evaluated individual differences in SAE susceptibility based on an in vitro model using hiPSC-derived cardiomyocytes (hiPSC-CMs as a pilot study. hiPSCs were generated from blood samples of ten healthy volunteers with different susceptibilities to moxifloxacin (Mox-induced QT prolongation. Different Mox-induced field potential duration (FPD prolongation values were observed in the hiPSC-CMs from each individual. Interestingly, the QT interval was significantly positively correlated with FPD at clinically relevant concentrations (r > 0.66 in multiple analyses including concentration-QT analysis. Genomic analysis showed no interindividual significant differences in known target-binding sites for Mox and other drugs such as the hERG channel subunit, and baseline QT ranges were normal. The results suggest that hiPSC-CMs from healthy subjects recapitulate susceptibility to Mox-induced QT prolongation and provide proof of concept for in vitro preclinical trials.

Physiologic effects of prolonged conducted electrical weapon discharge in ethanol-intoxicated adults.

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Moscati, Ronald; Ho, Jeffrey D; Dawes, Donald M; Miner, James R

2010-06-01

This study examines the physiologic effects of prolonged conducted electrical weapon (CEW) exposure on alcohol-intoxicated adult subjects. Adult volunteers were recruited at a TASER International training conference. All subjects ingested mixed drinks until clinical intoxication or until a minimum breath alcohol level of 0.08 mg/dL was achieved. Blood samples for venous pH, Pco(2), bicarbonate, and lactate were measured in all subjects at baseline, immediately after alcohol ingestion, immediately after exposure to a 15-second TASER X26 discharge (Taser International Inc, Scottsdale, AZ), and 24 hours post-alcohol ingestion. Laboratory values were compared at sampling times using repeated-measure analysis of variance. A focused analysis comparing time points within groups was then performed using paired t tests. Twenty-two subjects were enrolled into the study. There was a decrease in pH and bicarbonate and an increase in lactate after alcohol ingestion. There was a further increase in lactate and drop in pH after CEW exposure. No subject experienced a significant adverse event. All values had returned to baseline levels at 24 hours except lactate, which demonstrated a small but clinically insignificant increase. Prolonged continuous CEW exposure in the setting of acute alcohol intoxication has no clinically significant effect on subjects in terms of markers of metabolic acidosis. The acidosis seen is consistent with what occurs with ethanol intoxication or moderate exertion. Copyright (c) 2010 Elsevier Inc. All rights reserved.

The Role of Neurotrophic Factors Conjugated to Iron Oxide Nanoparticles in Peripheral Nerve Regeneration: In Vitro Studies

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Ofra Ziv-Polat

2014-01-01

Full Text Available Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (βNGF, glial cell-derived neurotrophic factor (GDNF, and basic fibroblast growth factor (FGF-2. Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37°C. The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF, accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF, a desirable scaffold for the reconstruction of severed peripheral nerve.

Prolonged carotid sinus reflex is a risk factor for contrast-induced nephropathy following carotid artery stenting.

Science.gov (United States)

Kato, T; Sakai, H; Tsujimoto, M; Nishimura, Y

2011-03-01

Although many studies have demonstrated that CIN is associated with in-hospital and long-term mortality, the incidence of CIN following CAS is unclear. We investigated the incidence of CIN, defined as an increase from a baseline creatinine value of at least 0.5 mg/dL or 25% within 72 hours of contrast administration, and we also examined renal function in the late phase after CAS. We examined 80 patients who underwent CAS between April 2005 and December 2009. Clinical background, laboratory data, contrast volume, and clinical course were collected and analyzed. The incidence of CIN was 8.8% (7/80), and no patients required hemodialysis. In the group that developed CIN, prolonged CSR after CAS was found in 57.1% (4/7) of cases; this incidence differed significantly (P = .001) from that in the group without development of CIN. Neither preoperative renal function, contrast volume, nor history was related to the incidence of CIN, while on multivariate analysis, prolonged CSR was found to be an independent risk factor for CIN. The incidence of elevation in creatinine values at 6 months after CAS was 8.2% (6/73). All patients who developed delayed renal impairment had pre-existing CKD; this finding differed significantly (P = .04) from that in the group without development of delayed renal impairment. Because patients who develop prolonged CSR after CAS are at increased risk of perioperative major adverse clinical events including CIN, patients at high risk for this condition should be carefully managed to prevent increased morbidity and mortality.

Hepatic scar in a case of healed candidiasis showing prolonged enhancement on CT

Energy Technology Data Exchange (ETDEWEB)

Itai, Yuji; Yashiro, Naobumi

1987-08-01

A patient with acute myelocytic leukemia recovering from hepatic candidiasis after long-term administration of amphotericin B had large scar in the liver which showed prominent prolonged enhancement on postcontrast CT. Prolonged enhancement can occur in regions other than hepatic masses.

Increase in the free radical scavenging capability of bitter gourd by a heat-drying process.

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Wei, Lu; Shaoyun, Wang; Shutao, Liu; Jianwu, Zhou; Lijing, Ke; Pingfan, Rao

2013-12-01

Bitter gourd (Momordica charantia Linn.) is widely regarded as one of the best remedy foods for diabetes. The positive effect of bitter gourd on diabetes has been attributed in part to the remarkable free radical scavenging activity of its boiled water extract from sun-dried fruits. It is well known that a heat process significantly influences the antioxidant activity of fresh fruits. However, the heat drying processes of bitter gourd have not been studied so far. Here, we show that the free radical scavenging capability of bitter gourd extract significantly increases after the heat drying process, while the content of flavonoids and phenols, which are generally regarded as the main antioxidant components in bitter gourd, remain unaffected. Furthermore, the content of free amino acids and the total reducing sugar were found to decrease with increasing browning index, indicating the progression of the Maillard reaction, products of which are known to possess significant antioxidant activity. Therefore, it suggests that Maillard reaction products may be the main contributors to the increase in antioxidant capability. Finally, the bitter gourd extract with the higher antioxidant activity, was shown to manifest a corresponding higher proliferation activity on NIT-1 beta-cells. These results suggest that controllable conditions in the heat-drying processing of fresh bitter gourd fruit is of significance for enhancing the total free radical scavenging capacity, beta-cell proliferation activity and possibly the anti-diabetic activity of this fruit.

Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

DEFF Research Database (Denmark)

Hvid, L G; Gejl, Kasper Degn; Bech, R D

2013-01-01

Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...... recovery on the contractile function of single muscle fibres obtained from elite athletes....

Prolonged operative time increases infection rate in tibial plateau fractures.

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Colman, Matthew; Wright, Adam; Gruen, Gary; Siska, Peter; Pape, Hans-Christoph; Tarkin, Ivan

2013-02-01

Fractures of the tibial plateau present a treatment challenge and are susceptible to both prolonged operative times and high postoperative infection rates. For those fractures treated with open plating, we sought to identify the relationship between surgical site infection and prolonged operative time as well as to identify other surgical risk factors. We performed a retrospective controlled analysis of 309 consecutive unicondylar and bicondylar tibial plateau fractures treated with open plate osteosynthesis at our institution's level I trauma centre during a recent 5-year period. We recorded operative times, injury characteristics, surgical treatment, and need for operative debridement due to infection. Operative times of infected cases were compared to uncomplicated surgical cases. Multivariable logistic regression analysis was performed to identify independent risk factors for postoperative infection. Mean operative time in the infection group was 2.8h vs. 2.2h in the non-infected group (p=0.005). 15 fractures (4.9%) underwent four compartment fasciotomies as part of their treatment, with a significantly higher infection rate than those not undergoing fasciotomy (26.7% vs. 6.8%, p=0.01). Open fracture grade was also significantly related to infection rate (closed fractures: 5.3%, grade 1: 14.3%, grade 2: 40%, grade 3: 50%, pinfection rates (13.9% vs. 8.7%, p=0.36). Multivariable logistic regression analysis of the entire study group identified longer operative times (OR 1.78, p=0.013) and open fractures (OR 7.02, psite infection. Operative times approaching 3h and open fractures are related to an increased overall risk for surgical site infection after open plating of the tibial plateau. Dual incision approaches with bicolumnar plating do not appear to expose the patient to increased risk compared to single incision approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Geodynamic Effects of Ocean Tides: Progress and Problems

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Richard, Ray

1999-01-01

Satellite altimetry, particularly Topex/Poseidon, has markedly improved our knowledge of global tides, thereby allowing significant progress on some longstanding problems in geodynamics. This paper reviews some of that progress. Emphasis is given to global-scale problems, particularly those falling within the mandate of the new IERS Special Bureau for Tides: angular momentum, gravitational field, geocenter motion. For this discussion I use primarily the new ocean tide solutions GOT99.2, CSR4.0, and TPXO.4 (for which G. Egbert has computed inverse-theoretic error estimates), and I concentrate on new results in angular momentum and gravity and their solid-earth implications. One example is a new estimate of the effective tidal Q at the M_2 frequency, based on combining these ocean models with tidal estimates from satellite laser ranging. Three especially intractable problems are also addressed: (1) determining long-period tides in the Arctic [large unknown effect on the inertia tensor, particularly for Mf]; (2) determining the global psi_l tide [large unknown effect on interpretations of gravimetry for the near-diurnal free wobble]; and (3) determining radiational tides [large unknown temporal variations at important frequencies]. Problems (2) and (3) are related.

Body composition during early infancy and developmental progression from 1 to 5 years of age

DEFF Research Database (Denmark)

Abera, Mubarek; Tesfaye, Markos; Admassu, Bitiya

2018-01-01