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Sample records for reduces prolonged frequency-adjusted

  1. Competing for Consciousness: Prolonged Mask Exposure Reduces Object Substitution Masking

    ERIC Educational Resources Information Center

    Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

    2011-01-01

    In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask impairs target identification, even though it has different contours from, and does not spatially overlap with the target. Here, we demonstrate a previously unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g., 640 ms) relative to intermediate…

  2. Frequency adjustable MEMS vibration energy harvester

    NASA Astrophysics Data System (ADS)

    Podder, P.; Constantinou, P.; Amann, A.; Roy, S.

    2016-10-01

    Ambient mechanical vibrations offer an attractive solution for powering the wireless sensor nodes of the emerging “Internet-of-Things”. However, the wide-ranging variability of the ambient vibration frequencies pose a significant challenge to the efficient transduction of vibration into usable electrical energy. This work reports the development of a MEMS electromagnetic vibration energy harvester where the resonance frequency of the oscillator can be adjusted or tuned to adapt to the ambient vibrational frequency. Micro-fabricated silicon spring and double layer planar micro-coils along with sintered NdFeB micro-magnets are used to construct the electromagnetic transduction mechanism. Furthermore, another NdFeB magnet is adjustably assembled to induce variable magnetic interaction with the transducing magnet, leading to significant change in the spring stiffness and resonance frequency. Finite element analysis and numerical simulations exhibit substantial frequency tuning range (25% of natural resonance frequency) by appropriate adjustment of the repulsive magnetic interaction between the tuning and transducing magnet pair. This demonstrated method of frequency adjustment or tuning have potential applications in other MEMS vibration energy harvesters and micromechanical oscillators.

  3. Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats.

    PubMed

    Meng, Li; Rijntjes, Eddy; Swarts, Hans J M; Keijer, Jaap; Teerds, Katja J

    2017-03-16

    There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically. At the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population. The induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular

  4. Some measures to reduce effects of prolonged sleep deprivation.

    PubMed

    Lagarde, D; Batejat, D

    1995-01-01

    Prolonged sleep deprivation is an exceptional situation, encountered in special environments such as sports, civilian and military, and which induces deficits in vigilance and performance. Among the array of measures which may be used to counteract these effects, the authors described a protocol using the combination of small naps, and administration of a pharmacological aid. A detailed description of advantages and drawbacks of each one of these measures is given, illustrated by several examples extracted from different studies. Four aspects of pharmacological aid are reviewed: the effects of amphetamines and amphetamine-like substances, caffeine, eugregoric substances, and the effect of the association small nap + eugregoric substances. The use of these various aids is discussed, and findings show that each one of them finds an application in a specific context.

  5. Prolonged photostress macular recovery after reduced blood pressure.

    PubMed

    Myhre, K; Brinchmann-Hansen, O

    1991-06-01

    In order to investigate an association between systemic blood pressure and restitution of normal visual function in dim illumination after photostress, macular recovery time and blood pressure were measured in two groups: 1) 90 young and healthy military pilots and applicants for military pilot training; and 2) 10 hypertensive patients before and after 12 weeks of antihypertensive treatment. Young normotensive subjects (20/20 vision) with low diastolic blood pressure performed less well (longer macular recovery time) than those with higher pressure (r = -0.42, p less than or equal to 0.05). Among the hypertensive patients three were given doxazosin, three, prazosin, and four, placebo. The treatment period produced significant fall in blood pressures, a small reduction in intraocular pressure (p less than or equal to 0.03) and a lengthening of initial monocular recovery period (p = 0.04) in addition to reduced monocular (p = 0.015) and binocular (p = 0.022) macular recovery in the remaining part of the 2-min test period. This observation may be important for antihypertensive treated patients whose occupation requires fast visual adjustment to changing stimuli in dim light.

  6. Standing on a declining surface reduces transient prolonged standing induced low back pain development.

    PubMed

    Gallagher, Kaitlin M; Callaghan, Jack P

    2016-09-01

    While alternating standing position on a sloped surface has proven successful at reducing low back pain during standing, the purpose of this study was to evaluate standing solely on a declining surface to isolate the influence of the postural change. Seventeen participants performed two 75-min prolonged standing occupational simulations- level ground and declining surface. Fifty-three percent of participants (9/17) were categorized as pain developers during the level ground standing condition. For these same pain developers, their average maximum pain scores were 58% lower during sloped standing. All participants showed greater hip flexion, trunk-to-thigh angle flexion, and posterior translation of the trunk center of gravity when standing on the sloped surface. These postural changes could cause the muscles crossing the hip posteriorly to increase passive stiffness and assist with stabilizing the pelvis. This study stresses the importance of hip kinematics, not just lumbar spine posture, in reducing prolonged standing induced low back pain.

  7. Safety pharmacology assessment of drug-induced QT-prolongation in dogs with reduced repolarization reserve.

    PubMed

    Vormberge, Thomas; Hoffmann, Michael; Himmel, Herbert

    2006-01-01

    Drug-induced QT-prolongation, often based on hERG K+ current inhibition, has become a major safety concern during drug development. Hence, regulatory guidelines require combined in vitro and in vivo assays to assess the potential of new chemical entities to delay ventricular repolarization. Here, results of a pharmacological validation study with the torsadogenic compound sotalol are presented. Alteration of ECG parameters was investigated in both conscious and anesthetized Beagle dogs (cumulative infusions of D,L-sotalol; n=6). The repolarization reserve of the latter was reduced by neurolept anesthesia using the hERG blocker droperidol (0.25 mg/kg/h yielding mean plasma concentrations of 0.5 microM). Furthermore, hERG K+ current and action potentials (AP; rabbit Purkinje fibers) were measured in vitro. The Fridericia corrected QT interval, QTcF, in conscious dogs (control: 254+/-15 ms), was dose-dependently prolonged by D,L-sotalol (+42 ms at plasma levels of 261 microM; dose 30 mg/kg). In anesthetized dogs, baseline QTcF (337+/-35 ms) was already prolonged compared to conscious dogs. In addition, QTcF-increase (+90 ms) was more pronounced at lower D,L-sotalol plasma levels (181 microM; dose 10 mg/kg), and proarrhythmic markers Tpeak-Tend and short term variability of QT were increased. These in vivo findings are supported by in vitro data. The hERG K+ current was blocked by D,L-sotalol (IC50 approximately 1.2 mM, IC20 approximately 250 microM) and droperidol (IC50 approximately 0.1 microM, IC20 approximately 0.02 microM). Purkinje fiber APs were concentration-dependently prolonged by D,L-sotalol (APD90:+60% at 30 microM) and droperidol (APD90:+55% at 1 microM). Low droperidol concentrations increased the sensitivity of Purkinje fibers towards D,L-sotalol-mediated AP prolongation. In conclusion, the higher sensitivity of anesthetized dogs towards sotalol-induced QT-prolongation is due to a reduced cardiac repolarization reserve caused by the hERG blocker

  8. Prolonged application of clopidogrel reduces inflammation after percutaneous coronary intervention in the porcine model.

    PubMed

    Ayral, Yunus; Rauch, Ursula; Goldin-Lang, Petra; Stellbaum, Caroline; Deiner, Carolin; Schwimmbeck, Peter L; Schultheiss, Heinz-Peter; Pels, Klaus

    2007-01-01

    We determined the effect of prolonged treatment with clopidogrel on C-reactive protein (CRP) concentrations and blood thrombogenicity after percutaneous transluminal coronary angioplasty followed by intracoronary brachytherapy in the porcine model. ANIMAL MODEL: All 48 pigs received antiplatelet therapy, including aspirin (325 mg, daily) and clopidogrel (300 mg, loading dose) 1 day before PCI, followed by a daily dose of clopidogrel (75 mg/day) in addition to aspirin. During PCI, one of two balloon-injured arteries was randomly assigned to receive immediate radiation treatment. Animals were sacrificed after 24 h, 1 month, and 3 months post-PCI. The pigs, which were sacrificed 3 months post-PCI, were divided into two groups. The first group received clopidogrel in addition to aspirin for 3 months, and the second group received clopidogrel in addition to aspirin for only 1 month after PCI and then aspirin alone. Blood was taken from all pigs before intervention, immediately after intervention, and before sacrifice. Serum CRP was measured by enzyme-linked immunosorbent assay. To analyze the procoagulant effects of PCI on blood thrombogenicity, a one-stage clotting assay was performed. Clopidogrel treatment for 3 months reduced CRP levels more than did clopidogrel therapy for 1 month only at 3 months post-PCI (27.9+/-3.9 vs. 56.6+/-11.3 microg/ml; P=.019). Baseline CRP levels were found to be 50.4+/-4.8 microg/ml. Plasma clotting was not affected by prolonged clopidogrel therapy (322.8+/-59.3 s vs. 295.2+/-52.5 s; P=ns). Prolonged treatment with clopidogrel reduced CRP levels post-PCI.

  9. Prolonged SDA and reduced digestive efficiency under elevated CO2 may explain reduced growth in Atlantic cod (Gadus morhua).

    PubMed

    Tirsgaard, Bjørn; Moran, Damian; Steffensen, John F

    2015-01-01

    Land-based aquaculture systems expose fish to elevated dissolved CO2 levels, a factor that is correlated with reduced growth, feed conversion efficiency and body condition index. The physiological basis underlying the pathological effects of environmental hypercapnia is poorly understood, in particular for marine fish species. We investigated whether changes in energy expenditure and the specific dynamic action (SDA) of digestion and assimilation could account for the lower growth of adult Atlantic cod (Gadus morhua) under environmental hypercapnia. Fish acclimated to a partial pressure of 800 μatm CO2 (0.6 mmHg, 1.5 mg/L) and 9200 μatm CO2 (7 mmHg, 18.7 mg/L) exhibited no difference in maintenance metabolic rates, which concurs with previous research for this species and other fish species. At 9200 μatm CO2 Atlantic cod had a significantly diminished (14%) maximum aerobic capacity. While hypercapnia did not affect the amount of oxygen required for the SDA process, it did prolong the SDA duration by 23%. The longer SDA process time may offer an explanation for the observation of lower feed intake, growth and condition factor in long-term hypercapnia studies. Comparison of aerobic scope and cardiac performance during digestion suggested that reduced oxygen delivery capacity under hypercapnia could be one mechanism by which CO2 prolongs SDA, although our results could not definitively demonstrate this effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Home-based detoxification for neonatal abstinence syndrome reduces length of hospital admission without prolonging treatment.

    PubMed

    Smirk, Cameron L; Bowman, Ellen; Doyle, Lex W; Kamlin, Omar

    2014-06-01

    Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome, secondary to in utero chemical exposure and characterised by tremor, irritability and feed intolerance. It often requires prolonged hospital treatment and separation of families. Outpatient therapy may reduce this burden, but current literature is sparse. This review aimed to evaluate the safety and efficacy of our home-based detoxification programme and compare it with standard inpatient care. Infants requiring treatment for NAS between January 2004 and December 2010 were reviewed. Data on demographics, drug exposure, length of stay and type of therapy were compared between infants selected for home-based therapy and those treated conventionally. Of the 118 infants who were admitted for treatment of NAS, 38 (32%) were managed at home. Infants receiving home-based detoxification had shorter hospital stays (mean 19 days vs. 39 days), with no increase in total duration of treatment (mean 36 days vs. 41 days), and were more likely to be breastfeeding on discharge from hospital care (45% vs. 22%). In selected infants, home-based detoxification is associated with reduced hospital stays and increased rates of breastfeeding, without prolonging therapy. Safety of the infants remains paramount, which precludes many from entering such a programme. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  11. Pain reported during prolonged standing is associated with reduced anticipatory postural adjustments of the deep abdominals.

    PubMed

    Marshall, Paul W M; Romero, Rick; Brooks, Cristy

    2014-11-01

    Within the context of low back pain, the measurement of deep abdominal anticipatory postural adjustments (APAs) during rapid limb movement has received much interest. There is dispute about the association between APAs and back pain. Moreover, there is limited evidence examining compensatory postural adjustments (CPAs) in back pain. This study examined the relationship between APAs and CPAs with pain reported in the low back during 2 h of prolonged standing. Twenty-six participants with no history of severe back pain performed 2-h prolonged standing. APAs and CPAs of the deep abdominal muscles (transverse abdominis/internal obliques) were measured by surface electromyography during rapid shoulder flexion and extension. APAs and CPAs measured pre-standing revealed symmetrical anticipatory activity, but an asymmetry between the different sides of the abdominal wall for CPAs. APAs and CPAs measured pre-standing were not associated with pain reported during standing. For the whole group, APA amplitudes were reduced post-standing during shoulder flexion (p = 0.005). Pain reported during standing was associated with the changes in APA amplitudes post-standing (rs = 0.43, p = 0.002). These findings support previous research using hypertonic saline injections to induce back pain that showed reduced APA amplitudes, and extends findings to suggest pain does not effect compensatory postural adjustments.

  12. An introduction to QT interval prolongation and non-clinical approaches to assessing and reducing risk

    PubMed Central

    Pollard, CE; Abi Gerges, N; Bridgland-Taylor, MH; Easter, A; Hammond, TG; Valentin, J-P

    2010-01-01

    Owing to its association with Torsades de Pointes, drug-induced QT interval prolongation has been and remains a significant hurdle to the development of safe, effective medicines. Genetic and pharmacological evidence highlighting the pivotal role the human ether-a-go-go-related gene (hERG) channel was a critical step in understanding how to start addressing this issue. It led to the development of hERG assays with the rapid throughput needed for the short timescales required in early drug discovery. The resulting volume of hERG data has fostered in silico models to help chemists design compounds with reduced hERG potency. In early drug discovery, a pragmatic approach based on exceeding a given potency value has been required to decide when a compound is likely to carry a low QT risk, to support its progression to late-stage discovery. At this point, the in vivo efficacy and metabolism characteristics of the potential drug are generally defined, as well its safety profile, which includes usually a dog study to assess QT interval prolongation risk. The hERG and in vivo QT data, combined with the likely indication and the estimated free drug level for efficacy, are put together to assess the risk that the potential drug will prolong QT in man. Further data may be required to refine the risk assessment before making the major investment decisions for full development. The non-clinical data are essential to inform decisions about compound progression and to optimize the design of clinical QT studies. This article is commented on by Guth and Rast, pp. 22–24 of this issue and is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 PMID:20141516

  13. Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI).

    PubMed

    Gelfand, R; Lambertsen, C J; Clark, J M; Hopkin, E

    1998-01-01

    Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

  14. Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

    NASA Technical Reports Server (NTRS)

    Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

    1998-01-01

    Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

  15. Prolonged clopidogrel application reduces tissue factor expression after percutaneous coronary intervention in the porcine model.

    PubMed

    Ayral, Yunus; Rauch, Ursula; Goldin-Lang, Petra; Eisenreich, Andreas; Pepke, Wojciech; Deiner, Carolin; Schwimmbeck, Peter L; Schultheiss, Heinz-Peter; Pels, Klaus

    2011-01-01

    Late thrombotic events are important complications associated with intracoronary brachytherapy (ICBT) using ionizing radiation (IR) or with antiproliferative treatment modalities such as drug-eluting stents (DES). The mechanism mediating these thrombotic events is not well understood. This study assessed the effect of prolonged clopidogrel treatment on tissue factor (TF) expression in coronary arteries and on the circulating TF level after percutaneous transluminal coronary angioplasty /ICBT in a porcine coronary model. Pigs were treated with aspirin plus a 300 mg loading dose of clopidogrel one day before percutaneous coronary intervention (PCI), followed by a daily dose of clopidogrel and aspirin. During PCI one of the two balloon-injured arteries was treated by brachytherapy. Animals were sacrificed at different time points. The pigs, which were sacrificed 3 months post-PCI, were divided into two groups (Group I: clopidogrel for 3 months; Group II: clopidogrel for 1 month). Plasma TF was measured by enzyme-linked immunosorbent assay in blood samples taken from all pigs before and immediately after intervention and before sacrifice. Morphometric analysis was performed on digitalized images employing the software LUCIA G for TF staining. Vascular TF expression levels were assessed by quantitative real-time polymerase chain reaction. Prolonged clopidogrel application significantly reduced coronary TF at the protein (Group I vs. II, 8.975 ± 3.947% vs. 26.44 ± 5.375%, P = .007) and mRNA level [Group I vs. II, (0.3501 ± 0.0519) × 10(-3) vs. (0.7073 ± 0.0436) × 10(-3), P<.0005]. Circulating TF protein tended to be lower after 3 months than after 1 month clopidogrel treatment post-PCI (Group I vs. Group II, 488.3 ± 35.37 pg/ml vs. 572.3 ± 39.9 pg/ml, P = .130). Prolonged clopidogrel treatment reduced coronary TF expression and tended to reduce the blood TF level post-PCI, thus possibly modulating the risk of late thrombosis. Copyright © 2011 Elsevier Inc. All

  16. Prolonged fermentation of whole wheat sourdough reduces phytate level and increases soluble magnesium.

    PubMed

    Lopez, H W; Krespine, V; Guy, C; Messager, A; Demigne, C; Remesy, C

    2001-05-01

    This work was designed to compare the effects of different leavens (yeast, sourdough, and a mixture of both) on phytic acid (PA) degradation and to assess the repercussions of PA breakdown on phosphorus and magnesium solubility during bread-making. Sourdough fermentation was more efficient than yeast fermentation in reducing the phytate content in whole wheat bread (-62 and -38%, respectively). Furthermore, lactic acid bacteria present in sourdough enhanced acidification, leading to increased magnesium and phosphorus solubility. To intensify phytate breakdown, bran was incubated with microorganisms (yeast or sourdough) before bread-making. Using this new method, the percentage of phytate breakdown was near 90%, whereas 40% of phytate remained in traditional French bread. In conclusion, a prolonged fermentation with sourdough still leads to improved Mg and P solubility by decreasing phytate content and through acidification.

  17. Reduced Left Ventricular Compliance and Mechanical Efficiency after Prolonged Inhibition of NO Synthesis in Conscious Dogs

    PubMed Central

    Post, Heiner; d'Agostino, Chiara; Lionetti, Vincenzo; Castellari, Michele; Kang, Elaine Y; Altarejos, Martin; Xu, Xiaobin; Hintze, Thomas H; Recchia, Fabio A

    2003-01-01

    Acute inhibition of NO synthesis decreases left ventricular (LV) work and external efficiency, but it is unknown whether compensatory mechanisms can limit the alterations in LV mechanoenergetics after prolonged NO deficiency. Eight chronically instrumented male mongrel dogs received 35 mg kg−1 day−1 of Nω-nitro-L-arginine methyl ester orally for 10 days to inhibit NO synthesis. At spontaneous beating frequency, heart rate, coronary blood flow, peak LV pressure, end-diastolic LV pressure and the maximum derivative of LV pressure (dP/dtmax) were not significantly different vs. baseline, whereas LV end-diastolic diameter (32.5 ± 1.0 vs. 37.6 ± 1.4 mm) and LV stroke work (515 ± 38 vs. 650 ± 44 mmHg mm), were reduced (all P < 0.05). The slope of the LV end-systolic pressure-diameter relationship was increased at 10 days vs. baseline (13.9 ± 1.0 vs. 9.6 ± 0.9 mmHg mm−1, P < 0.05), while the end-diastolic LV diameter was smaller at matched LV end-diastolic pressures. At fixed heart rate (130 beats min−1), cardiac oxygen consumption was increased (12.2 ± 1.5 vs. 9.9 ± 1.0 ml min−1), and the ratio between stroke work and oxygen consumption was decreased by 33 ±7 % (all P < 0.05) after NO inhibition. We conclude that sustained inhibition of NO synthesis in dogs causes a decrease in LV work despite an increased contractility, which is most probably due to reduced diastolic compliance and a decrease in external efficiency. Thus, prolonged NO deficiency is not compensated for on the level of LV mechanoenergetics in vivo. PMID:12878761

  18. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans.

    PubMed

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke; Lundby, Carsten; Olsen, Niels V; Secher, Niels H; van Lieshout, Johannes J

    2012-03-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3.7 to 47.6 ± 4.1% (P<0.01), whereas hematocrit was unaffected following acute EPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8±4 and 7±3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7±3 and 5±2%; P<0.05). Also, both EPO regimes widened the arterial-to-jugular O(2) differences at rest as well as during normoxic and hypoxic exercise (P<0.01), which indicated reduced cerebral blood flow despite preserved dynamic cerebral autoregulation, and an increase in middle cerebral artery mean blood flow velocity (P<0.05), therefore, reflected vasoconstriction. Thus, administration of EPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.

  19. Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice.

    PubMed

    Napoli, Claudio; Williams-Ignarro, Sharon; de Nigris, Filomena; Lerman, Lilach O; D'Armiento, Francesco P; Crimi, Ettore; Byrns, Russell E; Casamassimi, Amelia; Lanza, Alessandro; Gombos, Fernando; Sica, Vincenzo; Ignarro, Louis J

    2006-07-05

    Moderate physical exercise (PE) combined with metabolic treatment (MT) (antioxidants and l-arginine) are well known to reduce atherosclerotic lesion formation in hypercholesterolemic mice. However, the long-term beneficial effects on unstable atheroma remain poorly understood. We started early PE training in large groups of 6-week-old hypercholesterolemic mice (by graduated swimming) alone or in combination with nutritional supplementation (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water). Inactive controls did not receive PE. The spontaneous development of atherosclerotic plaque rupture (associated with advanced atherosclerosis) and survival rates were evaluated. Moderate PE elicited an increase in plasma levels of nitric oxide. Early combined treatment with PE and MT in the hypercholesterolemic mice significantly reduced lesions (also detected noninvasively at 10 months) and spontaneous atherosclerotic plaque rupture and prolonged survival more effectively than each intervention alone. Thus, early concerted actions of MT and PE improve the natural history of atherosclerotic lesions and reduce the plaque instability in hypercholesterolemic mice.

  20. Severe hypoxemia induced by prolonged expiration and reduced frequency breathing during submaximal swimming.

    PubMed

    Toubekis, Argyris G; Beidaris, Nikolaos; Botonis, Petros G; Koskolou, Maria

    2017-06-01

    The purpose of this study was to examine the metabolic responses during submaximal swimming with self-selected normal breathing (N) and prolonged expiration along with reduced frequency breathing (RB). Ten male swimmers (age: 23.1 ± 2.2 years; VO2max: 47.3 ± 7.2 ml · kg(-1) · min(-1)) performed 75-, 100-, 175-, 200-, 275-, 300-, 375- and 400-m trials with N and RB at intensity corresponding to 90% of the critical speed. In RB condition, all trials longer than 75 m were interspersed with 25 m of self-selected N in regular intervals. In RB, oxygen saturation during recovery was decreased compared to starting values after 75, 100, 175, 275 and 375 m (78-91%, P < 0.05), while it remained unchanged after all trials in N condition (98 ± 2%, P > 0.05). Lactate concentration was higher in RB than in N after 400 m (4.3 ± 1.5 vs. 3.3 ± 1.7 mmol · l(-1), P < 0.05). During recovery after the 375-m trial, partial pressure of carbon dioxide was increased and pH was decreased in RB compared to N condition. Prolonged expiration along with RB provokes severe hypoxemia during the recovery period after swimming, which is restored with self-selected N during submaximal swimming.

  1. Hydrazinonicotinamide prolongs quantum dot circulation and reduces reticuloendothelial system clearance by suppressing opsonization and phagocyte engulfment

    NASA Astrophysics Data System (ADS)

    Jung, Kyung-Ho; Park, Jin Won; Paik, Jin-Young; Lee, Eun Jeong; Choe, Yearn Seong; Lee, Kyung-Han

    2012-12-01

    In this study, we investigated the effects of hydrazinonicotinamide (HYNIC)—a bifunctional crosslinker widely used to 99mTc radiolabel protein and nanoparticles for imaging studies—on quantum dot opsonization, macrophage engulfment and in vivo kinetics. In streptavidin-coated quantum dots (SA-QDots), conjugation with HYNIC increased the net negative charge without affecting the zeta potential. Confocal microscopy and fluorescence-activated cell sorting showed HYNIC attachment to suppress SA-QDot engulfment by macrophages. Furthermore, HYNIC conjugation suppressed surface opsonization by serum protein including IgG. When intravenously injected into mice, HYNIC conjugation significantly prolonged the circulation of SA-QDots and reduced their hepatosplenic uptake. Diminished reticuloendothelial system clearance of SA-QDots and aminoPEG-QDots by HYNIC conjugation was also demonstrated by in vivo and ex vivo optical imaging. The effects of HYNIC on the opsonization, phagocytosis and in vivo kinetics of quantum dots were reversed by removal of the hydrazine component from HYNIC. Thus, surface functionalization with HYNIC can improve the in vivo kinetics of quantum dots by reducing phagocytosis via suppression of surface opsonization.

  2. Prolonged target deprivation reduces the capacity of injured motoneurons to regenerate.

    PubMed

    Furey, Matthew J; Midha, Rajiv; Xu, Qing-Gui; Belkas, Jason; Gordon, Tessa

    2007-04-01

    To investigate whether or not it is the frustrated growth state (no axon growth) that reduces regenerative capacity or the inability of axotomized motoneurons to remake muscle connections (axon growth-no muscle contact) that accounts for poor regenerative capacity of chronically axotomized motoneurons. We chronically axotomized rat femoral motoneurons for 2 months by cutting the nerve and either capping the proximal nerve to prevent axon regeneration (Group 1, no axon growth for 2 mo) or encouraging axon regeneration but not target reinnervation by suture to the distal stump of cut saphenous nerve (Group 2, axon growth with no muscle contact). In the control fresh axotomy group (axon growth with muscle contact), femoral nerve stumps were resutured immediately. Two months later, the femoral nerve was recut and sutured immediately to encourage regeneration in a freshly cut saphenous nerve stump for 6 weeks. Regenerating axons in the saphenous nerve were back-labeled with fluorogold for enumeration of the femoral motoneurons that regenerated their axons into the distal nerve stump. We found that significantly fewer chronically axotomized motoneurons regenerated their axons than freshly axotomized motoneurons that regenerated their axons to reform nerve-muscle connections in the same length of time. The number of motoneurons that regenerated their axons was reduced in both the conditions of no axon growth and axon growth with no muscle contact; thus chronic axotomy for a 2-month period reduced regenerative success irrespective of whether the motoneurons were prevented from regenerating or encouraged to regenerate their axons in that same period of time. Axonal regeneration does not protect motoneurons from the negative effects of prolonged axotomy on regenerative capacity. It is the period of chronic axotomy, in which motoneurons remain without target nerve-muscle connection, and not simply a state of frustrated growth that accounts for the reduced regenerative

  3. Muscle blood flow is reduced with dehydration during prolonged exercise in humans

    PubMed Central

    González-Alonso, José; Calbet, José A L; Nielsen, Bodil

    1998-01-01

    The present study examined whether the blood flow to exercising muscles becomes reduced when cardiac output and systemic vascular conductance decline with dehydration during prolonged exercise in the heat. A secondary aim was to determine whether the upward drift in oxygen consumption (V̇O2) during prolonged exercise is confined to the active muscles.Seven euhydrated, endurance-trained cyclists performed two bicycle exercise trials in the heat (35 °C; 40–50% relative humidity; 61 ± 2% of maximal V̇O2), separated by 1 week. During the first trial (dehydration trial, DE), they bicycled until volitional exhaustion (135 ± 4 min, mean ± s.e.m.), while developing progressive dehydration and hyperthermia (3.9 ± 0.3% body weight loss; 39.7 ± 0.2 °C oesophageal temperature, Toes). In the second trial (control trial), they bicycled for the same period of time while maintaining euhydration by ingesting fluids and stabilizing Toes at 38.2 ± 0.1 °C after 30 min exercise.In both trials, cardiac output, leg blood flow (LBF), vascular conductance and V̇O2 were similar after 20 min exercise. During the 20 min-exhaustion period of DE, cardiac output, LBF and systemic vascular conductance declined significantly (8–14%; P < 0.05) yet muscle vascular conductance was unaltered. In contrast, during the same period of control, all these cardiovascular variables tended to increase. After 135 ± 4 min of DE, the 2.0 ± 0.6 l min−1 lower blood flow to the exercising legs accounted for approximately two-thirds of the reduction in cardiac output. Blood flow to the skin also declined markedly as forearm blood flow was 39 ± 8% (P < 0.05) lower in DE vs. control after 135 ± 4 min.In both trials, whole body V̇O2 and leg V̇O2 increased in parallel and were similar throughout exercise. The reduced leg blood flow in DE was accompanied by an even greater increase in femoral arterial-venous O2 (a-vO2) difference.It is concluded that blood flow to the exercising muscles declines

  4. The effects of prolonged weightlessness and reduced gravity environments on human survival.

    PubMed

    Taylor, R L

    1993-03-01

    The manned exploration of the solar system and the surfaces of some of the smaller planets and larger satellites requires that we are able to keep the adverse human physiological response to long term exposure to near zero and greatly reduced gravity environments within acceptable limits consistent with metabolic function. This paper examines the physiological changes associated with microgravity conditions with particular reference to the weightless demineralizatoin of bone (WDB). It is suggested that many of these changes are the result of physical/mechanical processes and are not primarily a medical problem. There are thus two immediately obvious and workable, if relatively costly, solutions to the problem of weightlessness. The provision of a near 1 g field during prolonged space flights, and/or the development of rapid transit spacecraft capable of significant acceleration and short flight times. Although these developments could remove or greatly ameliorate the effects of weightlessness during long-distance space flights there remains a problem relating to the long term colonization of the surfaces of Mars, the Moon, and other small solar system bodies. It is not yet known whether or not there is a critical threshold value of 'g' below which viable human physiological function cannot be sustained. If such a threshold exists permanent colonization may only be possible if the threshold value of 'g' is less than that at the surface of the planet on which we wish to settle.

  5. Preoperative pregabalin prolongs duration of spinal anesthesia and reduces early postoperative pain

    PubMed Central

    Park, MiHye; Jeon, Younghoon

    2016-01-01

    Abstract Background: The administration of oral pregabalin preoperatively has been reported to reduce acute postoperative pain. However, no clinical study to date has yet fully investigated whether or not pregabalin premedication affects sensory and motor blocks using spinal anesthesia and its effect upon early postoperative pain management. This prospective, randomized, and double-blind clinical study was designed to evaluate the efficacy of a single dose of pregabalin in terms of spinal blockade duration and its potential opioid-sparing effect during the first 24 hours subsequent to urogenital surgery. Methods: Forty-four patients scheduled for urogenital surgery under spinal anesthesia were randomly allocated to 2 groups: group C (no premedication; orally administered placebo 2 hours before surgery) and group P (orally administered 150 mg pregabalin 2 hours before surgery). Results: The duration of sensory and motor blockade was significantly prolonged in group P patients when compared with that in group C patients, and the pain scores at postoperative 6 and 24 hours were significantly lower in group P patients. Requests for analgesics during the first postoperative 24 hours were lower among group P patients. Conclusion: Premedication with a single dose of 150 mg pregabalin before surgery promoted the efficacy of intrathecal bupivacaine and improved postoperative analgesia in patients undergoing urogenital surgery under spinal anesthesia. PMID:27603398

  6. Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease

    PubMed Central

    Cortez, Leonardo M.; Campeau, Jody; Norman, Grant; Kalayil, Marian; Van der Merwe, Jacques; McKenzie, Debbie

    2015-01-01

    ABSTRACT Prion diseases are fatal neurodegenerative disorders associated with the conversion of cellular prion protein (PrPC) into its aberrant infectious form (PrPSc). There is no treatment available for these diseases. The bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) have been recently shown to be neuroprotective in other protein misfolding disease models, including Parkinson's, Huntington's and Alzheimer's diseases, and also in humans with amyotrophic lateral sclerosis. Here, we studied the therapeutic efficacy of these compounds in prion disease. We demonstrated that TUDCA and UDCA substantially reduced PrP conversion in cell-free aggregation assays, as well as in chronically and acutely infected cell cultures. This effect was mediated through reduction of PrPSc seeding ability, rather than an effect on PrPC. We also demonstrated the ability of TUDCA and UDCA to reduce neuronal loss in prion-infected cerebellar slice cultures. UDCA treatment reduced astrocytosis and prolonged survival in RML prion-infected mice. Interestingly, these effects were limited to the males, implying a gender-specific difference in drug metabolism. Beyond effects on PrPSc, we found that levels of phosphorylated eIF2α were increased at early time points, with correlated reductions in postsynaptic density protein 95. As demonstrated for other neurodegenerative diseases, we now show that TUDCA and UDCA may have a therapeutic role in prion diseases, with effects on both prion conversion and neuroprotection. Our findings, together with the fact that these natural compounds are orally bioavailable, permeable to the blood-brain barrier, and U.S. Food and Drug Administration-approved for use in humans, make these compounds promising alternatives for the treatment of prion diseases. IMPORTANCE Prion diseases are fatal neurodegenerative diseases that are transmissible to humans and other mammals. There are no disease-modifying therapies available, despite decades

  7. [A project to reduce the incidence of facial pressure ulcers caused by prolonged surgery with prone positioning].

    PubMed

    Lee, Wen-Yi; Lin, Pao-Chen; Weng, Chia-Hsing; Lin, Yi-Lin; Tsai, Wen-Lin

    2012-06-01

    We observed in our institute a 13.6% incidence of prolonged surgery (>4 hours) induced facial pressure ulcers that required prone positioning. Causes identified included: (1) customized silicon face pillows used were not suited for every patient; (2) our institute lacked a standard operating procedure for prone positioning; (3) our institute lacked a postoperative evaluation and audit procedure for facial pressure ulcers. We designed a strategy to reduce post-prolonged surgery facial pressure ulcer incidence requiring prone positioning by 50% (i.e., from 13.6% to 6.8%). We implemented the following: (1) Created a new water pillow to relieve facial pressure; (2) Implemented continuing education pressure ulcer prevention and evaluation; (3) Established protocols on standard care for prone-position patients and proper facial pressure ulcer identification; (4) Established a face pressure ulcers accident reporting mechanism; and (5) Established an audit mechanism facial pressure ulcer cases. After implementing the resolution measures, 116 patients underwent prolonged surgery in a prone position (mean operating time: 298 mins). None suffered from facial pressure ulcers. The measures effectively reduced the incidence of facial pressure ulcers from 13.6% to 0.0%. The project used a water pillow to relieve facial pressure and educated staff to recognize and evaluate pressure ulcers. These measures were demonstrated effective in reducing the incidence of facial pressure ulcers caused by prolonged prone positioning.

  8. Reduced Lung Function in a Chronic Asthma Model Is Associated with Prolonged Inflammation, but Independent of Peribronchial Fibrosis

    PubMed Central

    Koerner-Rettberg, Cordula; Doths, Sandra; Stroet, Anke; Schwarze, Jürgen

    2008-01-01

    Background In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway changes after cessation of long term challenges to elucidate factors contributing to the development of prolonged lung function changes. Methodology/Principal Findings Mice sensitised systemically were consecutively challenged intranasally with ovalbumin for two or eight weeks. After the end of challenges, lung function, airway inflammation, features of airway remodelling, local T-cell cytokines and systemic ovalbumin-specific antibodies were monitored. Long term challenges resulted in airway hyperresponsiveness lasting 2 weeks and reduced baseline lung function for 6 weeks after their cessation. In contrast, these changes resolved within one week after short term challenges. Prolonged transforming growth factor beta (TGF-β)1 production and marked peribronchial fibrosis were only induced by long term challenges. Importantly, fibrosis became apparent only after the onset of lung function changes and outlasted them. Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response. In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response. Conclusions Prolonged lung function changes after long term allergen challenges seem to develop and resolve independently of the persistent peribronchial fibrosis. They are more closely associated with intense airway inflammation, marked lymphocytosis

  9. Clinical pharmacists' opportunities to reduce inappropriate prescription of QT-prolonging medications: calls to action.

    PubMed

    Dhanani, Trusha C; Mantovani, Emily H; Turner, J Rick

    2017-04-01

    All biologically active agents carry the potential to lead to adverse reactions in certain individuals, including serious cardiac adverse reactions. Since 2005, there has been an international regulatory landscape governing the investigation of a new drug's propensity to lead to the polymorphic ventricular tachycardia Torsades de Pointes (Torsades), a rare but potentially fatal occurrence. When a regulatory agency considers it appropriate, warning information is placed in a medicine's patient information leaflet (label) concerning drug-induced QT interval prolongation, a phenomenon associated with Torsades. In busy hospital settings, however, prescribers, including cardiologists, make injudicious prescribing decisions that put patients at risk. The science of cardiac safety, including the clinical trials that generate the information about QT prolongation in patient information leaflets, is frequently not part of the curriculum at Schools of Pharmacy. Given that medication-induced cardiotoxicity is extremely serious, we advocate that schools integrate the science of cardiac safety into existing therapeutics/therapeutic medication monitoring courses. Given their expert knowledge of pharmacology, pharmacists working as part of a hospital's clinical team would then be even better placed to review prescribing decisions concerning medications that prolong the QT interval, and alert prescribers in cases where reassessing their decisions seems prudent. National pharmacy societies or other pertinent professional societies could create practice guidelines to support graduates once employed as clinical pharmacists. Clinical pharmacists are well placed to be influential arbiters of safer prescribing decisions. Cardiac safety education during their pharmacy training and practice guideline support from professional societies during their careers can optimize this role.

  10. Interleukin-1β Can Reduce Manifestations of Delayed Effects of Prolonged Exposure to Low-Intensity γ-Radiation.

    PubMed

    Vorobyeva, N Yu; Grekhova, A K; Trubitsina, K Yu; Pchelka, A V; Rozhdestevenskiy, L M; Osipov, A N

    2016-02-01

    We showed that injection of IL-1β (Betaleukin) in a dose of 3 μg/kg 22 h before prolonged (21 h) exposure to low-intensity (10 mGy/min) γ-radiation in a dose of 12.6 Gy reduced the number of double-strand DNA breaks in murine spleen cells to the control level in 4 months after exposure and the number of double-strand DNA breaks induced by additional acute irradiation in a dose of 6 Gy. The results suggest that IL-1β can improve the efficiency of systems reducing the number of double-strand DNA breaks in murine spleen cells at delayed terms after exposure to prolonged low-intensity radiation.

  11. Prolonged Ocular Retention of Mucoadhesive Nanoparticle Eye Drop Formulation Enables Treatment of Eye Diseases Using Significantly Reduced Dosage.

    PubMed

    Liu, Shengyan; Dozois, Matthew D; Chang, Chu Ning; Ahmad, Aaminah; Ng, Deborah L T; Hileeto, Denise; Liang, Huiyuan; Reyad, Matthew-Mina; Boyd, Shelley; Jones, Lyndon W; Gu, Frank X

    2016-09-06

    Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance.

  12. Lupus nephritis: prolonged immunoadsorption (IAS) reduces proteinuria and stabilizes global disease activity.

    PubMed

    Stummvoll, Georg H; Schmaldienst, Sabine; Smolen, Josef S; Derfler, Kurt; Biesenbach, Peter

    2012-02-01

    Systemic lupus erythematosus (SLE) is characterized by pathogenic autoantibodies, which can be removed by extracorporeal procedures. While previous studies have shown short-term efficacy of immunoadsorption (IAS) in SLE, no information on long-term benefit and safety is available. IAS was offered to patients with highly active renal disease when conventional therapy had failed. Eleven patients entered the prolonged IAS programme and were followed for up to 10 years (mean 6.4 ± 3.5). Efficacy of IAS was determined by reduction in proteinuria (primary outcome), global disease activity [SLE Disease Activity Index (SLEDAI)] and anti-double-stranded DNA (anti-dsDNA) levels (secondary outcomes). Full/partial remission was defined as ≤ 0.5/≤ 1.0 g/day for proteinuria, ≤ 5/≤ 8 for SLEDAI and ≤ 25/≤ 50 IU/mL for anti-dsDNA levels. We further assessed flares, infections, malignancies and procedure-related adverse events. Short-term IAS (≤ 1 year) resulted in a significant reduction of proteinuria (9.2 ± 3.7 to 2.3 ± 2.4, P = 0.0001), disease activity (SLEDAI 19 ± 8 to 4 ± 2, P = 0.0004) and dsDNA levels (168 ± 205 to 45 ± 34, P = 0.001). In patients without remission after 1 year (n = 5), prolonged IAS decreased proteinuria from 4.3 ± 2.4 to 0.5 ± 0.4 g/day, P = 0.02. At the end of observation, complete remission in proteinuria was achieved in seven patients (64%) and partial remission in two (18%) additional patients. One patient flared and was discontinued; in all other patients, disease activity and anti-dsDNA stabilized at remission levels. Flares (0.28 ± 0.30) and infections (0.66 ± 0.70 per patient/year) were relatively uncommon; no malignancies, anaphylactic or orthostatic adverse events were observed. IAS is effective in short-term use but prolonged IAS can provide additional therapeutic benefit while showing an acceptable safety profile. The vast majority of initially therapy-refractory patients met the remission criteria at the end of

  13. Delayed adrenal insufficiency long after unilateral adrenalectomy: prolonged glucocorticoid therapy reduced reserved secretory capacity of cortisol.

    PubMed

    Kazama, Itsuro; Komatsu, Yasuhiro; Ohiwa, Takafumi; Sanayama, Kyo; Nagata, Mikio

    2005-06-01

    A 51-year-old woman with Cushing's syndrome underwent unilateral adrenalectomy for left adrenal adenoma. After 7 years of prednisolone treatment (with some interruptions), followed by 4 years of total withdrawal from prednisolone treatment, she presented with hypotension, weight loss, general fatigue, nausea, hyponatremia and hypoglycemia. These clinical features together with a low response in the rapid adrenocorticotropic hormone test led to the diagnosis of acute adrenal insufficiency. Relatively low serum adrenocorticotropic hormone levels in the face of increased demand for cortisol during adrenal crisis suggested a disordered hypothalamic-pituitary function, indicating secondary adrenal insufficiency. This patient demonstrated the etiology of acute adrenal insufficiency long after unilateral adrenalectomy in association with subsequent glucocorticoid therapy. A reduction in the reserved secretory capacity of cortisol after prolonged prednisolone treatment was considered to have induced secondary adrenal insufficiency, even after 4 years of total withdrawal from prednisolone.

  14. Prolonged fasting and cortisol reduce myostatin mRNA levels in tilapia larvae; short-term fasting elevates.

    PubMed

    Rodgers, Buel D; Weber, Gregory M; Kelley, Kevin M; Levine, Michael A

    2003-05-01

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indexes in adults, skeletal muscle myostatin mRNA levels were unaffected. By contrast, larval myostatin mRNA levels were sometimes elevated after a short-term fast and were consistently reduced with prolonged fasting. These effects were specific for myostatin, as mRNA levels of glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphatase were unchanged. Cortisol levels were elevated in fasted larvae with reduced myostatin mRNA, whereas in addition immersion of larvae in 1 ppm (2.8 microM) cortisol reduced myostatin mRNA in a time-dependent fashion. These results suggest that larval myostatin mRNA levels may initially rise but ultimately fall during a prolonged fast. The reduction is likely mediated by fasting-induced hypercortisolemia, indicating divergent evolutionary mechanisms of glucocorticoid regulation of myostatin mRNA, since these steroids upregulate myostatin gene expression in mammals.

  15. Reduced transpiration response to precipitation pulses precedes mortality in a piñon-juniper woodland subject to prolonged drought.

    PubMed

    Plaut, Jennifer A; Wadsworth, W Duncan; Pangle, Robert; Yepez, Enrico A; McDowell, Nate G; Pockman, William T

    2013-10-01

    Global climate change is predicted to alter the intensity and duration of droughts, but the effects of changing precipitation patterns on vegetation mortality are difficult to predict. Our objective was to determine whether prolonged drought or above-average precipitation altered the capacity to respond to the individual precipitation pulses that drive productivity and survival. We analyzed 5 yr of data from a rainfall manipulation experiment in piñon-juniper (Pinus edulis-Juniperus monosperma) woodland using mixed effects models of transpiration response to event size, antecedent soil moisture, and post-event vapor pressure deficit. Replicated treatments included irrigation, drought, ambient control and infrastructure control. Mortality was highest under drought, and the reduced post-pulse transpiration in the droughted trees that died was attributable to treatment effects beyond drier antecedent conditions and reduced event size. In particular, trees that died were nearly unresponsive to antecedent shallow soil moisture, suggesting reduced shallow absorbing root area. Irrigated trees showed an enhanced response to precipitation pulses. Prolonged drought initiates a downward spiral whereby trees are increasingly unable to utilize pulsed soil moisture. Thus, the additive effects of future, more frequent droughts may increase drought-related mortality. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  16. Reduced vergence adaptation is associated with a prolonged output of convergence accommodation in convergence insufficiency.

    PubMed

    Sreenivasan, Vidhyapriya; Bobier, William R

    2014-07-01

    Convergence insufficiency (CI) is a developmental visual anomaly defined clinically by a reduced near point of convergence, a reduced capacity to view through base-out prisms (fusional convergence); coupled with asthenopic symptoms typically blur and diplopia. Experimental studies show reduced vergence parameters and tonic adaptation. Based upon current models of accommodation and vergence, we hypothesize that the reduced vergence adaptation in CI leads to excessive amounts of convergence accommodation (CA). Eleven CI participants (mean age=17.4±2.3 years) were recruited with reduced capacity to view through increasing magnitudes of base out (BO) prisms (mean fusional convergence at 40 cm=12±0.9Δ). Testing followed our previous experimental design for (n=11) binocularly normal adults. Binocular fixation of a difference of Gaussian (DoG) target (0.2 cpd) elicited CA responses during vergence adaptation to a 12Δ BO. Vergence and CA responses were obtained at 3 min intervals over a 15 min period and time course were quantified using exponential decay functions. Results were compared to previously published data on eleven binocular normals. Eight participants completed the study. CI's showed significantly reduced magnitude of vergence adaptation (CI: 2.9Δ vs. normals: 6.6Δ; p=0.01) and CA reduction (CI=0.21 D, Normals=0.55 D; p=0.03). However, the decay time constants for adaptation and CA responses were not significantly different. CA changes were not confounded by changes in tonic accommodation (Change in TA=0.01±0.2D; p=0.8). The reduced magnitude of vergence adaptation found in CI patients resulting in higher levels of CA may potentially explain their clinical findings of reduced positive fusional vergence (PFV) and the common symptom of blur. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Statins are ineffective at reducing neuroinflammation or prolonging survival in scrapie-infected mice.

    PubMed

    Carroll, James A; Race, Brent; Phillips, Katie; Striebel, James F; Chesebro, Bruce

    2017-08-01

    Neuroinflammation is a prominent component of several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, tauopathies, amyotrophic lateral sclerosis and prion diseases. In such conditions, the ability to decrease neuroinflammation by drug therapy may influence disease progression. Statins have been used to treat hyperlipidemia as well as reduce neuroinflammation and oxidative stress in various tissues. In previous studies, treatment of scrapie-infected mice with the type 1 statins, simvastatin or pravastatin, showed a small beneficial effect on survival time. In the current study, to increase the effectiveness of statin therapy, we treated infected mice with atorvastatin, a type 2 statin that has improved pharmacokinetics over many type 1 statins. Treatments with either simvastatin or pravastatin were tested for comparison. We evaluated scrapie-infected mice for protease-resistant PrP (PrPres) accumulation, gliosis, neuroinflammation and time until advanced clinical disease requiring euthanasia. All three statin treatments reduced total serum cholesterol ≥40 % in mice. However, gliosis and PrPres deposition were similar in statin-treated and untreated infected mice. Time to euthanasia due to advanced clinical signs was not changed in statin-treated mice relative to untreated mice, a finding at odds with previous reports. Expression of 84 inflammatory genes involved in neuroinflammation was also quantitated. Seven genes were reduced by pravastatin, and one gene was reduced by atorvastatin. In contrast, simvastatin therapy did not reduce any of the tested genes, but did slightly increase the expression of Ccl2 and Cxcl13. Our studies indicate that none of the three statins tested were effective in reducing scrapie-induced neuroinflammation or neuropathogenesis.

  18. Frequency adjustment and synchrony in networks of delayed pulse-coupled oscillators

    NASA Astrophysics Data System (ADS)

    Nishimura, Joel

    2015-01-01

    We introduce a system of pulse-coupled oscillators that can change both their phases and frequencies and prove that when there is a separation of time scales between phase and frequency adjustment the system converges to exact synchrony on strongly connected graphs with time delays. The analysis involves decomposing the network into a forest of tree-like structures that capture causality. These results provide a robust method of sensor net synchronization as well as demonstrate a new avenue of possible pulse-coupled oscillator research.

  19. Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; Shibasaki, M.; Wilson, T. E.; Cui, J.; Levine, B. D.

    2003-01-01

    Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

  20. Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; Shibasaki, M.; Wilson, T. E.; Cui, J.; Levine, B. D.

    2003-01-01

    Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.

  1. A nanoparticle formulation of disulfiram prolongs corneal residence time of the drug and reduces intraocular pressure.

    PubMed

    Nagai, Noriaki; Yoshioka, Chiaki; Mano, Yu; Tnabe, Wataru; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

    2015-03-01

    The goal in the search for successful therapies for glaucoma is the reduction of intraocular pressure (IOP), and the search for effective eye drops that reduce IOP is a high priority. We previously reported the potential of a 2-hydroxypropyl-β-cyclodextrin (HPβCD) solution containing 0.5% DSF (DSF solution) to provide effective anti-glaucoma treatment in eye drop form. In this study, we designed new ophthalmic formulations containing 0.5% DSF nanoparticles prepared by a bead mill method (DSFnano dispersion; particle size 183 ± 92 nm, mean ± S.D.), and compared the IOP-reducing effects of a DSFnano dispersion with those of a DSF solution. The high stability of the DSFnano dispersion was observed until 7 days after preparation, and the DSFnano dispersion showed high antimicrobial activity against Escherichia coli (ATCC 8739). In transcorneal penetration experiments using rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous humor, while no DSF was detected. The DDC penetration level (area under the curve, AUC) and corneal residence time (mean residence time, MRT) of the DSFnano dispersion were approximately 1.45- and 1.44-fold higher than those of the DSF, respectively. Moreover, the IOP-reducing effects of the DSFnano dispersion were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, DSFnano dispersion are tolerated better by a corneal epithelial cell than DSF solution and commercially available timolol maleate eye drops. It is possible that dispersions containing DSF nanoparticles will provide new possibilities for the effective treatment of glaucoma, and that an ocular drug delivery system using drug nanoparticles may expand their usage as therapy in the ophthalmologic field. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma drugs. Copyright © 2015 Elsevier Ltd

  2. Extracellular protons reduce quantal content and prolong synaptic currents at the Drosophila larval neuromuscular junction.

    PubMed

    Sandstrom, David J

    2011-10-01

    Fluctuations in extracellular pH occur in the nervous system in response to a number of physiological and pathological processes, such as ischemia, hypercapnea, and high-frequency activity. Using the Drosophila larval neuromuscular junction, the author has examined acute effects of low and high pH on excitability and synaptic transmission. Acidification rapidly and reversibly reduces the size of electrically evoked excitatory junctional currents (EJCs) in a concentration-dependent manner, with transmission nearly abolished at pH 5.0. Conversely, raising pH to 7.8 increases EJC amplitude significantly. Further elevation to pH 8.5 causes an initial increase in amplitude, followed by profound, long-lasting depression of the synapse. Amplitudes of spontaneous miniature EJCs (mEJCs) are modestly, but significantly reduced at pH 5.0. It is therefore the number of quanta released per action potential, rather than the size of individual quanta, that is most strongly affected. Decay times of both EJCs and mEJCs are dramatically lengthened at low pH, suggesting that glutamate remains in the synaptic cleft for much longer than normal. Presynaptic excitability is also reduced, as indicated by increased latency between nerve shock and EJC onset. The response to low pH was not altered by mutations in genes encoding Transient Receptor Potential, Mucolipin subfamily (TRPML) and Slowpoke ion channels, which had previously been implicated as possible targets of extracellular protons. The author concludes that extracellular protons have strong effects on the release of glutamate and the time course of synaptic currents. These phenotypes can be exploited to study the mechanisms of acid-mediated changes in neuronal function, and to pursue the way in which pH modulates synaptic function in normal and pathophysiological conditions.

  3. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    PubMed Central

    Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

    2016-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

  4. Do Prolonged Prophylactic Antibiotics Reduce the Incidence of Surgical-Site Infections in Immediate Prosthetic Breast Reconstruction?

    PubMed

    Wang, Frederick; Chin, Robin; Piper, Merisa; Esserman, Laura; Sbitany, Hani

    2016-12-01

    Approximately 50,000 women in the United States undergo mastectomy and immediate prosthetic breast reconstruction annually, and most receive postoperative prophylactic antibiotics. The effect of these antibiotics on the risk of surgical-site infections remains unclear. The authors searched the Medline, Embase, and Cochrane Library databases for studies that compared less than 24 hours and greater than 24 hours of antibiotics following immediate prosthetic breast reconstruction. Primary outcomes were surgical-site infections and implant loss. Conservative random effects models were used to obtain pooled relative risk estimates. The authors identified 927 studies, but only four cohort studies and one randomized controlled trial met their inclusion criteria. Unadjusted incidences of surgical-site infections were 14 percent with more than 24 hours of antibiotics, 19 percent with less than 24 hours of antibiotics, and 16 percent overall. Unadjusted incidences of implant loss were 8 percent with more than 24 hours of antibiotics, 10 percent with less than 24 hours of antibiotics, and 9 percent overall. The pooled relative risk of implant loss was 1.17 (95 percent CI, 0.39 to 3.6) with less than 24 hours of antibiotics, which was not statistically significant. Prolonged antibiotic use did not have a statistically significant effect on reducing surgical-site infections or implant loss. There was significant heterogeneity between studies, and prolonged antibiotics may have increased the risk of implant loss in the randomized controlled trial. Definitive evidence may only be obtained with data from more prospective randomized controlled trials.

  5. Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

    PubMed

    Kawaguchi, Jun; Matsuura, Nobuyuki; Kasahara, Masataka; Ichinohe, Tatsuya

    2015-02-01

    The purpose of this study was to investigate the latency and amplitude of trigeminal somatosensory evoked potentials to clarify how nerve function on the contralateral side is affected after cervical sympathetic block (CSB). Subjects comprised 16 volunteers. For CSB, the tip of a needle was contacted with the transverse process of the sixth cervical vertebra on the right side, and lidocaine was injected. Trigeminal somatosensory evoked potentials were recorded bilaterally from C5/C6 scalp positions. Pupil diameters were also measured. Electrical stimulations were applied to the left-side lower lip, and trigeminal somatosensory evoked potentials waveforms derived from both sides of the scalp were recorded. Then, electrical stimulations were applied to the right-side of the lower lip, and recording was again performed. Recordings were performed at 5, 15, and 30 minutes after CSB. On the CSB side, pupil diameter decreased at 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials at contralateral stimulation showed a prolongation of the latency in both P20 and N25 components on bilateral recording sites 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials' amplitude at contralateral stimulation was smaller than at ipsilateral stimulation 5 minutes after CSB. Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

  6. Poly(DL:lactic acid-castor oil) 3:7-bupivacaine formulation: reducing burst effect prolongs efficacy in vivo.

    PubMed

    Sokolsky-Papkov, Marina; Golovanevski, Ludmila; Domb, Abraham J; Weiniger, Carolyn F

    2010-06-01

    Prolonged analgesia may be achieved using a single injection of slow-release local anesthetic formulation. The study objective was to improve the efficacy of a previously reported formulation comprising 10% bupivacaine in poly(DL:lactic acid co castor oil) 3:7. The polymer was loaded with 15% bupivacaine and injected through a 22G needle close to the sciatic nerve of ICR mice. Sensory and motor nerve blockade were measured. The efficacy and toxicity of the polymer-drug combination were determined. Sixty percent of the incorporated bupivacaine was released during 1 week in vitro. During in vitro release no burst effect was seen, suggesting low toxicity of the formulation. Single injection of 0.1 mL of 15% polymer-bupivacaine formulation caused motor block that lasted 64 h and sensory block that lasted 96 h. The MTD of the polymer-drug formulation was established as 0.175 mL. Microscopic examination of the injection sites revealed reversible nerve inflammation and normal internal organs. The polymer poly(DL:lactic acid co castor oil) 3:7 is a safe carrier for prolonged activity of bupivacaine up to 96 h. The increase of drug load in the formulation reduces the drug release rates due to stronger polymer-drug interactions and higher overall hydrophobicity of the formulation.

  7. Prolonged preoperative fasting in elective surgical patients: why should we reduce it?

    PubMed

    Pimenta, Gunther Peres; de Aguilar-Nascimento, José Eduardo

    2014-02-01

    Despite the abundance of evidence to the contrary, 6-8 hours of total preoperative fasting is still considered essential by many surgeons and anesthesiologists, based on the strength of old concepts. Patients frequently end up fasting for 12 hours or more because of delays and changes in operating room schedules. The metabolic response to long fasting leads to intensification of the organic response occurring after trauma, which is mainly manifested as increased insulin resistance, an acute-phase response, and loss of lean body mass. In fact, there has not been any evidence indicating that a shorter fast of 2-3 hours, which includes oral clear or carbohydrate (CHO)-rich (12.5% carbohydrates, 50 kcal/100 mL) fluids, results in an increased risk of aspiration, regurgitation, or related morbidity compared with the standard policy of "nil by mouth after midnight." In addition, preoperative treatment with CHO-rich fluids may reduce postoperative discomfort and, for patients undergoing major abdominal surgery, may decrease the duration of postoperative hospitalization. New formulas for preoperative oral fluids containing amino acid or protein such as glutamine or whey protein are also potential candidates for early preoperative treatment and merit further study.

  8. Prolonged High Fat Diet Reduces Dopamine Reuptake without Altering DAT Gene Expression

    PubMed Central

    Cone, Jackson J.; Chartoff, Elena H.; Potter, David N.; Ebner, Stephanie R.; Roitman, Mitchell F.

    2013-01-01

    The development of diet-induced obesity (DIO) can potently alter multiple aspects of dopamine signaling, including dopamine transporter (DAT) expression and dopamine reuptake. However, the time-course of diet-induced changes in DAT expression and function and whether such changes are dependent upon the development of DIO remains unresolved. Here, we fed rats a high (HFD) or low (LFD) fat diet for 2 or 6 weeks. Following diet exposure, rats were anesthetized with urethane and striatal DAT function was assessed by electrically stimulating the dopamine cell bodies in the ventral tegmental area (VTA) and recording resultant changes in dopamine concentration in the ventral striatum using fast-scan cyclic voltammetry. We also quantified the effect of HFD on membrane associated DAT in striatal cell fractions from a separate group of rats following exposure to the same diet protocol. Notably, none of our treatment groups differed in body weight. We found a deficit in the rate of dopamine reuptake in HFD rats relative to LFD rats after 6 but not 2 weeks of diet exposure. Additionally, the increase in evoked dopamine following a pharmacological challenge of cocaine was significantly attenuated in HFD relative to LFD rats. Western blot analysis revealed that there was no effect of diet on total DAT protein. However, 6 weeks of HFD exposure significantly reduced the 50 kDa DAT isoform in a synaptosomal membrane-associated fraction, but not in a fraction associated with recycling endosomes. Our data provide further evidence for diet-induced alterations in dopamine reuptake independent of changes in DAT production and demonstrates that such changes can manifest without the development of DIO. PMID:23516454

  9. Lean Six Sigma to Reduce Intensive Care Unit Length of Stay and Costs in Prolonged Mechanical Ventilation.

    PubMed

    Trzeciak, Stephen; Mercincavage, Michael; Angelini, Cory; Cogliano, William; Damuth, Emily; Roberts, Brian W; Zanotti, Sergio; Mazzarelli, Anthony J

    2016-11-29

    Patients with prolonged mechanical ventilation (PMV) represent important "outliers" of hospital length of stay (LOS) and costs (∼$26 billion annually in the United States). We tested the hypothesis that a Lean Six Sigma (LSS) approach for process improvement could reduce hospital LOS and the associated costs of care for patients with PMV. Before-and-after cohort study. Multidisciplinary intensive care unit (ICU) in an academic medical center. Adult patients admitted to the ICU and treated with PMV, as defined by diagnosis-related group (DRG). We implemented a clinical redesign intervention based on LSS principles. We identified eight distinct processes in preparing patients with PMV for post-acute care. Our clinical redesign included reengineering daily patient care rounds ("Lean ICU rounds") to reduce variation and waste in these processes. We compared hospital LOS and direct cost per case in patients with PMV before (2013) and after (2014) our LSS intervention. Among 259 patients with PMV (131 preintervention; 128 postintervention), median hospital LOS decreased by 24% during the intervention period (29 vs. 22 days, p < .001). Accordingly, median hospital direct cost per case decreased by 27% ($66,335 vs. $48,370, p < .001). We found that a LSS-based clinical redesign reduced hospital LOS and the costs of care for patients with PMV.

  10. Early start of combination therapy with hemodialysis and peritoneal dialysis prolongs survival and reduces cardiovascular events in male patients.

    PubMed

    Suzuki, Hiromichi; Hoshi, Hitosi; Inoue, Tsutomu; Kikuta, Tomohiro; Tsuda, Masahiro; Takenaka, Tsuneo

    2012-01-01

    Although peritoneal dialysis (PD) has been recommended for initial dialysis therapy, a larger proportion of patients with end-stage renal disease choose hemodialysis (HD) instead. Several previous studies comparing the outcomes of these two therapies, including survival rates and cardiovascular events, have not clearly demonstrated the superiority of one over the other. Our recent study indicated that, compared with HD or PD alone, renal replacement therapy with HD and PD in combination prolongs survival and reduces cardiovascular events. However, the use of combination dialysis therapy is not widely accepted. We set out to analyze the efficacy of combination dialysis therapy with PD and HD in patients who started with PD as initial dialysis therapy. Our single-center retrospective cohort study included 401 patients (165 women, 236 men; 61 +/- 12 and 62 +/- 9 years of age respectively) who started PD during 1995-2005. Chart and electronic databases were used to obtain information on the course of dialysis therapy, including mortality and cardiovascular events. Treatment with HD and PD in combination was used in 103 patients. During 5 years of follow-up after the start of PD, 80 patients died. We observed no differences in cumulative mortality between the men (49, 200%) and women (31, 18%) and no difference in the cumulative incidence of catheter removal for various reasons (35% vs. 31%). There was a significant difference (p < 0.05) in the time of HD start between men and women. In men on PD, HD therapy was started 22 +/- 2 months after the start of PD; in women, it was started 38 +/- 7 months after PD start. Although women have a survival advantage in both the general and the dialysis patient population, women on PD experience mortality similar to that in men. The reasons for those findings have not been fully explained. The present analysis suggests that an early start to HD therapy will prolong the survival of patients on PD, especially men.

  11. An e-health intervention designed to increase workday energy expenditure by reducing prolonged occupational sitting habits.

    PubMed

    Pedersen, Scott J; Cooley, Paul D; Mainsbridge, Casey

    2014-01-01

    Desk-based employees face multiple workplace health hazards such as insufficient physical activity and prolonged sitting. The objective of this study was to increase workday energy expenditure by interrupting prolonged occupational sitting time and introducing short-bursts of physical activity to employees' daily work habits. Over a 13-week period participants (n=17) in the intervention group were regularly exposed to a passive prompt delivered through their desktop computer that required them to stand up and engage in a short-burst of physical activity, while the control group (n=17) was not exposed to this intervention. Instead, the control group continued with their normal work routine. All participants completed a pre- and post- intervention survey to estimate workplace daily energy expenditure (calories). There was a significant 2 (Group) × 2 (Test) interaction, F (1, 32)=9.26, p < 0.05. The intervention group increased the calories expended during the workday from pre-test (M=866.29 ± 151.40) to post-test (M=1054.10 ± 393.24), whereas the control group decreased calories expended during the workday from pre-test (M=982.55 ± 315.66) to post-test (M=892.21 ± 255.36). An e-health intervention using a passive prompt was an effective mechanism for increasing employee work-related energy expenditure. Engaging employees in regular short-bursts of physical activity during the workday resulted in reduced sitting time, which may have long-term effects on the improvement of employee health.

  12. Prolonged vibration of the biceps brachii tendon reduces time to failure when maintaining arm position with a submaximal load.

    PubMed

    Mottram, Carol J; Maluf, Katrina S; Stephenson, Jennifer L; Anderson, Melissa K; Enoka, Roger M

    2006-02-01

    Vibration reduces the amplitudes of the tendon jerk response and the Hoffmann and stretch reflexes in the muscle exposed to the vibration, yet does not alter the time to task failure when the task involves exerting a submaximal force against a rigid restraint. Because the amplitude of the stretch reflex is greater when a limb acts against a compliant load than a rigid restraint, the purpose was to determine the influence of prolonged tendon vibration on the time to failure when maintaining limb position with the elbow flexor muscles. Twenty-five healthy men performed the fatiguing contraction by maintaining elbow angle at 1.57 rad until failure while supporting a load equal to 20% of maximal voluntary contraction (MVC) force. The fatiguing contraction was performed on 3 separate days with different levels of vibration applied to the biceps brachii tendon: no vibration, subthreshold for a tonic vibration reflex (TVR), and suprathreshold for a TVR. MVC force before the fatiguing contraction was similar across the three sessions (mean of 3 sessions: 313 +/- 54 N, P = 0.83). Despite a similar decline in MVC force after the fatiguing contraction across conditions (-18.0 +/- 8.0%, P > 0.05), the time to task failure was 3.7 +/- 1.4 min for the suprathreshold TVR condition, 4.3 +/- 2.1 min for the subthreshold TVR condition, and 5.0 +/- 2.2 min for the no-vibration condition (P < 0 0.001). The average EMG of the elbow flexor muscles was similar (P = 0.22) during the fatiguing contractions. However, the fluctuations in limb acceleration at task onset were greater for the suprathreshold TVR condition (P < 0.01), but were not different between the subthreshold TVR and no-vibration conditions (P > or = 0.22). Furthermore, the difference in the SD of limb acceleration between the no-vibration and vibration conditions was correlated with the difference in time to failure for the no-vibration and subthreshold TVR conditions (P = 0.03; r2 = 0.22), but not for the no-vibration and

  13. Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy.

    PubMed

    Kang, S H; Lee, Y B; Lee, J-H; Nam, J Y; Chang, Y; Cho, H; Yoo, J-J; Cho, Y Y; Cho, E J; Yu, S J; Kim, M Y; Kim, Y J; Baik, S K; Yoon, J-H

    2017-08-24

    Rifaximin might decrease the risk of portal hypertension-related complications by controlling small intestinal bacterial overgrowth. To evaluate whether rifaximin was associated with the risk of death and cirrhotic complications. We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non-HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding. In the non-HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio [aHR], 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile-associated diarrhoea was not different between the groups (aHR, 0.028; P = .338). In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy. © 2017 John Wiley & Sons Ltd.

  14. Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A Cost-Effectiveness Analysis.

    PubMed

    Poncet, Antoine; Gencer, Baris; Blondon, Marc; Gex-Fabry, Marianne; Combescure, Christophe; Shah, Dipen; Schwartz, Peter J; Besson, Marie; Girardin, François R

    2015-01-01

    Sudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT) is common in this population and predisposes to Torsades-de-Pointes (TdP) and subsequent mortality. To estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients. We built a decision analytic model based on a decision tree to evaluate the cost-effectiveness and utility of LQT screening from a health care perspective. LQT proportion parameters were derived from an in-hospital cross-sectional study. We performed experts' elicitation to estimate the risk of TdP, given extent of QT prolongation. A TdP reduction of 65% after LQT detection was based on positive drug dechallenge rate and through adequate treatment and electrolyte adjustments. The base-case model uncertainty was assessed with one-way and probabilistic sensitivity analyses. Finally, the TdP related mortality and TdP avoidance parameters were varied in a two-way sensitivity analysis to assess their effect on the Incremental Cost-Effectiveness Ratio (ICER). Costs, Quality Ajusted Life Year (QALY), ICER, and probability of cost effectiveness thresholds ($ 10,000, $25,000, and $50,000 per QALY). In the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498) per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50,000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT. In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion.

  15. CCK-58 prolongs the intermeal interval, whereas CCK-8 reduces this interval: not all forms of cholecystokinin have equal bioactivity.

    PubMed

    Sayegh, Ayman I; Washington, Martha C; Raboin, Shannon J; Aglan, Amnah H; Reeve, Joseph R

    2014-05-01

    It has been accepted for decades that "all forms of cholecystokinin (CCK) have equal bioactivity," despite accumulating evidence to the contrary. To challenge this concept, we compared two feeding responses, meal size (MS, 10% sucrose) and intermeal interval (IMI), in response to CCK-58, which is the major endocrine form of CCK, and CCK-8, which is the most abundantly utilized form. Doses (0, 0.1, 0.5, 0.75, 1, 3 and 5 nmol/kg) were administered intraperitoneally over a 210-min test to Sprague Dawley rats that had been food-deprived overnight. We found that (1) all doses of CCK-58, except the lowest dose, and all doses of CCK-8, except the lowest two doses, reduced food intake more than vehicle did; (2) at two doses, 0.75 and 3 nmol/kg, CCK-58 increased the IMI, while CCK-8 failed to alter this feeding response; and (3) CCK-58, at all but the lowest two doses, increased the satiety ratio (IMI between first and second meals (min) divided by first MS (ml)) relative to vehicle, while CCK-8 did not affect this value. These findings demonstrate that the only circulating form of CCK in rats, CCK-58, prolongs the IMI more than CCK-8, the peptide generally utilized in feeding studies. Taken together, these results add to a growing list of functions where CCK-8 and CCK-58 express qualitatively different bioactivities. In conclusion, the hypothesis that "all forms of cholecystokinin (CCK) have equal bioactivity" is not supported.

  16. Early heparin administration after traumatic brain injury: Prolonged cognitive recovery associated with reduced cerebral edema and neutrophil sequestration.

    PubMed

    Nagata, Katsuhiro; Browne, Kevin D; Suto, Yujin; Kumasaka, Kenichiro; Cognetti, John; Johnson, Victoria E; Marks, Joshua; Smith, Douglas H; Pascual, Jose L

    2017-09-01

    Early administration of unfractionated heparin (UFH) after traumatic brain injury (TBI) reduces early in vivo circulating leukocytes (LEUs) in peri-injury penumbral brain tissue, enhancing cognitive recovery 2 days after injury. It remains unclear how long this effect lasts and if this is related to persistently accumulating LEUs in penumbral brain tissue. We hypothesized that UFH reduces LEU brain tissue sequestration resulting in prolonged cognitive recovery. CD1 male mice underwent either TBI by controlled cortical impact (CCI) or sham craniotomy. Unfractionated heparin (75 or 225 U/kg) or vehicle was repeatedly administered after TBI. Neurologic function (Garcia Neurological Test [maximum score = 18]) and body weight loss ratios were evaluated at 24 hours to 96 hours after TBI. Brain and lung wet-to-dry ratios, hemoglobin levels, and brain LEU sequestration (Ly6G immunohistochemistry) were evaluated 96 hours postmortem. Analysis of variance with Bonferroni correction determined significance (p < 0.05). Compared with untreated CCI animals (24 hours, 14.7 ± 1.0; 48 hours, 15.5 ± 0.7; 72 hours, 15.0 ± 0.8; 96 hours, 16.5 ± 0.9), UFH75 (24 hours, 16.0 ± 1.0, p < 0.01; 48 hours, 16.5 ± 0.7, p < 0.05; 72 hours, 17.1 ± 0.6, p < 0.01; 96 hours, 17.4 ± 0.7, p < 0.05) increased cognitive recovery throughout the entire observation period after TBI. At 48 hours, UFH225 significantly worsened body weight loss (10.2 ± 4.7%) as compared with uninjured animals (5.5 ± 2.9%, p < 0.05). Both UFH75 (60.8 ± 40.9 PMNs per high-power field [HPF], p < 0.05) and UFH225 (36.0 ± 17.6 PMNs/HPF, p < 0.01) significantly decreased brain neutrophil sequestration found in untreated CCI animals (124.2 ± 44.1 PMNs/HPF) 96 hours after TBI. Compared with untreated CCI animals (78.8 ± 0.8%), UFH75 (77.3 ± 0.6%, p = 0.04) reduced cerebral edema to uninjured levels (77.4 ± 0.6%, p = 0.04 vs. CCI). Only UFH225 (10.6 ± 1.2 g/dL) resulted in lower hemoglobin than in uninjured animals

  17. Automatic notifications mediated by anesthesia information management systems reduce the frequency of prolonged gaps in blood pressure documentation.

    PubMed

    Ehrenfeld, Jesse M; Epstein, Richard H; Bader, Stephen; Kheterpal, Sachin; Sandberg, Warren S

    2011-08-01

    Arterial blood pressure (BP) measurement at least every 5 minutes is part of the American Society of Anesthesiologists' monitoring standard, but prolonged BP gaps in electronic anesthesia records have been noted. We undertook multicenter studies to determine the frequency of cases with at least 1 interval ≥10 minutes between successive BP measurements and then to ascertain whether educational feedback via an electronic, near real-time notification system alerting providers to the presence of such gaps would reduce their incidence. We evaluated 212,706 electronic anesthesia records from 3 large academic centers. We determined the fraction of cases with ≥10-minute BP monitoring gaps at baseline and did a root cause analysis to determine common causes for these lapses. We then designed and implemented automated systems at 2 of the hospitals to notify point-of-care providers immediately after such 10-minute gaps occurred and determined the subsequent impact of this feedback on BP gap incidence, compared with baseline. At Hospital A, the notification system reduced the incidence of cases with at least 1 BP gap (1.48%± 0.19% SD vs 0.79% ± 0.36% SD, P < 0.0001). At Hospital B, the gap incidence was not significantly altered when notification was provided after a 10-minute gap had already occurred (2.72% ± 0.60% SD vs 2.45% ± 0.48% SD, P = 0.27), but the incidence was reduced when such notification was provided after 6 minutes without a BP reading (2.72% ± 0.60% SD vs 1.54% ± 0.19% SD, P < 0.0001). At Hospital C, where notification was not implemented, the baseline rate of BP gaps was consistent across the preintervention and follow-up periods (7.03% ± 1.27% SD vs 7.13% ± 0.11% SD, P = 0.74). Although monitors disconnected during position change was the most common identifiable cause of BP gaps, reasons for the missing BP measurements were often not documented. During a week when the electronic charting system was temporarily inoperable, no BP gaps were noted

  18. Automatic Notifications Mediated by Anesthesia Information Management Systems Reduce the Frequency of Prolonged Gaps in Blood Pressure Documentation

    PubMed Central

    Ehrenfeld, Jesse M.; Epstein, Richard H.; Bader, Stephen; Kheterpal, Sachin; Sandberg, Warren S.

    2011-01-01

    Background Arterial blood pressure (BP) measurement at least every five minutes is part of the American Society of Anesthesiologists' (ASA) monitoring standard, but prolonged BP gaps in electronic anesthesia records have been noted. We undertook multicenter studies to determine the frequency of cases with at least one interval ≥ 10 minutes between successive BP measurements and then to ascertain if educational feedback via an electronic, near real-time notification system alerting providers to the presence of such gaps would reduce their incidence. Methods We evaluated 212,706 electronic anesthesia records from three large academic centers. We determined the fraction of cases with ≥ 10 minute BP monitoring gaps at baseline and did a root cause analysis to determine common causes for these lapses. We then designed and implemented automated systems at two of the hospitals to notify point-of-care providers immediately after such 10-minute gaps occurred and determined the subsequent impact of this feedback on BP gap incidence, compared to baseline. Results At Hospital A, the notification system reduced the incidence of cases with at least one BP gap (1.48% ± 0.19% SD vs 0.79% ± 0.36% SD, p<0.0001). At Hospital B, the gap incidence was not significantly altered when notification was provided after a 10-min gap had already occurred (2.72% ± 0.60% SD vs. 2.45% ± 0.48% SD, P=0.27), but the incidence was reduced when such notification was provided after 6 minutes without a BP reading (2.72% ± 0.60% SD vs 1.54% ± 0.19% SD, P<0.0001). At Hospital C, where notification was not implemented, the baseline rate of BP gaps was consistent across the preintervention and follow-up periods (7.03% ± 1.27% SD vs. 7.13% ± 0.11% SD, p=0.74). Although monitors disconnected during position change was the most common identifiable cause of BP gaps, reasons for the missing BPs were often not documented. During a week when the electronic charting system was temporarily inoperable, no

  19. Supratherapeutic international normalized ratio due to reduced vitamin K intake secondary to prolonged vomiting in a patient on warfarin.

    PubMed

    Reaves, Anne B; Clarke, Catherine J; Tillman, Emma M

    2013-06-01

    To report a case of prolonged vomiting during warfarin therapy, leading to an elevated international normalized ratio (INR). A 32-year-old female with a history of cyclic vomiting syndrome since early childhood and bilateral pulmonary emboli diagnosed 4 months prior to this acute event presented to the clinic for routine monitoring of warfarin therapy. The warfarin dose had been maintained at 35 mg/wk for 3½ months (INR 2-3.5), but it was increased to 37.5 mg/wk because the INR had trended down to the low goal range over the preceding month. At presentation, the patient reported a 15-day history of vomiting with minimal oral intake that required intravenous fluids to prevent dehydration. The INR was 4.7; warfarin was withheld, and oral vitamin K 5 mg as well as subcutaneous vitamin K 10 mg was administered the following day. The INR then decreased to 1.3. Therapy was transitioned to subcutaneous enoxaparin 1 mg/kg every 12 hours for the duration of the patient's anticoagulation therapy. Multiple reports have demonstrated malabsorption of warfarin and decreased INR response in the presence of underlying gastrointestinal disease. Despite a prolonged episode of cyclic vomiting syndrome, our patient had an elevated INR. In normal circumstances, warfarin is rapidly absorbed from the gastrointestinal tract and reaches maximum serum concentrations in approximately 90 minutes. Studies have shown that although the presence of food does not affect overall absorption of the medication, it can decrease the rate of absorption. Our patient was vomiting 20-30 minutes after oral dose administration. Because the patient was not consuming food, absorption of warfarin was potentially prompt, thus contributing to the elevated INR. The variability of vitamin K in the diet also can have significant impact on the response to warfarin. Our patient's INR had been stable while she consumed 3 servings each week of foods rich in vitamin K. This consumption was abruptly discontinued with the

  20. Brief Internet-based intervention reduces posttraumatic stress and prolonged grief in parents after the loss of a child during pregnancy: a randomized controlled trial.

    PubMed

    Kersting, Anette; Dölemeyer, Ruth; Steinig, Jana; Walter, Franziska; Kroker, Kristin; Baust, Katja; Wagner, Birgit

    2013-01-01

    The loss of a child during pregnancy causes significant psychological distress for many women and their partners, and may lead to long-lasting psychiatric disorders. Internet-based interventions using exposure techniques and cognitive restructuring have proved effective for posttraumatic stress disorder (PTSD) and prolonged grief. This study compared the effects of an Internet-based intervention for parents after prenatal loss with a waiting list condition (WLC). The Impact of Event Scale - Revised assessed symptoms of PTSD; the Inventory of Complicated Grief and the Brief Symptom Inventory assessed depression, anxiety, and general mental health. The 228 participants (92% female) were randomly allocated to a treatment group (TG; n = 115) or a WLC group (n = 113). The TG received a 5-week cognitive behavioral intervention including (1) self-confrontation, (2) cognitive restructuring, and (3) social sharing. The TG showed significantly reduced symptoms of posttraumatic stress, prolonged grief, depression, and anxiety relative to the WLC control group. Intention-to-treat analysis revealed treatment effects of between d = 0.84 and d = 1.02 for posttraumatic stress and prolonged grief from pre- to posttreatment time points. Further significant improvement in all symptoms of PTSD and prolonged grief was found from the posttreatment evaluation to the 12-month follow-up. The attrition rate of 14% was relatively low. The Internet-based intervention proved to be a feasible and cost-effective treatment, reducing symptoms of posttraumatic stress, grief, depression, anxiety, and general mental health after pregnancy loss. Low-threshold e-health interventions should be further evaluated and implemented routinely to improve psychological support after pregnancy loss. Copyright © 2013 S. Karger AG, Basel.

  1. Prolonged treatment with pramipexole promotes physical interaction of striatal dopamine D3 autoreceptors with dopamine transporters to reduce dopamine uptake.

    PubMed

    Castro-Hernández, Javier; Afonso-Oramas, Domingo; Cruz-Muros, Ignacio; Salas-Hernández, Josmar; Barroso-Chinea, Pedro; Moratalla, Rosario; Millan, Mark J; González-Hernández, Tomás

    2015-02-01

    The dopamine (DA) transporter (DAT), a membrane glycoprotein expressed in dopaminergic neurons, clears DA from extracellular space and is regulated by diverse presynaptic proteins like protein kinases, α-synuclein, D2 and D3 autoreceptors. DAT dysfunction is implicated in Parkinson's disease and depression, which are therapeutically treated by dopaminergic D2/D3 receptor (D2/D3R) agonists. It is, then, important to improve our understanding of interactions between D3R and DAT. We show that prolonged administration of pramipexole (0.1mg/kg/day, 6 to 21 days), a preferential D3R agonist, leads to a decrease in DA uptake in mouse striatum that reflects a reduction in DAT affinity for DA in the absence of any change in DAT density or subcellular distribution. The effect of pramipexole was absent in mice with genetically-deleted D3R (D3R(-/-)), yet unaffected in mice genetically deprived of D2R (D2R(-/-)). Pramipexole treatment induced a physical interaction between D3R and DAT, as assessed by co-immunoprecipitation and in situ proximity ligation assay. Furthermore, it promoted the formation of DAT dimers and DAT association with both D2R and α-synuclein, effects that were abolished in D3R(-/-) mice, yet unaffected in D2R(-/-) mice, indicating dependence upon D3R. Collectively, these data suggest that prolonged treatment with dopaminergic D3 agonists provokes a reduction in DA reuptake by dopaminergic neurons related to a hitherto-unsuspected modification of the DAT interactome. These observations provide novel insights into the long-term antiparkinson, antidepressant and additional clinical actions of pramipexole and other D3R agonists. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Does external pleural suction reduce prolonged air leak after lung resection? Results from the AirINTrial after 500 randomized cases.

    PubMed

    Leo, Francesco; Duranti, Leonardo; Girelli, Lara; Furia, Simone; Billè, Andrea; Garofalo, Giuseppe; Scanagatta, Paolo; Giovannetti, Riccardo; Pastorino, Ugo

    2013-10-01

    External pleural suction is used after lung resection to promote lung expansion and minimize air leak duration. Published randomized trials failed to prove this advantage but they are limited in number and underpowered in many cases. The aim of the AirINTrial study was to test the hypothesis that external pleural suction may reduce the rate of prolonged air leak in a large, randomized cohort. All candidates for lung resection (with the exception of pneumonectomy) were considered eligible for this single-center study. At the end of operation, patients were stratified by the type of resection (anatomic versus nonanatomic) and randomly allocated into the external suction arm (-15 cmH2O, group A) or into the no external suction arm (control arm, group B) in a 1:1 ratio. Chest drains were maintained for 3 days and then they were either removed or connected to an Heimlich valve, when an air leak was present. The main endpoint was to compare groups in terms of prolonged air leak (defined as the rate of patients having a chest drain still in place by postoperative day 7). Starting on February 2011, 500 patients were randomized over a 21-month period, 250 in group A and 250 in group B. Twenty-one patients in group B (8.4%) required pleural suction owing to large pneumothorax or diffuse subcutaneous emphysema. On postoperative day 7, the chest drain was still in place in 25 patients in group A and in 34 patients in group B (10% and 14%, respectively; p = 0.2). Subgroup analysis showed that external pleural suction reduced the prolonged air leak rate in the subgroup of patients who underwent anatomic resection (n = 296, 9.6% in group A and 16.8% in group B; p = 0.05). Results from the AirINTrial showed that the routine use of external suction reduces the rate of prolonged air leak after anatomic lung resection. More accurate strategies of pleural suction based on the amount of air flow and the degree of lung expansion should be probably established to improve its

  3. Nasal application of neuropeptide S reduces anxiety and prolongs memory in rats: social versus non-social effects.

    PubMed

    Lukas, Michael; Neumann, Inga D

    2012-01-01

    Recent studies demonstrated potent behavioral effects of centrally applied neuropeptide S (NPS) in mice and rats. These include increased arousal and wakefulness, facilitation of fear extinction and object memory consolidation and anxiolysis. Here, we compared the effects of NPS on both social and non-social memory, in male rats, and on social preference/social anxiety versus non-social anxiety after either intracerebroventricular (icv) or nasal application. Intranasal application of neuropeptides has been successfully employed to alter behavioral parameters in humans and rodents, but studies concerning nasal application of NPS are lacking so far. First, we confirmed the facilitatory effect of icv NPS (1 nmol) on object discrimination after an inter-exposure interval (IEI) of 240 min. These effects were context-dependent, as icv NPS (1 nmol) did not prolong social memory in a social discrimination paradigm. Second, we confirmed the anxiolytic effect of icv NPS (1 nmol) on the elevated plus-maze, whereas neither icv NPS (1 nmol) nor NPS receptor antagonist (10 nmol) altered social preference/social avoidance behavior. Third, nasal NPS (4-40 nmol applied topically on the rhinarium) facilitated object discrimination in a dose-dependent manner. Also, the anxiolytic effect of NPS on the elevated plus-maze could be confirmed after nasal administration (40 nmol). In contrast, identical doses of subcutaneously injected NPS failed to produce corresponding behavioral effects in both tests. Our findings provide evidence for memory-enhancing and anxiolytic effects of icv NPS in a non-social context. We could further show that these effects are context-specific, as social memory and social preference behavior remained unchanged after icv NPS. The effects of icv NPS were replicated by nasal application of the neuropeptide. Thus, nasal application of NPS seems to be a useful method in rodents for screening for behavioral or physiological effects before more specific and time

  4. Aldosterone-to-Renin Ratio Is Associated With Reduced 24-Hour Heart Rate Variability and QTc Prolongation in Hypertensive Patients.

    PubMed

    Grübler, Martin R; Kienreich, Katharina; Gaksch, Martin; Verheyen, Nicolas; Hartaigh, Bríain Ó; Fahrleitner-Pammer, Astrid; März, Winfried; Schmid, Johannes; Oberreither, Eva-Maria; Wetzel, Julia; Catena, Cristiana; Sechi, Leonardo A; Pieske, Burkert; Tomaschitz, Andreas; Pilz, Stefan

    2016-02-01

    Aldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. Both QT time and heart rate (HR) variability (HRV) are considered to be markers of arrhythmic risk and autonomous dysregulation. In this study, we investigated the associations between aldosterone, QT time, and HRV in patients with arterial hypertension.We recruited 477 hypertensive patients (age: 60.2 ± 10.2 years; 52.3% females) with a mean systolic/diastolic 24-hour ambulatory blood pressure monitoring (ABPM) value of 128 ± 12.8/77.1 ± 9.2 mmHg and with a median of 2 (IQR: 1-3) antihypertensive agents. Patients were recruited from the outpatient clinic at the Department of Internal Medicine of the Medical University of Graz, Austria. Blood samples, 24-hour HRV derived from 24-hour blood pressure monitoring (ABPM) and ECG's were obtained. Plasma aldosterone and plasma renin concentrations were measured by means of a radioimmunoassay. Twenty-four-hour urine specimens were collected in parallel with ABPM.Mean QTc was 423.3 ± 42.0 milliseconds for males and 434.7 ± 38.3 milliseconds for females. Mean 24H-HR and 24H-HRV was 71.9 ± 9.8 and 10.0 ± 3.6 bpm, respectively. In linear regression analyses adjusted for age, sex, body mass index, ABPM, and current medication, aldosterone to active renin ratio (AARR) was significantly associated with the QTc interval, a marker for cardiac repolarization abnormalities (mean = 426 ± 42.4 milliseconds; β-coefficient = 0.121; P = 0.03) as well as with the 24-hour heart rate variability a surrogate for autonomic dysfunction (median = 9.67 [IQR = 7.38-12.22 bpm]; β-coefficient = -0.133; P = 0.01).In hypertensive patients, AARR is significantly related to QTc prolongation as well as HRV. Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted.

  5. Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues

    PubMed Central

    Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Venditti, Paola

    2015-01-01

    We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. PMID:25874021

  6. PRAZOSIN REDUCES ALCOHOL DRINKING THROUGHOUT PROLONGED TREATMENT AND BLOCKS THE INITIATION OF DRINKING IN RATS SELECTIVELY BRED FOR HIGH ALCOHOL INTAKE

    PubMed Central

    Froehlich, Janice C; Hausauer, Brett J; Federoff, David L; Fischer, Stephen M; Rasmussen, Dennis D

    2013-01-01

    BACKGROUND This study examined whether prazosin reduces alcohol drinking over the course of prolonged treatment and whether it blocks initiation of alcohol drinking in rats with a genetic predisposition toward high alcohol drinking, i.e, alcohol-preferring (P) rats. METHODS In study one, alcohol-experienced P rats that had been drinking alcohol 2 hrs/day for several months were treated daily with prazosin (0, 0.5, 1.0 or 2.0 mg/kg BW) for 7 weeks. In study two, alcohol-naïve P rats were treated daily with prazosin (0, 1.0 or 2.0 mg/kg BW) for two weeks prior to, or concomitantly with, initiation of alcohol access and throughout 3 weeks of alcohol availability. Prazosin treatment and alcohol access were then discontinued for 2 weeks followed by reinstatement of alcohol access without prazosin treatment for 4 weeks, followed by resumption of daily prazosin treatment (2.0 mg/kg BW) for 3 weeks. RESULTS Prazosin reduced alcohol drinking throughout 7 weeks of treatment in P rats accustomed to drinking alcohol. Following termination of prazosin treatment, alcohol drinking slowly returned to pretreatment baseline. Reduced alcohol intake was accompanied by increased water intake. In alcohol-naïve P rats, prazosin administration prior to the first opportunity to drink alcohol and throughout 3 weeks of alcohol access retarded acquisition of alcohol drinking and reduced the amount of alcohol consumed. When prazosin was administered concomitantly with the first opportunity to drink alcohol, it abolished acquisition of alcohol drinking. Discontinuation of prazosin treatment allowed expression of a genetic predisposition toward high alcohol drinking to gradually emerge. Prazosin retained the ability to reduce alcohol intake with repeated treatments. CONCLUSIONS Prazosin decreased alcohol drinking during prolonged treatment and may be useful for treating alcoholism and alcohol use disorders. Prazosin may also be useful for deterring initiation of drinking in individuals with a

  7. Prolonged C2 spinal hemisection-induced inactivity reduces diaphragm muscle specific force with modest, selective atrophy of type IIx and/or IIb fibers.

    PubMed

    Mantilla, Carlos B; Greising, Sarah M; Zhan, Wen-Zhi; Seven, Yasin B; Sieck, Gary C

    2013-02-01

    The diaphragm muscle (DIAm) is critically responsible for sustaining ventilation. Previously we showed in a commonly used model of spinal cord injury, unilateral spinal cord hemisection at C(2) (SH), that there are minimal changes to muscle fiber cross-sectional area (CSA) and fiber type distribution following 14 days of SH-induced ipsilateral DIAm inactivity. In the present study, effects of long-term SH-induced inactivity on DIAm fiber size and force were examined. We hypothesized that prolonged inactivity would not result in substantial DIAm atrophy or force loss. Adult rats were randomized to control or SH groups (n = 34 total). Chronic bilateral DIAm electromyographic (EMG) activity was monitored during resting breathing. Minimal levels of spontaneous recovery of ipsilateral DIAm EMG activity were evident in 42% of SH rats (<25% of preinjury root mean square amplitude). Following 42 days of SH, DIAm specific force was reduced 39%. There was no difference in CSA for type I or IIa DIAm fibers in SH rats compared with age, weight-matched controls (classification based on myosin heavy chain isoform expression). Type IIx and/or IIb DIAm fibers displayed a modest 20% reduction in CSA (P < 0.05). Overall, there were no differences in the distribution of fiber types or the contribution of each fiber type to the total DIAm CSA. These data indicate that reduced specific force following prolonged inactivity of the DIAm is associated with modest, fiber type selective adaptations in muscle fiber size and fiber type distribution.

  8. Prolonged experimental drought reduces plant hydraulic conductance and transpiration and increases mortality in a piñon–juniper woodland

    DOE PAGES

    Pangle, Robert E.; Limousin, Jean -Marc; Plaut, Jennifer A.; ...

    2015-03-23

    Plant hydraulic conductance (ks) is a critical control on whole-plant water use and carbon uptake and, during drought, influences whether plants survive or die. To assess long-term physiological and hydraulic responses of mature trees to water availability, we manipulated ecosystem-scale water availability from 2007 to 2013 in a piñon pine (Pinus edulis) and juniper (Juniperus monosperma) woodland. We examined the relationship between ks and subsequent mortality using more than 5 years of physiological observations, and the subsequent impact of reduced hydraulic function and mortality on total woody canopy transpiration (EC) and conductance (GC). For both species, we observed significant reductionsmore » in plant transpiration (E) and ks under experimentally imposed drought. Conversely, supplemental water additions increased E and ks in both species. Interestingly, both species exhibited similar declines in ks under the imposed drought conditions, despite their differing stomatal responses and mortality patterns during drought. Reduced whole-plant ks also reduced carbon assimilation in both species, as leaf-level stomatal conductance (gs) and net photosynthesis (An) declined strongly with decreasing ks. Finally, we observed that chronically low whole-plant ks was associated with greater canopy dieback and mortality for both piñon and juniper and that subsequent reductions in woody canopy biomass due to mortality had a significant impact on both daily and annual canopy EC and GC. Our data indicate that significant reductions in ks precede drought-related tree mortality events in this system, and the consequence is a significant reduction in canopy gas exchange and carbon fixation. Our results suggest that reductions in productivity and woody plant cover in piñon–juniper woodlands can be expected due to reduced plant hydraulic conductance and increased mortality of both piñon pine and juniper under anticipated future conditions of more frequent and persistent

  9. Prolonged experimental drought reduces plant hydraulic conductance and transpiration and increases mortality in a piñon–juniper woodland

    PubMed Central

    Pangle, Robert E; Limousin, Jean-Marc; Plaut, Jennifer A; Yepez, Enrico A; Hudson, Patrick J; Boutz, Amanda L; Gehres, Nathan; Pockman, William T; McDowell, Nate G

    2015-01-01

    Plant hydraulic conductance (ks) is a critical control on whole-plant water use and carbon uptake and, during drought, influences whether plants survive or die. To assess long-term physiological and hydraulic responses of mature trees to water availability, we manipulated ecosystem-scale water availability from 2007 to 2013 in a piñon pine (Pinus edulis) and juniper (Juniperus monosperma) woodland. We examined the relationship between ks and subsequent mortality using more than 5 years of physiological observations, and the subsequent impact of reduced hydraulic function and mortality on total woody canopy transpiration (EC) and conductance (GC). For both species, we observed significant reductions in plant transpiration (E) and ks under experimentally imposed drought. Conversely, supplemental water additions increased E and ks in both species. Interestingly, both species exhibited similar declines in ks under the imposed drought conditions, despite their differing stomatal responses and mortality patterns during drought. Reduced whole-plant ks also reduced carbon assimilation in both species, as leaf-level stomatal conductance (gs) and net photosynthesis (An) declined strongly with decreasing ks. Finally, we observed that chronically low whole-plant ks was associated with greater canopy dieback and mortality for both piñon and juniper and that subsequent reductions in woody canopy biomass due to mortality had a significant impact on both daily and annual canopy EC and GC. Our data indicate that significant reductions in ks precede drought-related tree mortality events in this system, and the consequence is a significant reduction in canopy gas exchange and carbon fixation. Our results suggest that reductions in productivity and woody plant cover in piñon–juniper woodlands can be expected due to reduced plant hydraulic conductance and increased mortality of both piñon pine and juniper under anticipated future conditions of more frequent and persistent

  10. Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

    PubMed Central

    Chen, Hao; Zheng, Donghang; Abbott, Jeff; Liu, Liying; Bartee, Mee Y.; Long, Maureen; Davids, Jennifer; Williams, Jennifer; Feldmann, Heinz; Strong, James; Grau, Katrina R.; Tibbetts, Scott; Macaulay, Colin; McFadden, Grant; Thoburn, Robert; Lomas, David A.; Spinale, Francis G.; Virgin, Herbert W.

    2013-01-01

    Lethal viral infections produce widespread inflammation with vascular leak, clotting, and bleeding (disseminated intravascular coagulation [DIC]), organ failure, and high mortality. Serine proteases in clot-forming (thrombotic) and clot-dissolving (thrombolytic) cascades are activated by an inflammatory cytokine storm and also can induce systemic inflammation with loss of normal serine protease inhibitor (serpin) regulation. Myxomavirus secretes a potent anti-inflammatory serpin, Serp-1, that inhibits clotting factor X (fX) and thrombolytic tissue- and urokinase-type plasminogen activators (tPA and uPA) with anti-inflammatory activity in multiple animal models. Purified serpin significantly improved survival in a murine gammaherpesvirus 68 (MHV68) infection in gamma interferon receptor (IFN-γR) knockout mice, a model for lethal inflammatory vasculitis. Treatment of MHV68-infected mice with neuroserpin, a mammalian serpin that inhibits only tPA and uPA, was ineffective. Serp-1 reduced virus load, lung hemorrhage, and aortic, lung, and colon inflammation in MHV68-infected mice and also reduced virus load. Neuroserpin suppressed a wide range of immune spleen cell responses after MHV68 infection, while Serp-1 selectively increased CD11c+ splenocytes (macrophage and dendritic cells) and reduced CD11b+ tissue macrophages. Serp-1 altered gene expression for coagulation and inflammatory responses, whereas neuroserpin did not. Serp-1 treatment was assessed in a second viral infection, mouse-adapted Zaire ebolavirus in wild-type BALB/c mice, with improved survival and reduced tissue necrosis. In summary, treatment with this unique myxomavirus-derived serpin suppresses systemic serine protease and innate immune responses caused by unrelated lethal viral infections (both RNA and DNA viruses), providing a potential new therapeutic approach for treatment of lethal viral sepsis. PMID:23774438

  11. Prolonged experimental drought reduces plant hydraulic conductance and transpiration and increases mortality in a piñon-juniper woodland.

    PubMed

    Pangle, Robert E; Limousin, Jean-Marc; Plaut, Jennifer A; Yepez, Enrico A; Hudson, Patrick J; Boutz, Amanda L; Gehres, Nathan; Pockman, William T; McDowell, Nate G

    2015-04-01

    Plant hydraulic conductance (k s) is a critical control on whole-plant water use and carbon uptake and, during drought, influences whether plants survive or die. To assess long-term physiological and hydraulic responses of mature trees to water availability, we manipulated ecosystem-scale water availability from 2007 to 2013 in a piñon pine (Pinus edulis) and juniper (Juniperus monosperma) woodland. We examined the relationship between k s and subsequent mortality using more than 5 years of physiological observations, and the subsequent impact of reduced hydraulic function and mortality on total woody canopy transpiration (E C) and conductance (G C). For both species, we observed significant reductions in plant transpiration (E) and k s under experimentally imposed drought. Conversely, supplemental water additions increased E and k s in both species. Interestingly, both species exhibited similar declines in k s under the imposed drought conditions, despite their differing stomatal responses and mortality patterns during drought. Reduced whole-plant k s also reduced carbon assimilation in both species, as leaf-level stomatal conductance (g s) and net photosynthesis (A n) declined strongly with decreasing k s. Finally, we observed that chronically low whole-plant k s was associated with greater canopy dieback and mortality for both piñon and juniper and that subsequent reductions in woody canopy biomass due to mortality had a significant impact on both daily and annual canopy E C and G C. Our data indicate that significant reductions in k s precede drought-related tree mortality events in this system, and the consequence is a significant reduction in canopy gas exchange and carbon fixation. Our results suggest that reductions in productivity and woody plant cover in piñon-juniper woodlands can be expected due to reduced plant hydraulic conductance and increased mortality of both piñon pine and juniper under anticipated future conditions of more frequent and

  12. The role of nitric oxide synthase in reduced vasocontractile responsiveness induced by prolonged α1-adrenergic receptor stimulation in rat thoracic aorta

    PubMed Central

    Gürdal, Hakan; Can, Alp; Uğur, Mehmet

    2005-01-01

    Prolonged exposure (6–12 h) of rat aorta to alpha1-adrenergic receptor (α1AR) agonist phenylephrine (Phe) leads to a decrease in α1AR-mediated vasoconstriction. This reduced responsiveness to α1AR stimulation was strongly dependent on the intactness of the endothelium. We examined the effect of Phe on nitric oxide synthase (NOS) activity by measuring the conversion of [3H]L-arginine to [3H]L-citrulline in rat aorta or in endothelial cells isolated from rat aorta. Phe stimulation increased NOS activity in control aortas. This response was antagonized by prazosin. However, Phe increased neither the activity of NOS nor intracellular Ca2+ in the isolated endothelial cells from the control aortas, whereas acetylcholine (Ach) was able to stimulate both responses in these cells. This result suggests that Phe stimulates α1AR on vascular smooth muscle cells and has an indirect influence on endothelial cells to increase NOS activity. In Phe-exposed aortic rings, basal NOS activity was found to have increased compared to vehicle-exposed control rings. Stimulation with Phe or Ach caused a small increase over basal NOS activity in these preparations. Prolonged exposure to Phe also caused an enhancement of Ach-mediated vasorelaxation in rat aorta. Immunoblot and reverse transcription–polymerase chain reaction experiments showed that prolonged exposure of rat aorta to Phe resulted in an increased expression of eNOS, but not iNOS. This increase was antagonized by nonselective antagonist prazosin. Immunohistochemical staining experiments also showed that expression of eNOS increased in endothelial cells after Phe exposure of the aortas. These results, all together, showed that prolonged exposure of rat aorta to α1AR agonist Phe enhanced the expression of eNOS and basal NOS activity, which probably causes a decreased vasocontractile response to Phe or to other agonists such as 5HT (5-hydroxytryptamine) in rat aorta. This phenomenon can be considered more as a functional

  13. Dynamic Succession of Groundwater Sulfate-Reducing Communities during Prolonged Reduction of Uranium in a Contaminated Aquifer

    DOE PAGES

    Zhang, Ping; He, Zhili; Van Nostrand, Joy D.; ...

    2017-03-16

    To further understand the diversity and dynamics of SRB in response to substrate amendment, we sequenced genes coding for the dissimilatory sulfite reductase (dsrA) in groundwater samples collected after an emulsified vegetable oil (EVO) amendment, which sustained U(VI)-reducing conditions for one year in a fast-flowing aquifer. EVO amendment significantly altered the composition of groundwater SRB communities. Sequences having no closely related-described species dominated (80%) the indigenous SRB communities in nonamended wells. After EVO amendment, Desulfococcus, Desulfobacterium, and Desulfovibrio, known for long-chain-fatty-acid, short-chain-fatty-acid and H2 oxidation and U(VI) reduction, became dominant accounting for 7 ± 2%, 21 ± 8%, and 55more » ± 8% of the SRB communities, respectively. Succession of these SRB at different bioactivity stages based on redox substrates/products (acetate, SO4–2, U(VI), NO3–, Fe(II), and Mn(II)) was observed. Desulfovibrio and Desulfococcus dominated SRB communities at 4–31 days, whereas Desulfobacterium became dominant at 80–140 days. By the end of the experiment (day 269), the abundance of these SRB decreased but the overall diversity of groundwater SRB was still higher than non-EVO controls. Up to 62% of the SRB community changes could be explained by groundwater geochemical variables, including those redox substrates/products. A significant (P < 0.001) correlation was observed between groundwater U(VI) concentrations and Desulfovibrio abundance. Lastly, our results showed that the members of SRB and their dynamics were correlated significantly with slow EVO biodegradation, electron donor production and maintenance of U(VI)-reducing conditions in the aquifer.« less

  14. Dynamic Succession of Groundwater Sulfate-Reducing Communities during Prolonged Reduction of Uranium in a Contaminated Aquifer.

    PubMed

    Zhang, Ping; He, Zhili; Van Nostrand, Joy D; Qin, Yujia; Deng, Ye; Wu, Liyou; Tu, Qichao; Wang, Jianjun; Schadt, Christopher W; W Fields, Matthew; Hazen, Terry C; Arkin, Adam P; Stahl, David A; Zhou, Jizhong

    2017-04-04

    To further understand the diversity and dynamics of SRB in response to substrate amendment, we sequenced genes coding for the dissimilatory sulfite reductase (dsrA) in groundwater samples collected after an emulsified vegetable oil (EVO) amendment, which sustained U(VI)-reducing conditions for one year in a fast-flowing aquifer. EVO amendment significantly altered the composition of groundwater SRB communities. Sequences having no closely related-described species dominated (80%) the indigenous SRB communities in nonamended wells. After EVO amendment, Desulfococcus, Desulfobacterium, and Desulfovibrio, known for long-chain-fatty-acid, short-chain-fatty-acid and H2 oxidation and U(VI) reduction, became dominant accounting for 7 ± 2%, 21 ± 8%, and 55 ± 8% of the SRB communities, respectively. Succession of these SRB at different bioactivity stages based on redox substrates/products (acetate, SO4(-2), U(VI), NO3(-), Fe(II), and Mn(II)) was observed. Desulfovibrio and Desulfococcus dominated SRB communities at 4-31 days, whereas Desulfobacterium became dominant at 80-140 days. By the end of the experiment (day 269), the abundance of these SRB decreased but the overall diversity of groundwater SRB was still higher than non-EVO controls. Up to 62% of the SRB community changes could be explained by groundwater geochemical variables, including those redox substrates/products. A significant (P < 0.001) correlation was observed between groundwater U(VI) concentrations and Desulfovibrio abundance. Our results showed that the members of SRB and their dynamics were correlated significantly with slow EVO biodegradation, electron donor production and maintenance of U(VI)-reducing conditions in the aquifer.

  15. The Matrine Derivate MASM Prolongs Survival, Attenuates Inflammation, and Reduces Organ Injury in Murine Established Lethal Sepsis.

    PubMed

    Xu, Jing; Wang, Ke-Qi; Xu, Wei-Heng; Li, Ying-Hua; Qi, Yang; Wu, Hong-Yuan; Li, Jian-Zhong; He, Zhi-Gao; Hu, Hong-Gang; Wang, Yan; Zhang, Jun-Ping

    2016-12-01

     MASM, a novel derivative of matrine, has inhibitory effects on activation of macrophages, dendritic cells, and hepatic stellate cells and binds to ribosomal protein S5 (RPS5). This study was designed to evaluate the effect of MASM on murine-established lethal sepsis and its mechanisms.  Mouse peritoneal macrophages and RAW264.7 cells that were infected with recombinant lentiviruses encoding shRPS5 were incubated with lipopolysaccharide (LPS) in the absence or presence of MASM in vitro. Endotoxemia induced by LPS injection and sepsis induced by cecal ligation and puncture was followed by MASM treatment.  MASM markedly attenuated LPS-induced release and messenger RNA expression of tumor necrosis factor α, interleukin 6, and NO/inducible NO synthase in murine peritoneal macrophages and RAW264.7 cells. Meanwhile, MASM inhibited LPS-induced activation of nuclear factor κB and MAPK pathways. Consistently, RPS5 suppressed LPS-induced inflammatory responses and at least in part mediated the antiinflammatory effect of MASM in vitro. Remarkably, delayed administration of MASM could significantly reduce mortality in mouse sepsis models, which was associated with the reduction in the inflammatory response, the attenuation in multiple organ injury, and the enhanced bacterial clearance.  MASM could be further explored for the treatments of sepsis, especially for administration later after the onset of sepsis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Effects of prolonged and reduced warm-ups on diurnal variation in body temperature and swim performance.

    PubMed

    Arnett, Mark G

    2002-05-01

    Previous studies have suggested a diurnal variation in the performance of physical tasks. The theoretical basis for the effect of time-of-day on performance centers on the circadian rhythms of many physiological variables and especially the body temperature curve. This investigation had two purposes: (a) to determine if increasing the volume of the warm-up could eliminate diurnal variation in body temperature and swim performance, and (b) to determine if reduction of the warm-up volume in the late afternoon would affect body temperature and swim performance. Participants for this investigation included 6 male and 4 female competitive swimmers (mean age = 15 +/- 1 years). Before the swim performance trials in the morning, participants warmed up with either standard volume (2,011.68 m) or 200% of that volume. Before the afternoon swim performance trials, warm-up volumes were either 33% or 100% of the standard warm-up volume. Before entering the water and immediately after the warm-up, temperature was taken from the ear. After the swim performance, participants were asked to rate their perceived exertion on the basis of Borg's CR-10 rating scale. The order of test administration for time of day and warm-up condition was balanced and with tests carried out over 4 days. Each swimmer completed 1 test condition (warm-up) per day. Results indicated that increased morning warm-up time eliminated diurnal variation in body temperature; however, evening superiority in swimming performance was not eliminated. The results also indicated that reducing the volume of the afternoon warm-up to 33% of the standard warm-up had no effect on body temperature or swim performance.

  17. Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis

    PubMed Central

    Oguri, Masayoshi; Saito, Yoshiaki; Fukuda, Chisako; Kishi, Kazuko; Yokoyama, Atsushi; Lee, Sooyoung; Torisu, Hiroyuki; Toyoshima, Mitsuo; Sejima, Hitoshi; Kaji, Shunsaku; Hamano, Shin-ichiro; Okanishi, Toru; Tomita, Yutaka; Maegaki, Yoshihiro

    2016-01-01

    Background To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. Methods We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. Results Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. Conclusion Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD. PMID:27046946

  18. Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis.

    PubMed

    Oguri, Masayoshi; Saito, Yoshiaki; Fukuda, Chisako; Kishi, Kazuko; Yokoyama, Atsushi; Lee, Sooyoung; Torisu, Hiroyuki; Toyoshima, Mitsuo; Sejima, Hitoshi; Kaji, Shunsaku; Hamano, Shin-Ichiro; Okanishi, Toru; Tomita, Yutaka; Maegaki, Yoshihiro

    2016-03-01

    To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD.

  19. Conservation of body calcium by increased dietary intake of potassium: A potential measure to reduce the osteoporosis process during prolonged exposure to microgravity

    NASA Technical Reports Server (NTRS)

    Nechay, Bohdan R.

    1989-01-01

    During the 1988 NASA Summer Faculty Fellowship Program, it was proposed that the loss of skeletal calcium upon prolonged exposure to microgravity could be explained, in part, by a renal maladjustment characterized by an increased urinary excretion of calcium. It was theorized that because the conservation of body fluids and electrolytes depends upon the energy of adenosine triphosphate and enzymes that control the use of its energy for renal ion transport, an induction of renal sodium and potassium-dependent adenosine triphosphatase (Na + K ATPase) by oral loading with potassium would increase the reabsorption of sodium directly and that of calcium indirectly, leading to improved hydration and to reduced calcium loss. Preliminary studies showed the following. Rats drinking water containing 0.2 M potassium chloride for six to 13 days excreted in urine 22 muEq of calcium and 135 muEq of sodium per 100 grams of body weight per day. The corresponding values for control rats drinking tap water were 43 muEq and 269 muEq respectively. Renal Na + K ATPase activity in potassium loaded rats was higher than in controls. Thus, oral potassium loading resulted in increased Na + K ATPase activity and diminished urinary excretion of calcium and of sodium as predicted by the hypothesis. An extension of these studies to humans has the potential of resulting in development of harmless, non-invasive, drug-free, convenient measures to reduce bone loss and other electrolyte and fluid problems in space travelers exposed to prolonged periods of microgravity.

  20. A hip abduction exercise prior to prolonged standing increased movement while reducing cocontraction and low back pain perception in those initially reporting low back pain.

    PubMed

    Viggiani, Daniel; Callaghan, Jack P

    2016-12-01

    Persons who develop low back pain from prolonged standing exhibit increased muscle cocontraction, decreased movement and increased spine extension. However, it is unclear how these factors relate to pain development. The purpose of this study was to use hip abductor fatigue to manipulate muscle activity patterns and determine its effects on standing behaviours and pain development. Forty participants stood for two hours twice, once following a hip abductor fatigue exercise (fatigue), and once without exercise beforehand (control). Trunk and gluteal muscle activity were measured to determine cocontraction. Lumbo-pelvic angles and force plates were used to assess posture and movement strategies. Visual analog scales differentiated pain (PDs) and non-pain developers (NPDs). PDs reported less low back pain during the fatigue session, with females having earlier reductions of similar scale than males. The fatigue session reduced gluteal and trunk cocontraction and increased centre of pressure movement; male and female PDs had opposing spine posture compensations. Muscle fatigue prior to standing reduced cocontraction, increased movement during standing and reduced the low back pain developed by PDs; the timing of pain reductions depended on spine postures adopted during standing.

  1. Multifactorial Gene Therapy Enhancing the Glutamate Uptake System and Reducing Oxidative Stress Delays Symptom Onset and Prolongs Survival in the SOD1-G93A ALS Mouse Model.

    PubMed

    Benkler, Chen; Barhum, Yael; Ben-Zur, Tali; Offen, Daniel

    2016-01-01

    The 150-year-long search for treatments of amyotrophic lateral sclerosis (ALS) is still fueled by frustration over the shortcomings of available therapeutics. Contributing to the therapeutic limitations might be the targeting of a single aspect of this multifactorial-multisystemic disease. In an attempt to overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding: EAAT2, GDH2, and NRF2, that act synergistically to address the band and width of the effected excito-oxidative axis, reducing extracellular-glutamate and glutamate availability while improving the metabolic state and the anti-oxidant response. This strategy yielded particularly impressive results, as all three genes together but not separately prolonged survival in ALS mice by an average of 19-22 days. This was accompanied by improvement in every parameter evaluated, including body-weight loss, reflex score, neurologic score, and motor performance. We hope to provide a novel strategy to slow down disease progression and alleviate symptoms of patients suffering from ALS.

  2. Standard versus atrial fibrillation-specific management strategy (SAFETY) to reduce recurrent admission and prolong survival: pragmatic, multicentre, randomised controlled trial.

    PubMed

    Stewart, Simon; Ball, Jocasta; Horowitz, John D; Marwick, Thomas H; Mahadevan, Gnanadevan; Wong, Chiew; Abhayaratna, Walter P; Chan, Yih K; Esterman, Adrian; Thompson, David R; Scuffham, Paul A; Carrington, Melinda J

    2015-02-28

    Patients are increasingly being admitted with chronic atrial fibrillation, and disease-specific management might reduce recurrent admissions and prolong survival. However, evidence is scant to support the application of this therapeutic approach. We aimed to assess SAFETY--a management strategy that is specific to atrial fibrillation. We did a pragmatic, multicentre, randomised controlled trial in patients admitted with chronic, non-valvular atrial fibrillation (but not heart failure). Patients were recruited from three tertiary referral hospitals in Australia. 335 participants were randomly assigned by computer-generated schedule (stratified for rhythm or rate control) to either standard management (n=167) or the SAFETY intervention (n=168). Standard management consisted of routine primary care and hospital outpatient follow-up. The SAFETY intervention comprised a home visit and Holter monitoring 7-14 days after discharge by a cardiac nurse with prolonged follow-up and multidisciplinary support as needed. Clinical reviews were undertaken at 12 and 24 months (minimum follow-up). Coprimary outcomes were death or unplanned readmission (both all-cause), measured as event-free survival and the proportion of actual versus maximum days alive and out of hospital. Analyses were done on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTRN 12610000221055). During median follow-up of 905 days (IQR 773-1050), 49 people died and 987 unplanned admissions were recorded (totalling 5530 days in hospital). 127 (76%) patients assigned to the SAFETY intervention died or had an unplanned readmission (median event-free survival 183 days [IQR 116-409]) and 137 (82%) people allocated standard management achieved a coprimary outcome (199 days [116-249]; hazard ratio 0·97, 95% CI 0·76-1·23; p=0·851). Patients assigned to the SAFETY intervention had 99·5% maximum event-free days (95% CI 99·3-99·7), equating to a median

  3. Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model.

    PubMed

    Nodzo, Scott R; Tobias, Menachem; Ahn, Richard; Hansen, Lisa; Luke-Marshall, Nicole R; Howard, Craig; Wild, Linda; Campagnari, Anthony A; Ehrensberger, Mark T

    2016-07-01

    Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI; therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks); (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7); (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21); or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head

  4. Daily Oxygen/O₃ Treatment Reduces Muscular Fatigue and Improves Cardiac Performance in Rats Subjected to Prolonged High Intensity Physical Exercise.

    PubMed

    Di Filippo, C; Trotta, M C; Maisto, R; Siniscalco, D; Luongo, M; Mascolo, L; Alfano, R; Accardo, M; Rossi, C; Ferraraccio, F; D'Amico, M

    2015-01-01

    Rats receiving daily intraperitoneal administration of O2 and running on a treadmill covered an average distance of 482.8 ± 21.8 m/week as calculated during 5-week observation. This distance was increased in rats receiving daily intraperitoneal administration of an oxygen/O3 mixture at a dose of 100; 150; and 300 μg/kg with the maximum increase being +34.5% at 300 μg/kg and still present after stopping the administration of oxygen/O3. Oxygen/O3 decreased the mean arterial blood pressure (-13%), the heart rate (-6%), the gastrocnemius and cardiac hypertrophy, and fibrosis and reduced by 49% the left ventricular mass and relative wall thickness measurements. Systolic and diastolic functions were improved in exercised oxygen/O3 rats compared to O2 rats. Oxygen/O3 treatment led to higher MPI index starting from the dose of 150 μg/kg (p < 0.05) and more effective (+14%) at a dose of 300 μg/kg oxygen/O3. Oxygen/O3 dose-dependently increased the expression of the antioxidant enzymes Mn-SOD and GPx1 and of eNOS compared to the exercised O2 rats. The same doses resulted in decrease of LDH levels, CPK, TnI, and nitrotyrosine concentration in the heart and gastrocnemius tissues, arguing a beneficial effect of the ozone molecule against the fatigue induced by a prolonged high intensity exercise.

  5. P2X7 antagonism using Brilliant Blue G reduces body weight loss and prolongs survival in female SOD1G93A amyotrophic lateral sclerosis mice

    PubMed Central

    Bartlett, Rachael; Sluyter, Vanessa; Watson, Debbie

    2017-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterised by the accumulation of aggregated proteins, microglia activation and motor neuron loss. The mechanisms underlying neurodegeneration and disease progression in ALS are unknown, but the ATP-gated P2X7 receptor channel is implicated in this disease. Therefore, the current study aimed to examine P2X7 in the context of neurodegeneration, and investigate whether the P2X7 antagonist, Brilliant Blue G (BBG), could alter disease progression in a murine model of ALS. Methods Human SOD1G93A transgenic mice, which normally develop ALS, were injected with BBG or saline, three times per week, from pre-onset of clinical disease (62–64 days of age) until end-stage. During the course of treatment mice were assessed for weight, clinical score and survival, and motor coordination, which was assessed by rotarod performance. Various parameters from end-stage mice were assessed as follows. Motor neuron loss and microgliosis were assessed by immunohistochemistry. Relative amounts of lumbar spinal cord SOD1 and P2X7 were quantified by immunoblotting. Serum monocyte chemoattractant protein-1 was measured by ELISA. Splenic leukocyte populations were assessed by flow cytometry. Relative expression of splenic and hepatic P2X7 mRNA was measured by quantitative real-time PCR. Lumbar spinal cord SOD1 and P2X7 were also quantified by immunoblotting in untreated female SOD1G93A mice during the course of disease. Results BBG treatment reduced body weight loss in SOD1G93A mice of combined sex, but had no effect on clinical score, survival or motor coordination. BBG treatment reduced body weight loss in female, but not male, SOD1G93A mice. BBG treatment also prolonged survival in female, but not male, SOD1G93A mice, extending the mean survival time by 4.3% in female mice compared to female mice treated with saline. BBG treatment had no effect on clinical score or motor coordination in

  6. [Application of prolonged flow-aspiration drainage of laparotomy wounds in order to reduce suppurative septic complications in bowels reconstructive surgery].

    PubMed

    Shcherba, S N; Polovinkin, V V

    2014-01-01

    The article presents the follow-up study of 254 onco-proctologic patients after reconstructive abdominoperitoneal resections. Patients were divided into 4 statistically homogeneous groups (2 main and 2 control groups). A comparative analysis of middle and lateral laparotomy wounds healing was made. Laparotomy wounds were stitched up using conventional method (in layers, tightly) and using other method of prolonged flow-aspiration drainage of hypodermic tissue. Postoperative wound infections were noted in 11.4% patients in case of conventional means. The prolonged flow-aspiration drainage in laparotomy wounds causes only 1.5% of complications.

  7. Hyaluronidase inhibitors (sodium cromoglycate and sodium auro-thiomalate) reduce the local tissue damage and prolong the survival time of mice injected with Naja kaouthia and Calloselasma rhodostoma venoms.

    PubMed

    Yingprasertchai, Senee; Bunyasrisawat, Srisurat; Ratanabanangkoon, Kavi

    2003-11-01

    Experiments have been carried out to find potent inhibitors of hyaluronidases of Naja kaouthia (NK) and Calloselasma rhodostoma (CR) venoms with the aim of reducing local tissue damage and systemic toxicities caused by the venoms. Seven drugs/chemicals known to inhibit hyaluronidases were tested for their activity on venom enzymes. These were: sodium cromoglycate (SC), sodium aurothiomalate (SAT), apigenin, kaemferol, phenylbutazone, oxyphenbutazone and fenoprofen. The results showed that SC or SAT at 10 mM, completely inhibited the enzymes of both venoms. In in vivo experiments, SC or SAT, when incubated with NK venom prior to injection, significantly reduced edema and myonecrosis. In the case of CR venom, hemorrhage, in addition to edema and myonecrosis, was also significantly reduced. In the independent type experiment, SC or SAT were effective if injected within 1 min after the injection of venom. At longer time intervals of 3 and 10 min the inhibitors were effective in reducing some parameters of local tissue necrosis but the extent of inhibition was lower. SC and SAT at 256 and 195 microg/mouse, respectively, significantly prolonged the survival time of mice receiving lethal doses of NK. In the case of CR venoms, the two inhibitors not only prolonged the survival time but also prevented death of mice receiving lethal doses of the venom. The other inhibitors were poorly soluble in water and were studied only on enzyme inhibition and prolongation of survival time; they were mostly ineffective. Thus, SC and SAT when injected immediately at the sites of bites can reduce the systemic and local toxicity of NK and CR venoms. These results suggest that administration of these drugs at the site of venom injection may be useful in reducing venom-induced local tissue damage.

  8. Recombinant IL-33 prolongs leflunomide-mediated graft survival by reducing IFN-γ and expanding CD4(+)Foxp3(+) T cells in concordant heart transplantation.

    PubMed

    Dai, Chen; Lu, Fang-Na; Jin, Ning; Yang, Bo; Gao, Chang; Zhao, Bin; Fu, Jia-Zhao; Hong, Shi-Fu; Liang, Han-Ting; Chen, Li-Hong; Chen, Zhi-Shui; Chen, Jie; Qi, Zhong-Quan

    2016-08-01

    Interleukin (IL)-33 is a novel IL-1 family member, and its administration has been associated with promotion of T helper type-2 (Th2) cell activity and cytokines, particularly IL-4 and IL-5 in vivo. Recently, IL-33 was shown to increase CD4(+)Foxp3(+) regulatory T cells (Tregs) and to suppress levels of the Th1-type cytokine IFN-γ in allogeneic heart transplantation in mice. Therefore, we hypothesized that IL-33 and leflunomide (Lef) could prolong graft survival in the concordant mouse-to-rat heart transplantation model. In this model, xenografts undergo acute humoral xenograft rejection (AHXR) typically on day 3 or cell-mediated rejection approximately on day 7 if AHXR is inhibited by Lef treatment. Recipients were treated with Lef (n=6), IL-33 (n=6), IL-33 combined with Lef (n=6), or left untreated (n=6) for survival studies. Heart grafts were monitored until they stopped beating. Mouse heterotopic grafts were performed, and recipients were sacrificed on days 2 and 7 for histological and flow cytometric analyses. The combination of IL-33 and Lef significantly prolonged the grafts from 17.3±2.3 to 2.8±0.4 days, compared to untreated controls. IL-33 administration with Lef, while facilitating Th2-associated cytokines (IL-4 on day 2 but not day 7), also decreased IFN-γ on day 2 and day 7, compared with Lef treatment only. Furthermore, IL-33 with Lef administration caused an expansion of suppressive CD4(+)Foxp3(+) Tregs in rats. The IL-33 and Lef combination therapy resulted in significantly prolonged graft survival, associated with markedly decreased Th1 cells and increased IL-10 levels. In addition, the combination therapy significantly decreased the percentage of CD-45(+) B cells on days 2 and 7, compared with monotherapy. These findings reveal a new immunoregulatory property of IL-33. Specifically, it facilitates regulatory cells, particularly functional CD4(+)Foxp3(+) Tregs that underlie IL-33-mediated cardiac xenograft survival. Moreover, it can decrease Th

  9. Prolonged restraint stress increases IL-6, reduces IL-10, and causes persistent depressive-like behavior that is reversed by recombinant IL-10.

    PubMed

    Voorhees, Jeffrey L; Tarr, Andrew J; Wohleb, Eric S; Godbout, Jonathan P; Mo, Xiaokui; Sheridan, John F; Eubank, Timothy D; Marsh, Clay B

    2013-01-01

    Altered inflammatory cytokine profiles are often observed in individuals suffering from major depression. Recent clinical work reports on elevated IL-6 and decreased IL-10 in depression. Elevated IL-6 has served as a consistent biomarker of depression and IL-10 is proposed to influence depressive behavior through its ability to counterbalance pro-inflammatory cytokine expression. Clinical and animal studies suggest a role for IL-10 in modifying depressive behavior. Murine restraint stress (RST) is regularly employed in the study of behavioral and biological symptoms associated with depressive disorders. While responses to acute RST exposure have been widely characterized, few studies have examined the ongoing and longitudinal effects of extended RST and fewer still have examined the lasting impact during the post-stress period. Consistent with clinical data, we report that a protocol of prolonged murine RST produced altered cytokine profiles similar to those observed in major depressive disorder. Parallel to these changes in circulating cytokines, IL-10 mRNA expression was diminished in the cortex and hippocampus throughout the stress period and following cessation of RST. Moreover, chronic RST promoted depressive-like behavior throughout the 28-day stress period and these depressive-like complications were maintained weeks after cessation of RST. Because of the correlation between IL-10 suppression and depressive behavior and because many successful antidepressant therapies yield increases in IL-10, we examined the effects of IL-10 treatment on RST-induced behavioral changes. Behavioral deficits induced by RST were reversed by exogenous administration of recombinant IL-10. This work provides one of the first reports describing the biological and behavioral impact following prolonged RST and, taken together, this study provides details on the correlation between responses to chronic RST and those seen in depressive disorders.

  10. Melatonin produces a rapid onset and prolonged efficacy in reducing depression-like behaviors in adult rats exposed to chronic unpredictable mild stress.

    PubMed

    Sun, Xiaoran; Wang, Mengting; Wang, Yiqiang; Lian, Bo; Sun, Hongwei; Wang, Gang; Li, Qi; Sun, Lin

    2017-03-06

    The present study was aimed at evaluating the rapidity and duration of melatonin as an antidepressant in a rat model of depression. The rats were subjected to a six-week period of unpredictable mild stress followed by melatonin treatment. Three groups of rats were included in this study: Controls (CON - no stress exposure), Chronic Unpredictable Mild Stress (CUS) and CUS followed by melatonin (MT). Stressors consisted of exposure to rotation on a shaker, placement in a chamber maintained at 4°C, lights off for 3h, lights on overnight, exposure to an aversive odor, 45° tilted cages, food and water deprivation and crowding and isolated housing. Subsequently, the saline vehicle (CUS) or melatonin was administered at a dose of 10mg/kg for 14days period. Body weight and behavioral tests were used to evaluate depression-like behavior and its recovery following melatonin treatment. While body weight increases were significantly lower in rats exposed to CUS versus CON, body weights of the MT group increased significantly following melatonin treatment as compared with the CUS group. With regard to results obtained with behavioral assays indicative of depression, rapid and long-term functional recoveries in depression were observed in the MT as compared to the CUS group. The results indicate that not only does melatonin induce an antidepressant-like action within this rat model of depression, but does so with a rapid onset and prolonged efficacy. As most current treatments for depression require an extended period of administration, our current results suggest that melatonin may prove to be a particularly effect agent to promote a rapid onset and prolonged behavioral benefits in the treatment of depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants.

    PubMed

    Lin, Tsai-Ming; Tsai, Jin-Lian; Lin, Sin-Daw; Lai, Chung-Sheng; Chang, Chia-Cheng

    2005-02-01

    Human mesenchymal stem cells (MSCs) have been isolated from bone marrow and other adult tissues and are potentially useful for tissue engineering. Adipose tissue has several clear advantages as a starting material for harvesting stem cells, as it is abundant and relatively easy to procure. However, existing methods to expand adipose-derived MSCs are less than optimal. Here we describe a new cell culture method that accelerates greatly the growth rate and prolongs the lifespan of adipose MSCs. This was accomplished by using a growth medium with low calcium and supplemented with N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate. Cells produced early in these cultures displayed characteristics similar to those previously reported for multipotential stem cells, including a high frequency of anchorage- independent growth in soft agar, lack of gap junctional intercellular communication in a cell type with serpiginous morphology, and the expression of Oct-4. Furthermore, these cells could readily be induced to differentiate into adipocytes, osteoblasts, and chondrocytes. Thus, modification of growth medium by reduction of calcium and addition of antioxidants greatly enhanced the growth rate and extended the lifespan of adipose-derived multipotential human MSCs.

  12. Correction of low HDL cholesterol to reduce cardiovascular risk: practical considerations relating to the therapeutic use of prolonged-release nicotinic acid (Niaspan).

    PubMed

    Vogt, A; Kassner, U; Hostalek, U; Steinhagen-Thiessen, E

    2007-11-01

    Substantial residual cardiovascular risk persists despite effective LDL lowering treatment in populations at elevated risk for adverse cardiovascular outcomes. Low HDL cholesterol is an independent cardiovascular risk factor and occurs in about one-third of patients treated for dyslipidaemia in Europe. Moreover, randomised intervention studies have shown that increasing HDL cholesterol improves cardiovascular outcomes. Correcting low HDL cholesterol therefore presents a rational and proven strategy for intervention to produce further reductions in cardiovascular risk beyond those possible with a statin alone. Nicotinic acid (niacin in the USA) is the most effective agent currently available for increasing levels of HDL cholesterol. A once-daily, prolonged-release formulation of nicotinic acid (Niaspan) is as effective on HDL cholesterol as the immediate-release formulation, and is equally effective at increasing HDL cholesterol whether or not patients are already taking a statin. Niaspan also shares the antiatherogenic benefit of nicotinic acid, and induced regression of atherosclerosis in patients with cardiovascular disease during a period of treatment of up to 2 years. The incidence of flushing, the principal side effect of nicotinic acid, is lower with Niaspan than with immediate-release nicotinic acid. Simple practical measures are available to minimise the incidence and impact of flushing, including careful dose titration and avoiding hot or spicy foods near the time of ingestion of Niaspan. The potential for hepatotoxicity, muscle toxicity or marked exacerbation of hyperglycaemia in diabetes with Niaspan is very low, with or without concomitant statin treatment. Niaspan provides a practical means of delivering the cardioprotective benefits associated with correction of low HDL cholesterol.

  13. Decreased expression of the Ets family transcription factor Fli-1 markedly prolongs survival and significantly reduces renal disease in MRL/lpr mice.

    PubMed

    Zhang, Xian K; Gallant, Sarah; Molano, Ivan; Moussa, Omar M; Ruiz, Phillip; Spyropoulos, Demetri D; Watson, Dennis K; Gilkeson, Gary

    2004-11-15

    Increased Fli-1 mRNA is present in PBLs from systemic lupus erythematosus patients, and transgenic overexpression of Fli-1 in normal mice leads to a lupus-like disease. We report in this study that MRL/lpr mice, an animal model of systemic lupus erythematosus, have increased splenic expression of Fli-1 protein compared with BALB/c mice. Using mice with targeted gene disruption, we examined the effect of reduced Fli-1 expression on disease development in MRL/lpr mice. Complete knockout of Fli-1 is lethal in utero. Fli-1 protein expression in heterozygous MRL/lpr (Fli-1(+/-)) mice was reduced by 50% compared with wild-type MRL/lpr (Fli-1(+/+)) mice. Fli-1(+/-) MRL/lpr mice had significantly decreased serum levels of total IgG and anti-dsDNA Abs as disease progressed. Fli-1(+/-) MRL/lpr mice had significantly increased splenic CD8(+) and naive T cells compared with Fli-1(+/+) MRL/lpr mice. Both in vivo and in vitro production of MCP-1 were significantly decreased in Fli-1(+/-) MRL/lpr mice. The Fli-1(+/-) mice had markedly decreased proteinuria and significantly lower pathologic renal scores. At 48 wk of age, survival was significantly increased in the Fli-1(+/-) MRL/lpr mice, as 100% of Fli-1(+/-) MRL/lpr mice were alive, in contrast to only 27% of Fli-1(+/+) mice. These findings indicate that Fli-1 expression is important in lupus-like disease development, and that modulation of Fli-1 expression profoundly decreases renal disease and improves survival in MRL/lpr mice.

  14. Nonclassical export pathway: overexpression of NCE102 reduces protein and DNA damage and prolongs lifespan in an SGS1 deficient Saccharomyces cerevisiae.

    PubMed

    Desmyter, Liesbeth; Verstraelen, Jan; Dewaele, Sylviane; Libert, Claude; Contreras, Roland; Chen, Cuiying

    2007-10-01

    In this study, we used our recently developed screening method, Bud-Scar-based Screening (BSS), to screen a yeast cDNA expression library in an SGS1 deletion BY4742 yeast strain. One gene involved in a nonclassical export pathway, NCE102, was found to extend the life span of Deltasgs1 yeast. Deletion of NCE102 in a wild type yeast strain increased its sensitivity to oxidative stress upon diethylmaleate (DEM) treatment but did not shorten its lifespan, indicating that this gene is not essential in determining yeast lifespan. Transformation of NCE102 into either Deltance102 or Deltasgs1 strains could rescue its tolerance to DEM stress, indicating that NCE102 is protective during oxidative stress. Moreover, overexpression of NCE102 in Deltasgs1 strain leads to reduced protein damage. However, overexpression of NCE102 in wild type yeast strain BY4742 neither protected against oxidative stress due to DEM nor extended yeast lifespan compared to its parental wild type strain, indicating that nonclassical export is redundant and DNA repair is fully sufficient in the wild type strain. We therefore demonstrate that a nonclassical export pathway functions as an alternative clearance/detoxification pathway to eliminate damaged material, when the basic repair pathway is not sufficient.

  15. Prolonged shelf life and reduced drip loss of chicken filets by the use of carbon dioxide emitters and modified atmosphere packaging.

    PubMed

    Holck, Askild L; Pettersen, Marit K; Moen, Marie H; Sørheim, Oddvin

    2014-07-01

    Modified atmosphere packaging containing CO2 is widely used for extending the shelf life of chicken meat. Active packaging by adding CO2 emitter sachets to packages of meat is an alternative to traditional modified atmosphere packaging. The purpose of the study was to investigate the shelf life of chicken filets under different CO2 concentrations at 4°C storage. The inhibition of microbial growth was proportional to the CO2 concentration. Storage in 100% CO2 both with and without a CO2 emitter sachet gave a microbiological shelf-life extension of 7 days compared with 60% CO2. Carnobacterium divergens, Carnobacterium sp., and Lactococcus sp. were the dominating species at the end of the storage period. During storage in pure CO2, the carbon dioxide dissolved in the meat and caused the collapse of the packages. The resulting squeeze of the meat lead to a severe increase in drip loss. The drip loss was reduced profoundly by using the CO2 emitting sachet in the packages. The addition of CO2 emitters can easily be implemented at industrial packaging lines without reduction in production efficiency.

  16. GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease.

    PubMed

    Oksenberg, Donna; Dufu, Kobina; Patel, Mira P; Chuang, Chihyuan; Li, Zhe; Xu, Qing; Silva-Garcia, Abel; Zhou, Chengjing; Hutchaleelaha, Athiwat; Patskovska, Larysa; Patskovsky, Yury; Almo, Steven C; Sinha, Uma; Metcalf, Brian W; Archer, David R

    2016-10-01

    A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and destruction of red blood cells (RBCs) and end-organ damage. Pharmacologically increasing the proportion of oxygenated HbS in RBCs may inhibit polymerization, prevent sickling and provide long term disease modification. We report that GBT440, a small molecule which binds to the N-terminal α chain of Hb, increases HbS affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of RBCs. Moreover, in a murine model of SCD, GBT440 extends the half-life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. Thus, GBT440 has the potential for clinical use as a disease-modifying agent in sickle cell patients. © 2016 John Wiley & Sons Ltd.

  17. Human muscle net K(+) release during exercise is unaffected by elevated anaerobic metabolism, but reduced after prolonged acclimatization to 4,100 m.

    PubMed

    Nordsborg, Nikolai B; Calbet, José A L; Sander, Mikael; van Hall, Gerrit; Juel, Carsten; Saltin, Bengt; Lundby, Carsten

    2010-07-01

    It was investigated whether skeletal muscle K(+) release is linked to the degree of anaerobic energy production. Six subjects performed an incremental bicycle exercise test in normoxic and hypoxic conditions prior to and after 2 and 8 wk of acclimatization to 4,100 m. The highest workload completed by all subjects in all trials was 260 W. With acute hypoxic exposure prior to acclimatization, venous plasma [K(+)] was lower (P < 0.05) in normoxia (4.9 +/- 0.1 mM) than hypoxia (5.2 +/- 0.2 mM) at 260 W, but similar at exhaustion, which occurred at 400 +/- 9 W and 307 +/- 7 W (P < 0.05), respectively. At the same absolute exercise intensity, leg net K(+) release was unaffected by hypoxic exposure independent of acclimatization. After 8 wk of acclimatization, no difference existed in venous plasma [K(+)] between the normoxic and hypoxic trial, either at submaximal intensities or at exhaustion (360 +/- 14 W vs. 313 +/- 8 W; P < 0.05). At the same absolute exercise intensity, leg net K(+) release was less (P < 0.001) than prior to acclimatization and reached negative values in both hypoxic and normoxic conditions after acclimatization. Moreover, the reduction in plasma volume during exercise relative to rest was less (P < 0.01) in normoxic than hypoxic conditions, irrespective of the degree of acclimatization (at 260 W prior to acclimatization: -4.9 +/- 0.8% in normoxia and -10.0 +/- 0.4% in hypoxia). It is concluded that leg net K(+) release is unrelated to anaerobic energy production and that acclimatization reduces leg net K(+) release during exercise.

  18. Children and youth do not compensate for an imposed bout of prolonged sitting by reducing subsequent food intake or increasing physical activity levels: a randomised cross-over study.

    PubMed

    Saunders, Travis J; Chaput, Jean-Philippe; Goldfield, Gary S; Colley, Rachel C; Kenny, Glen P; Doucet, Eric; Tremblay, Mark S

    2014-02-01

    The behavioural impact of an imposed bout of prolonged sitting is yet to be investigated in the paediatric population. The objective of the present study was to determine the acute effect of prolonged sitting on ad libitum food intake and spontaneous physical activity (PA) levels in healthy children and youth. A total of twenty healthy youth (twelve males and eight females) aged 10-14 years, with a mean BMI of 18·6 (sd 4·3) kg/m², were exposed to three experimental conditions in a random order: (1) a day of uninterrupted sitting (Sedentary); (2) a day of sitting interrupted with a 2 min light-intensity walk break every 20 min (Breaks); (3) a day of sitting interrupted with a 2 min light-intensity walk break every 20 min as well as 2 × 20 min of moderate-intensity PA (Breaks+PA). Food intake (ad libitum buffet meal) and PA (accelerometry for 24 h) were assessed following exposure to each experimental condition. Despite significant differences in sedentary behaviour and activity levels during the three in-laboratory sessions (all P< 0·01), we did not observe any differences in ad libitum food intake immediately following exposure to each experimental condition or any changes in the levels of sedentary behaviour or PA in the 24 h following exposure to each experimental condition (all P>0·25). These findings suggest that children and youth may not compensate for an imposed bout of sedentary behaviour by reducing subsequent food intake or increasing PA levels.

  19. Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

    PubMed Central

    Fekete, Éva M; Inoue, Koki; Zhao, Yu; Rivier, Jean E; Vale, Wylie W; Szücs, Attila; Koob, George F; Zorrilla, Eric P

    2009-01-01

    Brain corticotropin-releasing factor/urocortin (CRF/Ucn) systems are hypothesized to control feeding, with central administration of ‘type 2’ urocortins producing delayed anorexia. The present study sought to identify the receptor subtype, brain site, and behavioral mode of action through which Ucn 3 reduces nocturnal food intake in rats. Non-food-deprived male Wistar rats (n = 176) were administered Ucn 3 into the lateral (LV) or fourth ventricle, or into the ventromedial or paraventricular nuclei of the hypothalamus (VMN, PVN) or the medial amygdala (MeA), regions in which Ucn 3 is expressed in proximity to CRF2 receptors. LV Ucn 3 suppressed ingestion during the third–fourth post-injection hours. LV Ucn 3 anorexia was reversed by cotreatment with astressin2-B, a selective CRF2 antagonist and not observed following equimole subcutaneous or fourth ventricle administration. Bilateral intra-VMN and intra-PVN infusion, more potently than LV infusion, reduced the quantity (57–73%) and duration of ingestion (32–68%) during the third–fourth post-infusion hours. LV, intra-PVN and intra-VMN infusion of Ucn 3 slowed the eating rate and reduced intake by prolonging the post-meal interval. Intra-VMN Ucn 3 reduced feeding bout size, and intra-PVN Ucn 3 reduced the regularity of eating from pellet to pellet. Ucn 3 effects were behaviorally specific, because minimal effective anorectic Ucn 3 doses did not alter drinking rate or promote a conditioned taste aversion, and site-specific, because intra-MeA Ucn 3 produced a nibbling pattern of more, but smaller meals without altering total intake. The results implicate the VMN and PVN of the hypothalamus as sites for Ucn 3-CRF2 control of food intake. PMID:17019404

  20. Antimicrobials and QT prolongation.

    PubMed

    Mason, Jay W

    2017-05-01

    Solithromycin, a ketolide/macrolide antibiotic, has recently been reported to be free of the expected QT-prolonging effect of macrolides. It appears that its keto substitution provides a structural basis for this observation, as the other two tested ketolides also have minimal QT effect.Among non-cardiovascular therapies, antimicrobials probably carry the greatest potential to cause cardiac arrhythmias. This is a result of their propensity to bind to the delayed rectifier potassium channel, IKr, inducing QT prolongation and risk of torsades de pointes ventricular tachycardia, their frequent interference with the metabolism of other QT prolongers and their susceptibility to metabolic inhibition by numerous commonly used drugs.Unfortunately, there is evidence that medical practitioners do not take account of the QT/arrhythmia risk of antimicrobials in their prescribing practices. Education on this topic is sorely needed. When a macrolide is indicated, a ketolide should be considered in patients with a QT risk. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Survival in a rat model of lethal hemorrhagic shock is prolonged following resuscitation with a small volume of a solution containing a drag-reducing polymer derived from aloe vera.

    PubMed

    Macias, Carlos A; Kameneva, Marina V; Tenhunen, Jyrki J; Puyana, Juan-Carlos; Fink, Mitchell P

    2004-08-01

    Drag-reducing polymers (DRP) increase tissue perfusion at constant driving pressure. We sought to evaluate the effects of small-volume resuscitation with a solution containing a DRP in a rat model of hemorrhage. Anesthetized rats were hemorrhaged at a constant rate over 25 min. In protocol A, total blood loss was 2.45 mL/100 g, whereas in protocol B, total blood loss was 3.15 mL/100 g. Five minutes after hemorrhage, the animals were resuscitated with 7 mL/kg of either normal saline (NS) or NS containing 50 microg/mL of an aloe vera-derived DRP. In protocol B, a third group (CON) was not resuscitated. Whole-body O2 consumption (Vo2) and CO2 production (Vco2) were measured using indirect calorimetry. In protocol A, 5/10 rats in the NS group and 8/10 rats in the DRP group survived for 4 h (P = 0.14). Mean arterial pressure was higher in the DRP-treated group than in the NS-treated group 45 min after resuscitation (89 +/- 8 vs. 68 +/- 5 mmHg, respectively; P < 0.05). In protocol B, survival rates over 2 h in the DRP, NS, and CON groups were 5/15, 1/14, and 0/7, respectively (P < 0.05). Compared with NS-treated rats, those resuscitated with DRP achieved a higher peak Vo2 (9.0 +/- 1.0 vs. 6,3+/- 1.0 mL/kg/min) and Vco2 (9.0 +/- 1.1 vs. 6.0 +/- 1.0 mL/kg/min) after resuscitation. We conclude that resuscitation with a small volume of DRP prolongs survival in rats with lethal hemorrhagic shock.

  2. IMC-EB10, an anti-FLT3 monoclonal antibody, prolongs survival and reduces nonobese diabetic/severe combined immunodeficient engraftment of some acute lymphoblastic leukemia cell lines and primary leukemic samples.

    PubMed

    Piloto, Obdulio; Nguyen, Bao; Huso, David; Kim, Kyu-Tae; Li, Yiwen; Witte, Larry; Hicklin, Daniel J; Brown, Patrick; Small, Donald

    2006-05-01

    The class III receptor tyrosine kinase FLT3 is expressed on the blasts of >90% of patients with B-lineage acute lymphoblastic leukemias (ALL). In addition, it is expressed at extremely high levels in ALL patients with mixed lineage leukemia rearrangements or hyperdiploidy and is sometimes mutated in these same patients. In this report, we investigate the effects of treating ALL cell lines and primary samples with human anti-FLT3 monoclonal antibodies (mAb) capable of preventing binding of FLT3 ligand. In vitro studies, examining the ability of two anti-FLT3 mAbs (IMC-EB10 and IMC-NC7) to affect FLT3 activation and downstream signaling in ALL cell lines and primary blasts, yielded variable results. FLT3 phosphorylation was consistently inhibited by IMC-NC7 treatment, but in some cell lines, IMC-EB10 actually stimulated FLT3 activation, possibly as a result of antibody-mediated receptor dimerization. Through antibody-dependent, cell-mediated cytotoxicity, such an antibody could still prove efficacious against leukemia cells in vivo. In fact, IMC-EB10 treatment significantly prolonged survival and/or reduced engraftment of several ALL cell lines and primary ALL samples in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This occurred even when IMC-EB10 treatment resulted in FLT3 activation in vitro. Moreover, fluorescence-activated cell sorting and PCR analysis of IMC-EB10-treated NOD/SCID mice surviving 150 days post-leukemic cell injection revealed that FLT3 immunotherapy reduced leukemic engraftment below the level of detection in these assays (<0.001%). Furthermore, in vivo IMC-EB10 treatment did not select for resistant cells, because cells surviving IMC-EB10 treatment remain sensitive to IMC-EB10 cytotoxicity upon retransplantation. In vivo studies involving either partial depletion or activation of natural killer (NK) cells show that most of the cytotoxic effect of IMC-EB10 is mediated through NK cells. Therefore, such an antibody, either

  3. Deciding about treatments that prolong life

    MedlinePlus

    Palliative care - treatments that prolong life; Palliative care - life support; End-of-life-treatments that prolong life; Ventilator - treatments that prolong life; Respirator - treatments that prolong life; Life-support - ...

  4. Familial qt prolongation and risk of sudden death.

    PubMed

    Furberg, C; Hörnell, H

    1975-09-01

    Two sisters with the syndrome of familial QT prolongation in the ECG and syncope are presented. A recently suggested mechanism of the syndrome is presented and preventive measures to reduce the risk of sudden death associated with it are proposed.

  5. Prolonged chewing at lunch decreases later snack intake.

    PubMed

    Higgs, Suzanne; Jones, Alison

    2013-03-01

    Prolonged chewing of food can reduce meal intake. However, whether prolonged chewing influences intake at a subsequent eating occasion is unknown. We hypothesised that chewing each mouthful for 30s would reduce afternoon snack intake more than (a) an habitual chewing control condition, and (b) an habitual chewing condition with a pauses in between each mouthful to equate the meal durations. We further hypothesised that this effect may be related to effects of prolonged chewing on lunch memory. Forty three participants ate a fixed lunch of sandwiches in the laboratory. They were randomly allocated to one of the three experimental groups according to a between-subjects design. Appetite, mood and lunch enjoyment ratings were taken before and after lunch and before snacking. Snack intake of candies at a taste test 2h after lunch was measured as well as rated vividness of lunch memory. Participants in the prolonged chewing group ate significantly fewer candies than participants in the habitual chewing group. Snack intake by the pauses group did not differ from either the prolonged or habitual chewing groups. Participants in the prolonged chewing group were less happy and enjoyed their lunch significantly less than participants in other conditions. Appetite ratings were not different across groups. Rated vividness of lunch memory was negatively correlated with intake but there was no correlation with rated lunch enjoyment. Prolonged chewing of a meal can reduce later snack intake and further investigation of this technique for appetite control is warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Acute prolongation of myocardial refractoriness by sotalol.

    PubMed Central

    Bennett, D H

    1982-01-01

    Sotalol, a beta adrenoceptor antagonist, was given intravenously to 15 patients with accessory atrioventricular pathways during intracardiac electrophysiological studies. Eleven patients had the Wolff-Parkinson-White syndrome and four patients had concealed left sided accessory pathways. Four patients were restudied while receiving oral sotalol. In contrast to the actions typical of beta blocking agents, intravenous sotalol prolonged the effective refractory periods of the ventricles and accessory pathways and reduced the ventricular response to atrial fibrillation in the patients with the Wolff-Parkinson-White syndrome. Similar results were obtained with oral administration. These findings support the observation that sotalol, unlike other beta blocking agents. causes acute prolongation of the myocardial action potential and suggest that this action might be of therapeutic use. PMID:7082500

  7. Brain glycogen decreases during prolonged exercise

    PubMed Central

    Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2011-01-01

    Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

  8. Physiology Of Prolonged Bed Rest

    NASA Technical Reports Server (NTRS)

    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.

  9. Physiology Of Prolonged Bed Rest

    NASA Technical Reports Server (NTRS)

    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.

  10. Inhibition in Prolonged Work Tasks.

    ERIC Educational Resources Information Center

    van der Ven, A. H. G. S.; And Others

    1989-01-01

    A new model is presented that explains reaction time fluctuations in prolonged work tasks. The model extends the so-called Poisson-Erlang model and accounts for long-term trend effects in the reaction time curve. The model is consistent with Spearman's hypothesis that inhibition increases during work and decreases during rest. (TJH)

  11. A multicentre randomized controlled trial of gentle assisted pushing in the upright posture (GAP) or upright posture alone compared with routine practice to reduce prolonged second stage of labour (the Gentle Assisted Pushing study): study protocol.

    PubMed

    Hofmeyr, G Justus; Singata, Mandisa; Lawrie, Theresa; Vogel, Joshua P; Landoulsi, Sihem; Seuc, Armando H; Gülmezoglu, A Metin

    2015-12-16

    Fundal pressure (pushing on the upper part of the uterus in the direction of the birth canal) is often performed in routine practice, however the benefit and indications for its use are unclear and vigorous pressure is potentially harmful. There is some evidence that it may be applied routinely or to expedite delivery in some situations (e.g. fetal distress or maternal exhaustion), particularly in settings where other methods of achieving delivery (forceps, vacuum) are not available. Gentle assisted pushing (GAP) is an innovative method of applying gentle but steady pressure to the uterine fundus with the woman in an upright posture. This trial aims to evaluate the use of GAP in an upright posture, or upright posture alone, on reducing the mean time of delivery and the associated maternal and neonatal complications in women not having delivered following 15-30 min in the second stage of labour. We will conduct a multicentre, randomized, unblinded, controlled trial with three parallel arms (1:1:1). 1,145 women will be randomized at three hospitals in South Africa. Women will be eligible for inclusion if they are ≥18 years old, nulliparous, gestational age ≥ 35 weeks, have a singleton pregnancy in cephalic presentation and vaginal delivery anticipated. Women with chronic medical conditions or obstetric complications are not eligible. If eligible women are undelivered following 15-30 min in the second stage of labour, they will be randomly assigned to: 1) GAP in the upright posture, 2) upright posture only and 3) routine practice (recumbent/supine posture). The primary outcome is the mean time from randomization to complete delivery. Secondary outcomes include operative delivery, adverse neonatal outcomes, maternal adverse events and discomfort. This trial will establish whether upright posture and/or a controlled method of applying fundal pressure (GAP) can improve labour outcomes for women and their babies. If fundal pressure is found to have a measurable

  12. Prolonged energy harvesting for ingestible devices

    PubMed Central

    Nadeau, Phillip; El-Damak, Dina; Glettig, Dean; Kong, Yong Lin; Mo, Stacy; Cleveland, Cody; Booth, Lucas; Roxhed, Niclas; Langer, Robert; Chandrakasan, Anantha P.; Traverso, Giovanni

    2016-01-01

    Ingestible electronics have revolutionized the standard of care for a variety of health conditions. Extending the capacity and safety of these devices, and reducing the costs of powering them, could enable broad deployment of prolonged monitoring systems for patients. Although prior biocompatible power harvesting systems for in vivo use have demonstrated short minute-long bursts of power from the stomach, not much is known about the capacity to power electronics in the longer term and throughout the gastrointestinal tract. Here, we report the design and operation of an energy-harvesting galvanic cell for continuous in vivo temperature sensing and wireless communication. The device delivered an average power of 0.23 μW per mm2 of electrode area for an average of 6.1 days of temperature measurements in the gastrointestinal tract of pigs. This power-harvesting cell has the capacity to provide power for prolonged periods of time to the next generation of ingestible electronic devices located in the gastrointestinal tract. PMID:28458955

  13. Prolonged energy harvesting for ingestible devices.

    PubMed

    Nadeau, Phillip; El-Damak, Dina; Glettig, Dean; Kong, Yong Lin; Mo, Stacy; Cleveland, Cody; Booth, Lucas; Roxhed, Niclas; Langer, Robert; Chandrakasan, Anantha P; Traverso, Giovanni

    2017-01-01

    Ingestible electronics have revolutionized the standard of care for a variety of health conditions. Extending the capacity and safety of these devices, and reducing the costs of powering them, could enable broad deployment of prolonged monitoring systems for patients. Although prior biocompatible power harvesting systems for in vivo use have demonstrated short minute-long bursts of power from the stomach, not much is known about the capacity to power electronics in the longer term and throughout the gastrointestinal tract. Here, we report the design and operation of an energy-harvesting galvanic cell for continuous in vivo temperature sensing and wireless communication. The device delivered an average power of 0.23 μW per mm(2) of electrode area for an average of 6.1 days of temperature measurements in the gastrointestinal tract of pigs. This power-harvesting cell has the capacity to provide power for prolonged periods of time to the next generation of ingestible electronic devices located in the gastrointestinal tract.

  14. [Prolonged neuromuscular block after mivacurium injection].

    PubMed

    Viggiano, M; Soler, C; Dumont, J C; Pellissier, D; François, G

    1995-01-01

    Mivacurium, a new short acting non depolarizing neuromuscular blocker, is metabolized, as suxamethonium, by plasma cholinesterase. Therefore its duration of action is increased in patients with reduced plasma cholinesterase activity. We report a case of prolonged neuromuscular block after an i.v. bolus of mivacurium (0.20 mg.kg-1) in a 69 year-old ASA II woman with an unrecognized cholinesterase deficiency undergoing a lumbar sympathectomy for arteriopathy of the lower limbs. The duration of the block was 6 h and plasma cholinesterase concentrations were very low (540 and 610 UI.L-1), as well as the dibucaine number (16%), which suggests an homozygous enzymatic deficiency. Mechanical ventilation and sedation were continued until spontaneous return of full neuromuscular function.

  15. Effects of Prolonged Centrifugation on Orthostasis

    NASA Technical Reports Server (NTRS)

    Cohen, Malcolm M..; Hargens, A. R.; Yates, B. J.; Bowley, Susan M. (Technical Monitor)

    2000-01-01

    A feasibility study conducted on the Ames 20-G Human Centrifuge examined how well humans can maintain orthostatic tolerance during and after prolonged exposures to hypergravity. Three adult males lived for periods of 22 hours in the centrifuge while it was at rest (1.00 G), and while it rotated at 9.38 RPM to provide 1.25 G-total at the mean radius of 7.62 m. Two participants also experienced 22-hour habitation sessions at 11.46 RPM, which provided 1.50 G-total. Both before and after each habitation session, the participants were given gradual onset rate (GOR) acceleration profiles at 0.067 G/sec to determine their Gz tolerance. In addition, cardiovascular responses were compared while subjects were supine, siting, and standing at various times during the habitation (stand test), and cardiovascular responsiveness was determined using a lower body negative pressure tilt table (LBNPTT) at the beginning of the experiment and after each session. Post-Pre changes in G tolerance were -0.33 (mean) +/- 0.11 (std. error) Gz for habitation at 1.00 G, -0.02 +/- 0.12 Gz for habitation at 1.25 G, and +0.41 +/- 0.13 Gz for habitation at 1.50 G. Performance on the stand test generally improved with duration of habitation in hypergravity. Our results suggest that habitation in a confined chamber at 1.00 G reduces G tolerance and leads to lowered LBNPTT tolerance. Exposure to increased G in the centrifuge leads to enhanced performance on the stand test, and to increased GOR acceleration tolerance, but only when fluid balance is maintained; when motion sickness and negative fluid balance were observed, G tolerance was reduced. The data indicate that enhanced G tolerance can result from prolonged exposure to hypergravity, but that these changes are complex and depend on multiple underlying physiological processes.

  16. Exemestane Following Tamoxifen Reduces Breast Cancer Recurrences and Prolongs Survival

    Cancer.gov

    Postmenopausal women with early-stage hormone receptor-positive breast cancer had delayed disease recurrence and longer survival after taking 2-3 years of tamoxifen followed by exemestane for a total of 5 years compared to taking tamoxifen for 5 years.

  17. Sponsored parachute jumps--can they cause prolonged pain?

    PubMed

    Straiton, N; Sterland, J

    1986-06-01

    A survey of parachute injuries sustained in 1984 at a local parachute club was made using hospital notes and a questionnaire. The overall injury rate was 0.2%. The injury rate in first time jumpers was 1.1%. The injuries often resulted in a prolonged hospital stay, time off work and residual pain and disability. Injury rates may be reduced by more prolonged and intensive training preceding the first jumps. Those people not interested in parachuting as a regular sport and who jump once only in order to raise money for charity are at risk of serious injury and perhaps should consider less dangerous alternatives.

  18. Sponsored parachute jumps--can they cause prolonged pain?

    PubMed Central

    Straiton, N; Sterland, J

    1986-01-01

    A survey of parachute injuries sustained in 1984 at a local parachute club was made using hospital notes and a questionnaire. The overall injury rate was 0.2%. The injury rate in first time jumpers was 1.1%. The injuries often resulted in a prolonged hospital stay, time off work and residual pain and disability. Injury rates may be reduced by more prolonged and intensive training preceding the first jumps. Those people not interested in parachuting as a regular sport and who jump once only in order to raise money for charity are at risk of serious injury and perhaps should consider less dangerous alternatives. PMID:3730756

  19. Moving frames and prolongation algebras

    NASA Technical Reports Server (NTRS)

    Estabrook, F. B.

    1982-01-01

    Differential ideals generated by sets of 2-forms which can be written with constant coefficients in a canonical basis of 1-forms are considered. By setting up a Cartan-Ehresmann connection, in a fiber bundle over a base space in which the 2-forms live, one finds an incomplete Lie algebra of vector fields in the fields in the fibers. Conversely, given this algebra (a prolongation algebra), one can derive the differential ideal. The two constructs are thus dual, and analysis of either derives properties of both. Such systems arise in the classical differential geometry of moving frames. Examples of this are discussed, together with examples arising more recently: the Korteweg-de Vries and Harrison-Ernst systems.

  20. Prolonged Cortisol Reactivity to Stress and White Matter in Schizophrenia

    PubMed Central

    Nugent, Katie L.; Chiappelli, Joshua; Sampath, Hemalatha; Rowland, Laura M.; Thangavelu, Kavita; Davis, Beshaun; Du, Xiaoming; Muellerklein, Florian; Daughters, Stacey; Kochunov, Peter; Hong, L. Elliot

    2015-01-01

    Objective While acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for which cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Methods Acute and prolonged salivary cortisol response was measured outside the scanner at pre-test and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n=45) and controls (n=53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n=30) and controls (n=33). Results Patients who did not tolerate and quit the psychological stress task had greater acute (t=2.52, p=0.016; t=3.51, p=0.001 at zero and 20 minutes) and prolonged (t=3.62, p=0.001 at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r=−0.468, p=0.009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. Conclusions This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages. PMID:26186431

  1. Physiology of prolonged bed rest

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.

    1988-01-01

    Bed rest has been a normal procedure used by physicians for centuries in the treatment of injury and disease. Exposure of patients to prolonged bed rest in the horizontal position induces adaptive deconditioning responses. While deconditioning responses are appropriate for patients or test subjects in the horizontal position, they usually result in adverse physiological responses (fainting, muscular weakness) when the patient assume the upright posture. These deconditioning responses result from reduction in hydrostatic pressure within the cardiovascular system, virtual elimination of longitudinal pressure on the long bones, some decrease in total body metabolism, changes in diet, and perhaps psychological impact from the different environment. Almost every system in the body is affected. An early stimulus is the cephalic shift of fluid from the legs which increases atrial pressure and induces compensatory responses for fluid and electrolyte redistribution. Without countermeasures, deterioration in strength and muscle function occurs within 1 wk while increased calcium loss may continue for months. Research should also focus on drug and carbohydrate metabolism.

  2. Managing prolonged disorders of consciousness.

    PubMed

    Wade, Derick T

    2014-03-01

    After acute severe brain damage, many people are rendered unconscious or comatose for more than 24 hours. Although a significant number can still recover fully, some will not and a substantial minority remain unconscious for days, weeks or longer. These patients have a prolonged disorder of consciousness. A specialist multidisciplinary team should be closely involved in the management of every patient from the outset. Assessment of a patient's level of awareness is not straightforward, and requires a team with suitable experience and expertise. The underlying neurological damage, whether or not there is an intact primary sensory input and motor output, and if there are reversible causes such as a high level of a sedating drug, or a subdural haematoma have to be established. If recovery of awareness has not occurred by six months after hypoxic or hypoglycaemic brain damage and 12 months after most other causes of brain damage, then the patient is very unlikely to recover any awareness and is described as being in a permanent vegetative state. The family must be closely and fully involved from the outset. Families legally cannot, and should not be asked to, make decisions concerning healthcare, unless a family member is a legally appointed deputy or has been given power of attorney in relation to healthcare matters. Family members can, and should be asked to, give information about the patient's wishes, life choices etc as part of the best interests decision-making process, and they should be involved in best interests meetings.

  3. Drug-induced QT interval prolongation and torsades de pointes

    PubMed Central

    Tisdale, James E.

    2016-01-01

    Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram. More than 100 drugs available in Canada, including widely used antibiotics, antidepressants, cardiovascular drugs and many others, may cause QTc interval prolongation and TdP. Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, treatment with diuretics and elevated plasma concentrations of QTc interval–prolonging drugs due to drug interactions, inadequate dose adjustment of renally eliminated drugs in patients with kidney disease and rapid intravenous administration. Pharmacokinetic drug interactions associated with the highest risk of TdP include antifungal agents, macrolide antibiotics (except azithromycin) and drugs to treat human immunodeficiency virus interacting with amiodarone, disopyramide, dofetilide or pimozide. Other important pharmacokinetic interactions include antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) interacting with flecainide, quinidine or thioridazine. Pharmacists play an important role in minimizing the risk of drug-induced QTc interval prolongation and TdP through knowledge of drugs that are associated with a known or possible risk of TdP, individualized assessment of risk of drug-induced QTc interval prolongation, awareness of drug interactions most likely to result in TdP and attention to dose reduction of renally eliminated QTc interval-prolonging drugs in patients with kidney disease. Treatment of hemodynamically stable TdP consists of discontinuation of the offending drug(s), correction of electrolyte abnormalities and administration of intravenous magnesium sulfate 1 to 2 g. PMID:27212965

  4. [Brain function recovery after prolonged posttraumatic coma].

    PubMed

    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.

  5. Deep, prolonged torpor by pregnant, free-ranging bats

    NASA Astrophysics Data System (ADS)

    Willis, Craig K. R.; Brigham, R. Mark; Geiser, Fritz

    2006-02-01

    Many mammals save energy during food shortage or harsh weather using controlled reductions in body temperature and metabolism called torpor. However, torpor slows offspring growth, and reproductive individuals are thought to avoid using it because of reduced fitness resulting from delayed offspring development. We tested this hypothesis by investigating torpor during reproduction in hoary bats ( Lasiurus cinereus, Vespertilionidae) in southern Canada. We recorded deep, prolonged torpor bouts, which meet the definition for hibernation, by pregnant females. Prolonged torpor occurred during spring storms. When conditions improved females aroused and gave birth within several days. Our observations imply a fitness advantage of torpor in addition to energy conservation because reduced foetal growth rate could delay parturition until conditions are more favourable for lactation and neonatal survival.

  6. [A case of prolonged paroxysmal sympathetic hyperactivity].

    PubMed

    Yamamoto, Akiko; Ide, Shuhei; Iwasaki, Yuji; Kaga, Makiko; Arima, Masataka

    2016-03-01

    We report the case of a 4-year-old girl who presented with paroxysmal sympathetic hyperactivity (PSH), after developing severe hypoxic-ischemic-encephalopathy because of cardiopulmonary arrest. She showed dramatic paroxysmal sympathetic activity with dystonia. She was treated with wide variety of medications against PSH, which were found to be effective in previous studies. Among them, morphine, bromocriptine, propranolol, and clonidine were effective in reducing the frequency of her attacks while gabapentin, baclofen, dantrolene, and benzodiazepine were ineffective. Though the paroxysms decreased markedly after the treatment, they could not be completely controlled beyond 500 days. Following the treatment, levels of plasma catecholamines and their urinary metabolites decreased to normal during inter- paroxysms. However, once a paroxysm had recurred, these levels were again very high. This case study is considered significant for two rea- sons. One is that PSH among children have been rarely reported, and the other is that this case of prolonged PSH delineated the transition of plasma catecholamines during the treatment. The excitatory: inhibitory ratio (EIR) model proposed by Baguley was considered while dis- cussing drug sensitivity in this case. Accumulation of similar case studies will help establish more effective treatment strategies and elucidate the pathophysiology of PSH.

  7. QTc Prolongation in Acute Pediatric Migraine.

    PubMed

    May, Lindsay J; Millar, Kelly; Barlow, Karen M; Dicke, Frank

    2015-06-01

    Migraine headache is common in pediatrics and is frequently assessed in emergency departments. Altered cardiac conduction, including prolongation of the QTc interval on electrocardiogram, has been observed in adults during migraine headache and resolves interictally. Prolonged QTc is associated with life-threatening arrhythmia, and many acute and prophylactic therapies for migraine can further prolong the QTc interval. It is the objective of this prospective cohort study to examine whether the QTc interval prolongs significantly during periods of acute migraine headache in children. Patients ages 6 to 17 years presenting to the emergency department with acute migraine headache were recruited prospectively. Exclusion criteria included the use of QTc-prolonging medications and medical illnesses, including cardiovascular abnormalities, infection, or head injury. Paired, one-tailed Student t tests compared QTc intervals with and without headache and evaluated for QTc prolongation of 30 ms or longer during headache. Thirteen patients with migraine (mean age, 11.6 ± 2.6 years) were evaluated. Mean QTc interval during headache was significantly longer than the QTc interval in the absence of headache (437.9 ± 27.7 ms compared with 419.3 ± 29.9 ms; p = 0.04). Three patients (23%) had unequivocal prolongation of the QTc (>460 ms) during the migraine, two of which normalized with headache resolution. The mean increase in QTc during headache did not reach or exceed 30 ms (p = 0.86) CONCLUSIONS: This study is the first to illustrate a connection between QTc prolongation and acute migraine headache in children. If confirmed in future studies, children should be monitored for QTc prolongation during the acute treatment of migraine in the emergency department when using medications that can lengthen the QTc interval.

  8. Fluids and hydration in prolonged endurance performance.

    PubMed

    Von Duvillard, Serge P; Braun, William A; Markofski, Melissa; Beneke, Ralph; Leithäuser, Renate

    2004-01-01

    Numerous studies have confirmed that performance can be impaired when athletes are dehydrated. Endurance athletes should drink beverages containing carbohydrate and electrolyte during and after training or competition. Carbohydrates (sugars) favor consumption and Na(+) favors retention of water. Drinking during competition is desirable compared with fluid ingestion after or before training or competition only. Athletes seldom replace fluids fully due to sweat loss. Proper hydration during training or competition will enhance performance, avoid ensuing thermal stress, maintain plasma volume, delay fatigue, and prevent injuries associated with dehydration and sweat loss. In contrast, hyperhydration or overdrinking before, during, and after endurance events may cause Na(+) depletion and may lead to hyponatremia. It is imperative that endurance athletes replace sweat loss via fluid intake containing about 4% to 8% of carbohydrate solution and electrolytes during training or competition. It is recommended that athletes drink about 500 mL of fluid solution 1 to 2 h before an event and continue to consume cool or cold drinks in regular intervals to replace fluid loss due to sweat. For intense prolonged exercise lasting longer than 1 h, athletes should consume between 30 and 60 g/h and drink between 600 and 1200 mL/h of a solution containing carbohydrate and Na(+) (0.5 to 0.7 g/L of fluid). Maintaining proper hydration before, during, and after training and competition will help reduce fluid loss, maintain performance, lower submaximal exercise heart rate, maintain plasma volume, and reduce heat stress, heat exhaustion, and possibly heat stroke.

  9. Providers' Response to Clinical Decision Support for QT Prolonging Drugs.

    PubMed

    Sharma, Sunita; Martijn Bos, J; Tarrell, Robert F; Simon, Gyorgy J; Morlan, Bruce W; Ackerman, Michael J; Caraballo, Pedro J

    2017-09-02

    Commonly used drugs in hospital setting can cause QT prolongation and trigger life-threatening arrhythmias. We evaluate changes in prescribing behavior after the implementation of a clinical decision support system to prevent the use of QT prolonging medications in the hospital setting. We conducted a quasi-experimental study, before and after the implementation of a clinical decision support system integrated in the electronic medical record (QT-alert system). This system detects patients at risk of significant QT prolongation (QTc>500ms) and alerts providers ordering QT prolonging drugs. We reviewed the electronic health record to assess the provider's responses which were classified as "action taken" (QT drug avoided, QT drug changed, other QT drug(s) avoided, ECG monitoring, electrolytes monitoring, QT issue acknowledged, other actions) or "no action taken". Approximately, 15.5% (95/612) of the alerts were followed by a provider's action in the pre-intervention phase compared with 21% (228/1085) in the post-intervention phase (p=0.006). The most common type of actions taken during pre-intervention phase compared to post-intervention phase were ECG monitoring (8% vs. 13%, p=0.002) and QT issue acknowledgment (2.1% vs. 4.1%, p=0.03). Notably, there was no significant difference for other actions including QT drug avoided (p=0.8), QT drug changed (p=0.06) and other QT drug(s) avoided (p=0.3). Our study demonstrated that the QT alert system prompted a higher proportion of providers to take action on patients at risk of complications. However, the overall impact was modest underscoring the need for educating providers and optimizing clinical decision support to further reduce drug-induced QT prolongation.

  10. QT Prolongation due to Graves' Disease

    PubMed Central

    Deol, Nisha; Tolly, Renee; Manocha, Rohan; Naseer, Maliha

    2017-01-01

    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. PMID:28154763

  11. Prolonged partial epilepsy: a case report

    SciTech Connect

    Wilson, M.A.

    1980-11-01

    The case study of a patient with prolonged partial epilepsy is presented. There was a discrepancy between the extent of the abnormality seen on the radionuclide angiogram and that seen on the static brain scan.

  12. Prolonged swimming performance of northern squawfish

    USGS Publications Warehouse

    Mesa, Matthew G.; Olson, Todd M.

    1993-01-01

    We determined the prolonged swimming performance of two size-classes of northern squawfish Ptychocheilus oregonensis at 12 and 18°C. The percentage of fish fatigued was positively related to water velocity and best described by an exponential model. At 12°C, the velocity at which 50% of the fish fatigued (FV50) was estimated to be 2.91 fork lengths per second (FL/s; 100 cm/s) for medium-sized fish (30–39 cm) and 2.45 FL/s (104 cm/s) for large fish (40–49 cm). At 18°C, estimated FV50 was 3.12 FL/s (107 cm/s) for medium fish and 2.65 FL/s (112 cm/s) for large fish. Rate of change in percent fatigue was affected by fish size and water temperature. Large fish fatigued at a higher rate than medium-sized fish; all fish fatigued faster at 12 than at 18°C. The mean times to fatigue at velocities of 102–115 cm/s ranged from 14 to 28 min and were not affected by fish size or water temperature. Our results indicate that water velocities from 100 to 130 cm/s may exclude or reduce predation by northern squawfish around juvenile salmonid bypass outfalls at Columbia River dams, at least during certain times of the year. We recommend that construction or modification of juvenile salmonid bypass facilities place the outfall in an area of high water velocity and distant from eddies, submerged cover, and littoral areas.

  13. Prolonged swimming performance of northern squawfish

    SciTech Connect

    Mesa, M.G.; Olson, T.M. )

    1993-11-01

    The authors determined the prolonged swimming performance of two size-classes of northern squawfish Ptychocheilus oregonensis at 12 and 18[degrees]C. The percentage of fish fatigued was positively related to water velocity and best described by an exponential model. At 12[degrees]C, the velocity at which 50% of the fish fatigued (FV50) was estimated to be 2.91 fork lengths per second (FL/s; 100 cm/s) for medium-sized fish (30-39 cm) and 2.45 FL/s (104 cm/s) for large fish (40-49 cm). At 18[degrees]C, estimated FV50 was 3.12 FL/s (107 cm/s) for medium fish and 2.65 FL/s (112 cm/s) for large fish. Rate of change in percent fatigue was affected by fish size and water temperature. Large fish fatigued at a higher rate than medium-sized fish; all fish fatigued faster at 12 than at 18[degrees]C. The mean times to fatigue at velocities of 102-115 cm/s ranged from 14 to 28 min and were not affected by fish size or water temperature. The results indicate that water velocities from 100 to 130 cm/s may exclude or reduce predation by northern squawfish around juvenile salmonid bypass outfalls at Columbia River dams, at least during certain times of the year. The authors recommend that construction or modification of juvenile salmonid bypass facilities place the outfall in an area of high water velocity and distant from eddies, submerged cover, and littoral areas. 35 refs., 1 fig., 2 tabs.

  14. Tissue vibration in prolonged running.

    PubMed

    Friesenbichler, Bernd; Stirling, Lisa M; Federolf, Peter; Nigg, Benno M

    2011-01-04

    The impact force in heel-toe running initiates vibrations of soft-tissue compartments of the leg that are heavily dampened by muscle activity. This study investigated if the damping and frequency of these soft-tissue vibrations are affected by fatigue, which was categorized by the time into an exhaustive exercise. The hypotheses were tested that (H1) the vibration intensity of the triceps surae increases with increasing fatigue and (H2) the vibration frequency of the triceps surae decreases with increasing fatigue. Tissue vibrations of the triceps surae were measured with tri-axial accelerometers in 10 subjects during a run towards exhaustion. The frequency content was quantified with power spectra and wavelet analysis. Maxima of local vibration intensities were compared between the non-fatigued and fatigued states of all subjects. In axial (i.e. parallel to the tibia) and medio-lateral direction, most local maxima increased with fatigue (supporting the first hypothesis). In anterior-posterior direction no systematic changes were found. Vibration frequency was minimally affected by fatigue and frequency changes did not occur systematically, which requires the rejection of the second hypothesis. Relative to heel-strike, the maximum vibration intensity occurred significantly later in the fatigued condition in all three directions. With fatigue, the soft tissue of the triceps surae oscillated for an extended duration at increased vibration magnitudes, possibly due to the effects of fatigue on type II muscle fibers. Thus, the protective mechanism of muscle tuning seems to be reduced in a fatigued muscle and the risk of potential harm to the tissue may increase. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Evidence of Health Risks Associated with Prolonged Standing at Work and Intervention Effectiveness

    PubMed Central

    Waters, Thomas R.; Dick, Robert B.

    2015-01-01

    Purpose Prolonged standing at work has been shown to be associated with a number of potentially serious health outcomes, such as lower back and leg pain, cardiovascular problems, fatigue, discomfort, and pregnancy related health outcomes. Recent studies have been conducted examining the relationship between these health outcomes and the amount of time spent standing while on the job. The purpose of this article was to provide a review of the health risks and interventions for workers and employers that are involved in occupations requiring prolonged standing. A brief review of recommendations by governmental and professional organizations for hours of prolonged standing is also included. Findings Based on our review of the literature, there seems to be ample evidence showing that prolonged standing at work leads to adverse health outcomes. Review of the literature also supports the conclusion that certain interventions are effective in reducing the hazards associated with prolonged standing. Suggested interventions include the use of floor mats, sit-stand workstations/chairs, shoes, shoe inserts and hosiery or stockings. Studies could be improved by using more precise definitions of prolonged standing (e.g., duration, movement restrictions, and type of work), better measurement of the health outcomes and more rigorous study protocols. Conclusion and Clinical Relevance Use of interventions and following suggested guidelines on hours of standing from governmental and professional organizations should reduce the health risks from prolonged standing. PMID:25041875

  16. Prolonged Nightly Fasting and Breast Cancer Prognosis.

    PubMed

    Marinac, Catherine R; Nelson, Sandahl H; Breen, Caitlin I; Hartman, Sheri J; Natarajan, Loki; Pierce, John P; Flatt, Shirley W; Sears, Dorothy D; Patterson, Ruth E

    2016-08-01

    % CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (β = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (β = 0.20; 95% CI, 0.14-0.26). Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.

  17. Desynchronization of glutamate release prolongs synchronous CA3 network activity.

    PubMed

    Jones, Jethro; Stubblefield, Elizabeth A; Benke, Timothy A; Staley, Kevin J

    2007-05-01

    Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca(2+) with Sr(2+). Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr(2+) substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 +/- 7.6 (SE) times the duration in control conditions. Sr(2+) also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 network activity.

  18. Management of children with prolonged diarrhea

    PubMed Central

    Giannattasio, Antonietta; Guarino, Alfredo; Lo Vecchio, Andrea

    2016-01-01

    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. PMID:26962439

  19. Prosthodontic Approach in Management of Prolonged Neonatal Intubation

    PubMed Central

    Shah, Shital K; Rathod, Vishnu B; Ambadkar, Priyanka S; Patil, Charudutt N

    2016-01-01

    Intubation is a routine intervention in the Neonatal Intensive Care Unit (NICU) for preterm neonates with respiratory distress, inadequate gag reflex, poor sucking and swallowing. Prolonged intubation in neonates can be done by nasal or oral route. Although naso-tracheal intubation may reduce movement of the tube, it may contribute to airway obstruction, possible hypoxia, and occlusion of the nasal aperture during a crucial period of development further contributing to laboured breathing. Being obligate nasal breathers, oro-tracheal route is the preferred method of intubation in premature infants as oral mucosa is less susceptible to damage than nasal mucosa. Ineffective stabilization of the tubes is a frequent problem often resulting in accidental extubation and displacement of orotracheal and orogastric tube. Hence, these tubes must be stabilized against displacement from tongue and jaw movements to prevent discomfort and subsequent tissue trauma. Complications of prolonged endotracheal intubation include palatal groove formation by pressure against the hard palate, infection, accidental extubation, malposition, laryngeal or tracheal edema and ulceration, tracheal stenosis, vocal cord injury. Various oral appliances are used for infants to stabilize the tubes and prevent complications associated with long term intubation. This case report describes a prosthodontic approach in management of prolonged neonatal intubation. PMID:28050517

  20. Prosthodontic Approach in Management of Prolonged Neonatal Intubation.

    PubMed

    Kamble, Vikas B; Shah, Shital K; Rathod, Vishnu B; Ambadkar, Priyanka S; Patil, Charudutt N

    2016-11-01

    Intubation is a routine intervention in the Neonatal Intensive Care Unit (NICU) for preterm neonates with respiratory distress, inadequate gag reflex, poor sucking and swallowing. Prolonged intubation in neonates can be done by nasal or oral route. Although naso-tracheal intubation may reduce movement of the tube, it may contribute to airway obstruction, possible hypoxia, and occlusion of the nasal aperture during a crucial period of development further contributing to laboured breathing. Being obligate nasal breathers, oro-tracheal route is the preferred method of intubation in premature infants as oral mucosa is less susceptible to damage than nasal mucosa. Ineffective stabilization of the tubes is a frequent problem often resulting in accidental extubation and displacement of orotracheal and orogastric tube. Hence, these tubes must be stabilized against displacement from tongue and jaw movements to prevent discomfort and subsequent tissue trauma. Complications of prolonged endotracheal intubation include palatal groove formation by pressure against the hard palate, infection, accidental extubation, malposition, laryngeal or tracheal edema and ulceration, tracheal stenosis, vocal cord injury. Various oral appliances are used for infants to stabilize the tubes and prevent complications associated with long term intubation. This case report describes a prosthodontic approach in management of prolonged neonatal intubation.

  1. Effect of sleep deprivation on tolerance of prolonged exercise.

    PubMed

    Martin, B J

    1981-01-01

    Acute loss of sleep produces few apparent physiological effects at rest. Nevertheless, many anecdotes suggest that adequate sleep is essential for optimum endurance athletic performance. To investigate this question, heavy exercise performance after 36 h without sleep was compared with that after normal sleep in eight subjects. During prolonged treadmill walking at about 80% of the VO2 max, sleep loss reduced work time to exhaustion by an average of 11% (p = 0.05). This decrease occurred despite doubling monetary incentives for subjects during work after sleeplessness. Subjects appeared to fall into "resistant" and "susceptible" categories: four showed less than a 5% change in performance after sleep loss, while four others showed decrements in exercise tolerance ranging from 15 to 40%. During the walk, sleep loss resulted in significantly greater perceived exertion (p less than 0.05), even though exercise heart rate and metabolic rate (VO2 and VCO2) were unchanged. Minute ventilation was significantly elevated during exercise after sleep loss ( p less than 0.05). Sleep loss failed to alter the continuous slow rises in VE and heart rate that occurred as work was prolonged. These findings suggest that the psychological effects of acute sleep loss may contribute to decreased tolerance of prolonged heavy exercise.

  2. Prolongation structures of nonlinear evolution equations

    NASA Technical Reports Server (NTRS)

    Wahlquist, H. D.; Estabrook, F. B.

    1975-01-01

    A technique is developed for systematically deriving a 'prolongation structure' - a set of interrelated potentials and pseudopotentials - for nonlinear partial differential equations in two independent variables. When this is applied to the Korteweg-de Vries equation, a new infinite set of conserved quantities is obtained. Known solution techniques are shown to result from the discovery of such a structure: related partial differential equations for the potential functions, linear 'inverse scattering' equations for auxiliary functions, Backlund transformations. Generalizations of these techniques will result from the use of irreducible matrix representations of the prolongation structure.

  3. Prolonged Soil Frost Affects Hydraulics and Phenology of Apple Trees.

    PubMed

    Beikircher, Barbara; Mittmann, Claudia; Mayr, Stefan

    2016-01-01

    Restoration of an adequate water supply in spring is a prerequisite for survival of angiosperm trees in temperate regions. Trees must re-establish access to soil water and recover xylem functionality. We thus hypothesized that prolonged soil frost impairs recovery and affects hydraulics and phenology of Malus domestica var. 'Golden Delicious.' To test this hypothesis, over two consecutive winters the soil around some trees was insulated to prolong soil frosting, From mid-winter to early summer, the level of native embolism, the water and starch contents of wood, bark and buds were quantified at regular intervals and findings correlated with various phenological parameters, xylogenesis and fine root growth. The findings confirm that prolonged soil frost affects tree hydraulics and phenology but the severity of the effect depends on the climatic conditions. In both study years, percentage loss of hydraulic conductivity (PLC) decreased from about 70% at the end of winter to about 10% in May. Thereby, xylem refilling strongly coincided with a decrease of starch in wood and bark. Also treated trees were able to restore their hydraulic system by May but, in the warm spring of 2012, xylem refilling, the increases in water content and starch depolymerization were delayed. In contrast, in the cold spring of 2013 only small differences between control and treated trees were observed. Prolongation of soil frost also led to a delay in phenology, xylogenesis, and fine root growth. We conclude that reduced water uptake from frozen or cold soils impairs refilling and thus negatively impacts tree hydraulics and growth of apple trees in spring. Under unfavorable circumstances, this may cause severe winter damage or even dieback.

  4. Tetrodotoxin-bupivacaine-epinephrine combinations for prolonged local anesthesia.

    PubMed

    Berde, Charles B; Athiraman, Umeshkumar; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel; Bognet, Christina

    2011-12-01

    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.

  5. Prolonged Soil Frost Affects Hydraulics and Phenology of Apple Trees

    PubMed Central

    Beikircher, Barbara; Mittmann, Claudia; Mayr, Stefan

    2016-01-01

    Restoration of an adequate water supply in spring is a prerequisite for survival of angiosperm trees in temperate regions. Trees must re-establish access to soil water and recover xylem functionality. We thus hypothesized that prolonged soil frost impairs recovery and affects hydraulics and phenology of Malus domestica var. ‘Golden Delicious.’ To test this hypothesis, over two consecutive winters the soil around some trees was insulated to prolong soil frosting, From mid-winter to early summer, the level of native embolism, the water and starch contents of wood, bark and buds were quantified at regular intervals and findings correlated with various phenological parameters, xylogenesis and fine root growth. The findings confirm that prolonged soil frost affects tree hydraulics and phenology but the severity of the effect depends on the climatic conditions. In both study years, percentage loss of hydraulic conductivity (PLC) decreased from about 70% at the end of winter to about 10% in May. Thereby, xylem refilling strongly coincided with a decrease of starch in wood and bark. Also treated trees were able to restore their hydraulic system by May but, in the warm spring of 2012, xylem refilling, the increases in water content and starch depolymerization were delayed. In contrast, in the cold spring of 2013 only small differences between control and treated trees were observed. Prolongation of soil frost also led to a delay in phenology, xylogenesis, and fine root growth. We conclude that reduced water uptake from frozen or cold soils impairs refilling and thus negatively impacts tree hydraulics and growth of apple trees in spring. Under unfavorable circumstances, this may cause severe winter damage or even dieback. PMID:27379146

  6. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

    PubMed Central

    Berde, Charles B.; Athiraman, Umeshkumar; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel; Bognet, Christina

    2011-01-01

    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. PMID:22363247

  7. Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

    PubMed Central

    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

  8. Intraocular pressure and cerebral oxygenation during prolonged headward acceleration.

    PubMed

    Eiken, Ola; Keramidas, Michail E; Taylor, Nigel A S; Grönkvist, Mikael

    2017-01-01

    Supra-tolerance head-to-foot directed gravitoinertial load (+Gz) typically induces a sequence of symptoms/signs, including loss of: peripheral vision-central vision-consciousness. The risk of unconsciousness is greater when anti-G-garment failure occurs after prolonged rather than brief exposures, presumably because, in the former condition, mental signs are not consistently preceded by impaired vision. The aims were to investigate if prolonged exposure to moderately elevated +Gz reduces intraocular pressure (IOP; i.e., improves provisions for retinal perfusion), or the cerebral anoxia reserve. Subjects were exposed to 4-min +Gz plateaux either at 2 and 3 G (n = 10), or at 4 and 5 G (n = 12). Measurements included eye-level mean arterial pressure (MAP), oxygenation of the cerebral frontal cortex, and at 2 and 3 G, IOP. IOP was similar at 1 (14.1 ± 1.6 mmHg), 2 (14.0 ± 1.6 mmHg), and 3 G (14.0 ± 1.6 mmHg). During the G exposures, MAP exhibited an initial prompt drop followed by a partial recovery, end-exposure values being reduced by ≤30 mmHg. Cerebral oxygenation showed a similar initial drop, but without recovery, and was followed by either a plateau or a further slight decrement to a minimum of about -14 μM. Gz loading did not affect IOP. That cerebral oxygenation remained suppressed throughout these G exposures, despite a concomitant partial recovery of MAP, suggests that the increased risk of unconsciousness upon G-garment failure after prolonged +Gz exposure is due to reduced cerebral anoxia reserve.

  9. [Cytokinetic evaluation of erythropoiesis on prolonged orbital flights].

    PubMed

    Iliukhin, A V; Burkovskaia, T E

    1981-01-01

    The purpose of the investigation was to understand better the mechanisms of erythropoietic changes at the cellular level during a prolonged exposure to weightlessness. Following 96-, 140- and 175-day space flights cytokinetic and morphological changes in erythropoiesis were observed. The count of circulating erythrocytes decreased inflight and their life time reduced postflight. The shortening of the life time of erythrocytes postflight was paralleled by increased proliferative activity of erythroid cells. The erythrocytic balance was not reached as late as R + 36. It is recommended that the number of research methods be enlarged.

  10. Prolonged fever associated with primary hyperparathyroidism.

    PubMed Central

    Ricci, J; Vlasschaert, J; Salit, I E

    1984-01-01

    A 36-year-old woman presented with hypercalcemia, hypercalciuria, elevated serum parathyroid hormone levels and prolonged fever. Surgical removal of the hyperplastic and adenomatous parathyroid glands led to reversal of the biochemical abnormalities as well as return of her temperature to normal. PMID:6467119

  11. Neurological complications of prolonged hunger strike.

    PubMed

    Başoğlu, M; Yetimalar, Y; Gürgör, N; Büyükçatalbaş, S; Kurt, T; Seçil, Y; Yeniocak, A

    2006-10-01

    We investigated neurological findings in 41 prisoners (mean age: 28.6) who participated in a hunger strike between 2000 and 2002. All cases were evaluated using neuropsychological, neuroradiological, and electrophysiological methods. The total duration of fasting ranged from 130 to 324 days (mean 199 days). All cases had 200-600 mg/day thiamine orally for 60-294 days (mean 156) during the hunger strike, and had neurological findings consistent with Wernicke-Korsakoff syndrome. All 41 patients exhibited altered consciousness which lasted from 3 to 31 days. All patients also presented gaze-evoked horizontal nystagmus and truncal ataxia. Paralysis of lateral rectus muscles was found in 14. Amnesia was apparent in all cases. Abnormal nerve conduction study parameters were not found in the patient group, but the amplitude of compound muscle action potential of the median and fibular nerves and sensory nerve action potential amplitude of the sural nerve were lower than the control group, and distal motor latency of the posterior tibial nerve was significantly prolonged as compared with the control group. The latency of visual evoked potential was prolonged in 22 cases. Somatosensory evoked potential (P37) was prolonged but not statistically significant. Our most significant finding was that the effect of hunger was more prominent on the central nervous system than on the neuromuscular system, despite the fact that all patients were taking thiamine. In our opinion, partial recovery of neurological, and neurocognitive signs in prolonged hunger could be a result of permanent neurological injury.

  12. Carotid Baroreflex Function During Prolonged Exercise

    NASA Technical Reports Server (NTRS)

    Raven, P. B.

    1999-01-01

    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  13. Carotid Baroreflex Function During Prolonged Exercise

    NASA Technical Reports Server (NTRS)

    Raven, P. B.

    1999-01-01

    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  14. Effects of the prolonged vertical tube on the separation performance of a cyclone.

    PubMed

    Qian, Fuping; Zhang, Jiguang; Zhang, Mingyao

    2006-08-25

    This article aims at the gas flow into the dustbin of conventional cyclones, the prolonged cyclone (attaching a vertical tube at the bottom of the dust outlet) is proposed by some researchers, which can make flow with dust enter into the tube and separate further. The Reynolds stress transport model (RSTM) has been employed to predict the gas flow fields of the conventional and prolonged cyclones. The tangential velocity, axial velocity profiles and turbulent kinetic energy profiles are presented, and the downward flow rates into the dustbin of the three cyclones are compared. The separation performances of these three cyclones are tested. The result indicates that the tangential velocity, axial velocity and turbulent kinetic energy in the dustbin reduce greatly when the prolonged vertical tube attaching into the dust outlet, which can avoid the re-entrainment of already separated dust effectively. Furthermore, the prolonged vertical tube increases the separation space of dusts. The downward flow rate into the dustbin of the prolonged cyclone decreases compared with the conventional cyclone. The experimental results show that the prolonged vertical tube can improve the separation efficiency by a slightly increased pressure drop. However, for an even longer tube, the separation efficiency is slightly reduced. Thus, there is an optimal tube length for a given cyclone.

  15. The effect of prolonged dietary nitrate supplementation on atherosclerosis development.

    PubMed

    Marsch, Elke; Theelen, Thomas L; Janssen, Ben J A; Briede, Jacco J; Haenen, Guido R; Senden, Joan M G; van Loon, Lucas J C; Poeze, Martijn; Bierau, Jörgen; Gijbels, Marion J; Daemen, Mat J A P; Sluimer, Judith C

    2016-02-01

    Short term dietary nitrate or nitrite supplementation has nitric oxide (NO)-mediated beneficial effects on blood pressure and inflammation and reduces mitochondrial oxygen consumption, possibly preventing hypoxia. As these processes are implicated in atherogenesis, dietary nitrate was hypothesized to prevent plaque initiation, hypoxia and inflammation. Study prolonged nitrate supplementation on atherogenesis, hypoxia and inflammation in low density lipoprotein receptor knockout mice (LDLr(-/-)). LDLr(-/-) mice were administered sodium-nitrate or equimolar sodium-chloride in drinking water alongside a western-type diet for 14 weeks to induce atherosclerosis. Plasma nitrate, nitrite and hemoglobin-bound nitric oxide were measured by chemiluminescence and electron parametric resonance, respectively. Plasma nitrate levels were elevated after 14 weeks of nitrate supplementation (NaCl: 40.29 ± 2.985, NaNO3: 78.19 ± 6.837, p < 0.0001). However, prolonged dietary nitrate did not affect systemic inflammation, hematopoiesis, erythropoiesis and plasma cholesterol levels, suggesting no severe side effects. Surprisingly, neither blood pressure, nor atherogenesis were altered. Mechanistically, plasma nitrate and nitrite were elevated after two weeks (NaCl: 1.0 ± 0.2114, NaNO3: 3.977 ± 0.7371, p < 0.0001), but decreased over time (6, 10 and 14 weeks). Plasma nitrite levels even reached baseline levels at 14 weeks (NaCl: 0.7188 ± 0.1072, NaNO3: 0.9723 ± 0.1279 p = 0.12). Also hemoglobin-bound NO levels were unaltered after 14 weeks. This compensation was not due to altered eNOS activity or conversion into peroxynitrite and other RNI, suggesting reduced nitrite formation or enhanced nitrate/nitrite clearance. Prolonged dietary nitrate supplementation resulted in compensation of nitrite and NO levels and did not affect atherogenesis or exert systemic side effects. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  16. Zoledronic acid, an aminobisphosphonate, prolongs survival of skin allografts.

    PubMed

    Liu, Chia-Yuan; Yang, Po-Sheng; Cheng, Shih-Ping; Huang, Yu-Chuen; Lee, Jie-Jen; Ko, Chun-Chuan; Shieh, Hui-Ru; Chen, Yu-Jen

    2012-08-04

    Zoledronic acid (ZOL), an effective nitrogen-containing bisphosphonate used to prevent excessive bone loss in clinical practice, has been shown to affect the development of dendritic cells by redirecting differentiation toward a state of atypical maturation. The study was aimed to examine whether ZOL can reduce acute rejection of skin allografts. A skin transplantation model using C57BL/6 to BALB/c mice was used. ZOL was injected intraperitoneally into transplant recipients post-surgically. Graft survival, body weight, leukocyte count, hepatic and renal functions were assessed. ZOL treatment significantly prolonged skin allograft survival in mice. In terms of toxicity, there were no significant differences in body weight, leukocyte count, plasma alanine aminotransferase or creatinine levels between the ZOL-treated and control groups. Histopathology showed that the loss of skin integrity seen in control group was prevented by ZOL treatment. In draining lymph nodes and spleen, the number and clustering extent of mononuclear cells were markedly declined by ZOL treatment. The plasma IL-6 levels were reduced by treatment of ZOL. ZOL can prolong skin allograft survival without major toxicity.

  17. Prolonged preconditioning with natural honey against myocardial infarction injuries.

    PubMed

    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 (P<0.001). At the ischemia, honey (1%) significantly reduced (P<0.05) the number and duration of ventricular tachycardia (VT). Honey (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% (P<0.05). During reperfusion, honey 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.

  18. Status of vestibular function after prolonged bedrest

    NASA Astrophysics Data System (ADS)

    Burgeat, M.; Toupet, M.; Loth, D.; Ingster, I.; Guell, A.; Coll, J.

    6 young, healthy, male volunteers were submitted to one week of head down (-4°) bedrest. This position simulates the cerebral hemodynamic conditions in weightlessness. Measurements of vestibular equilibrium and of oculomotor system function were made before and after the prolonged bedrest. Analysis of the results indicates that vestibular responses, as measured by the maximal speed of the slow phase of the provoked nystagmus (caloric and sinusoidal rotatory stimulations), are decreased after prolonged bedrest. This statistically significant diminution requires confirmation with a greater number of cases. The reflex conflicting or interacting with the cervico-ocular and optokinetic reflexes on the one hand and the foveal vision on the other, is one of several possible explanations for the observed changes.

  19. Severe bradycardia and prolonged hypotension in ciguatera.

    PubMed

    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.

  20. Prolonged Wars: A Post-Nuclear Challenge

    DTIC Science & Technology

    1994-10-01

    Leverage: The National Religious Party of Israel and Its Influence on Foreign Policy (1984); The x Israeli Arms Industry: Foreign Policy, Arms...PROLONGED WARS 8 “innumerable but indecisive battles.”20 This is, of course, anathema to short-war doctrines. Mao’s legacy influenced subsequent...historical rivalry with Iran and Saddam’s leadership ambitions, the Iraqi strongman feared his Shiaa and Kurdish population would be vulnerable to influence

  1. [Prolonged pain in neonates: retrospective analysis].

    PubMed

    Lilla, Michèle; Stadelman-Diaw, Corinne; Ramelet, Anne-Sylvie

    2013-12-01

    Infants hospitalised in neonatology are inevitably exposed to pain repeatedly. Premature infants are particularly vulnerable, because they are hypersensitive to pain and demonstrate diminished behavioural responses to pain. They are therefore at risk of developing short and long-term complications if pain remains untreated. Compared to acute pain, there is limited evidence in the literature on prolonged pain in infants. However, the prevalence is reported between 20 and 40 %. This single case study aimed to identify the bio-contextual characteristics of neonates who experienced prolonged pain. This study was carried out in the neonatal unit of a tertiary referral centre in Western Switzerland. A retrospective data analysis of seven infants' profile, who experienced prolonged pain ,was performed using five different data sources. The mean gestational age of the seven infants was 32weeks. The main diagnosis included prematurity and respiratory distress syndrome. The total observations (N=55) showed that the participants had in average 21.8 (SD 6.9) painful procedures that were estimated to be of moderate to severe intensity each day. Out of the 164 recorded pain scores (2.9 pain assessment/day/infant), 14.6 % confirmed acute pain. Out of those experiencing acute pain, analgesia was given in 16.6 % of them and 79.1 % received no analgesia. This study highlighted the difficulty in managing pain in neonates who are exposed to numerous painful procedures. Pain in this population remains underevaluated and as a result undertreated.Results of this study showed that nursing documentation related to pain assessment is not systematic.Regular assessment and documentation of acute and prolonged pain are recommended. This could be achieved with clear guidelines on the Assessment Intervention Reassessment (AIR) cyclewith validated measures adapted to neonates. The adequacy of pain assessment is a pre-requisite for appropriate pain relief in neonates.

  2. Prolonged Exposure: a Rapid Treatment for Phobias

    PubMed Central

    Watson, J. P.; Gaind, R.; Marks, I. M.

    1971-01-01

    Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

  3. SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

    PubMed Central

    Kuennen, M.; Gourley, C.; Schneider, S.; Dokladny, K.; Moseley, P.

    2013-01-01

    Introduction 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 (p < 0.05). Lys was unaffected by the race (p > 0.05). 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. PMID:24744458

  4. Variation in Definition of Prolonged Mechanical Ventilation.

    PubMed

    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

  5. Prolonging life: legal, ethical, and social dilemmas.

    PubMed

    Paulson, Steve; Comfort, Christopher P; Lee, Barbara Coombs; Shemie, Sam; Solomon, Mildred Z

    2014-11-01

    The ability of modern medicine to prolong life has raised a variety of difficult legal, ethical, and social issues on which reasonable minds can differ. Among these are the morality of euthanasia in cases of deep coma or irreversible injury, as well as the Dead Donor Rule with respect to organ harvesting and transplants. As science continues to refine and develop lifesaving technologies, questions remain as to how much medical effort and financial resources should be expended to prolong the lives of patients suspended between life and death. At what point should death be considered irreversible? What criteria should be used to determine when to withhold or withdraw life-prolonging treatments in cases of severe brain damage and terminal illness? To explore these complex dilemmas, Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion panel. Pediatrician Sam Shemie, hospice medical director Christopher P. Comfort, bioethicist Mildred Z. Solomon, and attorney Barbara Coombs Lee examined the underlying assumptions and considerations that ultimately shape individual and societal decisions surrounding these issues. The following is an edited transcript of the discussion that occurred November 12, 2013, 7:00-8:30 PM, at the New York Academy of Sciences in New York City. © 2014 New York Academy of Sciences.

  6. Prolonged blood circulation of methotrexate by modulation of liposomal composition.

    PubMed

    Hong, M S; Lim, S J; Lee, M K; Kim, Y B; Kim, C K

    2001-01-01

    Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmacokinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX.

  7. Abnormal vascular function in PR-interval prolongation.

    PubMed

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

    2011-10-01

    Underlying mechanisms of PR-interval prolongation leading to increased risk of adverse cardiovascular outcomes, including atrial fibrillation, are unclear. This study aims to investigate the relation between PR interval and changes in vascular function. We hypothesize that there exists an intermediate pathological stage between electrocardiographic PR prolongation and adverse cardiovascular outcomes, which could be reflected by changes in surrogate measurements of vascular function. We recruited 88 healthy subjects (mean age 57.5 ± 9.8 y, 46% male) from a community-based health screening program who had no history of cardiovascular disease or diabetes mellitus. PR interval was determined from a resting 12-lead electrocardiogram. Vascular function was noninvasively assessed by flow-mediated dilation (FMD) using high-resolution ultrasound and brachial-ankle pulse wave velocity (PWV) using a vascular profiling system. Only 3 subjects had a PR-interval length longer than the conventional cutoff of 200 ms. The PR-interval length was associated inversely with FMD (Pearson r = -0.30, P = 0.004) and positively with PWV (r = 0.40, P < 0.001). Adjusting for potential confounders, increased PR-interval length by each 25 ms was independently associated with reduced FMD by -1 unit (absolute %, B = -0.04 [95% confidence interval: -0.080 to -0.002, P = 0.040)] and increased PWV by +103 cm/second (B = +4.1 [95% confidence interval: 0.6-7.6, P = 0.023]). This study shows that PR-interval length, even in the conventionally normal range, is independently associated with endothelial dysfunction and increased arterial stiffness in healthy subjects free of atherosclerotic disease. This suggests the presence of a systemic, intermediate pathologic stage of the vasculature in PR prolongation before clinically manifest cardiovascular events, and could represent a mediating mechanism. © 2011 Wiley Periodicals, Inc.

  8. Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response.

    PubMed

    Oberlander, Tim F; Eckstein Grunau, Ruth; Fitzgerald, Colleen; Ellwood, Ann-Louise; Misri, Shaila; Rurak, Dan; Riggs, Kenneth Wayne

    2002-04-01

    Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are frequently used to treat maternal depression during pregnancy, however the effect of increased serotonin (5HT) and gamma-amino-butyric acid (GABA) agonists in the fetal human brain remains unknown. 5HT and GABA are active during fetal neurologic growth and play early roles in pain modulation, therefore, if prolonged prenatal exposure alters neurodevelopment this may become evident in altered neonatal pain responses. To examine biologic and behavioral effects of prenatal exposure, neonatal responses to acute pain (phenylketonuria heel lance) in infants with prolonged prenatal exposure were examined. Facial action (Neonatal Facial Coding System) and cardiac autonomic reactivity derived from the relationship between respiratory activity and short term variations of heart rate (HRV) were compared between 22 infants with SSRI exposure (SE) [fluoxetine (n = 7), paroxetine (n = 11), sertraline (n = 4)]; 16 infants exposed to SSRIs and clonazepam (SE+) [paroxetine (n = 14), fluoxetine (n = 2)]; and 23 nonexposed infants during baseline, lance, and recovery periods of a heel lance. Length of maternal SSRI use did not vary significantly between exposure groups-[mean (range)] SE:SE+ 183 (31-281):141 (54-282) d (p > 0.05). Infants exposed to SE and SE+ displayed significantly less facial activity to heel lance than control infants. Mean HR increased with lance, but was significantly lower in SE infants during recovery. Using measures of HRV and the transfer relationship between heart rate and respiration, SSRI infants had a greater return of parasympathetic cardiac modulation in the recovery period, whereas a sustained sympathetic response continued in the control group. Prolonged prenatal SSRI exposure appears to be associated with reduced behavioral pain responses and increased parasympathetic cardiac modulation in recovery following an acute neonatal noxious event. Possible 5HT-mediated pain inhibition

  9. Predicting prolonged dose titration in patients starting warfarin.

    PubMed

    Finkelman, Brian S; French, Benjamin; Bershaw, Luanne; Brensinger, Colleen M; Streiff, Michael B; Epstein, Andrew E; Kimmel, Stephen E

    2016-11-01

    Patients initiating warfarin therapy generally experience a dose-titration period of weeks to months, during which time they are at higher risk of both thromboembolic and bleeding events. Accurate prediction of prolonged dose titration could help clinicians determine which patients might be better treated by alternative anticoagulants that, while more costly, do not require dose titration. A prediction model was derived in a prospective cohort of patients starting warfarin (n = 390), using Cox regression, and validated in an external cohort (n = 663) from a later time period. Prolonged dose titration was defined as a dose-titration period >12 weeks. Predictor variables were selected using a modified best subsets algorithm, using leave-one-out cross-validation to reduce overfitting. The final model had five variables: warfarin indication, insurance status, number of doctor's visits in the previous year, smoking status, and heart failure. The area under the ROC curve (AUC) in the derivation cohort was 0.66 (95%CI 0.60, 0.74) using leave-one-out cross-validation, but only 0.59 (95%CI 0.54, 0.64) in the external validation cohort, and varied across clinics. Including genetic factors in the model did not improve the area under the ROC curve (0.59; 95%CI 0.54, 0.65). Relative utility curves indicated that the model was unlikely to provide a clinically meaningful benefit compared with no prediction. Our results suggest that prolonged dose titration cannot be accurately predicted in warfarin patients using traditional clinical, social, and genetic predictors, and that accurate prediction will need to accommodate heterogeneities across clinical sites and over time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Uncomplicated Caesarean section: is prolonged hospital stay necessary?

    PubMed

    Fasubaa, O B; Ogunniyi, S O; Dare, F O; Isawumi, A I; Ezechi, O C; Orji, E O

    2000-08-01

    Caesarean section among the Yoruba of western Nigerian is surrounded by a lot of fears, miseries, aversion, guilt and misconceptions for reasons varying from the desire by women to have a natural vaginal birth, fear of surgery, morbidity and deaths from the operation and prolonged hospital stay. To examine issues of reduced hospital stay following Caesarean section with a view of making the operation more acceptable and proffering solution to some of the problems faced by women when Caesarean section is indicated. A prospective case control study. Wesley Guild Hospital, Ilesha, Nigeria from 1st July, 1997 to 30th June, 1998. One hundred consecutive patients who had uncomplicated Caesarean section, randomised into two groups of short (three days) and prolonged (seven to eight days) hospital stay respectively. Observations of patients in both groups were made by an independent observer on day seven post-operation and the main outcomes measured included: wound infection rates, ability to maintain erect posture, mood changes, neonatal sepsis rate, immunisation rate of the neonates and average hospital bills. The findings revealed that wound infection rates of six per cent and ten per cent among the short and prolonged hospitalised patients respectively are not significantly different. Patients with short stay have better erect posture, lower incidence of depressive mood, lower neonatal sepsis rate, lower hospital bill and are more satisfied with early home discharge. Embracing the concept of early home discharge after Caesarean section in uncomplicated cases may remove some of the psychological upsets and economical impediments associated with the operation and make the operation more acceptable.

  11. Fetal brain hypometabolism during prolonged hypoxaemia in the llama.

    PubMed

    Ebensperger, Germán; Ebensperger, Renato; Herrera, Emilio A; Riquelme, Raquel A; Sanhueza, Emilia M; Lesage, Florian; Marengo, Juan J; Tejo, Rodrigo I; Llanos, Aníbal J; Reyes, Roberto V

    2005-09-15

    In this study we looked for additional evidence to support the hypothesis that fetal llama reacts to hypoxaemia with adaptive brain hypometabolism. We determined fetal llama brain temperature, Na(+) and K(+) channel density and Na(+)-K(+)-ATPase activity. Additionally, we looked to see whether there were signs of cell death in the brain cortex of llama fetuses submitted to prolonged hypoxaemia. Ten fetal llamas were instrumented under general anaesthesia to measure pH, arterial blood gases, mean arterial pressure, heart rate, and brain and core temperatures. Measurements were made 1 h before and every hour during 24 h of hypoxaemia (n = 5), which was imposed by reducing maternal inspired oxygen fraction to reach a fetal arterial partial pressure of oxygen (P(a,O(2))) of about 12 mmHg. A normoxaemic group was the control (n = 5). After 24 h of hypoxaemia, we determined brain cortex Na(+)-K(+)-ATPase activity, ouabain binding, and the expression of NaV1.1, NaV1.2, NaV1.3, NaV1.6, TREK1, TRAAK and K(ATP) channels. The lack of brain cortex damage was assessed as poly ADP-ribose polymerase (PARP) proteolysis. We found a mean decrease of 0.56 degrees C in brain cortex temperature during prolonged hypoxaemia, which was accompanied by a 51% decrease in brain cortex Na(+)-K(+)-ATPase activity, and by a 44% decrease in protein content of NaV1.1, a voltage-gated Na(+) channel. These changes occurred in absence of changes in PARP protein degradation, suggesting that the cell death of the brain was not enhanced in the fetal llama during hypoxaemia. Taken together, these results provide further evidence to support the hypothesis that the fetal llama responds to prolonged hypoxaemia with adaptive brain hypometabolism, partly mediated by decreases in Na(+)-K(+)-ATPase activity and expression of NaV channels.

  12. Effects of prolonged quiescence on neuclei and chromatin of WI-38 fibroblasts.

    PubMed

    Rossini, M; Lin, J C; Baserga, R

    1976-05-01

    DNA synthesis and cell division are markedly reduced in confluent mono-layers of WI-38 diploid fibroblasts, but resume again if the depleted medium is replaced by fresh medium containing 10% fetal calf serum. If the cells are kept quiescent for prolonged periods of time after confluence (1 or 2 weeks), the fraction of cells that can be stimulated to proliferate by fresh serum decreases and the length of the prereplicative phase increases. The template activity of isolated nuclei decreases with increasing time of quiescence, and parallel changes occur in chromatin as evidenced by circular dichroism spectra and capacity to bind the intercalating dye, ethidium bromide. When WI-38 cells are stimulated to proliferate after prolonged quiescence, the increase in template activity of nuclei is delayed by several hours in comparison to cells stimulated after short periods of quiescence. Two distinct steps, both requiring serum, can be identified in the prereplicative phase of cells stimulated to proliferative after prolonged quiescence. We interpret the results as indicating that, during prolonged quiescence, WI-38 fibroblasts go into a deeper GO state from which they can be rescued only after prolonged stimulation. In this respect, prolonged quiescence may bear some resemblance to the process of aging.

  13. QTc Prolongation in Patients Acutely Admitted to Hospital for Psychosis and Treated with Second Generation Antipsychotics

    PubMed Central

    Kroken, Rune A.; Løberg, Else-Marie; Jørgensen, Hugo A.

    2013-01-01

    QTc interval prolongation is a side effect of several antipsychotic drugs, with associated risks of torsade de pointes arrhythmias and sudden cardiac death. There is an ongoing debate of whether or not electrocardiogram (ECG) assessments should be mandatory in patients starting antipsychotic drugs. To investigate QTc prolongation in a clinically relevant patient group 171 adult patients acutely admitted to an emergency ward for psychosis were consecutively recruited. ECGs were recorded at baseline and then at discharge or after 6 weeks at the latest (discharge/6 weeks), thus reflecting the acute phase treatment period. The mean QTc interval was 421.1 (30.4) ms at baseline and there was a positive association between the QTc interval and the agitation score whereas the QTc interval was inversely associated with the serum calcium level. A total of 11.6% had abnormally prolonged QTc intervals and another 14.3% had borderline prolongation. At discharge/6 weeks, the corresponding proportions were reduced to 4.2% and 5.3%, respectively. The reduction of the proportion with prolonged QTc intervals reached statistical significance (chi-square exact test: P = 0.046). The finding of about one-quarter of the patients with borderline or prolonged QTc intervals could indicate mandatory ECG recordings in this population. This trial is registered with ClinicalTrials.gov ID: NCT00932529. PMID:24490070

  14. A review of ropinirole prolonged release in Parkinson’s disease

    PubMed Central

    Nashatizadeh, Muhammad M; Lyons, Kelly E; Pahwa, Rajesh

    2009-01-01

    Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson’s disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily “off” time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD. PMID:19503779

  15. Prolonged use of seclusion and mechanical restraint in mental health services: A statewide retrospective cohort study.

    PubMed

    McKenna, Brian; McEvedy, Samantha; Maguire, Tessa; Ryan, Jo; Furness, Trentham

    2017-10-01

    Seclusion and mechanical restraint are restrictive interventions that should be used only as a last resort and for the shortest possible time, yet little is known about duration of use in the broader context. Adult area mental health services throughout Victoria, Australia, were asked to complete a report form for prolonged episodes of seclusion (>8 hours) and mechanical restraint (>1 hour). The present, retrospective cohort study aimed to understand the individual (age, sex, type of service, duration of intervention) and contextual factors associated with prolonged use of restrictive interventions. Contextual factors describing the reasons for prolonged use of the restrictive interventions were captured qualitatively, and then coded using content analysis. Median duration was compared across individual factors using Mann-Whitney U-tests. During 2014, 690 episodes of prolonged restrictive intervention involving 311 consumers were reported. Close to half (n = 320, 46%) involved mechanical restraint. Seclusion episodes (n = 370) were longer in forensic mental health services compared to adult area mental health services (median: 24 hours and 18 min vs 16 hours and 42 min, P < 0.001). Mechanical restraint episodes (n = 320) were shorter in forensic mental health services compared to adult area mental health services (median: 3 hours and 25 min vs 4 hours and 15 min, P = 0.008). Some consumers were subject to multiple episodes of prolonged seclusion (55/206, 27%) and/or prolonged mechanical restraint (31/131, 24%). The most commonly occurring contextual factor for prolonged restrictive interventions was 'risk of harm to others'. Means for reducing the use of prolonged restrictive interventions are discussed in light of the findings. © 2017 Australian College of Mental Health Nurses Inc.

  16. Capacitance-Based Frequency Adjustment of Micro Piezoelectric Vibration Generator

    PubMed Central

    Mao, Xinhua; He, Qing; Li, Hong; Chu, Dongliang

    2014-01-01

    Micro piezoelectric vibration generator has a wide application in the field of microelectronics. Its natural frequency is unchanged after being manufactured. However, resonance cannot occur when the natural frequencies of a piezoelectric generator and the source of vibration frequency are not consistent. Output voltage of the piezoelectric generator will sharply decline. It cannot normally supply power for electronic devices. In order to make the natural frequency of the generator approach the frequency of vibration source, the capacitance FM technology is adopted in this paper. Different capacitance FM schemes are designed by different locations of the adjustment layer. The corresponding capacitance FM models have been established. Characteristic and effect of the capacitance FM have been simulated by the FM model. Experimental results show that the natural frequency of the generator could vary from 46.5 Hz to 42.4 Hz when the bypass capacitance value increases from 0 nF to 30 nF. The natural frequency of a piezoelectric vibration generator could be continuously adjusted by this method. PMID:25133237

  17. Capacitance-based frequency adjustment of micro piezoelectric vibration generator.

    PubMed

    Mao, Xinhua; He, Qing; Li, Hong; Chu, Dongliang

    2014-01-01

    Micro piezoelectric vibration generator has a wide application in the field of microelectronics. Its natural frequency is unchanged after being manufactured. However, resonance cannot occur when the natural frequencies of a piezoelectric generator and the source of vibration frequency are not consistent. Output voltage of the piezoelectric generator will sharply decline. It cannot normally supply power for electronic devices. In order to make the natural frequency of the generator approach the frequency of vibration source, the capacitance FM technology is adopted in this paper. Different capacitance FM schemes are designed by different locations of the adjustment layer. The corresponding capacitance FM models have been established. Characteristic and effect of the capacitance FM have been simulated by the FM model. Experimental results show that the natural frequency of the generator could vary from 46.5 Hz to 42.4 Hz when the bypass capacitance value increases from 0 nF to 30 nF. The natural frequency of a piezoelectric vibration generator could be continuously adjusted by this method.

  18. Model Frequency Adjustment of the EU:CROPIS Satellite Structure

    NASA Astrophysics Data System (ADS)

    Mierheim, Olaf; Glaser, Thilo; Huhne, Christian; Muller, Hartmut; Kheiri, Elnaz

    2014-06-01

    Satellites are subject to different dynamic loads during launch. The load acting on the satellite and its systems is highly dependent on its own natural frequencies. It is possible to tune these frequencies in a certain range to meet set requirements such as related to space, mass, strength stiffness and required minimum frequency.The typical satellite being beard on one side has two bending modes and one elongation mode. These modes have coupled frequencies so that stiffening the structure will influence the lowest natural frequencies in all three axis. This paper focuses on how to influence the depending frequencies and their effects on the loads.

  19. Metabolism of normothermic woodchucks during prolonged fasting.

    PubMed

    Reidy, Shannon P; Weber, Jean-Michel

    2004-12-01

    The energy metabolism of hibernators has not been characterized for normothermic fasting, and our goal was to quantify oxidative fuel selection of non-hibernating woodchucks Marmota monax during prolonged food deprivation. Indirect calorimetry and nitrogen excretion measurements were used to assess changes in metabolic rate (VO2), fuel selection and composition of nitrogen wastes, as well as seasonal differences. For reference, matching experiments were also performed on rabbits. The results show that woodchucks have a higher metabolic rate in summer (271 micromol O2 kg(-1) min(-1)) than in spring (200 micromol O2 kg(-1) min(-1)) and that fasting-induced metabolic depression is only possible in summer (-25% in 14 days). The metabolic rate of rabbits is high at all times (383 micromol O2 kg(-1) min(-1)), but they show a more rapid depression in response to fasting (-32% in 7 days). Woodchucks have a naturally low reliance on proteins in the fed state (accounting for 8% VO2) in spring; 17% VO2 in summer; vs 28% VO2 in rabbits) and are able to decrease it even further during fasting (spring, 5% VO2); summer, 6% VO2; vs 20% VO2 in rabbits). This study shows that, apart from their notorious capacity for hibernation, woodchucks are particularly well adapted for normothermic fasting. Their ability to cope with prolonged food deprivation is based on a series of integrated responses eliciting deep metabolic depression and a rapid change in fuel selection to spare limited protein reserves. Information presently available on prolonged fasting suggests that such an ability for metabolic depression, possibly down to minimal levels still compatible with normothermic life, may be common among mammals. In contrast, the extreme protein sparing demonstrated in woodchucks is a unique metabolic feature of fasting champions.

  20. Clinical dysphagia risk predictors after prolonged orotracheal intubation

    PubMed Central

    de Medeiros, Gisele Chagas; Sassi, Fernanda Chiarion; Mangilli, Laura Davison; Zilberstein, Bruno; de Andrade, Claudia Regina Furquim

    2014-01-01

    OBJECTIVES: To elucidate independent risk factors for dysphagia after prolonged orotracheal intubation. METHODS: The participants were 148 consecutive patients who underwent clinical bedside swallowing assessments from September 2009 to September 2011. All patients had received prolonged orotracheal intubations and were admitted to one of several intensive care units of a large Brazilian school hospital. The correlations between the conducted water swallow test results and dysphagia risk levels were analyzed for statistical significance. RESULTS: Of the 148 patients included in the study, 91 were male and 57 were female (mean age, 53.64 years). The univariate analysis results indicated that specific variables, including extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking, and other signs, were possible significant high-risk indicators of dysphagia onset. The multivariate analysis results indicated that cervical auscultation and coughing were independent predictive variables for high dysphagia risk. CONCLUSIONS: Patients displaying extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking and other signs should benefit from early swallowing evaluations. Additionally, early post-extubation dysfunction recognition is paramount in reducing the morbidity rate in this high-risk population. PMID:24473554

  1. Survival without sequelae after prolonged cardiopulmonary resuscitation after electric shock.

    PubMed

    Motawea, Mohamad; Al-Kenany, Al-Sayed; Hosny, Mostafa; Aglan, Omar; Samy, Mohamad; Al-Abd, Mohamed

    2016-03-01

    "Electrical shock is the physiological reaction or injury caused by electric current passing through the human body. It occurs upon contact of a human body part with any source of electricity that causes a sufficient current through the skin, muscles, or hair causing undesirable effects ranging from simple burns to death." Ventricular fibrillation is believed to be the most common cause of death after electrical shock. "The ideal duration of cardiac resuscitation is unknown. Typically prolonged cardiopulmonary resuscitation is associated with poor neurologic outcomes and reduced long term survival. No consensus statement has been made and traditionally efforts are usually terminated after 15-30 minutes." The case under discussion seems worthy of the somewhat detailed description given. It is for a young man who survived after 65 minutes after electrical shock (ES) after prolonged high-quality cardiopulmonary resuscitation (CPR), multiple defibrillations, and artificial ventilation without any sequelae. Early start of adequate chest compressions and close adherence to advanced cardiac life support protocols played a vital role in successful CPR.

  2. Electrical shock survival after prolonged cardiopulmonary resuscitation.

    PubMed

    Ahmad, Maqsood; Shabbir, Khawar

    2013-07-01

    Electrical shock is typically an untoward exposure of human body to any source of electricity that causes a sufficient current to pass through the skin, muscles or hair causing undesirable effects ranging from simple burns to death. Ventricular fibrillation is believed to be the most common cause of death following electrical shock. The case under discussion is of a young man who survived following electrical shock after prolonged cardiopulmonary resuscitation (CPR), multiple defibrillations and artificial ventilation due to poor respiratory effort. Early start of chest compressions played a vital role in successful CPR.

  3. Survival of soil bacteria during prolonged desiccation.

    NASA Technical Reports Server (NTRS)

    Chen, M.; Alexander, M.

    1973-01-01

    A determination was made of the kinds and numbers of bacteria surviving when two soils were maintained in the laboratory under dry conditions for more than half a year. Certain non-spore-forming bacteria were found to survive in the dry condition for long periods. A higher percentage of drought-tolerant than drought-sensitive bacteria was able to grow at low water activities. When they were grown in media with high salt concentrations, bacteria generally became more tolerant of prolonged drought and they persisted longer. The percent of cells in a bacterial population that remained viable when exposed to drought stress varied with the stage of growth.

  4. Mutant models of prolonged life span.

    PubMed

    Mahler, J F

    2001-01-01

    Aging is an important biological process that affects all creatures. For humans, age-related diseases and the question of why we age and die also have tremendous social and philosophical impact. We can therefore expect that models to study mechanisms of the aging process will always attract much interest. Until recently, the mutant model approach to study molecular mechanisms of aging has been limited to lower animals such as yeast, worms, and flies. However, given the current power of genetic technology in mammals, we can expect that phenotypes of prolonged life span will increasingly be seen in mice and subject to evaluation by pathologists. A brief review of current models is presented.

  5. Survival of soil bacteria during prolonged desiccation.

    NASA Technical Reports Server (NTRS)

    Chen, M.; Alexander, M.

    1973-01-01

    A determination was made of the kinds and numbers of bacteria surviving when two soils were maintained in the laboratory under dry conditions for more than half a year. Certain non-spore-forming bacteria were found to survive in the dry condition for long periods. A higher percentage of drought-tolerant than drought-sensitive bacteria was able to grow at low water activities. When they were grown in media with high salt concentrations, bacteria generally became more tolerant of prolonged drought and they persisted longer. The percent of cells in a bacterial population that remained viable when exposed to drought stress varied with the stage of growth.

  6. Skeletal muscle water and electrolytes following prolonged dehydrating exercise.

    PubMed

    Mora-Rodríguez, R; Fernández-Elías, V E; Hamouti, N; Ortega, J F

    2015-06-01

    We studied if dehydrating exercise would reduce muscle water (H2Omuscle ) and affect muscle electrolyte concentrations. Vastus lateralis muscle biopsies were collected prior, immediately after, and 1 and 4 h after prolonged dehydrating exercise (150 min at 33 ± 1 °C, 25% ± 2% humidity) on nine endurance-trained cyclists (VO2max  = 54.4 ± 1.05 mL/kg/min). Plasma volume (PV) changes and fluid shifts between compartments (Cl(-) method) were measured. Exercise dehydrated subjects 4.7% ± 0.3% of body mass by losing 2.75 ± 0.15 L of water and reducing PV 18.4% ± 1% below pre-exercise values (P < 0.05). Right after exercise H2Omuscle remained at pre-exercise values (i.e., 398 ± 6 mL/100 g dw muscle(-1)) but declined 13% ± 2% (342 ± 12 mL/100 g dw muscle(-1); P < 0.05) after 1 h of supine rest. At that time, PV recovered toward pre-exercise levels. The Cl(-) method corroborated the shift of fluid between extracellular and intracellular compartments. After 4 h of recovery, PV returned to pre-exercise values; however, H2Omuscle remained reduced at the same level. Muscle Na(+) and K(+) increased (P < 0.05) in response to the H2Omuscle reductions. Our findings suggest that active skeletal muscle does not show a net loss of H2O during prolonged dehydrating exercise. However, during the first hour of recovery H2Omuscle decreases seemly to restore PV and thus cardiovascular stability.

  7. Standardized Approach to Prolonged Air Leak Reduction After Pulmonary Resection.

    PubMed

    Drahush, Nicholas; Miller, Ashley D; Smith, Jeremiah S; Royer, Anna M; Spiva, Marlana; Headrick, James R

    2016-06-01

    Prolonged air leaks after pulmonary resection lead to patient discomfort, increased hospital length of stay, greater health care costs, and increased morbidity. A standardized approach to air leak reduction (STAR) after lung resection was developed and studied. A retrospective review was conducted of a prospective database from 1 surgeon who had adopted STAR as standard of care. Three independent factors shown to reduce air leaks are incorporated in STAR: fissureless operative technique, staple line buttressing, and protocol-driven chest tube management. Patient characteristics and outcomes were compared against aggregate data from The Society of Thoracic Surgeons National Database (2012-2014). From June 2010 through May 2015, 475 patients met the study criteria. Of these, 264 (55.6%) had lobectomies, 198 (41.7%) had wedge resections, and 13 (2.7%) had segmentectomies. Prolonged air leaks were reduced in the STAR lobectomy group by 52% (5.7% versus 10.9%; p = 0.0079) and in the STAR wedge group by 40% (2.5% versus 4.2%; p = 0.38). Hospital length of stay for lobectomies (3.2 versus 6.3 days; p = 0.0001), wedge resections (3.3 versus 4.5 days; p = 0.0152), and segmentectomies (3.2 versus 5.2 days; p = 0.0001) was significantly reduced. Readmission rate was 4% and none were related to air leak. No difference was seen in mortality rates. Use of STAR for pulmonary resection, particularly for lobectomies, shows decreased postoperative prolonged air leaks when compared with The Society of Thoracic Surgeons National Database. This aggressive approach did not lead to air leak-related hospital readmissions nor compromise postoperative mortality. The STAR protocol is an innovative strategy that has the potential to improve postoperative pulmonary resection outcomes. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Review and Outcome of Prolonged Cardiopulmonary Resuscitation

    PubMed Central

    Youness, Houssein; Al Halabi, Tarek; Hussein, Hussein; Awab, Ahmed; Jones, Kellie; Keddissi, Jean

    2016-01-01

    The maximal duration of cardiopulmonary resuscitation (CPR) is unknown. We report a case of prolonged CPR. We have then reviewed all published cases with CPR duration equal to or more than 20 minutes. The objective was to determine the survival rate, the neurological outcome, and the characteristics of the survivors. Measurements and Main Results. The CPR data for 82 patients was reviewed. The median duration of CPR was 75 minutes. Patients mean age was 43 ± 21 years with no significant comorbidities. The main causes of the cardiac arrests were myocardial infarction (29%), hypothermia (21%), and pulmonary emboli (12%). 74% of the arrests were witnessed, with a mean latency to CPR of 2 ± 6 minutes and good quality chest compression provided in 96% of the cases. Adjunct therapy included extracorporeal membrane oxygenation (18%), thrombolysis (15.8%), and rewarming for hypothermia (19.5%). 83% were alive at 1 year, with full neurological recovery reported in 63 patients. Conclusion. Patients undergoing prolonged CPR can survive with good outcome. Young age, myocardial infarction, and potentially reversible causes of cardiac arrest such as hypothermia and pulmonary emboli predict a favorable result, especially when the arrest is witnessed and followed by prompt and good resuscitative efforts. PMID:26885387

  9. [Left ventricular dyssynchrony in prolonged septal stimulation].

    PubMed

    Ferrando-Castagnetto, Federico; Ricca-Mallada, Roberto; Vidal, Alejandro; Martínez, Fabián; Ferrando, Rodolfo

    2016-01-01

    Pacemaker stimulation is associated with unpredictable severe cardiac events. We evaluated left ventricular mechanical dyssynchrony (LVMD) during prolonged septal right ventricular pacing. We performed 99mTc-MIBI gated-SPECT and phase analysis in 6 patients with pacemakers implanted at least one year before scintigraphy due to advanced atrioventricular block. Using V-Sync of Emory Cardiac Toolbox we obtained phase bandwidth (PBW) and standard deviation (PSD) from rest phase histogram. Clinical variables, QRS duration, rate and mode of pacing in septal right ventricle wall, chamber diameters, presence and extension of myocardial scar and ischemia and rest LVEF were recorded. Prolonged septal endocardial pacing is associated with marked LVMD, even when systolic function was preserved. More severe dyssynchrony was found in patients with impaired LVEF, higher left ventricle diameters, extensive infarct or severe ischemia than in patients with preserved LVEF (PBW: 177.3o vs. 88.3o; PSD: 53.1o vs. 33.8o). In the patients with ischemic heart disease and pacemaker, gated-SPECT phase analysis is a valid and potentially useful technique to evaluate LMVD associated with myocardial scar and to decide the upgrading to biventricular pacing mode.

  10. Blueberry extract prolongs lifespan of Drosophila melanogaster.

    PubMed

    Peng, Cheng; Zuo, Yuanyuan; Kwan, Kin Ming; Liang, Yintong; Ma, Ka Ying; Chan, Ho Yin Edwin; Huang, Yu; Yu, Hongjian; Chen, Zhen-Yu

    2012-02-01

    Blueberry possesses greater antioxidant capacity than most other fruits and vegetables. The present study investigated the lifespan-prolonging activity of blueberry extracts in fruit flies and explored its underlying mechanism. Results revealed that blueberry extracts at 5mg/ml in diet could significantly extend the mean lifespan of fruit flies by 10%, accompanied by up-regulating gene expression of superoxide dismutase (SOD), catalase (CAT) and Rpn11 and down-regulating Methuselah (MTH) gene. Intensive H(2)O(2) and Paraquat challenge tests showed that lifespan was only extended in Oregon-R wild type flies but not in SOD(n108) or Cat(n1) mutant strains. Chronic Paraquat exposure shortened the maximum survival time from 73 to 35days and decreased the climbing ability by 60% while blueberry extracts at 5mg/ml in diet could significantly increase the survival rate and partially restore the climbing ability with up-regulating SOD, CAT, and Rpn11. Furthermore, gustatory assay demonstrated that those changes were not due to the variation of food intake between the control and the experimental diet containing 5mg/ml blueberry extracts. It was therefore concluded that the lifespan-prolonging activity of blueberry extracts was at least partially associated with its interactions with MTH, Rpn11, and endogenous antioxidant enzymes SOD and CAT.

  11. Topical Drug Formulations for Prolonged Corneal Anesthesia

    PubMed Central

    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

  12. Prolonged sensory-selective nerve blockade

    PubMed Central

    Sagie, Itay; Kohane, Daniel S.

    2010-01-01

    Sensory-selective local anesthesia has long been a key goal in local anesthetic development. For example, it allows women to be pain-free during labor without compromising their ability to push. Here we show that prolonged sensory-selective nerve block can be produced by specific concentrations of surfactants—such as are used to enhance drug flux across skin—in combination with QX-314, a lidocaine derivative that has relative difficulty penetrating nerves. For example, injection of 25 mM QX-314 in 30 mM octyltrimethylammonium bromide (OTAB) lasted up to 7 h. Sensory selectivity was imparted to varying degrees by cationic, neutral, and anionic surfactants, and also was achieved with another lidocaine derivative, QX-222. Simultaneous injection of OTAB at a s.c. injection site remote from the sciatic nerve did not result in prolonged sensory-specific nerve blockade from QX-314, suggesting that the observed effect is due to a local interaction between the surfactant and the lidocaine derivative, not a systemic effect. PMID:20133669

  13. Prolonged grief disorder and depression in a German community sample.

    PubMed

    Schaal, Susanne; Richter, Anne; Elbert, Thomas

    2014-01-01

    The aims of this study were to examine rates and risk factors for prolonged grief and to investigate the association between prolonged grief and depression. The authors interviewed a heterogeneous bereaved sample of 61 Germans, 6 of whom had prolonged grief and depression, respectively. The 2 syndromes were strongly linked to one another. Risk factors for prolonged grief were being a woman and having high levels of religious beliefs and low levels of satisfaction with one's religious beliefs, emotional closeness to the deceased, and unanticipated loss. Symptoms of prolonged grief may endure years post-loss and often overlap with depression.

  14. Impact of prolonged leucine supplementation on protein synthesis and lean growth in neonatal pigs

    USDA-ARS?s Scientific Manuscript database

    Most low-birth weight infants experience extrauterine growth failure due to reduced nutrient intake as a result of feeding intolerance. The objective of this study was to determine whether prolonged enteral leucine supplementation improves lean growth in neonatal pigs fed a restricted protein diet. ...

  15. Does prolonged breastfeeding adversely affect a child's nutritional status?

    PubMed

    Brakohiapa, L A; Yartey, J; Bille, A; Harrison, E; Quansah, E; Armar, M A; Kishi, K; Yamamoto, S

    1988-08-20

    In 202 children who visited a children's hospital in the city of Accra, Ghana, breastfeeding beyond the age of 19 months was found to be associated with malnutrition. The effect of weaning on food intake was then studied in 15 breastfed malnourished children in a rural community. Before weaning (complete cessation of breast-feeding) protein and energy intakes of all the malnourished children were about half those of 5 normal children. 10 of the malnourished children were weaned, and their intakes rose to the levels of the normal children; the 5 who continued breastfeeding maintained their low intakes. These results indicate that prolonged breastfeeding can reduce total food intake and thus predispose to malnutrition. They also suggest that in Ghana and other developing countries the proper weaning age may be about 18 months.

  16. Drug-induced QT interval prolongation: mechanisms and clinical management

    PubMed Central

    Nachimuthu, Senthil; Assar, Manish D.

    2012-01-01

    The prolonged QT interval is both widely seen and associated with the potentially deadly rhythm, Torsades de Pointes (TdP). While it can occur spontaneously in the congenital form, there is a wide array of drugs that have been implicated in the prolongation of the QT interval. Some of these drugs have either been restricted or withdrawn from the market due to the increased incidence of fatal polymorphic ventricular tachycardia. The list of drugs that cause QT prolongation continues to grow, and an updated list of specific drugs that prolong the QT interval can be found at www.qtdrugs.org. This review focuses on the mechanism of drug-induced QT prolongation, risk factors for TdP, culprit drugs, prevention and monitoring of prolonged drug-induced QT prolongation and treatment strategies. PMID:25083239

  17. Caffeine, carbohydrate, and cooling use during prolonged simulated tennis.

    PubMed

    Hornery, Daniel J; Farrow, Damian; Mujika, Inigo; Young, Warren B

    2007-12-01

    To determine the effects of prolonged simulated tennis on performance and the ergogenic potential of caffeine, carbohydrates, and cooling. Twelve highly trained male tennis players (age 18.3 +/- 3.0 y, height 178.8 +/- 8.5 cm, body mass 73.95 +/- 12.30 kg, mean +/- SD) performed 4 simulated matches (2 h 40 min) against a ball machine on an indoor hard court. The counterbalanced experimental trials involved caffeine supplementation (3 mg/kg), carbohydrate supplementation (6% solution), precooling and intermittent cooling, and placebo control. Physiological markers (core temperature, heart rate, blood lactate, and blood glucose), subjective responses (ratings of perceived exertion and thermal sensation), stroke velocity and accuracy, serve kinematics, and tennis-specific perceptual skill quantified the efficacy of interventions. Significant effects of time (P < .01) reflected increased physiological demand, reduced serve velocity and ground-stroke velocity and accuracy, and a slowing of the serve racket-arm acceleration phase. Caffeine increased serve velocity (165 +/- 15 km/h) in the final set of the match (P = .014) compared with placebo (159 +/- 15 km/h, P = .008) and carbohydrate (158 +/- 13 km/h, P = .001) conditions. Carbohydrate and cooling conditions afforded physiological advantage (increased blood glucose, P < .01, and reduced preexercise thermal sensation, P < .01) but did not affect performance relative to the placebo condition. Prolonged simulated tennis induced significant decrements in tennis skills. Caffeine supplementation partly attenuated the effects of fatigue and increased serve velocity. In contrast, carbohydrate and cooling strategies had little ergogenic effect on tennis performance.

  18. Factors associated with prolonged length of stay in older patients

    PubMed Central

    Toh, Hui Jin; Lim, Zhen Yu; Yap, Philip; Tang, Terence

    2017-01-01

    INTRODUCTION Prolonged stay in acute hospitals increases the risk of hospital-acquired infections in older patients, and disrupts patient flow and access to care due to bed shortages. We aimed to investigate the factors associated with prolonged length of stay (pLOS) among older patients (aged ≥ 78 years) in a tertiary hospital, to identify the potentially modifiable risk factors that could direct interventions to reduce length of stay (LOS). METHODS During a three-month period from January 2013 to March 2013, we identified 72 patients with pLOS (LOS ≥ 21 days) and compared their demographic and clinical variables with that of 281 randomly selected control patients (LOS < 21 days) using univariate and multivariate logistic regression analyses. RESULTS The mean age of the patients was 85.30 ± 5.34 years; 54% of them were female and 72% were of Chinese ethnicity. Logistic regression revealed the following significant factors for increased LOS: discharge to intermediate and long-term care services (odds ratio [OR] 9.22, 95% confidence interval [CI] 3.56–23.89; p < 0.001); increased severity of illness (OR 2.41, 95% CI 1.12–5.21; p = 0.025); and presence of caregiver stress (OR 3.85, 95% CI 1.67–8.91; p = 0.002). CONCLUSION Presence of caregiver stress and nursing home placement are potential modifiable risk factors of pLOS among older patients. Early identification and management of caregiver stress, as well as expediting discharge planning, may help to reduce the length of stay for this cohort. PMID:27609507

  19. Bilateral Scapulohumeral Ankylosis after Prolonged Mechanical Ventilation

    PubMed Central

    Schreinemakers, J. Rieneke; van Noort, Arthur; Rademakers, Maarten V.

    2016-01-01

    This case demonstrates a rarely reported bilateral scapulohumeral bony ankylosis. A young woman developed extensive heterotopic ossifications (HOs) in both shoulder joints after being mechanically ventilated for several months at the intensive care unit in a comatose status. She presented with a severe movement restriction of both shoulder joints. Surgical resection of the bony bridges was performed in 2 separate sessions with a significant improvement of shoulder function afterwards. No postoperative complications, pain, or recurrence of HOs were noted at 1-year follow-up. Mechanical ventilation, immobilization, neuromuscular blockage, and prolonged sedation are known risk factors for the development of HOs in the shoulder joints. Relatively early surgical resection of the HOs can be performed safely in contrary to earlier belief. Afterwards, nonsteroidal anti-inflammatory drugs and/or radiation therapy can be possible treatment modalities to prevent recurrence of HOs. PMID:27583120

  20. Prolonging Microgravity on Parabolic Airplane Flights

    NASA Technical Reports Server (NTRS)

    Robinson, David W.

    2003-01-01

    Three techniques have been proposed to prolong the intervals of time available for microgravity experiments aboard airplanes flown along parabolic trajectories. Typically, a pilot strives to keep an airplane on such a trajectory during a nominal time interval as long as 25 seconds, and an experimental apparatus is released to float freely in the airplane cabin to take advantage of the microgravitational environment of the trajectory for as long as possible. It is usually not possible to maintain effective microgravity during the entire nominal time interval because random aerodynamic forces and fluctuations in pilot control inputs cause the airplane to deviate slightly from a perfect parabolic trajectory, such that the freely floating apparatus bumps into the ceiling, floor, or a wall of the airplane before the completion of the parabola.

  1. Prolonging entanglement dynamics near periodic plasmonic nanostructures

    NASA Astrophysics Data System (ADS)

    Iliopoulos, Nikos; Terzis, Andreas F.; Yannopapas, Vassilios; Paspalakis, Emmanuel

    2017-08-01

    We study the dynamics of two initially entangled qubits, where each one interacts locally and independently of the other, with a plasmonic nanostructure. By considering two different cases for the qubits, two identical two-level systems and two identical V-type quantum systems, where one two-level transition plays the role of the qubit while the third level acts as an "umbrella level", we study the corresponding entanglement dynamics for several pure and mixed initial states. As the plasmonic nanostructure we take a two-dimensional lattice of metal-coated dielectric nanoparticles. The presence of this nanostructure leads to highly suppressed spontaneous emission rates of the individual quantum systems, as well as to highly anisotropic spontaneous decay rates for orthogonal dipole matrix elements due to the anisotropic Purcell effect, leading to quantum interference in spontaneous emission. Both of the effects can be used for significantly prolonging the time evolution of entanglement for several system parameters.

  2. Evolution of microbial diversity during prolonged starvation

    PubMed Central

    Finkel, Steven E.; Kolter, Roberto

    1999-01-01

    Models of evolutionary processes postulate that new alleles appear in populations through random spontaneous mutation. Alleles that confer a competitive advantage in particular environments are selected and populations can be taken over by individuals expressing these advantageous mutations. We have studied the evolutionary process by using Escherichia coli cultures incubated for prolonged periods of time in stationary phase. The populations of surviving cells were shown to be highly dynamic, even after many months of incubation. Evolution proceeded along different paths even when the initial conditions were identical. As cultures aged, the takeovers by fitter mutants were incomplete, resulting in the coexistence of multiple mutant forms and increased microbial diversity. Thus, the study of bacterial populations in stationary phase provides a model system for understanding the evolution of diversity in natural populations. PMID:10097156

  3. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    PubMed

    Mao, Sheng-Chun; Chang, Chih-Hua; Wu, Chia-Chen; Orejarena, M Juliana; Orejanera, Maria Juliana; Manzoni, Olivier J; Gean, Po-Wu

    2013-01-01

    Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  4. Inhibition of Spontaneous Recovery of Fear by mGluR5 after Prolonged Extinction Training

    PubMed Central

    Wu, Chia-Chen; Orejanera, Maria Juliana; Manzoni, Olivier J.; Gean, Po-Wu

    2013-01-01

    Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1−/− mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR23Y, a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias. PMID:23555716

  5. Prolonged cold storage of red blood cells by oxygen removal and additive usage

    DOEpatents

    Bitensky, M.W.; Yoshida, Tatsuro

    1998-08-04

    Prolonged cold storage of red blood cells by oxygen removal and additive usage. A cost-effective, 4 C storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. The improved in vivo survival and the preservation of adenosine triphosphate levels, along with reduction in hemolysis and membrane vesicle production of red blood cells stored at 4 C for prolonged periods of time, is achieved by reducing the oxygen level therein at the time of storage; in particular, by flushing the cells with an inert gas, and storing them in an aqueous solution which includes adenine, dextrose, mannitol, citrate ion, and dihydrogen phosphate ion, but no sodium chloride, in an oxygen-permeable container which is located in an oxygen-free environment containing oxygen-scavenging materials. 8 figs.

  6. Risperidone prolongs cardiac action potential through reduction of K+ currents in rabbit myocytes.

    PubMed

    Gluais, Pascale; Bastide, Michèle; Caron, Jacques; Adamantidis, Monique

    2002-05-31

    Prolongation of QT interval by antipsychotic drugs is an unwanted side effect that may lead to ventricular arrhythmias. The antipsychotic agent risperidone has been shown to cause QT prolongation, especially in case of overdosage. We investigated risperidone effects on action potentials recorded from rabbit Purkinje fibers and ventricular myocardium and on potassium currents recorded from atrial and ventricular rabbit isolated myocytes. The results showed that (1) risperidone (0.1-3 microM) exerted potent lengthening effects on action potential duration in both tissues with higher potency in Purkinje fibers and caused the development of early afterdepolarizations at low stimulation rate; (2) risperidone (0.03-0.3 microM) reduced significantly the current density of the delayed rectifier current and at 30 microM decreased the transient outward and the inward rectifier currents. This study might explain QT prolongation observed in some patients treated with risperidone and gives enlightenment on the risk of cardiac adverse events.

  7. Prolonged cold storage of red blood cells by oxygen removal and additive usage

    DOEpatents

    Bitensky, Mark W.; Yoshida, Tatsuro

    1998-01-01

    Prolonged cold storage of red blood cells by oxygen removal and additive usage. A cost-effective, 4.degree. C. storage procedure that preserves red cell quality and prolongs post-transfusion in vivo survival is described. The improved in vivo survival and the preservation of adenosine triphosphate levels, along with reduction in hemolysis and membrane vesicle production of red blood cells stored at 4.degree. C. for prolonged periods of time, is achieved by reducing the oxygen level therein at the time of storage; in particular, by flushing the cells with an inert gas, and storing them in an aqueous solution which includes adenine, dextrose, mannitol, citrate ion, and dihydrogen phosphate ion, but no sodium chloride, in an oxygen-permeable container which is located in an oxygen-free environment containing oxygen-scavenging materials.

  8. Prolonged pain and disability are common after rib fractures.

    PubMed

    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.

  9. Predicting Prolonged Stay in the ICU Attributable to Bleeding in Patients Offered Plasma Transfusion

    PubMed Central

    Ngufor, Che; Murphree, Dennis; Upadhyaya, Sudhi; Madde, Nageswar; Pathak, Jyotishman; Carter, Rickey; Kor, Daryl

    2016-01-01

    In blood transfusion studies, plasma transfusion (PPT) and bleeding are known to be associated with risk of prolonged ICU length of stay (ICU-LOS). However, as patients can show significant heterogeneity in response to a treatment, there might exists subgroups with differential effects. The existence and characteristics of these subpopulations in blood transfusion has not been well-studied. Further, the impact of bleeding in patients offered PPT on prolonged ICU-LOS is not known. This study presents a causal and predictive framework to examine these problems. The two-step approach first estimates the effect of bleeding in PPT patients on prolonged ICU-LOS and then estimates risks of bleeding and prolonged ICU-LOS. The framework integrates a classification model for risks prediction and a regression model to predict actual LOS. Results showed that the effect of bleeding in PPT patients significantly increases risk of prolonged ICU-LOS (55%, p=0.00) while no bleeding significantly reduces ICU-LOS (4%, p=0.046). PMID:28269892

  10. Arytenoid Dislocation as a Cause of Prolonged Hoarseness after Cervical Discectomy and Fusion

    PubMed Central

    Goz, Vadim; Qureshi, Sheeraz; Hecht, Andrew C.

    2012-01-01

    Study Design Case series of two arytenoid dislocations after anterior cervical discectomy. Objective To recognize arytenoid dislocation as a possible cause of prolonged hoarseness in patients after anterior cervical discectomies. Summary of Background Data Prolonged hoarseness is a common postoperative complication after anterior cervical spine surgery. The etiology of prolonged postoperative hoarseness is usually related to a paresis of the recurrent laryngeal nerve. However, other causes of postoperative hoarseness may be overlooked in this clinical scenario. Other possible etiologies include pharyngeal and laryngeal trauma, hematoma and edema, injury of the superior laryngeal nerve, as well as arytenoid cartilage dislocation. Arytenoid dislocation is often misdiagnosed as vocal fold paresis due to recurrent or laryngeal nerve injury. Methods We report two cases of arytenoid dislocation and review the literature on this pathology. Results Two patients treated with anterior cervical discectomy and fusion experienced prolonged postoperative hoarseness. Arytenoid dislocation was confirmed by flexible fiber-optic laryngoscopy in both cases. The dislocations experienced spontaneous reduction at 6 weeks and 3 months postsurgery. Conclusions Arytenoid dislocation must be considered in the differential diagnosis of prolonged postoperative hoarseness and evaluated for using direct laryngoscopy, computed tomography, or a laryngeal electromyography. Upon diagnosis, treatment must be considered immediately. Slight dislocations can reduce spontaneously without surgical intervention; however, operative intervention may be required at times. PMID:24436851

  11. Arytenoid dislocation as a cause of prolonged hoarseness after cervical discectomy and fusion.

    PubMed

    Goz, Vadim; Qureshi, Sheeraz; Hecht, Andrew C

    2013-03-01

    Study Design Case series of two arytenoid dislocations after anterior cervical discectomy. Objective To recognize arytenoid dislocation as a possible cause of prolonged hoarseness in patients after anterior cervical discectomies. Summary of Background Data Prolonged hoarseness is a common postoperative complication after anterior cervical spine surgery. The etiology of prolonged postoperative hoarseness is usually related to a paresis of the recurrent laryngeal nerve. However, other causes of postoperative hoarseness may be overlooked in this clinical scenario. Other possible etiologies include pharyngeal and laryngeal trauma, hematoma and edema, injury of the superior laryngeal nerve, as well as arytenoid cartilage dislocation. Arytenoid dislocation is often misdiagnosed as vocal fold paresis due to recurrent or laryngeal nerve injury. Methods We report two cases of arytenoid dislocation and review the literature on this pathology. Results Two patients treated with anterior cervical discectomy and fusion experienced prolonged postoperative hoarseness. Arytenoid dislocation was confirmed by flexible fiber-optic laryngoscopy in both cases. The dislocations experienced spontaneous reduction at 6 weeks and 3 months postsurgery. Conclusions Arytenoid dislocation must be considered in the differential diagnosis of prolonged postoperative hoarseness and evaluated for using direct laryngoscopy, computed tomography, or a laryngeal electromyography. Upon diagnosis, treatment must be considered immediately. Slight dislocations can reduce spontaneously without surgical intervention; however, operative intervention may be required at times.

  12. Prolonged Initial Empirical Antibiotic Treatment is Associated with Adverse Outcomes in Premature Infants

    PubMed Central

    Kuppala, Venkata S; Meinzen-Derr, Jareen; Morrow, Ardythe L.; Schibler, Kurt R.

    2011-01-01

    Objective To investigate the outcomes following prolonged empirical antibiotic administration to premature infants in the first week of life, concluding subsequent late onset sepsis (LOS), necrotizing enterocolitis (NEC), and death. Study design Study infants were ≤32 weeks gestational age and ≤ 1500 grams birth weight who survived free of sepsis and NEC for 7 days. Multivariable logistic regression was conducted to determine independent relationships between prolonged initial empirical antibiotic therapy (≥ 5 days) and study outcomes controlling for birth weight, gestational age, race, prolonged premature rupture of membranes, days on high frequency ventilation in 7 days, and the amount of breast milk received in the first 14 days of life. Results Of the 365 premature infants surviving 7 days free of sepsis or NEC, 36% received prolonged initial empirical antibiotics, which was independently associated with subsequent outcomes: LOS (odds ratio [OR] 2.45, 95% confidence interval [CI] 1.28–4.67) and the combination of LOS, NEC, or death (OR 2.66, 95% CI 1.12–6.3). Conclusions Prolonged administration of empirical antibiotics to premature infants with sterile cultures in the first week of life is associated with subsequent severe outcomes. Judicious restriction of antibiotic use should be investigated as a strategy to reduce severe outcomes for premature infants. PMID:21784435

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

    PubMed

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

    2017-01-01

    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.

  14. Prolonged Inner Retinal Photoreception Depends on the Visual Retinoid Cycle

    PubMed Central

    Zhao, Xiwu; Pack, Weston; Khan, Naheed W.

    2016-01-01

    In addition to rods and cones, mammals have inner retinal photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGCs), which use the photopigment melanopsin and mediate nonimage-forming visual responses, such as pupil reflexes and circadian entrainment. After photic activation, photopigments must be reverted to their dark state to be light-sensitive again. For rods and to some extent cones, photopigment regeneration depends on the retinoid cycle in the adjacent retinal pigment epithelium (RPE). By contrast, ipRGCs are far from the RPE, and previous work suggests that melanopsin is capable of light-dependent self-regeneration. Here, we used in vitro ipRGC recording and in vivo pupillometry to show that the RPE is required for normal melanopsin-based responses to prolonged light, especially at high stimulus intensities. Melanopsin-based photoresponses of rat ipRGCs were remarkably sustained when a functional RPE was attached to the retina, but became far more transient if the RPE was removed, or if the retinoid cycle was inhibited, or when Müller glia were poisoned. Similarly, retinoid cycle inhibition markedly reduced the steady-state amplitude of melanopsin-driven pupil reflexes in both mice and rats. However, melanopsin photoresponses in RPE-separated rat retinas became more sustained in the presence of an 11-cis-retinal analog. In conclusion, during prolonged illumination, melanopsin regeneration depends partly on 11-cis-retinal from the RPE, possibly imported via Müller cells. Implications for RPE-related eye diseases and the acne drug isotretinoin (a retinoid cycle inhibitor) are discussed. SIGNIFICANCE STATEMENT Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin and drive subconscious physiological responses to light, e.g., pupillary constriction and neuroendocrine regulation. In darkness, each photopigment molecule in ipRGCs, as well as rod/cone photoreceptors, contains 11-cis-retinal (a

  15. Fetal brain hypometabolism during prolonged hypoxaemia in the llama

    PubMed Central

    Ebensperger, Germán; Ebensperger, Renato; Herrera, Emilio A; Riquelme, Raquel A; Sanhueza, Emilia M; Lesage, Florian; Marengo, Juan J; Tejo, Rodrigo I; Llanos, Aníbal J; Reyes, Roberto V

    2005-01-01

    In this study we looked for additional evidence to support the hypothesis that fetal llama reacts to hypoxaemia with adaptive brain hypometabolism. We determined fetal llama brain temperature, Na+ and K+ channel density and Na+–K+-ATPase activity. Additionally, we looked to see whether there were signs of cell death in the brain cortex of llama fetuses submitted to prolonged hypoxaemia. Ten fetal llamas were instrumented under general anaesthesia to measure pH, arterial blood gases, mean arterial pressure, heart rate, and brain and core temperatures. Measurements were made 1 h before and every hour during 24 h of hypoxaemia (n = 5), which was imposed by reducing maternal inspired oxygen fraction to reach a fetal arterial partial pressure of oxygen (Pa,O2) of about 12 mmHg. A normoxaemic group was the control (n = 5). After 24 h of hypoxaemia, we determined brain cortex Na+–K+-ATPase activity, ouabain binding, and the expression of NaV1.1, NaV1.2, NaV1.3, NaV1.6, TREK1, TRAAK and KATP channels. The lack of brain cortex damage was assessed as poly ADP-ribose polymerase (PARP) proteolysis. We found a mean decrease of 0.56°C in brain cortex temperature during prolonged hypoxaemia, which was accompanied by a 51% decrease in brain cortex Na+–K+-ATPase activity, and by a 44% decrease in protein content of NaV1.1, a voltage-gated Na+ channel. These changes occurred in absence of changes in PARP protein degradation, suggesting that the cell death of the brain was not enhanced in the fetal llama during hypoxaemia. Taken together, these results provide further evidence to support the hypothesis that the fetal llama responds to prolonged hypoxaemia with adaptive brain hypometabolism, partly mediated by decreases in Na+–K+-ATPase activity and expression of NaV channels. PMID:16037083

  16. Prolonged Inner Retinal Photoreception Depends on the Visual Retinoid Cycle.

    PubMed

    Zhao, Xiwu; Pack, Weston; Khan, Naheed W; Wong, Kwoon Y

    2016-04-13

    In addition to rods and cones, mammals have inner retinal photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGCs), which use the photopigment melanopsin and mediate nonimage-forming visual responses, such as pupil reflexes and circadian entrainment. After photic activation, photopigments must be reverted to their dark state to be light-sensitive again. For rods and to some extent cones, photopigment regeneration depends on the retinoid cycle in the adjacent retinal pigment epithelium (RPE). By contrast, ipRGCs are far from the RPE, and previous work suggests that melanopsin is capable of light-dependent self-regeneration. Here, we used in vitro ipRGC recording and in vivo pupillometry to show that the RPE is required for normal melanopsin-based responses to prolonged light, especially at high stimulus intensities. Melanopsin-based photoresponses of rat ipRGCs were remarkably sustained when a functional RPE was attached to the retina, but became far more transient if the RPE was removed, or if the retinoid cycle was inhibited, or when Müller glia were poisoned. Similarly, retinoid cycle inhibition markedly reduced the steady-state amplitude of melanopsin-driven pupil reflexes in both mice and rats. However, melanopsin photoresponses in RPE-separated rat retinas became more sustained in the presence of an 11-cis-retinal analog. In conclusion, during prolonged illumination, melanopsin regeneration depends partly on 11-cis-retinal from the RPE, possibly imported via Müller cells. Implications for RPE-related eye diseases and the acne drug isotretinoin (a retinoid cycle inhibitor) are discussed. Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin and drive subconscious physiological responses to light, e.g., pupillary constriction and neuroendocrine regulation. In darkness, each photopigment molecule in ipRGCs, as well as rod/cone photoreceptors, contains 11-cis-retinal (a vitamin A derivative

  17. Argon and xenon ventilation during prolonged ex vivo lung perfusion.

    PubMed

    Martens, An; Montoli, Matteo; Faggi, Giulio; Katz, Ira; Pype, Jan; Vanaudenaerde, Bart M; Van Raemdonck, Dirk E M; Neyrinck, Arne P

    2016-03-01

    Evidence supports the use of ex vivo lung perfusion (EVLP) as a platform for active reconditioning before transplantation to increase the potential donor pool and to reduce the incidence of primary graft dysfunction. A promising reconditioning strategy is the administration of inhaled noble gases based on their organoprotective effects. Our aim was to validate a porcine warm ischemic lung injury model and investigate postconditioning with argon (Ar) or xenon (Xe) during prolonged EVLP. Domestic pigs were divided in four groups (n = 5 per group). In the negative control group, lungs were flushed immediately. In the positive control (PC) and treatment (Ar, Xe) groups, lungs were flushed after a warm ischemic interval of 2-h in situ. All grafts were evaluated and treated during normothermic EVLP for 6 h. In the control groups, lungs were ventilated with 70% N2/30% O2 and in the treatment groups with 70% Ar/30% O2 or 70% Xe/30% O2, respectively. Outcome parameters were physiological variables (pulmonary vascular resistance, peak airway pressures, and PaO2/FiO2), histology, wet-to-dry weight ratio, bronchoalveolar lavage, and computed tomography scan. A significant difference between negative control and PC for pulmonary vascular resistance, peak airway pressures, PaO2/FiO2, wet-to-dry weight ratio, histology, and computed tomography-imaging was observed. No significant differences between the injury group (PC) and the treatment groups (Ar, Xe) were found. We validated a reproducible prolonged 6-h EVLP model with 2 h of warm ischemia and described the physiological changes over time. In this model, ventilation during EVLP with Ar or Xe administered postinjury did not improve graft function. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Knee abduction angular impulses during prolonged running with wedged insoles.

    PubMed

    Lewinson, Ryan T; Worobets, Jay T; Stefanyshyn, Darren J

    2013-07-01

    Wedged insoles may produce immediate effects on knee abduction angular impulses during running; however, it is currently not known whether these knee abduction angular impulse magnitudes are maintained throughout a run when fatigue sets in. If changes occur, this could affect the clinical utility of wedged insoles in treating conditions such as patellofemoral pain. Thus, the purpose of this study was to determine whether knee abduction angular impulses are altered during a prolonged run with wedged insoles. It was hypothesized that knee abduction angular impulses would be reduced following a prolonged run with wedged insoles. Nine healthy runners participated. Runners were randomly assigned to either a 6-mm medial wedge condition or a 6-mm lateral wedge condition and then ran continuously overground for 30 min. Knee abduction angular impulses were quantified at 0 and 30 min using a gait analysis procedure. After 2 days, participants returned to perform the same test but with the other wedge type. Two-way repeated-measures analysis of variance was used to evaluate main effects of wedge condition and time and interactions between wedge condition and time (α = 0.05). Paired t-tests were used for post hoc analysis (α = 0.01). No interaction effects (p = 0.958) were found, and knee abduction angular impulses were not significantly different over time (p = 0.384). Lateral wedge conditions produced lesser knee abduction angular impulses than medial conditions at 0 min (difference of 2.79 N m s, p = 0.006) and at 30 min (difference of 2.76 N m s, p < 0.001). It is concluded that significant knee abduction angular impulse changes within wedge conditions do not occur during a 30-min run. Additionally, knee abduction angular impulse differences between wedge conditions are maintained during a 30-min run.

  19. Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest

    PubMed Central

    Spinelli, Elena; Davis, Ryan P.; Ren, Xiaodan; Sheth, Parth S.; Tooley, Trevor R.; Iyengar, Amit; Sowell, Brandon; Owens, Gabe E.; Bocks, Martin L.; Jacobs, Teresa L.; Yang, Lynda J.; Stacey, William C.; Bartlett, Robert H.; Rojas-Peña, Alvaro; Neumar, Robert W.

    2016-01-01

    Objective To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation (ECPR) and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest. Design Laboratory investigation Setting University Laboratory Subjects Pigs Interventions Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation (ECPR) for 6 hours. Animals were allocated into two experimental groups: t-ECPR, which received Streptokinase 1 MU and c-ECPR which did not receive Streptokinase. In both groups the resuscitation protocol included the following physiologic targets: mean arterial pressure (MAP) > 70 mmHg, Cerebral perfusion pressure (CerPP) > 50 mmHg, PaO2 150 ± 50 mmHg, PaCO2 40 ± 5 mmHg and core temperature 33 ± 1 °C. Defibrillation was attempted after 30 minutes of ECPR. Measurements and Main Results A cardiac resuscitability score was assessed on the basis of: success of defibrillation; return of spontaneous heart beat; weanability form ECPR; and left ventricular systolic function after weaning. The addition of thrombolytic to ECPR significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40 ± 15% VS 18 ± 21 %). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of EEG signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages. Conclusions In a porcine model of prolonged cardiac arrest, thrombolytic-enhanced ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early EEG recovery and ischemic neuronal injury were

  20. Grace's story: prolonged incestuous abuse from childhood into adulthood.

    PubMed

    Salter, Michael

    2013-02-01

    Some sexually abused women in mental health settings are reporting prolonged incest and yet little is known about the circumstances that enable fathers to sexually abuse their daughters over a period of decades. This article draws from the life history of Grace, a woman who survived prolonged incest, in order to document and analyze the interplay of familial, social, and political factors that entrap girls and women within prolonged incestuous abuse.

  1. Predictors of prolonged fluoroscopy time in diagnostic coronary angiography.

    PubMed

    Adachi, Yusuke; Sakakura, Kenichi; Wada, Hiroshi; Funayama, Hiroshi; Umemoto, Tomio; Momomura, Shin-Ichi; Fujita, Hideo

    2016-07-01

    Prolonged fluoroscopy time during coronary angiography is a major concern for interventional cardiologists as well as for patients. It is unknown which factors affect the prolonged fluoroscopy time. A total of 458 patients who underwent diagnostic coronary angiography were included. The patients who had the highest decile of fluoroscopy time were assigned to the prolonged fluoroscopy group (fluoroscopy time ≥15.7min), while the other patients were assigned to the non-prolonged fluoroscopy group (fluoroscopy time <15.7min). We performed univariate and multivariate logistic regression analysis to identify the predictors of prolonged fluoroscopy time. Mean fluoroscopy time in 458 patients was 8.5±5.8min. Median and ranges of fluoroscopy time were 19.0 [15.7-47.0]min in the prolonged fluoroscopy group and 6.0 [2.0-15.3]min in the non-prolonged fluoroscopy group, respectively. The multivariate logistic regression analysis showed that significant predictors of prolonged fluoroscopy time were prior surgery of ascending aorta replacement [odds ratios (OR) 11.46, 95% confidence intervals (CI) 1.53-85.74, p=0.02] and the prevalence of moderate to severe aortic regurgitation (OR 2.83, 95% CI 1.20-6.66, p=0.02). The prior surgery of ascending aorta replacement and moderate to severe aortic regurgitation were significant predictors of the prolonged fluoroscopy time. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  2. Pregbalin induced recurrent syncopal attacks with prolong QT interval.

    PubMed

    Adar, Adem; Cakan, Fahri; Önalan, Orhan

    2017-08-30

    Long QT syndrome may lead to fatal dysrhythmia. Prolongation of QT interval due to pregabalin has been shown in rats and no data is available in humans. We report a 80-year-old female patient using pregabalin. She was presented to emergency room with syncope attacks. Her admission electrocardiography demonstrated prolonged QT interval. After excluding the possible causes of the long QT syndrome, we attributed prolonged QT interval to pregabalin therapy. After discontinuation of pregabalin QT interval returned to normal range and patient experienced no further syncope attacks. It is first time for documentation of prolonged QT due to pregabalin in humans. © 2017 Wiley Periodicals, Inc.

  3. Prolonged cholestasis and ductopenia associated with tenoxicam.

    PubMed

    Trak-Smayra, Viviane; Cazals-Hatem, Dominique; Asselah, Tarik; Duchatelle, Veronique; Degott, Claude

    2003-07-01

    Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.

  4. Prolonged incarceration: effects on hostages of terrorism.

    PubMed

    Busuttil, W

    2008-06-01

    In recent years there has been an explosion in the publicity surrounding hostage taking. There have been many well-publicized hostage, prisoner of war and politically motivated incarcerations. Increasingly hostages are being paraded on television and sometimes even films of executions posted on the Internet. Hostage taking has usually occurred in countries where there has been political strife and war, especially, in recent years, in Iraq and Afghanistan, most recently involving British Royal Navy Personnel in Iran and a British journalist in Palestine. The aim of this paper is to review the adult literature regarding hostage taking with a view to highlighting the most likely psychiatric disorders that can develop during such an experience. This will aid planning and implementation of hostage rehabilitation and family reintegration post release. This paper will help build insight into the experiences and potential clinical presentations of those held hostage under conditions of torture and threat of death. It presents a framework of needs allowing the planning of rehabilitation including how to manage the family and the media. Further specific research is needed in order to assess the full needs of those released from prolonged incarceration held under threat of death. This will allow better planning for, and delivery of, rehabilitation of those released.

  5. Prolonging life and allowing death: infants.

    PubMed

    Campbell, A G; McHaffie, H E

    1995-12-01

    Dilemmas about resuscitation and life-prolonging treatment for severely compromised infants have become increasingly complex as skills in neonatal care have developed. Quality of life and resource issues necessarily influence management. Our Institute of Medical Ethics working party, on whose behalf this paper is written, recognises that the ultimate responsibility for the final decision rests with the doctor in clinical charge of the infant. However, we advocate a team approach to decision-making, emphasising the important role of parents and nurses in the process. Assessing the relative burdens and benefits can be troubling, but doctors and parents need to retain a measure of discretion; legislation which would determine action in all cases is inappropriate. Caution should be exercised in involving committees in decision-making and, where they exist, their remit should remain to advise rather than to decide. Support for families who bear the consequences of their decisions is often inadequate, and facilitating access to such services is part of the wider responsibilities of the intensive care team. The authors believe that allowing death by withholding or withdrawing treatment is legitimate, where those closely involved in the care of the infant together deem the burdens to be unacceptable without compensating benefits for the infant. As part of the process accurate and careful recording is essential.

  6. [Prospective study of patients with prolonged fever].

    PubMed

    Calderón, E; Legorreta, J; Sztabinski, G; Hernández, M; Wilkins, A; Gómez, D; Dávila, A

    1975-01-01

    A prospective study was made in 283 patients who attended IMAN's Children's Hospital, with fever the main symptom. A clinical and paraclinical procedure was designed for the study of each patient. 112 patients were eliminated because they did not follow the established criteria. All patients had acute infectious diseases considered trivial; 85% were 3 weeks to 2 years of age. They all had an antibacterial treatment without precise diagnosis. It was considered that on admission the patients showed a normal course in the natural history of the basic disease. The study group included 171 patients 2 months to 13 years of age; 62.5% had fever due to infection, 12.2% to collagenopathies, 7% to neoplasias 5.2% to miscellaneous causes and 12.8% were not diagnosed. The most common infectious causes for prolonged fever were tuberculosis, upper respiratory infections, amoebic liver abscess, typhoid fever and malaria. Careful questioning and clinical examination were enough to enlighten diagnosis in more than 80% of the patients.

  7. Pulmonary diffusion limitation after prolonged strenuous exercise.

    PubMed

    Manier, G; Moinard, J; Téchoueyres, P; Varène, N; Guénard, H

    1991-02-01

    To determine the effect of strenuous prolonged exercise on alveolo-capillary membrane diffusing capacity, 11 marathon runners aged 37 +/- 7 years (mean +/- SD) were studied before and during early recovery (28 +/- 14 min) from a marathon race. Lung capillary blood volume (Vc) and the alveolo-capillary diffusing capacity (Dm) were determined in a one-step maneuver by simultaneous measurements of CO and NO lung transfer (DLCO and DLNO, respectively) using the single breath, breath-holding method. After the race, both DLCO and DLNO were significantly decreased in all subjects (-10.9 +/- 4.8%, P less than 10(-4) and -29.0 +/- 11.1%, P less than 10(-4), respectively). The mean value of the derived DmCO decreased by -29.3 +/- 11.1%, whereas Vc had not entirely returned to control resting value. Although these results do not indicate the detailed mechanism involved, interstitial lung fluid was suspected to accumulate, particularly in alveoli, during the race. We concluded that the high overall work load and the extended duration of the exercise both contributed to a transient change in the structure of the alveolo-capillary membrane thereby affecting the diffusing capacity of the alveolo-capillary membrane.

  8. Persistent telomere cohesion triggers a prolonged anaphase.

    PubMed

    Kim, Mi Kyung; Smith, Susan

    2014-01-01

    Telomeres use distinct mechanisms (not used by arms or centromeres) to mediate cohesion between sister chromatids. However, the motivation for a specialized mechanism at telomeres is not well understood. Here we show, using fluorescence in situ hybridization and live-cell imaging, that persistent sister chromatid cohesion at telomeres triggers a prolonged anaphase in normal human cells and cancer cells. Excess cohesion at telomeres can be induced by inhibition of tankyrase 1, a poly(ADP-ribose) polymerase that is required for resolution of telomere cohesion, or by overexpression of proteins required to establish telomere cohesion, the shelterin subunit TIN2 and the cohesin subunit SA1. Regardless of the method of induction, excess cohesion at telomeres in mitosis prevents a robust and efficient anaphase. SA1- or TIN2-induced excess cohesion and anaphase delay can be rescued by overexpression of tankyrase 1. Moreover, we show that primary fibroblasts, which accumulate excess telomere cohesion at mitosis naturally during replicative aging, undergo a similar delay in anaphase progression that can also be rescued by overexpression of tankyrase 1. Our study demonstrates that there are opposing forces that regulate telomere cohesion. The observation that cells respond to unresolved telomere cohesion by delaying (but not completely disrupting) anaphase progression suggests a mechanism for tolerating excess cohesion and maintaining telomere integrity. This attempt to deal with telomere damage may be ultimately futile for aging fibroblasts but useful for cancer cells.

  9. Haploinsufficiency of Akt1 Prolongs the Lifespan of Mice

    PubMed Central

    Nojima, Aika; Yamashita, Masakatsu; Yoshida, Yohko; Shimizu, Ippei; Ichimiya, Harumi; Kamimura, Naomi; Kobayashi, Yoshio; Ohta, Shigeo; Ishii, Naoaki; Minamino, Tohru

    2013-01-01

    There is increasing evidence that nutrient-sensing machinery is critically involved in the regulation of aging. The insulin/insulin-like growth factor-1 signaling pathway is the best-characterized pathway with an influence on longevity in a variety of organisms, ranging from yeast to rodents. Reduced expression of the receptor for this pathway has been reported to prolong the lifespan; however, the underlying mechanisms are largely unknown. Here we show that haploinsufficiency of Akt1 leads to an increase of the lifespan in mice. Akt1+/– mice had a lower body weight than their littermates with less fat mass and normal glucose metabolism. Ribosomal biogenesis and the mitochondrial DNA content were significantly reduced in these mice, along with a decrease of oxidative stress. Consistent with the results obtained in mice, inhibition of Akt-1 promoted longevity in nematodes (Caenorhabditis elegans), whereas activation of Akt-1 shortened the lifespan. Inhibition of Akt-1 led to a decrease of ribosomal gene expression and the mitochondrial DNA content in both human cells and nematodes. Moreover, deletion of ribosomal gene expression resulted in a decrease of the mitochondrial DNA content and normalized the lifespan shortened by Akt-1 activation in nematodes. These results suggest that an increase of mitochondrial amount and energy expenditure associated with enhanced protein synthesis accelerates both aging and the onset of age-associated diseases. PMID:23935948

  10. Fatigue associated with prolonged graded running.

    PubMed

    Giandolini, Marlene; Vernillo, Gianluca; Samozino, Pierre; Horvais, Nicolas; Edwards, W Brent; Morin, Jean-Benoît; Millet, Guillaume Y

    2016-10-01

    Scientific experiments on running mainly consider level running. However, the magnitude and etiology of fatigue depend on the exercise under consideration, particularly the predominant type of contraction, which differs between level, uphill, and downhill running. The purpose of this review is to comprehensively summarize the neurophysiological and biomechanical changes due to fatigue in graded running. When comparing prolonged hilly running (i.e., a combination of uphill and downhill running) to level running, it is found that (1) the general shape of the neuromuscular fatigue-exercise duration curve as well as the etiology of fatigue in knee extensor and plantar flexor muscles are similar and (2) the biomechanical consequences are also relatively comparable, suggesting that duration rather than elevation changes affects neuromuscular function and running patterns. However, 'pure' uphill or downhill running has several fatigue-related intrinsic features compared with the level running. Downhill running induces severe lower limb tissue damage, indirectly evidenced by massive increases in plasma creatine kinase/myoglobin concentration or inflammatory markers. In addition, low-frequency fatigue (i.e., excitation-contraction coupling failure) is systematically observed after downhill running, although it has also been found in high-intensity uphill running for different reasons. Indeed, low-frequency fatigue in downhill running is attributed to mechanical stress at the interface sarcoplasmic reticulum/T-tubule, while the inorganic phosphate accumulation probably plays a central role in intense uphill running. Other fatigue-related specificities of graded running such as strategies to minimize the deleterious effects of downhill running on muscle function, the difference of energy cost versus heat storage or muscle activity changes in downhill, level, and uphill running are also discussed.

  11. Diaphragmatic energetics during prolonged exhaustive exercise.

    PubMed

    Manohar, M; Hassan, A S

    1991-08-01

    The present study was carried out to examine diaphragmatic O2 extraction and lactate and ammonia production during prolonged exhaustive exercise. Experiments were performed on nine healthy exercise-conditioned ponies in which catheters had been implanted in the phrenic vein previously. Blood-gas variables and lactate and ammonia concentrations were determined on simultaneously obtained arterial and phrenic-venous blood samples at rest and during 30 min of exertion at 15 mph + 7% grade (heart rate, 200 beats/min; approximately 90% of maximum). Arterial O2 tension and saturation were maintained near resting value but CO2 tension decreased markedly with exercise, and because of increased hemoglobin concentration, arterial O2 content rose. Concomitantly, phrenic venous O2 tension, saturation and content decreased markedly (23.6 +/- 1 mm Hg, 24.5 +/- 2%, 5.2 +/- 0.3 ml/dl at 3 min of exertion) and significant fluctuations did not occur as exercise duration progressed to 30 min. Diaphragmatic arteriovenous O2 content difference and O2 extraction rose from 4 +/- 0.3 to 16 +/- 0.5 ml/dl and from 30 +/- 3 to 75 +/- 1% at 3 min of exercise, and significant deviations did not occur as exercise duration progressed. Arterial lactate and ammonia levels increased during exercise, indicating their release from working limb muscles. Phrenic-venous values of lactate and ammonia did not exceed arterial values. Ponies sweated profusely and were unable to keep up with the belt speed in the last 4 to 5 min of exercise. Constancy of phrenic arteriovenous O2 content difference in exercise indicated ability to adjust perfusion in diaphragm so as to adequately meet its O2 needs.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Exceptionally prolonged tooth formation in elasmosaurid plesiosaurians

    PubMed Central

    Kear, Benjamin P.; Larsson, Dennis; Lindgren, Johan; Kundrát, Martin

    2017-01-01

    Elasmosaurid plesiosaurians were globally prolific marine reptiles that dominated the Mesozoic seas for over 70 million years. Their iconic body-plan incorporated an exceedingly long neck and small skull equipped with prominent intermeshing ‘fangs’. How this bizarre dental apparatus was employed in feeding is uncertain, but fossilized gut contents indicate a diverse diet of small pelagic vertebrates, cephalopods and epifaunal benthos. Here we report the first plesiosaurian tooth formation rates as a mechanism for servicing the functional dentition. Multiple dentine thin sections were taken through isolated elasmosaurid teeth from the Upper Cretaceous of Sweden. These specimens revealed an average of 950 daily incremental lines of von Ebner, and infer a remarkably protracted tooth formation cycle of about 2–3 years–other polyphyodont amniotes normally take ~1–2 years to form their teeth. Such delayed odontogenesis might reflect differences in crown length and function within an originally uneven tooth array. Indeed, slower replacement periodicity has been found to distinguish larger caniniform teeth in macrophagous pliosaurid plesiosaurians. However, the archetypal sauropterygian dental replacement system likely also imposed constraints via segregation of the developing tooth germs within discrete bony crypts; these partly resorbed to allow maturation of the replacement teeth within the primary alveoli after displacement of the functional crowns. Prolonged dental formation has otherwise been linked to tooth robustness and adaption for vigorous food processing. Conversely, elasmosaurids possessed narrow crowns with an elongate profile that denotes structural fragility. Their apparent predilection for easily subdued prey could thus have minimized this potential for damage, and was perhaps coupled with selective feeding strategies that ecologically optimized elasmosaurids towards more delicate middle trophic level aquatic predation. PMID:28241059

  13. Utilization of extracorporeal membrane oxygenation alleviates intestinal ischemia-reperfusion injury in prolonged hemorrhagic shock animal model.

    PubMed

    Zhao, Liang; Luo, Lin; Chen, Jinjin; Xiao, Juan; Jia, Weikun; Xiao, Yingbin

    2014-12-01

    Intestinal ischemia-reperfusion injury is one of the main factors leading to multiple organ failure after resuscitation of prolonged hemorrhagic shock; however, the current conventional fluid resuscitation still cannot effectively reduce intestinal injury caused by prolonged hemorrhagic shock. To investigate the effect of ECMO resuscitation on alleviating intestinal ischemia-reperfusion injury in a prolonged hemorrhagic shock rabbit model. Thirty New Zealand white rabbits were randomly divided into three groups: control group, conventional fluid resuscitation group, and ECMO resuscitation group. The prolonged hemorrhagic shock model was established by keeping the arterial blood pressure from 31 to 40 mmHg for 3 h through the femoral artery bleeding, and performing the resuscitation for 2 h by conventional fluid resuscitation and ECMO resuscitation, respectively. Chiu's score of intestinal injury, serum lactate and TNF-α levels, intestinal mucosamyeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM-1), and Claudin-1expression were detected. The mean arterial blood pressure in Group 2 was significantly higher after resuscitation than in Group 1, but serum lactate and inflammatory cytokines TNF-α level were significantly lower. And Chiu's score of intestinal injury and myeloperoxidase (MPO) activity level and ICAM-1 expression were significantly lower in the ECMO resuscitation group, in which the Claudin-1 levels were significantly increased. ECMO resuscitation for the prolonged hemorrhagic shock improves tissue perfusion and reduces the systemic inflammation, and thus alleviates intestinal damage caused by prolonged hemorrhagic shock.

  14. Prolonged exposure to insulin induces mitochondrion-derived oxidative stress through increasing mitochondrial cholesterol content in hepatocytes.

    PubMed

    Mei, Shuang; Gu, Haihua; Yang, Xuefeng; Guo, Huailan; Liu, Zhenqi; Cao, Wenhong

    2012-05-01

    We addressed the link between excessive exposure to insulin and mitochondrion-derived oxidative stress in this study and found that prolonged exposure to insulin increased mitochondrial cholesterol in cultured hepatocytes and in mice and stimulated production of reactive oxygen species (ROS) and decreased the reduced glutathione to glutathione disulfide ratio in cultured hepatocytes. Exposure of isolated hepatic mitochondria to cholesterol alone promoted ROS emission. The oxidative stress induced by the prolonged exposure to insulin was prevented by inhibition of cholesterol synthesis with simvastatin. We further found that prolonged exposure to insulin decreased mitochondrial membrane potential and the increased ROS production came from mitochondrial respiration complex I. Finally, we observed that prolonged exposure to insulin decreased mitochondrial membrane fluidity in a cholesterol synthesis-dependent manner. Together our results demonstrate that excess exposure to insulin causes mitochondrion-derived oxidative stress through cholesterol synthesis in hepatocytes.

  15. Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats.

    PubMed

    Zhao, Hailin; Yoshida, Akira; Xiao, Wei; Ologunde, Rele; O'Dea, Kieran P; Takata, Masao; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

    2013-10-01

    Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

  16. As time goes by: reasons and characteristics of prolonged episodes of mechanical restraint in forensic psychiatry.

    PubMed

    Gildberg, Frederik A; Fristed, Peter; Makransky, Guido; Moeller, Elsebeth H; Nielsen, Lea D; Bradley, Stephen K

    2015-01-01

    Evidence suggests the prevalence and duration of mechanical restraint are particularly high among forensic psychiatric inpatients. However, only sparse knowledge exists regarding the reasons for, and characteristics of, prolonged use of mechanical restraint in forensic psychiatry. This study therefore aimed to investigate prolonged episodes of mechanical restraint on forensic psychiatric inpatients. Documentary data from medical records were thematically analyzed. Results show that the reasons for prolonged episodes of mechanical restraint on forensic psychiatric inpatients can be characterized by multiple factors: "confounding" (behaviors associated with psychiatric conditions, substance abuse, medical noncompliance, etc.), "risk" (behaviors posing a risk for violence), and "alliance parameters" (qualities of the staff-patient alliance and the patients' openness to alliance with staff), altogether woven into a mechanical restraint spiral that in itself becomes a reason for prolonged mechanical restraint. The study also shows lack of consistent clinical assessment during periods of restraint. Further investigation is indicated to develop an assessment tool with the capability to reduce time spent in mechanical restraint.

  17. Dexamethasone added to mepivacaine prolongs the duration of analgesia after supraclavicular brachial plexus blockade.

    PubMed

    Parrington, Simon J; O'Donnell, Dermot; Chan, Vincent W S; Brown-Shreves, Danielle; Subramanyam, Rajeev; Qu, Melody; Brull, Richard

    2010-01-01

    Corticosteroids have been used successfully to prolong the duration of local anesthetic action after peripheral nerve and epidural blockade. We hypothesized that the addition of dexamethasone to mepivacaine would prolong the duration of analgesia after ultrasound-guided supraclavicular brachial plexus block for patients undergoing upper-limb surgery. After Federal Health Department and institutional review board approval, 45 adult patients undergoing elective hand or forearm surgery under supraclavicular brachial plexus blockade were randomized to receive either 30 mL mepivacaine 1.5% plus dexamethasone 8 mg (4 mg/mL), or 30 mL mepivacaine 1.5% plus 2 mL normal saline. The primary outcome measure was duration of analgesia. Secondary outcomes included onset times of sensory and motor blockade, pain and satisfaction scores, analgesic consumption, and block-related complications. Patient characteristics were similar between groups. The median duration of analgesia was significantly prolonged in the Dexamethasone group (332 mins; interquartile range, 225-448 mins) compared with the Normal Saline group (228 mins; interquartile range, 207-263 mins; P = 0.008). The onset times of sensory and motor block were similar between the groups. Complications were minor and transient and did not differ between groups at 2 weeks postoperatively. The addition of dexamethasone to mepivacaine prolongs the duration of analgesia but does not reduce the onset of sensory and motor blockade after ultrasound-guided supraclavicular block compared with mepivacaine alone.

  18. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity.

    PubMed

    Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R; Kuipers, Eline N; Loef, Marieke; Zonneveld, Tom C M; Lucassen, Eliane A; Sips, Hetty C M; Chatzispyrou, Iliana A; Houtkooper, Riekelt H; Meijer, Johanna H; Coomans, Claudia P; Biermasz, Nienke R; Rensen, Patrick C N

    2015-05-26

    Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity.

  19. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

    PubMed Central

    Kooijman, Sander; van den Berg, Rosa; Ramkisoensing, Ashna; Boon, Mariëtte R.; Kuipers, Eline N.; Loef, Marieke; Zonneveld, Tom C. M.; Lucassen, Eliane A.; Sips, Hetty C. M.; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Meijer, Johanna H.; Coomans, Claudia P.; Biermasz, Nienke R.; Rensen, Patrick C. N.

    2015-01-01

    Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16- and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. PMID:25964318

  20. Micronutrient status of children receiving prolonged enteral nutrition.

    PubMed

    Gottrand, M; Muyshont, L; Couttenier, F; Beghin, L; Martigne, L; Coopman, S; Turck, D; Michaud, L; Guimber, D; Gottrand, F

    2013-01-01

    The aim of this study was to assess the micronutrient status of children receiving prolonged enteral nutrition. This cross-sectional single-center study included all 64 children (median age 6.8 years) receiving enteral nutrition providing >50% of daily energy intake for more than 6 months (median duration of enteral nutrition 43 months). The characteristics of the patients and mode of enteral nutrition were recorded. The concentrations of iron, zinc, copper, selenium and vitamins A, D, E and C were measured in plasma. Twelve children (19%) had iron deficiency. A high 25-hydroxyvitamin D concentration was recorded in 20% of the children, but none had associated hypercalcemia. Fifty-two children (81%) had low zinc concentrations in both plasma and erythrocytes. Plasma zinc, calcium, phosphorus and vitamin D concentrations were significantly lower in children receiving fiber supplementation. Abnormal micronutrient concentrations were found more frequently in the children receiving fiber supplementation. No other predisposing factors were associated with micronutrient deficiencies. Long-term enteral nutrition can lead to micronutrient deficiencies in children, whose micronutrient concentrations may require regular checking. Fiber supplementation might reduce the bioavailability of zinc, calcium, phosphorus and vitamin D. Copyright © 2013 S. Karger AG, Basel.

  1. Supporting prolonged COPD monitoring using an application for mobile devices.

    PubMed

    Haller, Andreas; Schuerg, Sebastian; Schudt, Florian; Koczulla, Andreas Rembert; Mursina, Ljudmila; Gross, Volker; Sohrabi, Keywan

    2015-01-01

    COPD (chronic obstructive pulmonary disease) is the most frequent form of chronic respiratory disease. During the progress of this disease, phases of aggravation of pulmonary function (exacerbations) can occur, which reduce the quality of life. Clinical experience shows that single investigations are insufficient. Therefore a prolonged monitoring is required to recognize an exacerbation early. This home monitoring will involve a quick respiratory test and a related application for Android, iOS and Windows phones. This rapid test transmits the relevant pulmonary parameters, converted in an Extensible Markup Language file to the smartphone. The application will analyze the incoming data to evaluate the current health status of the patient. Additionally the data will be transferred to the virtual control point (server) and stored in a database. If critical values are detected, the server will send a notification to prior defined relatives and doctors. A connection to a Hospital Information System will be possible through an included Health Level 7 interface. This offers an improved site-independent patient care. The project is planned to be in development until 2016.

  2. Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Brimmer, C. J.

    1985-01-01

    The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.

  3. Racial Susceptibility for QT Prolongation in Acute Drug Overdoses Authors

    PubMed Central

    Manini, Alex F.; Stimmel, Barry; Vlahov, David

    2014-01-01

    Background and Purpose QT prolongation independently predicts adverse cardiovascular events in suspected poisoning. We aimed to evaluate the association between race and drug-induced QT prolongation for patients with acute overdose. Methods This was a cross-sectional observational study at two urban teaching hospitals. Consecutive adult ED patients with acute drug overdose were prospectively enrolled over a two year period. The primary outcome, long-QT, was defined using standard criteria: QTc >470ms in females and >460ms in males. The association between race and drug-induced QT prolongation was tested, considering several confounding variables. Results In 472 patients analyzed (46% female, mean age 42.3), QT prolongation occurred in 12.7%. Blacks had two-fold increased odds of drug-induced QT prolongation (OR 2.01, CI 1.03-3.91) and Hispanics had 48% decreased odds of drug-induced QT prolongation (OR 0.52, CI 0.29-0.94). Conclusions We found significant racial susceptibility to drug-induced QT prolongation in this large urban study of acute overdoses. PMID:24438862

  4. Cetirizine and loratadine: minimal risk of QT prolongation.

    PubMed

    2010-02-01

    Some antihistamines, such as mizolastine and ebastine, can prolong the QT interval and provoke severe cardiac arrhythmias. This review examines the effects of two widely used antihistamines, cetirizine and loratadine, on the QT interval. As of mid 2009 very few clinical data had been published on the risk of QT prolongation with cetirizine or loratadine. The very rare reported cases of torsades de pointes linked to loratadine mainly appear to involve drug interactions, especially with amiodarone and enzyme inhibitors. We found no reports of QT prolongation attributed to desloratadine, the main metabolite of loratadine. Two cases of QT prolongation with cetirizine have been published, one of which involved overdose and renal failure. The reports are too vague to conclude that cetirizine was implicated. We found no reports of QT prolongation attributed to levocetirizine. Cetirizine is a metabolite of hydroxyzine, another antihistamine. In the 1960s, a study of patients with psychosis showed a risk of QT prolongation. A case of recurrent syncope with QT prolongation has since been reported, along with rare cases of cardiac arrhythmia. In practice, cetirizine and loratadine are first-line antihistamines. However, caution is needed in certain circumstances. In particular, it is best that patients who have risk factors for torsades de pointes or who are taking certain enzyme inhibitors avoid using loratadine. It is best to avoid using cetirizine in cases of renal failure.

  5. Low nonrelapse mortality and prolonged long-term survival after reduced-intensity allogeneic stem cell transplantation for relapsed or refractory diffuse large B cell lymphoma: report of the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Sirvent, Anne; Dhedin, Nathalie; Michallet, Mauricette; Mounier, Nicolas; Faucher, Catherine; Yakoub-Agha, Ibrahim; Mohty, Mohamad; Robin, Marie; Tabrizi, Reza; Clement, Laurence; Bilger, Karin; Larosa, Fabrice; Contentin, Nathalie; Huyn, Anne; François, Sylvie; Bulabois, Claude-Eric; Ceballos, Patrice; Bourrhis, Jean-Henri; Buzyn, Agnès; Cornillon, Jérôme; Guillerm, Gaelle; de Revel, Thierry; Bay, Jacques-Olivier; Guilhot, François; Milpied, Noël

    2010-01-01

    Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a very poor prognosis. However, they may achieve long-term survival by undergoing allogeneic stem cell transplantation (SCT). The purpose of this study was to assess the outcome of all adult patients with DLBCL whose treatment included a reduced-intensity conditioning (RIC) regimen for allogeneic SCT and whose data were reported in the French Society of Marrow Transplantation and Cellular Therapy registry. Sixty-eight patients (median age: 48 years) were transplanted from October 1998 to January 2007. They had received a median of 2 regimens of therapy prior to allogeneic SCT, and 54 (79%) had already undergone SCT. Prior to transplantation, 32 patients (47%) were in complete remission (CR). For all patients but 1, conditioning regimens were based on fludarabine (Flu), which was combined with other chemotherapy drugs in 50 cases (74%) and with total body irradiation (TBI) in 17 (25%). For 56 patients (82%), the donor was an HLA-matched sibling, and peripheral blood was the most widely used source of stem cells (57 patients, 84%). With a median follow-up of 49 months, estimated 2-year overall survival (OS), progression-free survival (PFS), and the cumulative incidence of relapse were 49%, 44%, and 41%, respectively. The 1-year cumulative incidence of nonrelapse mortality (NRM) was 23%. According to multivariate analysis, the patients in CR before transplantation had a significantly longer PFS and a lower CI of relapse than patients transplanted during partial remission or stable or progressive disease. These results suggest that reduced-intensity allergenic transplantation is an attractive therapeutic option for patients with high-risk DLBCL.

  6. Reactivity of organism in prolonged space flights

    NASA Technical Reports Server (NTRS)

    Vasilyev, P. V.

    1980-01-01

    An analysis of published data are presented as well as the results of experiments which show that the state of weightlessness and hypodynamia result in a reduced orthostatic and vestibular resistance, increased sensitivity to infections, decreased endurance of accelerations and physical exercises, and altered reactivity of the organism to drugs. Various consequences of weightlessness on the human body, especially weightlessness combined with other factors linked to long space flights are also considered.

  7. Investigation of connexin 43 uncoupling and prolongation of the cardiac QRS complex in preclinical and marketed drugs

    PubMed Central

    Burnham, M P; Sharpe, P M; Garner, C; Hughes, R; Pollard, C E; Bowes, J

    2014-01-01

    Background and Purpose Prolongation of the cardiac QRS complex is linked to increased mortality and may result from drug-induced inhibition of cardiac sodium channels (hNaV1.5). There has been no systematic evaluation of preclinical and marketed drugs for their additional potential to cause QRS prolongation via gap junction uncoupling. Experimental Approach Using the human cardiac gap junction connexin 43 (hCx43), a dye transfer ‘parachute’ assay to determine IC50 values for compound ranking was validated with compounds known to uncouple gap junctions. Uncoupling activity (and hNaV1.5 inhibition by automated patch clamp) was determined in a set of marketed drugs and preclinical candidate drugs, each with information regarding propensity to prolong QRS. Key Results The potency of known gap junction uncouplers to uncouple hCx43 was ranked (according to IC50) as phorbol ester>digoxin>meclofenamic acid>carbenoxolone>heptanol. Among the drugs associated with QRS prolongation, 29% were found to uncouple hCx43 (IC50 < 50 μM), whereas no uncoupling activity was observed in drugs not associated with QRS prolongation. In preclinical candidate drugs, hCx43 and hNaV1.5 IC50 values were similar (within threefold). No consistent margin over preclinical Cmax (free) was apparent for QRS prolongation associated with Cx43 inhibition. However, instances were found of QRS prolonging compounds that uncoupled hCx43 with significantly less activity at hNaV1.5. Conclusion and Implications These results demonstrate that off-target uncoupling activity is apparent in drug and drug-like molecules. Although the full ramifications of Cx inhibition remain to be established, screening for hCx43 off-target activity could reduce the likelihood of developing candidate drugs with a risk of causing QRS prolongation. PMID:24328991

  8. Modelling of drug-induced QT-interval prolongation: estimation approaches and translational opportunities.

    PubMed

    Marostica, Eleonora; Van Ammel, Karel; Teisman, Ard; Boussery, Koen; Van Bocxlaer, Jan; De Ridder, Filip; Gallacher, David; Vermeulen, An

    2015-12-01

    Safety pharmacology studies are performed to assess whether compounds may provoke severe arrhythmias (e.g. Torsades de Pointes, TdP) and sudden death in man. Although there is strong evidence that drugs inducing TdP in man prolong the QT interval in vivo and block the human ether-a-go-go-related gene (hERG) ion channel in vitro, not all drugs affecting the QT interval or the hERG will induce TdP. Nevertheless, QT-interval prolongation and hERG blockade currently represent the most accepted early risk biomarkers to deselect drugs. An extensive pharmacokinetic/pharmacodynamic (PK/PD) analysis is developed to understand moxifloxacin's-induced effects on the QT interval by comparing the relationship between results of an in vitro patch-clamp model to in vivo models. The frequentist and the fully Bayesian estimation procedures were compared and provided similar performances when the best model selected in NONMEM is subsequently implemented in WinBUGS, which guarantees a straightforward calculation of the probability of QT-interval prolongation greater than 2.5 % (10 ms). The use of the percent threshold to account for the intrinsic differences between species and a new calculation of the probability curve are introduced. The concentration providing the 50 % probability indicates that dogs are more sensitive than humans to QT-interval prolongation. However, based on the drug effect, a clear distinction between species cannot be made. An operational PK/PD model of agonism was used to investigate the relationship between effects on the hERG and QT-interval prolongation in dogs. The proposed analysis contributes to establish a translational relationship that could potentially reduce the need for thorough QT studies.

  9. Prolonged Antibiotic Use Tied to Precancerous Colon Growths

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_164445.html Prolonged Antibiotic Use Tied to Precancerous Colon Growths Drugs that ... 2017 TUESDAY, April 4, 2017 (HealthDay News) -- Taking antibiotics for an extended period in early to middle ...

  10. Drug Xeloda Prolongs Survival for Some Breast Cancer Patients

    MedlinePlus

    ... 166103.html Drug Xeloda Prolongs Survival for Some Breast Cancer Patients It cut risk of relapse, death by ... can extend the lives of some women whose breast cancer is not wiped out by standard treatment, a ...

  11. QT Interval Prolongation Associated with Azithromycin/Methadone Combination.

    PubMed

    Amer, S; Hassan, S; Shariffi, M; Chueca, L

    2013-11-01

    This report documents the occurrence of QT prolongation in a 57-year old man, on methadone replacement therapy, treated with azithromycin for community acquired pneumonia. This case highlights a hitherto unknown drug interaction. In light of ever-increasing use of azithromycin, it is imperative that azithromycin be used with caution in patients who are already on drugs that are known to cause QT prolongation or that cause torsades de pointes.

  12. A comparative study of QT prolongation with serotonin reuptake inhibitors.

    PubMed

    Ojero-Senard, Ana; Benevent, Justine; Bondon-Guitton, Emmanuelle; Durrieu, Geneviève; Chebane, Leila; Araujo, Melanie; Montastruc, Francois; Montastruc, Jean-Louis

    2017-08-03

    QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the "suspected" SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD. In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90-3.87]) or escitalopram (2.50 [2.11-2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients. This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.

  13. Prolongation of RBC survival in the hypophysectomized rat.

    NASA Technical Reports Server (NTRS)

    Landaw, S. A.; Bristol, S. K.

    1971-01-01

    Red blood cell (RBC) survival was prolonged in hypophysectomized rats. While the rate of random hemolysis was decreased in some hypophysectomized hosts, in all directly injected and cross-transfused hypophysectomized rat hosts, there was a significant prolongation of the phase of senescent death. In contrast, RBCs from hypophysectomized donors survived normally in normal hosts. These experiments are further evidence of a relationship between RBC aging and metabolic rate, and suggest an intimate involvement with the calorigenic hormones.

  14. Prolongation of RBC survival in the hypophysectomized rat.

    NASA Technical Reports Server (NTRS)

    Landaw, S. A.; Bristol, S. K.

    1971-01-01

    Red blood cell (RBC) survival was prolonged in hypophysectomized rats. While the rate of random hemolysis was decreased in some hypophysectomized hosts, in all directly injected and cross-transfused hypophysectomized rat hosts, there was a significant prolongation of the phase of senescent death. In contrast, RBCs from hypophysectomized donors survived normally in normal hosts. These experiments are further evidence of a relationship between RBC aging and metabolic rate, and suggest an intimate involvement with the calorigenic hormones.

  15. Two cases of lichen striatus with prolonged active phase.

    PubMed

    Feely, Meghan A; Silverberg, Nanette B

    2014-01-01

    Lichen striatus is a localized, eczematous disorder distributed along the lines of Blaschko, primarily affecting children. In the literature, lesions have been described as having an active phase of inflamed lesions for 6 to 12 months followed by flattening and persistent pigmentary alteration. We describe two girls who had prolonged active-phase lesions for 2.5 and 3.5 years, respectively. Practitioners should be aware that lesions of lichen striatus may have a prolonged active phase.

  16. Outcome of Induction of Labour in Prolonged Pregnancy.

    PubMed

    Nasrin, S; Islam, S; Shahida, S M; Begum, R A; Haque, N

    2015-10-01

    This was a hospital based prospective clinical study conducted among women having prolonged pregnancy to assess the outcome of induction of labour in prolonged pregnancy cases. One hundred and thirty nine women having uncomplicated prolonged pregnancy were studied. The study was carried out in Sir Salimullah Medical College & Mitford Hospital, Dhaka from 01 July 2010 to 30 March 2011. In this study 66% of the respondents had vaginal delivery on routine induction of labour and in 34% cases induction failed. Ninety three percent (93%) of the multigravida had vaginal delivery and in primigravida their vaginal delivery rate was 47.5%. Regarding cervical condition for delivery, 75% of the respondents having favourable cervix had vaginal delivery and in case of unfavourable cervix respondents, they had 55% cases of vaginal delivery. About the foetal outcome it was evidenced from this study that the perinatal adverse outcome increases with the increasing age of gestation beyond 40 completed weeks of gestation. This study showed that the use of prostaglandins for cervical ripening and by confirming the diagnosis of prolonged pregnancy, the delivery outcome in prolonged pregnancy can be improved. The study also showed that induction of labour is not associated with any major complications and the routine induction of labour in prolonged pregnancy is beneficial for both mother and the baby.

  17. QTc interval prolongation in patients with HIV and AIDS.

    PubMed Central

    Sani, Mahmoud U.; Okeahialam, Basil N.

    2005-01-01

    A higher prevalence of QT prolongation has been reported among HIV/AIDS patients, possibly related to drugs prescribed for them or to an acquired form of long QT syndrome. A prolonged QTc is a predictor of cardiovascular mortality. We set out to study this interval in a group of AIDS patients. One-hundred consecutive AIDS patients admitted into the Jos University Teaching Hospital and who satisfied the inclusion criteria were recruited. All were evaluated for symptomatology of cardiovascular disease and had a 12-lead surface electrocardiogram recording. QT interval, taken from the onset of the QRS complex to the end of the T wave, was corrected for heart rate. Eighty HIV-negative, healthy persons and 78 HIV-positive, asymptomatic subjects were used as controls. Forty-five percent of the AIDS patients had prolonged QTc interval. Prolonged QTc was present in 28% of HIV-positive controls and 10% of HIV-negative controls. The mean QTc interval differs significantly between the AIDS patients and the two control groups. From our study, Nigerian HIV-positive asymptomatic subjects have higher prevalence of QTc prolongation compared to HIV-negative subjects and, as they move to AIDS, the prevalence of QTc prolongation increases. This makes for increased cardiovascular mortality. PMID:16396057

  18. Effect of fluid ingestion on neuromuscular function during prolonged cycling exercise.

    PubMed

    Vallier, J-M; Grego, F; Basset, F; Lepers, R; Bernard, T; Brisswalter, J

    2005-04-01

    To investigate the effects of fluid ingestion on neuromuscular function during prolonged cycling exercise. Eight well trained subjects exercised for 180 minutes in a moderate environment at a workload requiring approximately 60% maximal oxygen uptake. Two conditions, fluid (F) and no fluid (NF) ingestion, were investigated. During maximal voluntary isometric contraction (MVC), prolonged cycling exercise reduced (p<0.05) the maximal force generating capacity of quadriceps muscles (after three hours of cycling) and root mean square (RMS) values (after two hours of cycling) with no difference between the two conditions despite greater body weight loss (p<0.05) in NF. The mean power frequency (MPF) for vastus lateralis muscle was reduced (p<0.05) and the rate of force development (RFD) was increased (p<0.05) only during NF. During cycling exercise, integrated electromyographic activity and perceived exertion were increased in both conditions (p<0.05) with no significant effect of fluid ingestion. The results suggest that fluid ingestion did not prevent the previously reported decrease in maximal force with exercise duration, but seems to have a positive effect on some indicators of neuromuscular fatigue such as mean power frequency and rate of force development during maximal voluntary contraction. Further investigations are needed to assess the effect of change in hydration on neural mechanisms linked to the development of muscular fatigue during prolonged exercise.

  19. Benefits of rice seed priming are offset permanently by prolonged storage and the storage conditions.

    PubMed

    Hussain, Saddam; Zheng, Manman; Khan, Fahad; Khaliq, Abdul; Fahad, Shah; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao

    2015-01-29

    Seed priming is a commercially successful practice, but reduced longevity of primed seeds during storage may limit its application. We established a series of experiments on rice to test: (1) whether prolonged storage of primed and non-primed rice seeds for 210 days at 25°C or -4°C would alter their viability, (2) how long primed rice seed would potentially remain viable at 25°C storage, and (3) whether or not post-storage treatments (re-priming or heating) would reinstate the viability of stored primed seeds. Two different rice cultivars and three priming agents were used in all experiments. Prolonged storage of primed seeds at 25°C significantly reduced the germination (>90%) and growth attributes (>80%) of rice compared with un-stored primed seeds. However, such negative effects were not observed in primed seeds stored at -4°C. Beneficial effects of seed priming were maintained only for 15 days of storage at 25°C, beyond which the performance of primed seeds was worse even than non-primed seeds. The deteriorative effects of 25°C storage were related with hampered starch metabolism in primed rice seeds. None of the post-storage treatments could reinstate the lost viability of primed seeds suggesting that seeds become unviable by prolonged post-priming storage at 25°C.

  20. Benefits of rice seed priming are offset permanently by prolonged storage and the storage conditions

    PubMed Central

    Hussain, Saddam; Zheng, Manman; Khan, Fahad; Khaliq, Abdul; Fahad, Shah; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao

    2015-01-01

    Seed priming is a commercially successful practice, but reduced longevity of primed seeds during storage may limit its application. We established a series of experiments on rice to test: (1) whether prolonged storage of primed and non-primed rice seeds for 210 days at 25°C or −4°C would alter their viability, (2) how long primed rice seed would potentially remain viable at 25°C storage, and (3) whether or not post-storage treatments (re-priming or heating) would reinstate the viability of stored primed seeds. Two different rice cultivars and three priming agents were used in all experiments. Prolonged storage of primed seeds at 25°C significantly reduced the germination (>90%) and growth attributes (>80%) of rice compared with un-stored primed seeds. However, such negative effects were not observed in primed seeds stored at −4°C. Beneficial effects of seed priming were maintained only for 15 days of storage at 25°C, beyond which the performance of primed seeds was worse even than non-primed seeds. The deteriorative effects of 25°C storage were related with hampered starch metabolism in primed rice seeds. None of the post-storage treatments could reinstate the lost viability of primed seeds suggesting that seeds become unviable by prolonged post-priming storage at 25°C. PMID:25631923

  1. [Use of benzodiazepines in prolonged seizures and status epilepticus in the community].

    PubMed

    Sánchez-Carpintero, R; Camino, R; Smeyers, P; Raspall-Chaure, M; Martínez-Bermejo, A; Ruiz-Falcó, M L; Verdú, A; Sanmarti, F X; Blanco, O; Santos Borbujo, J; Picó, G; Cebollero, M A

    2014-12-01

    Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management.

  2. Perfusion and pH MRI in familial hemiplegic migraine with prolonged aura.

    PubMed

    Blicher, Jakob Udby; Tietze, Anna; Donahue, Manus J; Smith, Seth A; Østergaard, Leif

    2016-03-01

    To investigate tissue flow disturbance and hypoxia during migraine aura, we studied a case of familial hemiplegic migraine (FHM) using novel magnetic resonance imaging (MRI) techniques. A 44-year-old male was admitted with suspected stroke because of confusion and aphasia. Initial gadolinium-based perfusion MRI showed a decrease in cerebral blood flow and an increase in capillary flow disturbances within the left hemisphere. Later during the prolonged aura phase, chemical exchange saturation transfer MRI indicated a drop in pH in the affected area. The patient was diagnosed with an R908Q mutation in the ATP1A2 gene causing FHM type 2. During prolonged aura in FHM, MRI shows reduced CBF, capillary flow disturbances and a possible pH drop that could indicate tissue hypoxia. © International Headache Society 2015.

  3. Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia

    PubMed Central

    Ying, Shaozhen; Cao, Hong; Hu, He; Wang, Xin; Tang, Yanhong; Huang, Congxin

    2016-01-01

    We aimed to investigate the role of activin receptor-like kinase (ALK7) in regulating cardiac electrophysiology. Here, we showed that Alk7-/- mice exhibited prolonged QT intervals in telemetry ECG recordings. Furthermore, Langendorff-perfused Alk7-/- hearts had significantly longer action potential duration (APD) and greater incidence of ventricular arrhythmia (AV) induced by burst pacing. Using whole-cell patch clamp, we found that the densities of repolarizing K+ currents Ito and IK1 were profoundly reduced in Alk7-/- ventricular cardiomyocytes. Mechanistically, the expression of Kv4.2 (a major subunit of Ito carrying channel) and KCHIP2 (a key accessory subunit of Ito carrying channel), was markedly decreased in Alk7-/- hearts. These findings suggest that endogenous expression of ALK7 is necessary to maintain repolarizing K+ currents in ventricular cardiomyocytes, and finally prevent action potential prolongation and ventricular arrhythmia. PMID:26882027

  4. Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

    SciTech Connect

    Orozco, Johnnie J.; Back, Tom; Kenoyer, Aimee L.; Balkin, Ethan R.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Frayo, Shani; Hylarides, Mark; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2013-05-15

    Anti-CD45 Radioimmunotherapy using an Alpha-Emitting Radionuclide 211At Combined with Bone Marrow Transplantation Prolongs Survival in a Disseminated Murine Leukemia Model ABSTRACT Despite aggressive chemotherapy combined with hematopoietic cell transplant (HCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using antibodies (Ab) labeled primarily with beta-emitting radionuclides has been explored to reduce relapse.

  5. Alpha1-antitrypsin monotherapy prolongs islet allograft survival in mice.

    PubMed

    Lewis, Eli C; Shapiro, Leland; Bowers, Owen J; Dinarello, Charles A

    2005-08-23

    Islet transplantation for type 1 diabetic patients shows promising results with the use of nondiabetogenic immunosuppressive therapy. However, in addition to compromising the immune system of transplant recipients, long-term studies demonstrate that islet viability is impaired. Here, we demonstrate that, in the absence of immunosuppressive agents, monotherapy with clinical-grade human alpha1-antitrypsin (hAAT), the major serum serine-protease inhibitor, prolongs islet graft survival and normoglycemia in transplanted allogeneic diabetic mice, lasting until the development of anti-hAAT antibodies. Compared to untreated or albumin-control-treated graft recipients, which rejected islets at day 10, AAT-treated mice displayed diminished cellular infiltrates and intact intragraft insulin production throughout treatment. Using peritoneal infiltration models, we demonstrate that AAT decreases allogeneic fibroblast-elicited natural-killer-cell influx by 89%, CD3-positive cell influx by 44%, and thioglycolate-elicited neutrophil emigration by 66%. ATT also extended islet viability in mice after streptozotocin-induced beta cell toxicity. In vitro, several islet responses to IL-1beta/IFNgamma stimulation were examined. In the presence of AAT, islets displayed enhanced viability and inducible insulin secretion. Islets also released 36% less nitric oxide and 82% less macrophage inflammatory protein 1 alpha and expressed 63% fewer surface MHC class II molecules. TNFalpha release from IL-1beta/IFNgamma-stimulated islet cells was reduced by 99%, accompanied by an 8-fold increase in the accumulation of membrane TNFalpha on CD45-positive islet cells. In light of the established safety record and the nondiabetogenic potential of AAT, these data suggest that AAT may be beneficial as adjunctive therapy in patients undergoing islet transplantation.

  6. Prolonged cannabis withdrawal in young adults with lifetime psychiatric illness.

    PubMed

    Schuster, Randi Melissa; Fontaine, Madeleine; Nip, Emily; Zhang, Haiyue; Hanly, Ailish; Eden Evins, A

    2017-02-27

    Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18-25, recruited from the Boston-area in 2015-2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD+ vs PD-), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD+ and PD- groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46)=3.8, p=0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD- had significantly reduced withdrawal symptom severity in abstinent week one [t(46)=-2.2, p=0.03], while PD+ did not report improved withdrawal symptoms until the second abstinent week [t(46)=-4.1, p=0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting.

  7. Speech outcomes of a prolonged-speech treatment for stuttering.

    PubMed

    Onslow, M; Costa, L; Andrews, C; Harrison, E; Packman, A

    1996-08-01

    It has been shown that people who stutter can speak with greatly reduced stuttering after treatments that use variations of Goldiamond's (1965) prolonged-speech (PS). However, outcome research to date has not taken account of several important issues. In particular, speech outcome measures in that research have been insufficient to show that lasting relief from stuttering has been achieved by clients outside the clinic for meaningful periods. The present study used extensive speech outcome measures across a variety of situations in evaluating the outcome of an intensive PS treatment (Ingham, 1987). The speech of 12 clients in this treatment was assessed on three occasions prior to treatment and frequently-on eight occasions-after discharge from the residential setting. For 7 clients, a further assessment occurred at 3 years posttreatment. Concurrent dependent measures were percent syllables stuttered, syllables per minute, and speech naturalness. The dependent measures were collected in many speaking situations within and beyond the clinic. Dependent measures were based on speech samples of substantive duration, and covert assessments were included in the study. Detailed data were presented for individual subjects. Results showed that 12 subjects who remained with the entire 2-3-year program achieved zero or near-zero stuttering. The majority of subjects did not show a regression trend in %SS or speech naturalness scores during the posttreatment period, either within or beyond the clinic. Some subjects showed higher posttreatment %SS scores during covert assessment than during overt assessment. Results also showed that stuttering was eliminated without using unusually slow and unnatural speech patterns. This treatment program does not specify a target speech rate range, and many clients maintained stutter-free speech using speech rates that were higher than the range typically specified in intensive PS programs. A significant correlation was found between speech

  8. Exacerbated and prolonged inflammation impairs wound healing and increases scarring.

    PubMed

    Qian, Li-Wu; Fourcaudot, Andrea B; Yamane, Kazuyoshi; You, Tao; Chan, Rodney K; Leung, Kai P

    2016-01-01

    Altered inflammation in the early stage has long been assumed to affect subsequent steps of the repair process that could influence proper wound healing and remodeling. However, the lack of explicit experimental data makes the connection between dysregulated wound inflammation and poor wound healing elusive. To bridge this gap, we used the established rabbit ear hypertrophic scar model for studying the causal effect of dysregulated inflammation. We induced an exacerbated and prolonged inflammatory state in these wounds with the combination of trauma-related stimulators of pathogen-associated molecular patterns from heat-killed Pseudomonas aeruginosa and damage-associated molecular patterns from a dermal homogenate. In stimulated wounds, a heightened and lengthened inflammation was observed based on quantitative measurements of IL-6 expression, tissue polymorphonuclear leukocytes infiltration, and tissue myeloperoxidase activity. Along with the high level of inflammation, wound healing parameters (epithelial gap and others) at postoperative day 7 and 16 were significantly altered in stimulated wounds compared to unstimulated controls. By postoperative day 35, scar elevation of stimulated wounds was higher than that of control wounds (scar elevation index: 1.90 vs. 1.39, p < 0.01). Moreover, treatment of these inflamed wounds with Indomethacin (at concentrations of 0.01, 0.1, and 0.4%) reduced scar elevation but with adverse effects of delayed wound closure and increased cartilage hypertrophy. In summary, successful establishment of this inflamed wound model provides a platform to understand these detrimental aspects of unchecked inflammation and to further test agents that can modulate local inflammation to improve wound outcomes. © 2016 by the Wound Healing Society.

  9. Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

    PubMed

    Park, Jeonghyeon; Noh, Keumhan; Lee, Hae Won; Lim, Mi-sun; Seong, Sook Jin; Seo, Jeong Ju; Kim, Eun-Jung; Kang, Wonku; Yoon, Young-Ran

    2013-01-01

    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.

  10. Pharmacometabolomic Approach to Predict QT Prolongation in Guinea Pigs

    PubMed Central

    Lee, Hae Won; Lim, Mi-sun; Seong, Sook Jin; Seo, Jeong Ju; Kim, Eun-Jung; Kang, Wonku; Yoon, Young-Ran

    2013-01-01

    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. PMID:23593245

  11. From prolonging life to prolonging working life: Tackling unemployment among liver-transplant recipients

    PubMed Central

    Åberg, Fredrik

    2016-01-01

    Return to active and productive life is a key goal of modern liver transplantation (LT). Despite marked improvements in quality of life and functional status, a substantial proportion of LT recipients are unable to resume gainful employment. Unemployment forms a threat to physical and psychosocial health, and impairs LT cost-utility through lost productivity. In studies published after year 2000, the average post-LT employment rate is 37%, ranging from 22% to 55% by study. Significant heterogeneity exists among studies. Nonetheless, these employment rates are lower than in the general population and kidney-transplant population. Most consistent employment predictors include pre-LT employment status, male gender, functional/health status, and subjective work ability. Work ability is impaired by physical fatigue and depression, but affected also by working conditions and society. Promotion of post-LT employment is hampered by a lack of interventional studies. Prevention of pre-LT disability by effective treatment of (minimal) hepatic encephalopathy, maintaining mobility, and planning work adjustments early in the course of chronic liver disease, as well as timely post-LT physical rehabilitation, continuous encouragement, self-efficacy improvements, and depression management are key elements of successful employment-promoting strategies. Prolonging LT recipients’ working life would further strengthen the success of transplantation, and this is likely best achieved through multidisciplinary efforts ideally starting even before LT candidacy. PMID:27076755

  12. From prolonging life to prolonging working life: Tackling unemployment among liver-transplant recipients.

    PubMed

    Åberg, Fredrik

    2016-04-14

    Return to active and productive life is a key goal of modern liver transplantation (LT). Despite marked improvements in quality of life and functional status, a substantial proportion of LT recipients are unable to resume gainful employment. Unemployment forms a threat to physical and psychosocial health, and impairs LT cost-utility through lost productivity. In studies published after year 2000, the average post-LT employment rate is 37%, ranging from 22% to 55% by study. Significant heterogeneity exists among studies. Nonetheless, these employment rates are lower than in the general population and kidney-transplant population. Most consistent employment predictors include pre-LT employment status, male gender, functional/health status, and subjective work ability. Work ability is impaired by physical fatigue and depression, but affected also by working conditions and society. Promotion of post-LT employment is hampered by a lack of interventional studies. Prevention of pre-LT disability by effective treatment of (minimal) hepatic encephalopathy, maintaining mobility, and planning work adjustments early in the course of chronic liver disease, as well as timely post-LT physical rehabilitation, continuous encouragement, self-efficacy improvements, and depression management are key elements of successful employment-promoting strategies. Prolonging LT recipients' working life would further strengthen the success of transplantation, and this is likely best achieved through multidisciplinary efforts ideally starting even before LT candidacy.

  13. Correcting magnesium deficiencies may prolong life

    PubMed Central

    Rowe, William J

    2012-01-01

    The International Space Station provides an extraordinary facility to study the accelerated aging process in microgravity, which could be triggered by significant reductions in magnesium (Mg) ion levels with, in turn, elevations of catecholamines and vicious cycles between the two. With space flight there are significant reductions of serum Mg (P < 0.0001) that have been shown in large studies of astronauts and cosmonauts. The loss of the functional capacity of the cardiovascular system with space flight is over ten times faster than the course of aging on Earth. Mg is an antioxidant and calcium blocker and in space there is oxidative stress, insulin resistance, and inflammatory conditions with evidence in experimental animals of significant endothelial injuries and damage to mitochondria. The aging process is associated with progressive shortening of telomeres, repetitive DNA sequences, and proteins that cap and protect the ends of chromosomes. Telomerase can elongate pre-existing telomeres to maintain length and chromosome stability. Low telomerase triggers increased catecholamines while the sensitivity of telomere synthesis to Mg ions is primarily seen for the longer elongation products. Mg stabilizes DNA and promotes DNA replication and transcription, whereas low Mg might accelerate cellular senescence by reducing DNA stability, protein synthesis, and function of mitochondria. Telomerase, in binding to short DNAs, is Mg dependent. On Earth, in humans, a year might be required to detect changes in telomeres, but in space there is a predictably much shorter duration required for detection, which is therefore more reasonable in time and cost. Before and after a space mission, telomere lengths and telomerase enzyme activity can be determined and compared with age-matched control rats on Earth. The effect of Mg supplementation, both on maintaining telomere length and extending the life span, can be evaluated. Similar studies in astronauts would be fruitful. PMID

  14. No Evidence for Prolonged Visible Persistence in Patients with Schizophrenia

    PubMed Central

    Grimsen, Cathleen; Brand, Andreas; Fahle, Manfred

    2013-01-01

    Background Temporal visual processing is strongly deteriorated in patients with schizophrenia. For example, the interval required between a visual stimulus and a subsequent mask has to be much longer in schizophrenic patients than in healthy controls. We investigated whether this deficit in temporal resolution is accompanied by prolonged visual persistence and/or deficient temporal precision (temporal asynchrony perception). Methodology/Principal Findings We investigated visual persistence in three experiments. In the first, measuring temporal processing by so-called backward masking, prolonged visible persistence is supposed to decrease performance. In the second experiment, requiring temporal integration, prolonged persistence is supposed to improve performance. In the third experiment, we investigated asynchrony detection, as another measure of temporal resolution. Eighteen patients with schizophrenia and 15 healthy controls participated. Asynchrony detection was intact in the patients. However, patients' performance was inferior compared to healthy controls in the first two experiments. Hence, temporal processing in schizophrenic patients is indeed significantly impaired but this impairment is not caused by prolonged temporal integration. Conclusions/Significance Our results argue against a generally prolonged visual persistence in patients with schizophrenia. Together with the preserved ability of patients, to detect temporal asynchronies in permanently presented stimuli, the results indicate a more specific deficit in temporal processing of schizophrenic patients. PMID:23536838

  15. Integration of asynchronously released quanta prolongs the postsynaptic spike window.

    PubMed

    Iremonger, Karl J; Bains, Jaideep S

    2007-06-20

    Classically, the release of glutamate in response to a presynaptic action potential causes a brief increase in postsynaptic excitability. Previous reports indicate that at some central synapses, a single action potential can elicit multiple, asynchronous release events. This raises the possibility that the temporal dynamics of neurotransmitter release may determine the duration of altered postsynaptic excitability. In response to physiological challenges, the magnocellular neurosecretory cells (MNCs) in the paraventricular nucleus of the hypothalamus (PVN) exhibit robust and prolonged increases in neuronal activity. Although the postsynaptic conductances that may facilitate this form of activity have been investigated thoroughly, the role of presynaptic release has been largely overlooked. Because the specific patterns of activity generated by MNCs require the activation of excitatory synaptic inputs, we sought to characterize the release dynamics at these synapses and determine whether they contribute to prolonged excitability in these cells. We obtained whole-cell recordings from MNCs in brain slices of postnatal day 21-44 rats. Stimulation of glutamatergic inputs elicited large and prolonged postsynaptic events that resulted from the summation of multiple, asynchronously released quanta. Asynchronous release was selectively inhibited by the slow calcium buffer EGTA-AM and potentiated by brief high-frequency stimulus trains. These trains caused a prolonged increase in postsynaptic spike activity that could also be eliminated by EGTA-AM. Our results demonstrate that glutamatergic terminals in PVN exhibit asynchronous release, which is important in generating large postsynaptic depolarizations and prolonged spiking in response to brief, high-frequency bursts of presynaptic activity.

  16. Prolonged exposure therapy for combat- and terror-related posttraumatic stress disorder: a randomized control comparison with treatment as usual.

    PubMed

    Nacasch, Nitzah; Foa, Edna B; Huppert, Jonathan D; Tzur, Dana; Fostick, Leah; Dinstein, Yula; Polliack, Michael; Zohar, Joseph

    2011-09-01

    Empirically based studies have demonstrated that prolonged exposure therapy effectively reduces posttraumatic stress disorder (PTSD) symptoms in a vast range of traumas, yet reports of the efficacy of such therapies in combat- and terror-related PTSD are scarce. In this article, we examine the efficacy of prolonged exposure therapy in combat- and terror-related PTSD in comparison to treatment as usual (TAU). Between July 2002 and October 2005, 30 patients of a trauma unit within a psychiatric outpatient clinic were recruited and randomized into prolonged exposure versus TAU therapies. Patients were diagnosed with chronic PTSD (Mini-International Neuropsychiatric Interview criteria) related to combat- (n = 19) or terror-related (n = 11) trauma. Main outcome measures included symptoms of PTSD and depression, as measured by the PTSD Symptom Scale-Interview Version and the Beck Depression Inventory. Posttraumatic stress disorder symptom severity was significantly lower in patients who received prolonged exposure therapy in comparison to patients who received TAU (F(1,24) = 35.3, P < .001). Similar results have emerged in measures of depression and state and trait anxiety. In addition, a significant change from pretreatment to follow-up was found for the prolonged exposure group (F(1,14) = 80.5, P < .0001), but not for the TAU group (F(1,10.3) = 0.6, P = .44). Findings indicate that, similar to PTSD related to other types of trauma, prolonged exposure therapy is beneficial in the amelioration of combat- and terror-related PTSD symptoms. In addition, prolonged exposure was superior to TAU in the short- and long-term reduction of PTSD and depression symptoms. clinicaltrials.gov Identifier: NCT00229372. © Copyright 2011 Physicians Postgraduate Press, Inc.

  17. l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats.

    PubMed

    Jang, Jiwoong; Park, Jonghoon; Chang, Hyukki; Lim, Kiwon

    2016-12-01

    l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg(-1)·day(-1)) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

  18. Novel gel formulations with catanionic aggregates enable prolonged drug release and reduced skin permeation.

    PubMed

    Dew, Noel; Edsman, Katarina; Björk, Erik

    2011-10-01

    The aim of this study was to investigate skin permeation rates of a drug substance when applied in novel gel formulations with catanionic aggregates. Reference gel without catanionic aggregates was compared with formulations with catanionic aggregates composed of tetracaine and either sodium dodecyl sulphate (SDS) or capric acid. Carbomer and SoftCAT were used to compare the effect of different gel types to elucidate if physically cross-linked, 'self-destructing' systems had benefits compared with classical, covalently cross-linked, gels. The rheological investigation showed that the interactions between the SoftCAT polymer and tetracaine/SDS aggregates were stronger than when the tetracaine/capric acid aggregates were used. The skin permeation was measured ex vivo in horizontal Ussing chambers and the permeation of tetracaine was significantly lower when formulations with tetracaine/SDS aggregates were applied (P < 0.001), but not statistically different from the reference when capric acid was used. No morphological differences could be distinguished between the skin samples exposed to the different formulations or the reference. Skin permeation was compared with silicone sheet permeation and the results indicated that silicone sheets could be used as a model of skin when using these formulations. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  19. Assessment of the impact of a workplace intervention to reduce prolonged occupational sitting time.

    PubMed

    Cooley, Dean; Pedersen, Scott; Mainsbridge, Casey

    2014-01-01

    We aim to provide a better picture of the outcomes associated with implementing a nonpurposeful, physical activity, e-health intervention in a professional workplace. There is a need for health professionals to evaluate physical-activity-based workplace health interventions with a full range of measures. Using a social ecological model as a basis, we identify a range of subjective outcomes from 15 interviews of a cross section of participants. We document that not only did participants report a range of positive outcomes across multiple systems of influence, but they experienced some negative outcomes because of disruption to work flow and a changing of work habit. We conclude that using subjective evaluations provides a comprehensive picture of the factors that influence judgments of the efficacy of a workplace health intervention.

  20. Unusually Prolonged Presentation of Designer Drug Encephalopathy Responsive to Steroids.

    PubMed

    Albadareen, Rawan; Thornton, Stephen; Heshmati, Arezou; Gerona, Roy; Lowry, Jennifer

    2015-07-01

    The availability and use of novel psychoactive substances has risen dramatically over the last decade. The unpredictability of their toxicity constitutes a real challenge. We report a case of an adolescent who developed prolonged encephalopathy after ingesting "Hot Molly," which was found to contain the novel psychoactive substance, methylenedioxybenzylpiperazine when analyzed by high resolution mass spectrometry assay. This is the first case of human toxicity from methylenedioxybenzylpiperazine ingestion in the medical literature confirmed by body fluid analysis presenting with significant and prolonged encephalopathy. The prolonged course may be due to CYP2D6 inhibition from a combination of the methylenedioxyphenyl moiety and the patient's ultrarapid metabolizer pharmacokinetics. The response to high dose corticosteroids suggests a possible inflammatory effect that warrants further investigation.

  1. The difficult coughing child: prolonged acute cough in children

    PubMed Central

    2013-01-01

    Cough is one of the most common symptoms that patients bring to the attention of primary care clinicians. Cough can be designated as acute (<3 weeks in duration), prolonged acute cough (3 to 8 weeks in duration) or chronic (> 8 weeks in duration). The use of the term ‘prolonged acute cough’ in a cough guideline allows a period of natural resolution to occur before further investigations are warranted. The common causes are in children with post viral or pertussis like illnesses causing the cough. Persistent bacterial bronchitis typically occurs when an initial dry acute cough due to a viral infection becomes a prolonged wet cough remaining long after the febrile illness has resolved. This cough responds to a completed course of appropriate antibiotics. PMID:23574624

  2. Relationship between prolonged standing and symptoms of varicose veins and nocturnal leg cramps among women and men.

    PubMed

    Bahk, Jin Wook; Kim, Hyunjoo; Jung-Choi, Kyunghee; Jung, Myung-Chul; Lee, Inseok

    2012-01-01

    The relationships between occupational characteristics and symptoms of varicose veins and nocturnal leg cramps and their gender differences were explored in a Korean population. The study population was 2165 workers from various occupations (55.6% female). Multiple logistic regression analyses were conducted to reveal factors related to symptoms of varicose veins and nocturnal leg cramps. The prevalence of varicose veins and nocturnal leg cramps was higher among women than men. The characteristics of standing work were different according to gender. In gender stratified analysis, the odds ratio of varicose veins was significantly high for prolonged standing for male and female workers. However, the odds ratio of nocturnal leg cramps was only significant among prolonged standing male workers. The models including gender, prolonged standing and occupations in this order presented that gender is not significantly associated with varicose veins after occupations were added to the model. Prolonged standing at work may be a more important risk factor for varicose veins and nocturnal leg cramps than biological differences between women and men. Therefore, effective interventions to interrupt or reduce prolonged standing at work should be implemented for the prevention of varicose veins and nocturnal leg cramps. This paper shows associations between occupational characteristics and symptoms of varicose veins and nocturnal leg cramps and their gender differences. These findings will contribute to knowledge of gender-specific occupational risk factors for symptoms in the distal lower extremities.

  3. Prolonged Eyelid Closure Episodes during Sleep Deprivation in Professional Drivers

    PubMed Central

    Alvaro, Pasquale K.; Jackson, Melinda L.; Berlowitz, David J.; Swann, Philip; Howard, Mark E.

    2016-01-01

    Study Objectives: Real life ocular measures of drowsiness use average blink duration, amplitude and velocity of eyelid movements to reflect drowsiness in drivers. However, averaged data may conceal the variability in duration of eyelid closure episodes, and more prolonged episodes that indicate higher levels of drowsiness. The current study aimed to describe the frequency and duration of prolonged eyelid closure episodes during acute sleep deprivation. Methods: Twenty male professional drivers (mean age ± standard deviation = 41.9 ± 8.3 years) were recruited from the Transport Workers Union newsletter and newspaper advertisements in Melbourne, Australia. Each participant underwent 24 hours of sleep deprivation and completed a simulated driving task (AusEd), the Psychomotor Vigilance Task, and the Karolinska Sleepiness Scale. Eyelid closure episodes during the driving task were recorded and analyzed manually from digital video recordings. Results: Eyelid closure episodes increased in frequency and duration with a median of zero s/h of eyelid closure after 3 h increasing to 34 s/h after 23 h awake. Eyelid closure episodes were short and infrequent from 3 to 14 h of wakefulness. After 17 h of sleep deprivation, longer and more frequent eyelid closure episodes began to occur. Episodes lasting from 7 seconds up to 18 seconds developed after 20 h of wakefulness. Length of eyelid closure episodes was moderately to highly correlated with the standard deviation of lateral lane position, braking reaction time, crashes, impaired vigilance, and subjective sleepiness. Conclusions: The frequency and duration of episodes of prolonged eyelid closure increases during acute sleep deprivation, with very prolonged episodes after 17 hours awake. Automated devices that assess drowsiness using averaged measures of eyelid closure episodes need to be able to detect prolonged eyelid closure episodes that occur during more severe sleep deprivation. Citation: Alvaro PK, Jackson ML

  4. Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes

    PubMed Central

    Antzelevitch, Charles

    2008-01-01

    Torsade de pointes (TdP) is a life-threatening arrhythmia that develops as a consequence of a reduction in the repolarization reserve of cardiac cells leading to amplification of electrical heterogeneities in the ventricular myocardium as well as to the development of early after depolarization-induced triggered activity. Electrical heterogeneities within the ventricles are due to differences in the time course of repolarization of the three predominant cell types that make up the ventricular myocardium, giving rise to transmural voltage gradients and a dispersion of repolarization that contributes to the inscription of the electrocardiographic T wave. A number of non-antiarrhythmic drugs and antiarrhythmic agents with class III actions and/or the various mutations and cardiomyopathies associated with the long QT syndrome reduce net repolarizing current and amplify spatial dispersion of repolarization, thus creating the substrate for re-entry. This results in a prolongation of the QT interval, abnormal T waves, and development of TdP. Agents that prolong the QT interval but do not cause an increase in transmural dispersion of repolarization (TDR) do not induce TdP, suggesting that QT prolongation is not the sole or optimal determinant for arrhythmogenesis. This article reviews recent advances in our understanding of these mechanisms, particularly the role of TDR in the genesis of drug-induced TdP, and examines how these may guide us towards development of safer drugs. PMID:17766323

  5. Invariant NKT cells promote skin wound healing by preventing a prolonged neutrophilic inflammatory response.

    PubMed

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Kanno, Emi; Suzuki, Aiko; Takagi, Naoyuki; Yamamoto, Hideki; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

    2017-09-23

    The wound-healing process consists of the inflammation, proliferation, and remodeling phases. In chronic wounds, the inflammation phase is prolonged with persistent neutrophil infiltration. The inflammatory response is critically regulated by cytokines and chemokines that are secreted from various immune cells. Recently, we showed that skin wound healing was delayed and the healing process was impaired under conditions lacking invariant natural killer T (iNKT) cells, an innate immune lymphocyte with potent immuno-regulatory activity. In the present study, we investigated the effect of iNKT cell deficiency on the neutrophilic inflammatory response during the wound healing process. Neutrophil infiltration was prolonged in wound tissue in mice genetically lacking iNKT cells (Jα18KO mice) compared with wild-type (WT) control mice on days 1 and 3 after wounding. MIP-2, KC, and IL-17A were produced at a significantly higher level in Jα18KO mice than in WT mice. In addition, neutrophil apoptosis was significantly reduced in the wound tissue in Jα18KO mice compared with WT mice. Treatment with either anti-IL-17A mAb, anti-Gr-1 mAb, or neutrophil elastase inhibitor reversed the impaired wound healing in Jα18KO mice. These results suggest that iNKT cells may promote the wound healing process through preventing the prolonged inflammatory response mediated by neutrophils. This article is protected by copyright. All rights reserved. © 2017 by the Wound Healing Society.

  6. Xenon treatment protects against cold ischemia associated delayed graft function and prolongs graft survival in rats.

    PubMed

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

    2013-08-01

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

  7. The influence of a seated break on prolonged standing induced low back pain development.

    PubMed

    Gallagher, Kaitlin M; Campbell, Troy; Callaghan, Jack P

    2014-01-01

    With the recent attention to 'sitting disease', health practitioners and scientists are promoting standing in the workplace to decrease sedentary time, despite a high prevalence of low back pain (LBP) development during prolonged standing. The purpose of this study was to assess how a seated break inserted between bouts of prolonged standing would influence LBP development, posture and movement. A total of 20 participants stood for 45 minutes, sat for 15 minutes and repeated this sequence while lumbar and thoracic angles were measured, and LBP visual analogue scale reports were taken. Of the sample, 55% participants reported LBP in standing. A stand to sit ratio of 3:1 did not provide lasting recovery of LBP from standing and pain developers utilised a limited range of their lumbar spine angle and increased thoracic extension, resulting in static postures that caused tissue aggravation that was not resolved after 15 minutes of sitting. Prolonged standing in the workplace has the potential to result in LBP for some workers and alternate ways to reduce sedentary time should be investigated.

  8. QT interval prolongation and torsade de pointes: Synergistic effect of flecainide and H1 receptor antagonists

    PubMed Central

    Acosta-Materán, Carlos; Díaz-Oliva, Eloy; Fernández-Rodríguez, Diego; Hernández-Afonso, Julio

    2016-01-01

    A high percentage of patients having atrial fibrillation (AF) presents with paroxysmal AF. Flecainide, the prototypic class Ic anti-arrhythmic drug is the most effective drug to maintain sinus rhythm in this subgroup of patients, though the drug has potential pro-arrhythmic effects. Furthermore, the H1 receptor antagonists are the most commonly prescribed drugs for the symptomatic treatment of pruritus. Despite having low number of adverse effects, the H1 receptor antagonists have cardiotoxic effects. Flecainide and H1 receptor antagonists present arrhythmic complications including QT interval prolongation and torsade de pointes (TdP). The case presented here is a 65-year-old female who was diagnosed of atrial fibrillation and presented with rashes in lower extremities. The patient was treated using flecainide and H1 receptor antagonists (loratadine and hydroxyzine) that prolonged QT interval and induced TdP. The concomitant administration of flecainide and H1 receptor antagonists seems to have a synergistic effect in QT interval prolongation and subsequent TdP. The concurrent administration of H1 receptor antagonists to patients receiving class Ic anti-arrhythmic drugs should be avoided in order to reduce arrhythmic risk in this population. PMID:27440957

  9. Efficacy of metacognitive therapy for prolonged grief disorder: protocol for a randomised controlled trial

    PubMed Central

    Wenn, Jenine; O'Connor, Moira; Breen, Lauren J; Kane, Robert T; Rees, Clare S

    2015-01-01

    Introduction Studies of effective psychotherapy for individuals suffering from the effects of prolonged grief disorder (PGD) are scarce. This paper describes the protocol for an evaluation of a metacognitive therapy programme designed specifically for PGD, to reduce the psychological distress and loss of functioning resulting from bereavement. Methods and analysis The proposed trial comprises three phases. Phase 1 consists of a review of the literature and semistructured interviews with key members of the target population to inform the development of a metacognitive therapy programme for Prolonged Grief. Phase 2 involves a randomised controlled trial to implement and evaluate the programme. Male and female adults (N=34) will be randomly assigned to either a wait list or an intervention group. Measures of PGD, anxiety, depression, rumination, metacognitions and quality of life will be taken pretreatment and posttreatment and at the 3-month and 6-month follow-up. The generalised linear mixed model will be used to assess treatment efficacy. Phase 3 will test the social validity of the programme. Discussion This study is the first empirical investigation of the efficacy of a targeted metacognitive treatment programme for PGD. A focus on identifying and changing the metacognitive mechanisms underpinning the development and maintenance of prolonged grief is likely to be beneficial to theory and practice. Ethics Ethics approval was obtained from Curtin University Human Research Ethics Committee (Approval number HR 41/2013.) Trial registration number ACTRN12613001270707. PMID:26646828

  10. The effect of estrogen on muscle damage biomarkers following prolonged aerobic exercise in eumenorrheic women

    PubMed Central

    Walz, E; Lane, AR; Pebole, M; Hackney, AC

    2015-01-01

    This study assessed the influence of estrogen (E2) on muscle damage biomarkers [skeletal muscle - creatine kinase (CK); cardiac muscle - CK-MB] responses to prolonged aerobic exercise. Eumenorrheic women (n=10) who were physically active completed two 60-minute treadmill running sessions at ∼60-65% maximal intensity during low E2 (midfollicular menstrual phase) and high E2 (midluteal menstrual phase) hormonal conditions. Blood samples were collected prior to exercise (following supine rest), immediately post-, 30 min post-, and 24 hours post-exercise to determine changes in muscle biomarkers. Resting blood samples confirmed appropriate E2 hormonal levels Total CK concentrations increased following exercise and at 24 hours post-exercise were higher in the midfollicular low E2 phase (p<0.001). However, CK-MB concentrations were unaffected by E2 level or exercise (p=0.442) resulting in the ratio of CK-MB to total CK being consistently low in subject responses (i.e., indicative of skeletal muscle damage). Elevated E2 levels reduce the CK responses of skeletal muscle, but had no effect on CK-MB responses following prolonged aerobic exercise. These findings support earlier work showing elevated E2 is protective of skeletal muscle from exercise-induced damage associated with prolonged aerobic exercise. PMID:26424921

  11. The effect of estrogen on muscle damage biomarkers following prolonged aerobic exercise in eumenorrheic women.

    PubMed

    Williams, T; Walz, E; Lane, A R; Pebole, M; Hackney, A C

    2015-09-01

    This study assessed the influence of estrogen (E2) on muscle damage biomarkers [skeletal muscle - creatine kinase (CK); cardiac muscle - CK-MB] responses to prolonged aerobic exercise. Eumenorrheic women (n=10) who were physically active completed two 60-minute treadmill running sessions at ∼60-65% maximal intensity during low E2 (midfollicular menstrual phase) and high E2 (midluteal menstrual phase) hormonal conditions. Blood samples were collected prior to exercise (following supine rest), immediately post-, 30 min post-, and 24 hours post-exercise to determine changes in muscle biomarkers. Resting blood samples confirmed appropriate E2 hormonal levels Total CK concentrations increased following exercise and at 24 hours post-exercise were higher in the midfollicular low E2 phase (p<0.001). However, CK-MB concentrations were unaffected by E2 level or exercise (p=0.442) resulting in the ratio of CK-MB to total CK being consistently low in subject responses (i.e., indicative of skeletal muscle damage). Elevated E2 levels reduce the CK responses of skeletal muscle, but had no effect on CK-MB responses following prolonged aerobic exercise. These findings support earlier work showing elevated E2 is protective of skeletal muscle from exercise-induced damage associated with prolonged aerobic exercise.

  12. Prolongation of survival of rat cardiac allografts by T cell vaccination.

    PubMed Central

    Shapira, O M; Mor, E; Reshef, T; Pfeffermann, R A; Cohen, I R

    1993-01-01

    Administration of attenuated, activated autoimmune T lymphocytes to syngeneic mice and rats has been shown to prevent or induce remission of experimental autoimmune diseases specific for the autoimmune T cells. The process has been termed "T cell vaccination." In a recent study, T cell vaccination was done using T cells sensitized to rat alloantigens. The procedure produced a significant reduction of the mixed lymphocyte reaction (MLR) against allogeneic cells. The reduction in MLR was not specific: Vaccination with T cells specific for stimulator cells of one allotype led to a reduced MLR stimulated by cells of another allotype. The present study was undertaken to examine whether T cell vaccination can induce tolerance to transplantation antigens in vivo. We used the model of heterotopic cardiac transplantation in rats. We now report that vaccinating rats with syngeneic, activated, alloantigen-primed T lymphocytes significantly prolonged survival of rat cardiac allografts. The effect of T cell vaccination was most evident when the T cells had been obtained from rats specifically sensitized against the donor rats: Brown-Norway (BN) allografts in control Wistar rats survived 8.5 +/- 0.4 d while BN allografts survived 29.2 +/- 7.1 d in Wistar rats that had been vaccinated with Wistar anti-BN cells. Vaccination of Wistar rats with Wistar anti-hooded T cells prolonged survival of BN heart allografts to a lesser but significant degree (13.0 +/- 1.1 d). Thus, T cell vaccination of recipients can prolong survival of allografts. PMID:8432846

  13. Prolonged vasoconstriction of resistance arteries involves vascular smooth muscle actin polymerization leading to inward remodelling

    PubMed Central

    Staiculescu, Marius C.; Galiñanes, Edgar L.; Zhao, Guiling; Ulloa, Uri; Jin, Minshan; Beig, Mirza I.; Meininger, Gerald A.; Martinez-Lemus, Luis A.

    2013-01-01

    Aims Inward remodelling of the resistance vasculature is predictive of hypertension and life-threatening cardiovascular events. We hypothesize that the contractile mechanisms responsible for maintaining a reduced diameter over time in response to prolonged stimulation with vasoconstrictor agonists are in part responsible for the initial stages of the remodelling process. Here we investigated the role of vascular smooth muscle (VSM) actin polymerization on agonist-induced vasoconstriction and development of inward remodelling. Methods and results Experiments were conducted in Sprague–Dawley rat resistance vessels isolated from the cremaster and mesentery. Within blood vessels, actin dynamics of VSM were monitored by confocal microscopy after introduction of fluorescent actin monomers through electroporation and by differential centrifugation to probe globular (G) and filamentous (F) actin content. Results indicated that 4 h of agonist-dependent vasoconstriction induced inward remodelling and caused significant actin polymerization, elevating the F-/total-actin ratio. Inhibition of actin polymerization prevented vessels from maintaining prolonged vasoconstriction and developing inward remodelling. Activation of the small GTPases Rho/Rac/Cdc42 also increased the F-/total-actin ratio and induced inward remodelling, while inhibition of Rho kinase or Rac-1 prevented inward remodelling. Disruption of the actin cytoskeleton reversed the inward remodelling caused by prolonged vasoconstriction, but did not affect the passive diameter of freshly isolated vessels. Conclusion These results indicate that vasoconstriction-induced inward remodelling is in part caused by the polymerization of actin within VSM cells through activation of small GTPases. PMID:23417038

  14. Prolonged vasoconstriction of resistance arteries involves vascular smooth muscle actin polymerization leading to inward remodelling.

    PubMed

    Staiculescu, Marius C; Galiñanes, Edgar L; Zhao, Guiling; Ulloa, Uri; Jin, Minshan; Beig, Mirza I; Meininger, Gerald A; Martinez-Lemus, Luis A

    2013-06-01

    Inward remodelling of the resistance vasculature is predictive of hypertension and life-threatening cardiovascular events. We hypothesize that the contractile mechanisms responsible for maintaining a reduced diameter over time in response to prolonged stimulation with vasoconstrictor agonists are in part responsible for the initial stages of the remodelling process. Here we investigated the role of vascular smooth muscle (VSM) actin polymerization on agonist-induced vasoconstriction and development of inward remodelling. Experiments were conducted in Sprague-Dawley rat resistance vessels isolated from the cremaster and mesentery. Within blood vessels, actin dynamics of VSM were monitored by confocal microscopy after introduction of fluorescent actin monomers through electroporation and by differential centrifugation to probe globular (G) and filamentous (F) actin content. Results indicated that 4 h of agonist-dependent vasoconstriction induced inward remodelling and caused significant actin polymerization, elevating the F-/total-actin ratio. Inhibition of actin polymerization prevented vessels from maintaining prolonged vasoconstriction and developing inward remodelling. Activation of the small GTPases Rho/Rac/Cdc42 also increased the F-/total-actin ratio and induced inward remodelling, while inhibition of Rho kinase or Rac-1 prevented inward remodelling. Disruption of the actin cytoskeleton reversed the inward remodelling caused by prolonged vasoconstriction, but did not affect the passive diameter of freshly isolated vessels. These results indicate that vasoconstriction-induced inward remodelling is in part caused by the polymerization of actin within VSM cells through activation of small GTPases.

  15. [Prolonged phase II neuromuscular blockade following succinylcholine administration].

    PubMed

    Jurkolow, G; Fuchs-Buder, T; Lemoine, A; Raft, J; Rocq, N; Meistelman, C

    2014-03-01

    Patients who are given a single dose of succinylcholine normally undergo a short-acting depolarizing phase I neuromuscular block but rarely a phase II block. Prolonged neuromuscular blockade occurs after a single dose of succinylcholine in case of genetically determined abnormal plasma butyrylcholinesterase activity. It is mandatory to use monitoring to detect this side effect. We report a case of a patient with abnormal plasma butyrylcholinesterase activity undergoing a six-hour prolonged neuromuscular phase II block, after a single dose of succinylcholine.

  16. Bartonella henselae Infective Endocarditis Detected by a Prolonged Blood Culture

    PubMed Central

    Mito, Tsutomu; Hirota, Yusuke; Suzuki, Shingo; Noda, Kazutaka; Uehara, Takanori; Ohira, Yoshiyuki; Ikusaka, Masatomi

    2016-01-01

    A 65-year-old Japanese man was admitted with a 4-month history of fatigue and exertional dyspnea. Transthoracic echocardiography revealed a vegetation on the aortic valve and severe aortic regurgitation. Accordingly, infective endocarditis and heart failure were diagnosed. Although a blood culture was negative on day 7 after admission, a prolonged blood culture with subculture was performed according to the patient's history of contact with cats. Consequently, Bartonella henselae was isolated. Bartonella species are fastidious bacteria that cause blood culture-negative infective endocarditis. This case demonstrates that B. henselae may be detected by prolonged incubation of blood cultures. PMID:27746451

  17. Bartonella henselae Infective Endocarditis Detected by a Prolonged Blood Culture.

    PubMed

    Mito, Tsutomu; Hirota, Yusuke; Suzuki, Shingo; Noda, Kazutaka; Uehara, Takanori; Ohira, Yoshiyuki; Ikusaka, Masatomi

    A 65-year-old Japanese man was admitted with a 4-month history of fatigue and exertional dyspnea. Transthoracic echocardiography revealed a vegetation on the aortic valve and severe aortic regurgitation. Accordingly, infective endocarditis and heart failure were diagnosed. Although a blood culture was negative on day 7 after admission, a prolonged blood culture with subculture was performed according to the patient's history of contact with cats. Consequently, Bartonella henselae was isolated. Bartonella species are fastidious bacteria that cause blood culture-negative infective endocarditis. This case demonstrates that B. henselae may be detected by prolonged incubation of blood cultures.

  18. Neonatal and maternal outcomes with prolonged second stage of labor.

    PubMed

    Laughon, S Katherine; Berghella, Vincenzo; Reddy, Uma M; Sundaram, Rajeshwari; Lu, Zhaohui; Hoffman, Matthew K

    2014-07-01

    To assess neonatal and maternal outcomes when the second stage of labor was prolonged according to American College of Obstetricians and Gynecologists guidelines. Electronic medical record data from a retrospective cohort (2002-2008) from 12 U.S. clinical centers (19 hospitals), including 43,810 nulliparous and 59,605 multiparous singleton deliveries at 36 weeks of gestation or greater, vertex presentation, who reached 10-cm cervical dilation were analyzed. Prolonged second stage was defined as: nulliparous women with epidural greater than 3 hours and without greater than 2 hours and multiparous women with epidural greater than 2 hours and without greater than 1 hour. Maternal and neonatal outcomes were compared and adjusted odds ratios calculated controlling for maternal race, body mass index, insurance, and region. Prolonged second stage occurred in 9.9% and 13.9% of nulliparous and 3.1% and 5.9% of multiparous women with and without an epidural, respectively. Vaginal delivery rates with prolonged second stage compared with within guidelines were 79.9% compared with 97.9% and 87.0% compared with 99.4% for nulliparous women with and without epidural, respectively, and 88.7% compared with 99.7% and 96.2% compared with 99.9% for multiparous women with and without epidural, respectively (P<.001 for all comparisons). Prolonged second stage was associated with increased chorioamnionitis and third-degree or fourth-degree perineal lacerations. Neonatal morbidity with prolonged second stage included sepsis in nulliparous women (with epidural: 2.6% compared with 1.2% [adjusted odds ratio (OR) 2.08, 95% confidence interval (CI) 1.60-2.70]; without epidural: 1.8% compared with 1.1% [adjusted OR 2.34, 95% CI 1.28-4.27]); asphyxia in nulliparous women with epidural (0.3% compared with 0.1% [adjusted OR 2.39, 95% CI 1.22-4.66]) and perinatal mortality without epidural (0.18% compared with 0.04% for nulliparous women [adjusted OR 5.92, 95% CI 1.43-24.51]); and 0.21% compared

  19. Changes in the human blood coagulating system during prolonged hypokinesia

    NASA Technical Reports Server (NTRS)

    Filatova, L. M.; Anashkin, O. D.

    1978-01-01

    Changes in the coagulating system of the blood were studied in six subjects during prolonged hypokinesia. Thrombogenic properties of the blood rose in all cases on the 8th day. These changes are explained by stress reaction due to unusual conditions for a healthy person. Changes in the blood coagulating system in the group subjected to physical exercise and without it ran a practically parallel course. Apparently physical exercise is insufficient to prevent such changes that appear in the coagulating system of the blood during prolonged hypokinesia.

  20. Connexin-purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation.

    PubMed

    Bhave, Sukhada; Gade, Aravind; Kang, Minho; Hauser, Kurt F; Dewey, William L; Akbarali, Hamid I

    2017-06-01

    Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance, limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut, predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment (in vivo) but not upon direct exposure of glia to morphine (in vitro). LPS, a major bacterial product, also increased ATP-induced currents, as well as expression of P2X4, P2X7, IL6, IL-1β mRNA in enteric glia. LPS increased connexin43 (Cx43) expression and enhanced ATP release from enteric glia cells. LPS-induced P2X currents and proinflammatory cytokine mRNA expression were blocked by the Cx43 blockers Gap26 and carbenoxolone. Likewise, colonic inflammation related to prolonged exposure to morphine was significantly attenuated by carbenoxolone (25 mg/kg). Carbenoxolone also prevented gut wall disruption and significantly reduced morphine-induced constipation. These findings imply that enteric glia activation is a significant modulator of morphine-related inflammation and constipation.-Bhave, S., Gade, A., Kang, M., Hauser, K. F., Dewey, W. L., Akbarali, H. I. Connexin-purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation. © FASEB.

  1. Alterations of neuromuscular function after prolonged running, cycling and skiing exercises.

    PubMed

    Millet, Guillaume Y; Lepers, Romuald

    2004-01-01

    It is well known that impairment of performance resulting from muscle fatigue differs according to the types of contraction involved, the muscular groups tested and the exercise duration/intensity. Depending on these variables, strength loss with fatigue can originate from several sites from the motor cortex through to contractile elements. This has been termed 'task dependency of muscle fatigue'. Only recently have studies focused on the origin of muscle fatigue after prolonged exercise lasting 30 minutes to several hours. Central fatigue has been shown to contribute to muscle fatigue during long-distance running by using different methods such as the twitch interpolation technique, the ratio of the electromyogram (EMG) signal during maximal voluntary contraction normalised to the M-wave amplitude or the comparison of the forces achieved with voluntary- and electrically-evoked contractions. Some central activation deficit has also been observed for knee extensor muscles in cycling but central fatigue after activities inducing low muscular damage was attenuated compared with running. While supraspinal fatigue cannot be ruled out, it can be suggested that spinal adaptation, such as inhibition from type III and IV group afferents or disfacilitation from muscle spindles, contributes to the reduced neural drive after prolonged exercise. It has been shown that after a 30 km run, individuals with the greatest knee extensor muscle strength loss experienced a significant activation deficit. However, central fatigue alone cannot explain the entire strength loss after prolonged exercise. Alterations of neuromuscular propagation, excitation-contraction coupling failure and modifications of the intrinsic capability of force production may also be involved. Electrically-evoked contractions and associated EMG can help to characterise peripheral fatigue. The purpose of this review is to further examine the central and peripheral mechanisms contributing to strength loss after

  2. Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise.

    PubMed

    Shockett, Penny E; Khanal, Januka; Sitaula, Alina; Oglesby, Christopher; Meachum, William A; Castracane, V Daniel; Kraemer, Robert R

    2016-01-01

    Increased plasma cell-free mitochondrial DNA (cf-mDNA), a damage-associated molecular pattern (DAMP) produced by cellular injury, contributes to neutrophil activation/inflammation in trauma patients and arises in cancer and autoimmunity. To further understand relationships between cf-mDNA released by tissue injury, inflammation, and health benefits of exercise, we examined cf-mDNA response to prolonged moderate aerobic exercise. Seven healthy moderately trained young men (age = 22.4 ± 1.2) completed a treadmill exercise trial for 90 min at 60% VO2 max and a resting control trial. Blood was sampled immediately prior to exercise (0 min = baseline), during (+18, +54 min), immediately after (+90 min), and after recovery (R40). Plasma was analyzed for cf-mDNA, IL-6, and lactate. A significant difference in cf-mDNA response was observed between exercise and control trials, with cf-mDNA levels reduced during exercise at +54 and +90 (with or without plasma volume shift correction). Declines in cf-mDNA were accompanied by increased lactate and followed by an increase in IL-6, suggesting a temporal association with muscle stress and inflammatory processes. Our novel finding of cf-mDNA decline with prolonged moderate treadmill exercise provides evidence for increased clearance from or reduced release of cf-mDNA into the blood with prolonged exercise. These studies contrast with previous investigations involving exhaustive short-term treadmill exercise, in which no change in cf-mDNA levels were reported, and contribute to our understanding of differences between exercise- and trauma-induced inflammation. We propose that transient declines in cf-mDNA may induce health benefits, by reducing systemic inflammation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  3. No effect of menstrual cycle phase on glucose and glucoregulatory endocrine responses to prolonged exercise.

    PubMed

    Kraemer, Robert R; Francois, Michelle; Webb, Nancy Dardis; Worley, Jennifer R; Rogers, Sharon N; Norman, Reid L; Shah, Urvi; Castracane, V Daniel; Daniel Castracane, V

    2013-09-01

    Prolonged exercise requires increased utilization of blood glucose and adjustment of glucoregulatory hormones. Estrogen can reduce hepatic gluconeogenesis which could affect insulin concentrations. Amylin is co-secreted with insulin and controls influx of glucose into the blood. To determine the effect of menstrual cycle stage on glucose, leptin, and pancreatic hormone responses to prolonged (90 min) exercise. Five healthy, eumenorrheic women (24.6 ± 5.1 years; 67.4 ± 1 kg) were monitored for 3 months to determine menstrual cycle length. Subjects completed a preliminary session to determine exercise workloads and, in a fasted condition, completed two randomized 90-min treadmill exercise trials at 60 % VO2max during the early follicular (EFX) and mid-luteal phase (MLX) of their menstrual cycle. Blood samples were analyzed for glucose, insulin, C-peptide, amylin, glucagon, leptin, and cortisol concentrations at rest (-30 and 0 min), during exercise (18, 36, 54, 72, and 90 min) and after 20 min of recovery. No changes in amylin, leptin, or cortisol occurred for EFX and MLX trials. A significant (p < 0.05) time effect occurred for glucose, insulin, and glucagon with reduced insulin across the exercise trial and increases in glucose and glucagon later in the trial, but there were no differences between the EFX and MLX trials. Menstrual cycle stage does not affect glucose, insulin, C-peptide, amylin, glucagon, cortisol, and leptin responses to prolonged exercise; however, the exercise reduces insulin and increases glucose and glucagon concentrations. This is the first study to determine acute effects of exercise on amylin and other glucoregulatory hormone responses in women.

  4. Prolonged neuromuscular block in a preeclamptic patient induced by magnesium sulfate

    PubMed Central

    Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha

    2016-01-01

    Recent large use of magnesium in the obstetric population should incite anesthesiologists to control its side effects and drugs interactions. We report a case of a 30-year-old woman, with severe preeclampsia and HELLP syndrome, receiving sulfate magnesium and nicardipine, who underwent a cesarean section under general anesthesia. She developed a prolonged and deep neuromuscular blockade, which was antagonized three hours later with neostigmine. In case of therapeutic hypermagnesaemia, non-depolarizing relaxants must be used in reduced doses, and at increased time intervals, with appropriate neuromuscular monitoring. PMID:28154698

  5. Resveratrol treatment controls microbial flora, prolongs shelf life, and preserves nutritional quality of fruit.

    PubMed

    Jiménez, Jorge Bernardo; Orea, José María; Montero, Carlos; Ureña, Angel González; Navas, Elena; Slowing, Karla; Gómez-Serranillos, María Pilar; Carretero, Emilia; De Martinis, Domenico

    2005-03-09

    Resveratrol is known as a grapevine secondary metabolite with fungicide activity. Its exogenous application on harvested grapes resulted in the reduction of microbial flora growth, and consequently, prolonged shelf life, without affecting the nutritional quality of the fruit. Resveratrol treatment also resulted in being effective on fruit that normally does not accumulate such metabolites as, for example, tomatoes, apples, avocado pears, and peppers. As a result, all treated fruits maintained their post-harvest quality and health longer than the untreated ones. This study demonstrates the potential use of resveratrol as a natural pesticide to reduce post-harvest fungi development on a broad spectrum of fruit types.

  6. Prolonged neuromuscular block in a preeclamptic patient induced by magnesium sulfate.

    PubMed

    Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha

    2016-01-01

    Recent large use of magnesium in the obstetric population should incite anesthesiologists to control its side effects and drugs interactions. We report a case of a 30-year-old woman, with severe preeclampsia and HELLP syndrome, receiving sulfate magnesium and nicardipine, who underwent a cesarean section under general anesthesia. She developed a prolonged and deep neuromuscular blockade, which was antagonized three hours later with neostigmine. In case of therapeutic hypermagnesaemia, non-depolarizing relaxants must be used in reduced doses, and at increased time intervals, with appropriate neuromuscular monitoring.

  7. Fitness benefits of prolonged post-reproductive lifespan in women.

    PubMed

    Lahdenperä, Mirkka; Lummaa, Virpi; Helle, Samuli; Tremblay, Marc; Russell, Andrew F

    2004-03-11

    Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction.

  8. Community Use of Intranasal Midazolam for Managing Prolonged Seizures

    ERIC Educational Resources Information Center

    Kyrkou, Margaret; Harbord, Michael; Kyrkou, Nicole; Kay, Debra; Coulthard, Kingsley

    2006-01-01

    Background: Until a few years ago, rectal diazepam (RD) was the only option available to parents and carers managing prolonged seizures. However, its use in the community was limited due to the requirement for privacy, and because education staff in South Australia are not permitted to carry out invasive procedures. Method: Following a literature…

  9. QTc prolongation with antipsychotics: is routine ECG monitoring recommended?

    PubMed

    Shah, Asim A; Aftab, Awais; Coverdale, John

    2014-05-01

    Whether or not QTc interval should be routinely monitored in patients receiving antipsychotics is a controversial issue, given logistic and fiscal dilemmas. There is a link between antipsychotic medications and prolongation of QTc interval, which is associated with an increased risk of torsade de pointes (TdP). Our goal is to provide clinically practical guidelines for monitoring QTc intervals in patients being treated with antipsychotics. We provide an overview of the pathophysiology of the QT interval, its relationship to TdP, and a discussion of the QT prolonging effects of antipsychotics. A literature search for articles relevant to the QTc prolonging effects of antipsychotics and TdP was conducted utilizing the databases PubMed and Embase with various combinations of search words. The overall risk of TdP and sudden death associated with antipsychotics has been observed to be low. Medications, genetics, gender, cardiovascular status, pathological conditions, and electrolyte disturbances have been found to be related to prolongation of the QTc interval. We conclude that, while electrocardiogram (ECG) monitoring is useful when administering antipsychotic medications in the presence of co-existing risk factors, it is not mandatory to perform ECG monitoring as a prerequisite in the absence of cardiac risk factors. An ECG should be performed if the initial evaluation suggests increased cardiac risk or if the antipsychotic to be prescribed has been established to have an increased risk of TdP and sudden death.

  10. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    ERIC Educational Resources Information Center

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

  11. Endogenous Opioids and Ventilatory Adaptation to Prolonged Hypoxia in Goats,

    DTIC Science & Technology

    1984-06-25

    the rise in arterial PCO 2 with .- gA. IV. 10 long-term acclimatization in goats and attributed it to. augmented production of CO2 by the rumen of the...proposed that, with prolonged hypoxia, partial non-respiratory compensation for metabolic acidosis in the central nervous system acts to decrease ventilatory

  12. Prolonged-release melatonin for children with neurodevelopmental disorders.

    PubMed

    De Leersnyder, Hélène; Zisapel, Nava; Laudon, Moshe

    2011-07-01

    Previous studies demonstrated the efficacy and safety of prolonged-release melatonin in children and adolescents with neurodevelopmental and behavioral disorders. The long-term effectiveness and safety of prolonged-release melatonin treatment were assessed in 88 children (42 girls and 46 boys) with neurodevelopmental disorders. These patients participated in a compassionate-use program with the drug Circadin (2 mg; Neurim Pharmaceuticals, Tel Aviv, Israel) in France, and received treatment in the context of regular care by a specialized physician. The study involved a structured questionnaire for the parents, comprising a combination of multiple-choice and numeric questions addressing sleep onset/offset, sleep quality problems, and mood. The dose of melatonin ranged from 4-6 mg, and treatment duration ranged from 6-72 months. Within 3 months, sleep latency with prolonged-release melatonin decreased by 44.0% (P < 0.001), sleep duration increased by 10.1% (P < 0.001), the number of awakenings decreased by 75% (P < 0.001), and sleep quality improved by 75%, compared with baseline (P < 0.001). No serious adverse events or treatment-related comorbidities were reported. Prolonged-release melatonin remains a safe, effective therapy for the long-term treatment of sleep disorders in children with neurodevelopmental disorders.

  13. Intrinsic motivation and amotivation in first episode and prolonged psychosis.

    PubMed

    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.

  14. Prolonged unassisted survival in an infant with anencephaly.

    PubMed

    Dickman, Holly; Fletke, Kyle; Redfern, Roberta E

    2016-10-31

    Anencephaly is one of the most lethal congenital defects. This case report is of an anencephalic infant who lived to 28 months of life and defies current literature. She is the longest surviving anencephalic infant who did not require life-sustaining interventions. This case presents the obstacles that arose from this infant's prolonged life and recommendations based on these findings.

  15. Family presence during cardiopulmonary resuscitation: grief therapy or prolonged futility?

    PubMed

    Sherman, David A

    2008-01-01

    Nursing leaders are responsible in part for implementing procedures supporting family presence during cardiopulmonary resuscitation. Family presence has received broad support in nursing literature and from professional organizations. A case study suggests that, when a patient's spokesperson is struggling with the question of whether to set limits to treatments, allowing family presence may inappropriately prolong futile care.

  16. Economic viability of beef cattle grazing systems under prolonged drought

    USDA-ARS?s Scientific Manuscript database

    Prolonged drought in the Southern Great Plains of the USA in recent years has raised concerns about vulnerability of beef cattle grazing systems under adverse climate change. To help address the economic viability of beef grazing operations in the Southern Great Plains, this paper provides an econom...

  17. Diet-consumer nitrogen isotope fractionation for prolonged fasting arthropods.

    PubMed

    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.

  18. Preferences for Prolonging Life: A Prospect Theory Approach

    ERIC Educational Resources Information Center

    Winter, Laraine; Lawton, M. Powell; Ruckdeschel, Katy

    2003-01-01

    Kahneman and Tversky's (1979) Prospect theory was tested as a model of preferences for prolonging life under various hypothetical health statuses. A sample of 384 elderly people living in congregate housing (263 healthy, 131 frail) indicated how long (if at all) they would want to live under each of nine hypothetical health conditions (e.g.,…

  19. Listener perceptions of stuttering, prolonged speech, and verbal avoidance behaviors.

    PubMed

    Von Tiling, Johannes

    2011-01-01

    This study examined listener perceptions of different ways of speaking often produced by people who stutter. Each of 115 independent listeners made quantitative and qualitative judgments upon watching one of four randomly assigned speech samples. Each of the four video clips showed the same everyday conversation between three young men, but differed in how the target person spoke. The four ways of speaking comprised: (1) stuttered speech, i.e., a speech containing repetitions, prolongations, and blocks, (2) hesitant speech, i.e., a speech containing verbal avoidance behaviors like interjections and revisions, (3) a mix of both, and (4) prolonged speech learned in fluency-shaping therapy. Quantitative data revealed that listeners perceived a speaker producing hesitant speech as less pleasant, self-confident, and communicatively competent than a speaker producing stuttered speech or prolonged speech. There were no differences between stuttered speech and prolonged speech. Ratings were partly dependent on the listeners' implicit theory of speaking difficulties, that is, whether they assumed a chronic speech defect or a temporary problem. Implications of these findings are discussed. The reader will: (1) be able to summarize how different ways of speaking produced by people who stutter are connected with different listener perceptions; (2) be able to explain how the listener's implicit theory of speaking problems influences these perceptions; (3) learn about the clinical implications of the data from this study. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. The effects of prolonged exposure to weightlessness on postural equilibrium

    NASA Technical Reports Server (NTRS)

    Homick, J. L.; Reschke, M. F.; Miller, E. F., II

    1977-01-01

    A postflight postural equilibrium rail tests on spacecrews was used to prove a pronounced decrement in ability to maintain an upright posture after prolonged exposure to weightlessness. Support for the hypothesis that central neural reorganization occurs in response to environmental change is obtained when postflight decrease in stability on the rails and the time course for recovery are compared with preflight performance.

  1. Effect of prolonged bed rest on the anterior hip muscles.

    PubMed

    Dilani Mendis, M; Hides, Julie A; Wilson, Stephen J; Grimaldi, Alison; Belavý, Daniel L; Stanton, Warren; Felsenberg, Dieter; Rittweger, Joern; Richardson, Carolyn

    2009-11-01

    Prolonged bed rest and inactivity is known to cause muscular atrophy with previous research indicating that muscles involved in joint stabilisation are more susceptible. The anterior hip muscles are important for hip joint function and stability but little is known about the effects of prolonged inactivity on their function. This study investigated the effect of prolonged bed rest on the size of the anterior hip muscles and their pattern of recovery. The effect of resistive vibration exercise (RVE) as a countermeasure to muscle atrophy was also investigated. 12 male participants, randomly assigned to either a control or an exercise group, underwent 8 weeks of bed rest with 6 months follow-up. Changes in muscle cross-sectional area (CSA) of the iliacus, psoas, iliopsoas, sartorius and rectus femoris muscles were measured by magnetic resonance imaging at regular intervals during bed rest and recovery phases. CSAs of iliopsoas and sartorius decreased at the hip joint (p<0.05) during bed rest but iliacus, psoas, and rectus femoris CSAs were unchanged (p>0.05). No significant difference was found between the two groups for all muscles (all p>0.1), suggesting inefficacy of the countermeasure in this sample. These findings suggest that prolonged bed rest can result in the atrophy of specific muscles across the hip joint which may affect its stability and function.

  2. Preferences for Prolonging Life: A Prospect Theory Approach

    ERIC Educational Resources Information Center

    Winter, Laraine; Lawton, M. Powell; Ruckdeschel, Katy

    2003-01-01

    Kahneman and Tversky's (1979) Prospect theory was tested as a model of preferences for prolonging life under various hypothetical health statuses. A sample of 384 elderly people living in congregate housing (263 healthy, 131 frail) indicated how long (if at all) they would want to live under each of nine hypothetical health conditions (e.g.,…

  3. Delirium in Prolonged Hospitalized Patients in the Intensive Care Unit

    PubMed Central

    Vahedian Azimi, Amir; Ebadi, Abbas; Ahmadi, Fazlollah; Saadat, Soheil

    2015-01-01

    Background: Prolonged hospitalization in the intensive care unit (ICU) can impose long-term psychological effects on patients. One of the most significant psychological effects from prolonged hospitalization is delirium. Objectives: The aim of this study was to assess the effect of prolonged hospitalization of patients and subsequent delirium in the intensive care unit. Patients and Methods: This conventional content analysis study was conducted in the General Intensive Care Unit of the Shariati Hospital of Tehran University of Medical Sciences, from the beginning of 2013 to 2014. All prolonged hospitalized patients and their families were eligible participants. From the 34 eligible patients and 63 family members, the final numbers of actual patients and family members were 9 and 16, respectively. Several semi-structured interviews were conducted face-to-face with patients and their families in a private room and data were gathered. Results: Two main themes from two different perspectives emerged, 'patients' perspectives' (experiences during ICU hospitalization) and 'family members' perspectives' (supportive-communicational experiences). The main results of this study focused on delirium, Patients' findings were described as pleasant and unpleasant, factual and delusional experiences. Conclusions: Family members are valuable components in the therapeutic process of delirium. Effective use of family members in the delirium caring process can be considered to be one of the key non-medical nursing components in the therapeutic process. PMID:26290854

  4. Efficacy of an Emotion-Focused Treatment for Prolonged Fatigue

    ERIC Educational Resources Information Center

    Schutte, Nicola S.; Malouff, John M.; Brown, Rhonda F.

    2008-01-01

    Previous research findings have suggested a relationship between less adaptive emotional functioning and fatigue. The present study used a research design involving multiple baselines across participants to evaluate the efficacy of a new emotion-focused treatment for prolonged fatigue delivered in a cognitive behavioral therapy framework. The 13…

  5. Prolonged idiopathic gastric dilatation following revascularization for chronic mesenteric ischemia.

    PubMed

    Gauci, Julia L; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A

    2014-01-01

    A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described.

  6. Long term cognitive development in children with prolonged crying

    PubMed Central

    Rao, M; Brenner, R; Schisterman, E; Vik, T; Mills, J

    2004-01-01

    Background: Long term studies of cognitive development and colic have not differentiated between typical colic and prolonged crying. Objective: To evaluate whether colic and excessive crying that persists beyond 3 months is associated with adverse cognitive development. Design: Prospective cohort study. A sample of 561 women was enrolled in the second trimester of pregnancy. Colic and prolonged crying were based on crying behaviour assessed at 6 and 13 weeks. Children's intelligence, motor abilities, and behaviour were measured at 5 years (n = 327). Known risk factors for cognitive impairment were ascertained prenatally, after birth, at 6 and 13 weeks, at 6, 9, and 13 months, and at 5 years of age. Results: Children with prolonged crying (but not those with colic only) had an adjusted mean IQ that was 9 points lower than the control group. Their performance and verbal IQ scores were 9.2 and 6.7 points lower than the control group, respectively. The prolonged crying group also had significantly poorer fine motor abilities compared with the control group. Colic had no effect on cognitive development. Conclusions: Excessive, uncontrolled crying that persists beyond 3 months of age in infants without other signs of neurological damage may be a marker for cognitive deficits during childhood. Such infants need to be examined and followed up more intensively. PMID:15499048

  7. Metabolic and Cardiovascular Responses of Children during Prolonged Physical Activity.

    ERIC Educational Resources Information Center

    Chausow, Sharon A.; And Others

    1984-01-01

    Metabolic and cardiovascular responses during 45 minutes of continuous moderate intensity exercise were investigated in 11 children, 8-11 years of age. Results indicate that children exhibit metabolic and cardiovascular adjustments similar to those noted in adults during prolonged exercise. (Author/JMK)

  8. Prolonged idiopathic gastric dilatation following revascularization for chronic mesenteric ischemia

    PubMed Central

    Gauci, Julia L.; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A.

    2014-01-01

    A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described. PMID:24975870

  9. Metabolic and Cardiovascular Responses of Children during Prolonged Physical Activity.

    ERIC Educational Resources Information Center

    Chausow, Sharon A.; And Others

    1984-01-01

    Metabolic and cardiovascular responses during 45 minutes of continuous moderate intensity exercise were investigated in 11 children, 8-11 years of age. Results indicate that children exhibit metabolic and cardiovascular adjustments similar to those noted in adults during prolonged exercise. (Author/JMK)

  10. Frequency and cause of transient QT prolongation after surgery.

    PubMed

    Joyce, Daniel D; Bos, J Martijn; Haugaa, Kristina H; Tarrell, Robert F; Morlan, Bruce W; Caraballo, Pedro J; Ackerman, Michael J

    2015-11-15

    Patients undergoing surgery are often exposed to QT-inciting factors that may increase the risk for complications. We evaluated the clinical characteristics and outcomes of patients with QTc ≥500 ms within the first 24 hours after surgery as identified by an institution-wide electrocardiogram alert system. From November 2010 to June 2011, 470 patients exhibited an electrocardiographically isolated QTc ≥500 ms. QT prolongation after surgery was the setting for >1 of every 10 QTc alerts (59 patients). We determined the presence of QT prolonging medical conditions, drugs, electrolyte abnormalities, and the surgical patient's clinical outcome. The average preoperative QTc of the 59 patients demonstrating perioperative QT prolongation was 463 ± 56 ms with a postoperative QTc increase of 54 ± 37 ms. Most patients (n = 48, 83%) had ≥1 known QT-inciting factor before surgery. Compared with presurgical findings, there was a significant increase in pro-QTc score after surgery (1.8 ± 1.5 vs 3.5 ± 2.0, p <0.01) indicating a greater burden of perioperative QT-inciting factors. In conclusion, nearly all cases of QT prolongation could be explained by known etiologic or iatrogenic factors suggesting that maladaptive cardiac repolarization is most likely not a transient, postoperative stress response and may be avoided by altering clinical management.

  11. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    ERIC Educational Resources Information Center

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel

    2012-01-01

    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  12. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    ERIC Educational Resources Information Center

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

  13. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    ERIC Educational Resources Information Center

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel

    2012-01-01

    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  14. Efficacy of an Emotion-Focused Treatment for Prolonged Fatigue

    ERIC Educational Resources Information Center

    Schutte, Nicola S.; Malouff, John M.; Brown, Rhonda F.

    2008-01-01

    Previous research findings have suggested a relationship between less adaptive emotional functioning and fatigue. The present study used a research design involving multiple baselines across participants to evaluate the efficacy of a new emotion-focused treatment for prolonged fatigue delivered in a cognitive behavioral therapy framework. The 13…

  15. Technologies for Prolonging Cardiac Implantable Electronic Device Longevity.

    PubMed

    Lau, Ernest W

    2017-01-01

    Prolonged longevity of cardiac implantable electronic devices (CIEDs) is needed not only as a passive response to match the prolonging life expectancy of patient recipients, but will also actively prolong their life expectancy by avoiding/deferring the risks (and costs) associated with device replacement. CIEDs are still exclusively powered by nonrechargeable primary batteries, and energy exhaustion is the dominant and an inevitable cause of device replacement. The longevity of a CIED is thus determined by the attrition rate of its finite energy reserve. The energy available from a battery depends on its capacity (total amount of electric charge), chemistry (anode, cathode, and electrolyte), and internal architecture (stacked plate, folded plate, and spiral wound). The energy uses of a CIED vary and include a background current for running electronic circuitry, periodic radiofrequency telemetry, high-voltage capacitor reformation, constant ventricular pacing, and sporadic shocks for the cardiac resynchronization therapy defibrillators. The energy use by a CIED is primarily determined by the patient recipient's clinical needs, but the energy stored in the device battery is entirely under the manufacturer's control. A larger battery capacity generally results in a longer-lasting device, but improved battery chemistry and architecture may allow more space-efficient designs. Armed with the necessary technical knowledge, healthcare professionals and purchasers will be empowered to make judicious selection on device models and maximize the utilization of all their energy-saving features, to prolong device longevity for the benefits of their patients and healthcare systems.

  16. Causes of Death Associated With Prolonged TV Viewing

    PubMed Central

    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

  17. Recognition memory is impaired in children after prolonged febrile seizures

    PubMed Central

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal injury may be evident in human children after prolonged febrile seizures. The current study addressed this question by investigating memory abilities in 26 children soon after a prolonged febrile seizure (median: 37.5 days) and compared their results to those of 37 normally developing children. Fifteen patients were reassessed at a mean of 12.5 months after their first assessment to determine the transiency of any observed effects. We used the visual paired comparison task to test memory abilities in our group, as this task does not depend on verbal abilities and also because successful performance on the task has been proven to depend on the presence of functional hippocampi. Our findings show that patients perform as well as controls in the absence of a delay between the learning phase and the memory test, suggesting that both groups are able to form representations of the presented stimulus. However, after a 5-min delay, patients’ recognition memory is not different from chance, and comparison of patients and controls points to an accelerated forgetting rate in the prolonged febrile seizure group. The patients’ performance was not related to the time elapsed from the acute event or the duration of the prolonged febrile seizure, suggesting that the observed effect is not a by-product of the seizure itself or a delayed effect of medication administered to terminate the seizure. By contrast, performance was related to hippocampal size; participants with the smallest mean hippocampal volumes revealed the biggest drop in performance from the immediate to the delayed paradigm. At follow-up, children were still showing

  18. Prolonging Survival of Corneal Transplantation by Selective Sphingosine-1-Phosphate Receptor 1 Agonist

    PubMed Central

    Gao, Min; Liu, Yong; Xiao, Yang; Han, Gencheng; Jia, Liang; Wang, Liqiang; Lei, Tian; Huang, Yifei

    2014-01-01

    Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1) selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P) receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival. PMID:25216235

  19. Impaired calcium pump function does not slow relaxation in human skeletal muscle after prolonged exercise.

    PubMed

    Booth, J; McKenna, M J; Ruell, P A; Gwinn, T H; Davis, G M; Thompson, M W; Harmer, A R; Hunter, S K; Sutton, J R

    1997-08-01

    This study examined the effects of prolonged exercise on human quadriceps muscle contractile function and homogenate sarcoplasmic reticulum Ca2+ uptake and Ca2+-adenosinetriphosphatase activity. Ten untrained men cycled at 75 +/- 2% (SE) peak oxygen consumption until exhaustion. Biopsies were taken from the right vastus lateralis muscle at rest, exhaustion, and 20 and 60 min postexercise. Peak tension and half relaxation time of the left quadriceps muscle were measured during electrically evoked twitch and tetanic contractions and a maximal voluntary isometric contraction at rest, exhaustion, and 10, 20, and 60 min postexercise. At exhaustion, homogenate Ca2+ uptake and Ca2+ adenosinetriphosphatase activity were reduced by 17 +/- 4 and 21 +/- 5%, respectively, and remained depressed after 60 min recovery (P reduced after exercise by 28 +/- 3, 45 +/- 6, 65 +/- 5%, respectively (P prolonged exercise reduced muscle Ca2+ uptake, but this did not cause a slower relaxation of evoked contractions.

  20. Prolonged-release nicotinic acid in patients with atherosclerotic disease in the Netherlands.

    PubMed

    Poldermans, D; Dunkelgrun, M; Schouten, O; Hostalek, U

    2008-01-01

    High-density lipoprotein (HDL) cholesterol elevation is associated with an improved outcome in patients with atherosclerotic disease. Niaspan, a prolonged-release nicotinic acid, was evaluated during the Niaspan-Induced HDL Elevation for Optimizing Risk Control (NEMO) study in The Netherlands. NEMO was a 6-month, prospective, observational, multicentre, open-label study. Niaspan was prescribed in statin-treated patients with known or suspected atherosclerotic disease. The main outcome measures were treatment-related adverse drug reactions (ADRs) and effects on lipids and cardiovascular-risk score based on the algorithm derived from the Prospective Cardiovascular Münster study. 612 patients were included in The Netherlands. Flushing was the most common ADR (29% of patients during the first month of treatment). The main reasons for treatment discontinuation were flushing (10.5%), patient request (8.0%) and being lost to follow-up (6.0%). About half of all patients (52%) continued treatment after the study. Tolerability was rated 'good' or 'very good' in 54% of these patients. HDL cholesterol increased by 23% from baseline, and triglycerides were reduced by 16%, with little change in low-density lipoprotein or total cholesterol. Cardiovascular risk score was reduced by 3.3 points. The use of the prolonged-release nicotinic acid Niaspan in patients with or at risk for atherosclerotic disease showed good tolerability, a marked increase in HDL cholesterol and a reduced cardiovascular risk score. (c) 2008 S. Karger AG, Basel.

  1. Prolonged patient emergence time among clinical anesthesia resident trainees

    PubMed Central

    House, L. McLean; Calloway, Nathan H.; Sandberg, Warren S.; Ehrenfeld, Jesse M.

    2016-01-01

    Background and Aims: Emergence time, or the duration between incision closure and extubation, is costly nonoperative time. Efforts to improve operating room efficiency and identify trainee progress make such time intervals of interest. We sought to calculate the incidence of prolonged emergence (i.e., >15 min) for patients under the care of clinical anesthesia (CA) residents. We also sought to identify factors from resident training, medical history, anesthetic use, and anesthesia staffing, which affect emergence. Material and Methods: In this single-center, historical cohort study, perioperative information management systems provided data for surgical cases under resident care at a tertiary care center in the United States from 2006 to 2008. Using multiple logistic regression, the effects of variables on emergence was analyzed. Results: Of 7687 cases under the care of 27 residents, the incidence of prolonged emergence was 13.9%. Emergence prolongation decreased by month in training for 1st-year (CA-1) residents (r2 = 0.7, P < 0.001), but not for CA-2 and CA-3 residents. Mean patient emergence time differed among 27 residents (P < 0.01 for 58.4% or 205/351 paired comparisons). In a model restricted to 1st-year residents, patient male gender, American Society of Anesthesiologists (ASA) physical status >II, emergency surgical case, operative duration ≥2 h, and paralytic agent use were associated with higher frequency of prolonged emergence, while sevoflurane or desflurane use was associated with lower frequency. Attending anesthesiologist handoff was not associated with longer emergence. Conclusion: Incidence of prolonged emergence from general anesthesia differed significantly among trainees, by resident training duration, and for patients with ASA >II. PMID:28096573

  2. Use of in vitro methods to predict QT prolongation

    SciTech Connect

    Hammond, T.G. . E-mail: tim.hammond@astrazeneca.com; Pollard, C.E.

    2005-09-01

    The inhibition of the hERG-encoded potassium channel can lead to prolongation of the cardiac action potential-manifested as a prolongation of the QT interval on the ECG. Although QT interval prolongation is not dangerous per se, in a small percentage of cases, it is associated with a potentially fatal arrhythmia: Torsades de Pointes (TdP). This channel type is pharmacologically promiscuous, so many compounds have caused QT interval prolongation in man and this has led to drugs being withdrawn from the market following evidence of TdP. From a drug discovery perspective, focusing as early as possible on screening out hERG activity is important. Retrospective analysis of hERG potency versus clinical incidence of TdP suggests provisional safety margins that could be used as target values by medicinal chemists. Large safety margins will not always be possible; however, and in such circumstances, if the risk-benefit ratio still favours developing the compound, a pre-clinical assessment of the likelihood that any QT interval prolongation will or will not lead to TdP in man may be important. An isolated rabbit heart model of arrhythmia shows promise in this respect, based on a comparison of clinical data with that obtained from this assay. Specific regulatory guidance on this topic is still in the draft form but the pre-clinical document (ICH S7B) contains a largely useful perspective on how an integrated risk assessment could be formed using in vitro and in vivo assays. The role of this document is evolving however, since the draft clinical guideline (E14) suggests that irrespective of the pre-clinical data, a thorough clinical ECG study will be required at some point during development.

  3. Prolonged restricted sitting effects in UH-60 helicopters.

    PubMed

    Games, Kenneth E; Lakin, Joni M; Quindry, John C; Weimar, Wendi H; Sefton, JoEllen M

    2015-01-01

    Advances in flight technologies and the demand for long-range flight have increased mission lengths for U.S. Army Black Hawk UH-60 crewmembers. Prolonged mission times have increased reports of pilot discomfort and symptoms of paresthesia thought to be due to UH-60 seat design and areas of locally high pressure. Discomfort created by the seat-system decreases situational awareness, putting aviators and support crew at risk of injury. Therefore, the purpose of this study was to examine the effects of prolonged restricted sitting in a UH-60 on discomfort, sensory function, and vascular measures in the lower extremities. There were 15 healthy men (age = 23.4 ± 3.1 yr) meeting physical flight status requirements who sat in an unpadded, UH-60 pilot's seat for 4 h while completing a common cognitive task. During the session, subjective discomfort, sensory function, and vascular function were measured. Across 4 h of restricted sitting, subjective discomfort increased using the Category Partitioning Scale (30.27 point increase) and McGill Pain Questionnaire (8.53 point increase); lower extremity sensory function was diminished along the S1 dermatome; and skin temperature decreased on both the lateral (2.85°C decrease) and anterior (2.78°C decrease) aspects of the ankle. The results suggest that prolonged sitting in a UH-60 seat increases discomfort, potentially through a peripheral nervous or vascular system mechanism. Further research is needed to understand the etiology and onset of pain and paresthesia during prolonged sitting in UH-60 pilot seats. Games KE, Lakin JM, Quindry JC, Weimar WH, Sefton JM. Prolonged restricted sitting effects in UH-60 helicopters.

  4. Relationship between brief and prolonged repeated sprint ability.

    PubMed

    Oliver, Jonathan L; Armstrong, Neil; Williams, Craig A

    2009-01-01

    Repeated sprint ability (RSA) is often assessed over a brief time period with limited recovery between sprints; however, it is not known how performance in such tests is related to the ability to perform repeated sprints over a more prolonged duration. Eighteen boys aged 15.3+/-0.5 years completed both a brief and prolonged RSA test on a non-motorised treadmill. The brief RSA test consisted of seven 5s sprints with 20s of recovery between sprints and the prolonged RSA test lasted for 42min and included a 5s sprint every 2min. There was a moderate but significant relationship between the mean speed in both tests (r=0.51, p<0.05). The maximal speed achieved in a single sprint provided strong relationships with both brief RSA speed (r> or =0.72, p<0.001) and prolonged RSA speed (r> or =0.77, p<0.001). Total work done during the brief protocol was significantly correlated to both total work (r=0.81, p<0.001) and total sprint distance (r=0.79, p<0.001) during the prolonged test. There were no significant relationships between percentage decrement scores across the two protocols (r< or =0.33, p>0.05). Maximal speed in a single sprint and total work done during repeated sprints represent general qualities related to RSA that are independent of the test protocol. The mean speed and decrements in performance represent specific RSA qualities, which are dependent on the frequency of sprints and duration of the test protocol.

  5. Cognitive Changes During Prolonged Exposure versus Prolonged Exposure Plus Cognitive Restructuring in Female Assault Survivors with Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Foa, Edna B.; Rauch, Sheila A. M.

    2004-01-01

    The authors report on changes in cognitions related to posttraumatic stress disorder (PTSD) among 54 female survivors of sexual and nonsexual assault with chronic PTSD who completed either prolonged exposure alone or in combination with cognitive restructuring. Treatment included 9-12 weekly sessions, and assessment was conducted at pretreatment,…

  6. Reduction over time of QTc prolongation in patients with sotalol after cardioversion of atrial fibrillation.

    PubMed

    Lenhoff, Hanna; Darpö, Börje; Ferber, Georg; Rosenqvist, Mårten; Frick, Mats

    2016-03-01

    Sotalol is recommended to prevent relapse of atrial fibrillation after cardioversion (CV). Sotalol prolongs the action potential by blocking the rapid component of the delayed rectifier potassium current, which results in corrected QT (QTc) prolongation on the electrocardiogram. Pronounced QTc prolongation may lead to proarrhythmias and sudden death. We investigated the dynamics of the QTc interval during the week after CV in patients treated with sotalol compared with patients treated with a β-blocker. Patients who underwent elective CV for persistent atrial fibrillation and maintained sinus rhythm for 1 week were included prospectively. All patients were on the highest tolerable stable dose of metoprolol or sotalol. Twelve-lead electrocardiograms were recorded 1 hour and 1 week after CV. A total of 104 patients on sotalol and 104 on metoprolol were included; clinical characteristics between groups were comparable. One hour after CV, the QTc interval was significantly longer in sotalol-treated patients than in metoprolol-treated patients (465 ± 25 ms vs 423 ± 30 ms; P ≤ .0001). After 1 week, the QTc interval was reduced by -20.3 ± 24 ms in sotalol-treated patients (P ≤ .001); no such effect was seen in metoprolol-treated patients (-2.5 ± 18 ms; P = 0.28). The heart rate was stable during the week in both groups. In multivariate analysis of sotalol-treated patients, factors contributing to pronounced reduction in the QTc interval were longer QTc interval after CV and renal function. The QTc interval is significantly reduced during the week after CV to sinus rhythm in sotalol-treated patients. This provides insight into the increased risk of proarrhythmias in the immediate time period after CV. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  7. A Parallelized Pumpless Artificial Placenta System Significantly Prolonged Survival Time in a Preterm Lamb Model.

    PubMed

    Miura, Yuichiro; Matsuda, Tadashi; Usuda, Haruo; Watanabe, Shimpei; Kitanishi, Ryuta; Saito, Masatoshi; Hanita, Takushi; Kobayashi, Yoshiyasu

    2016-05-01

    An artificial placenta (AP) is an arterio-venous extracorporeal life support system that is connected to the fetal circulation via the umbilical vasculature. Previously, we published an article describing a pumpless AP system with a small priming volume. We subsequently developed a parallelized system, hypothesizing that the reduced circuit resistance conveyed by this modification would enable healthy fetal survival time to be prolonged. We conducted experiments using a premature lamb model to test this hypothesis. As a result, the fetal survival period was significantly prolonged (60.4 ± 3.8 vs. 18.2 ± 3.2 h, P < 0.01), and circuit resistance and minimal blood lactate levels were significantly lower in the parallel circuit group, compared with our previous single circuit group. Fetal physiological parameters remained stable until the conclusion of the experiments. In summary, parallelization of the AP system was associated with reduced circuit resistance and lactate levels and allowed preterm lamb fetuses to survive for a significantly longer period when compared with previous studies.

  8. Temporal changes in motor variability during prolonged lifting/lowering and the influence of work experience.

    PubMed

    Sedighi, Alireza; Nussbaum, Maury A

    2017-09-15

    Existing research indicates that repetitive motions are strongly correlated with the development of work-related musculoskeletal disorders (WMSDs). Resulting from the redundant degrees-of-freedom in the human body, there are variations in motions that occur while performing a repetitive task. These variations are termed motor variability (MV), and may be beneficial for reducing WMSD risks. To better understand the potential role of MV in preventing injury risk, we evaluated the effects of fatigue on MV using data collected during a lab-based prolonged, repetitive lifting/lowering task. We also investigated whether experienced workers used different motor control strategies than novices to adapt to fatigue. MV of the whole-body center-of-mass (COM) and box trajectory were quantified using cycle-to-cycle standard deviation, sample entropy, and goal equivalent manifold (GEM) methods. In both groups, there were significantly increased variations of the COM with fatigue, and with a more substantial increase in a direction that did not affect task performance. Fatigue deteriorated the task goal and made it more difficult for participants to maintain their performance. Experienced workers also had higher MV than novices. Based on these results, we conclude that flexible motor control strategies are employed to reduce fatigue effects during a prolonged repetitive task. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

    PubMed Central

    Jimenez-Mateos, Eva M.; Engel, Tobias; Merino-Serrais, Paula; McKiernan, Ross C.; Tanaka, Katsuhiro; Mouri, Genshin; Sano, Takanori; O’Tuathaigh, Colm; Waddington, John L.; Prenter, Suzanne; Delanty, Norman; Farrell, Michael A.; O’Brien, Donncha F.; Conroy, Ronán M.; Stallings, Raymond L.; deFelipe, Javier; Henshall, David C.

    2012-01-01

    Temporal lobe epilepsy is a common, chronic neurologic disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have important roles in the pathogenesis of neurologic disorders. In models of prolonged, injurious seizures (status epilepticus) and in experimental and human epilepsy, we found up-regulation of miR-134, a brain-specific, activity-regulated miRNA implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21%, and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus reduced the later occurrence of spontaneous seizures by over 90% and mitigated attendant pathologic features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure suppressant and neuroprotective actions; whether these represent anticonvulsant or truly antiepileptogenic effects requires additional experimentation. PMID:22683779

  10. Hydrogen sulfide prolongs postharvest shelf life of strawberry and plays an antioxidative role in fruits.

    PubMed

    Hu, Lan-Ying; Hu, Shu-Li; Wu, Jun; Li, Yan-Hong; Zheng, Ji-Lian; Wei, Zhao-Jun; Liu, Jian; Wang, Hui-Li; Liu, Yong-Sheng; Zhang, Hua

    2012-09-05

    Accumulating evidence shows that hydrogen sulfide (H(2)S) plays various physiological roles in plants, such as seed germination, root organogenesis, abiotic stress tolerance, and senescence of cut flowers. However, whether H(2)S participates in the regulation of ripening and senescence in postharvest fruits remains unknown. In the present study, the effect of H(2)S on postharvest shelf life and antioxidant metabolism in strawberry fruits was investigated. Fumigation with H(2)S gas released from the H(2)S donor NaHS prolonged postharvest shelf life of strawberry fruits in a dose-dependent manner. Strawberry fruits fumigated with various concentrations of H(2)S sustained significantly lower rot index, higher fruit firmness, and kept lower respiration intensity and polygalacturonase activities than controls. Further investigation showed that H(2)S treatment maintained higher activities of catalase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase and lower activities of lipoxygenase relative to untreated controls. H(2)S also reduced malondialdehyde, hydrogen peroxide, and superoxide anion to levels below control fruits during storage. Moreover, H(2)S treatment maintained higher contents of reducing sugars, soluble proteins, free amino acid, and endogenous H(2)S in fruits. We interpret these data as indicating that H(2)S plays an antioxidative role in prolonging postharvest shelf life of strawberry fruits.

  11. Prolonged and tunable residence time using reversible covalent kinase inhibitors

    PubMed Central

    Bradshaw, J. Michael; McFarland, Jesse M.; Paavilainen, Ville O.; Bisconte, Angelina; Tam, Danny; Phan, Vernon T.; Romanov, Sergei; Finkle, David; Shu, Jin; Patel, Vaishali; Ton, Tony; Li, Xiaoyan; Loughhead, David G.; Nunn, Philip A.; Karr, Dane E.; Gerritsen, Mary E.; Funk, Jens Oliver; Owens, Timothy D.; Verner, Erik; Brameld, Ken A.; Hill, Ronald J.; Goldstein, David M.; Taunton, Jack

    2015-01-01

    Drugs with prolonged, on-target residence time often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here, we demonstrate progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Utilizing an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrate biochemical residence times spanning from minutes to 7 days. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK more than 18 hours after clearance from the circulation. The inverted cyanoacrylamide strategy was further utilized to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating generalizability of the approach. Targeting noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates “residence time by design”, the ability to modulate and improve the duration of target engagement in vivo. PMID:26006010

  12. Is prolonged and excessive cooling of a scalded wound effective?

    PubMed

    Sawada, Y; Urushidate, S; Yotsuyanagi, T; Ishita, K

    1997-02-01

    An experimental study was carried out using rats to evaluate the effectiveness of prolonged and excessive cooling on the burned wound just immediately after injury. The wound was produced by applying a lint immersed in boiled water at 99 degrees C. The wound produced by applying a lint for 3 s, and then immediately soaking with tap water for 1 min, resulted in little damage. However, the wound produced by applying a lint for 10 s, and immediately after an ice cube applied for 10 min, resulted in the most severe damage. The wound produced by applying a lint for 10 s, and no treatment applied thereafter, and the wound produced by applying a lint for 10 s and immediately after soaked with tap water for 1 min, resulted in moderate damage. From this experiment, it is suggested excessive and prolonged cooling of the burn wound, such as using an ice cube immediately after injury, is harmful in some instances.

  13. Prolonged and tunable residence time using reversible covalent kinase inhibitors.

    PubMed

    Bradshaw, J Michael; McFarland, Jesse M; Paavilainen, Ville O; Bisconte, Angelina; Tam, Danny; Phan, Vernon T; Romanov, Sergei; Finkle, David; Shu, Jin; Patel, Vaishali; Ton, Tony; Li, Xiaoyan; Loughhead, David G; Nunn, Philip A; Karr, Dane E; Gerritsen, Mary E; Funk, Jens Oliver; Owens, Timothy D; Verner, Erik; Brameld, Ken A; Hill, Ronald J; Goldstein, David M; Taunton, Jack

    2015-07-01

    Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo.

  14. Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

    PubMed

    Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

    2015-09-01

    Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

  15. Diagnostic and clinical considerations in prolonged grief disorder

    PubMed Central

    Maercker, Andreas; Lalor, John

    2012-01-01

    This review focuses on the similarities and differences between prolonged grief disorder (PGD) and post-traumatic stress disorder (PTSD). It highlights how a PTSD-related understanding aids the investigation and clinical management of PGD. Grief has long been understood as a natural response to bereavement, as serious psychological and physiological stress has been regarded as a potential outcome of extreme or traumatic stress. PTSD was first included in DSM-III in 1980. In the mid-1980s, the first systematic investigation began into whether there is an extreme or pathological form of mourning. Meanwhile, there is much research literature on complicated, traumatic, or prolonged grief This literature is reviewed in this article, with the following questions: Is it possible to distinguish normal from non-normal grief? Which clinical presentation does PGD have—and how does this compare with PTSD? Finally, diagnostic, preventive, and therapeutic approaches and existing tools are presented. PMID:22754289

  16. Infection prevention and control during prolonged human space travel.

    PubMed

    Mermel, Leonard A

    2013-01-01

    Prolonged human spaceflight to another planet or an asteroid will introduce unique challenges of mitigating the risk of infection. During space travel, exposure to microgravity, radiation, and stress alter human immunoregulatory responses, which can in turn impact an astronaut's ability to prevent acquisition of infectious agents or reactivation of latent infection. In addition, microgravity affects virulence, growth kinetics, and biofilm formation of potential microbial pathogens. These interactions occur in a confined space in microgravity, providing ample opportunity for heavy microbial contamination of the environment. In addition, there is the persistence of aerosolized, microbe-containing particles. Any mission involving prolonged human spaceflight must be carefully planned to minimize vulnerabilities and maximize the likelihood of success.

  17. Hormone supply of the organism in prolonged emotional stress

    NASA Technical Reports Server (NTRS)

    Amiragova, M. G.; Stulnikov, B. V.; Svirskaya, R. I.

    1980-01-01

    The effect of prolonged emotional stress of varying genesis on the hormonal function of the pancreas, thyroid gland, and adrenal cortex was studied. The amount of the hormonal secretion was found to depend on the type of adaptation activity and its duration. High secretion of the hormones observed outside the adaptation activity was examined as an index of the phase transition of defense reactions to the phase of overstress.

  18. Drug Hypersensitivity Syndrome with Prolonged Course Complicated by Parvovirus Infection.

    PubMed

    Coughlin, Carrie C; Jen, Melinda V; Boos, Markus D

    2016-11-01

    Drug hypersensitivity syndrome (DHS) is a severe medication reaction involving multiple organ systems that is characterized by rash, lymphadenopathy, and laboratory aberrations, including hepatic enzyme changes. Viral reactivation in the setting of DHS can significantly affect the course of disease. We report two children in whom parvovirus infection prolonged and complicated their course of DHS. Most other DHS-complicating viruses are herpesviruses; this report broadens the scope of DHS-modifying infections to include activation of Parvoviridae. © 2016 Wiley Periodicals, Inc.

  19. Translating QT interval prolongation from conscious dogs to humans.

    PubMed

    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.

  20. Prolonged Detection of Zika Virus RNA in Pregnant Women.

    PubMed

    Meaney-Delman, Dana; Oduyebo, Titilope; Polen, Kara N D; White, Jennifer L; Bingham, Andrea M; Slavinski, Sally A; Heberlein-Larson, Lea; St George, Kirsten; Rakeman, Jennifer L; Hills, Susan; Olson, Christine K; Adamski, Alys; Culver Barlow, Lauren; Lee, Ellen H; Likos, Anna M; Muñoz, Jorge L; Petersen, Emily E; Dufort, Elizabeth M; Dean, Amy B; Cortese, Margaret M; Santiago, Gilberto A; Bhatnagar, Julu; Powers, Ann M; Zaki, Sherif; Petersen, Lyle R; Jamieson, Denise J; Honein, Margaret A

    2016-10-01

    Zika virus infection during pregnancy is a cause of microcephaly and other fetal brain abnormalities. Reports indicate that the duration of detectable viral RNA in serum after symptom onset is brief. In a recent case report involving a severely affected fetus, Zika virus RNA was detected in maternal serum 10 weeks after symptom onset, longer than the duration of RNA detection in serum previously reported. This report summarizes the clinical and laboratory characteristics of pregnant women with prolonged detection of Zika virus RNA in serum that were reported to the U.S. Zika Pregnancy Registry. Data were obtained from the U.S. Zika Pregnancy Registry, an enhanced surveillance system of pregnant women with laboratory evidence of confirmed or possible Zika virus infection. For this case series, we defined prolonged detection of Zika virus RNA as Zika virus RNA detection in serum by real-time reverse transcription-polymerase chain reaction (RT-PCR) 14 or more days after symptom onset or, for women not reporting signs or symptoms consistent with Zika virus disease (asymptomatic), 21 or more days after last possible exposure to Zika virus. Prolonged Zika virus RNA detection in serum was identified in four symptomatic pregnant women up to 46 days after symptom onset and in one asymptomatic pregnant woman 53 days postexposure. Among the five pregnancies, one pregnancy had evidence of fetal Zika virus infection confirmed by histopathologic examination of fetal tissue, three pregnancies resulted in live births of apparently healthy neonates with no reported abnormalities, and one pregnancy is ongoing. Zika virus RNA was detected in the serum of five pregnant women beyond the previously estimated timeframe. Additional real-time RT-PCR testing of pregnant women might provide more data about prolonged detection of Zika virus RNA and the possible diagnostic, epidemiologic, and clinical implications for pregnant women.

  1. Prolongation technologies for campaign life of tall oven

    SciTech Connect

    Doko, Yoshiji; Saji, Takafumi; Kitayama, Yoshiteru; Yoshida, Shuhei

    1997-12-31

    In Kashima Steel Works, 25-year-old 7-meter-high coke ovens have damage on their walls. However, by using new methods of internal in-situ investigation, ceramic welding for the extended central and upper portions of coke ovens has prolonged the campaign life for over 40 years without large-scale hot repair. In this paper, introduction of these new methods, its application in Kashima and the policy of repairing the tall coke oven are reported.

  2. A Case of QT Prolongation Associated with Panhypopituitarism

    PubMed Central

    Garip, Tayfun; Tamer, Ali

    2013-01-01

    We describe a 37-year-old patient with panhypopituitarism who experienced symptoms and signs of hormonal insufficiency and QT prolongation on electrocardiogram without electrolyte disturbances. After hormonal (steroidal and thyroid) replacement therapy electrocardiographic findings were normalized. Hormonal disorders should be considered as a cause of long QT intervals which may lead to torsade de pointes, even if plasma electrolyte levels are normal, because life-threatening arrhythmia is treatable by supplementation of the hormone that is lacking. PMID:23762665

  3. Fetal renal pulsed Doppler waveform in prolonged pregnancies.

    PubMed

    Veille, J C; Penry, M; Mueller-Heubach, E

    1993-10-01

    Our purpose was to determine Doppler waveforms of the fetal human renal artery in prolonged pregnancy in the presence or absence of oligohydramnios. Fifty patients at or after 40 weeks were studied. Ultrasonography was performed to determine the amniotic fluid index by the four-quadrants technique. Two groups of patients were obtained on the basis of the amniotic fluid index. Group 1 had an amniotic fluid index > 5 (normal) (n = 33); group 2 had amniotic fluid index < or = 5 (oligohydramnios) (n = 17). Umbilical artery and fetal renal pulsed Doppler waveforms were determined and analyzed. The fetal renal artery systolic-to-diastolic ratio of the two groups was compared. Fetuses with a low amniotic fluid index had a significantly higher ratio. A significant negative correlation coefficient between amniotic fluid index and fetal renal systolic/diastolic ratio was found (r = -0.435 and p < 0.01). In prolonged pregnancies there is a significant relationship between the amniotic fluid index and the fetal renal systolic/diastolic ratio. In pregnancies associated with oligohydramnios the systolic/diastolic ratio is significantly higher than in those with normal amniotic fluid volume. These data suggest that intrarenal flow in prolonged pregnancies complicated with oligohydramnios is significantly different.

  4. Opioid/naloxone prolonged release combinations for opioid induced constipation.

    PubMed

    Kapoor, Shailendra

    2012-08-07

    I read with great interest the recent article by Chen et al in a recent issue of your esteemed journal. The article is highly thought provoking. One emerging therapeutic alternative for opioid induced constipation is the emergence of opioid/naloxone prolonged release combinations. For instance, naloxone when administered in a 1:2 ratio with oxycodone reverses the inhibitory effect of oxycodone on the gastrointestinal tract. The advantage of oxycodone/naloxone prolonged release (OXN) is that while its anti-nociceptive efficacy is equivalent to that of oxycodone prolonged release (OXC), it significantly decreases the "Bowel Function Index" thereby ameliorating symptoms of opioid induced constipation to a large extent. Schutter et al in a recent study have reported a decrease in the bowel function index from 38.2 to 15.1. Similarly, Löwenstein et al in another recent study have reported that following a month of therapy, complete spontaneous bowel movements per week is increased from one in OXC therapy to three in OXN therapy.

  5. Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

    PubMed Central

    Ayub, Ahmar; Poulose, Ninu; Raju, Raghavan

    2015-01-01

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

  6. A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

    PubMed Central

    Dage, R.C.

    1979-01-01

    1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

  7. Kaolin-correctable prolongation of the activated partial thromboplastin time.

    PubMed

    Briselli, M F; Ellman, L

    1980-11-01

    Seven patients who had normal prothrombin times but prolonged activated partial thromboplastin times (aPTT) are described. The prolonged aPTT, obtained with micronized silica as the contact activating agent in a semi-automated optical end-point system, a nonautomated optical end-point system, and a conductivity end-point system, corrected to normal when kaolin was used as the contact activating agent. Abnormal results were also obtained with celite and ellagic acid as contact activating agents. The activities of various clotting factors were within normal limits in all cases where they were assayed. The thromboplastin dilution test was uniformly negative, and mixtures of one patient's plasma with that of another patient failed to correct the abnormal aPTT. No patients had a personal or family history of bleeding, and all underwent surgery without bleeding difficulties. This pattern of a prolonged aPTT that corrects to normal when kaolin is used as the contact activator appears to represent a previously unrecognized laboratory phenomenon.

  8. Secondary bacteraemia in adult patients with prolonged dengue fever.

    PubMed

    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.

  9. Prolonged Prevention of Retinal Degeneration with Retinylamine Loaded Nanoparticles

    PubMed Central

    Puntel, Anthony; Maeda, Akiko; Golczak, Marcin; Gao, Song-Qi; Yu, Guanping; Palczewski, Krzysztof; Lu, Zheng-Rong

    2015-01-01

    Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amines, including retinylamine, are effective in lowing the concentration of all-trans-retinal within the retina and thus prevent retina degeneration in mouse models of human retinopathies. Here we achieved prolonged prevention of retinal degeneration by controlled delivery of retinylamine to the eye from polylactic acid nanoparticles in Abca4−/−Rdh8−/− (DKO) mice, an animal model of Stargardt disease/age-related macular degeneration. Subcutaneous administration of the nanoparticles containing retinylamine provided a constant supply of the drug to the eye for about a week and resulted in effective prolonged prevention of light-induced retinal degeneration in DKO mice. Retinylamine nanoparticles hold promise for prolonged prophylactic treatment of human retinal degenerative diseases, including Stargardt disease and age-related macular degeneration. PMID:25617130

  10. Designing carbohydrate nanoparticles for prolonged efficacy of antimicrobial peptide.

    PubMed

    Bi, Lin; Yang, Lei; Narsimhan, Ganesan; Bhunia, Arun K; Yao, Yuan

    2011-03-10

    In this work, carbohydrate nanoparticles were created to prolong the efficacy of antimicrobial peptide against pathogens. Nisin and Listeria monocytogenes were used as the peptide and pathogen models, respectively, and phytoglycogen (PG)-based nanoparticles were developed as carriers of nisin. PG from su1 mutant maize was subjected to β-amylolysis as well as subsequent succinate or octenyl succinate substitutions. The goal was to minimize the loss of peptide during storage and meanwhile realize an effective release in the presence of bacteria. The capabilities of PG derivatives as carriers of nisin were evaluated using centrifugal ultrafiltration, zeta-potential, and the initial availability of nisin against L. monocytogenes. All methods indicated that nisin loading was favored by a high degree of substitution (DS), presence of hydrophobic octenyl moiety, and β-amylolysis of PG nanoparticles. To evaluate the prolonged nisin efficacy, preparations containing nisin and PG derivatives were loaded into a BHI-agar deep-well model (mimicking nisin depletion at the nutrient-containing surface). The residual inhibitory activities of preparations against L. monocytogenes were monitored during 21 days of storage at 4 °C. The results showed that all PG derivatives led to the prolonged retention of nisin activity and the longest retention was associated with high DS, β-amylolysis, and octenyl succinate. Evidently, both electrostatic and hydrophobic interactions are the driving forces of nisin adsorption, and the glucan structure at the nanoparticle surface also affects nisin loading and retention during storage.

  11. Slow recovery in desert perennial vegetation following prolonged human disturbance

    USGS Publications Warehouse

    Guo, Q.

    2004-01-01

    Questions: How long may it take for desert perennial vegetation to recover from prolonged human disturbance and how do different plant community variables (i.e. diversity, density and cover) change during the recovery process? Location: Sonoran Desert, Arizona, USA. Methods: Since protection from grazing from 1907 onwards, plant diversity, density and cover of perennial species were monitored intermittently on ten 10 m x 10 m permanent plots on Tumamoc Hill, Tucson, Arizona, USA. Results: The study shows an exceptionally slow recovery of perennial vegetation from prolonged heavy grazing and other human impacts. Since protection, overall species richness and habitat heterogeneity at the study site continued to increase until the 1960s when diversity, density and cover had been stabilized. During the same period, overall plant density and cover also increased. Species turnover increased gradually with time but no significant relation between any of the three community variables and precipitation or Palmer Drought Severity Index (PDSI) was detected. Conclusions: It took more than 50 yr for the perennial vegetation to recover from prolonged human disturbance. The increases in plant species richness, density, and cover of the perennial vegetation were mostly due to the increase of herbaceous species, especially palatable species. The lack of a clear relationship between environment (e.g. precipitation) and community variables suggests that site history and plant life history must be taken into account in examining the nature of vegetation recovery processes after disturbance.

  12. Prolonged weaning: from the intensive care unit to home.

    PubMed

    Navalesi, P; Frigerio, P; Patzlaff, A; Häußermann, S; Henseke, P; Kubitschek, M

    2014-01-01

    Weaning is the process of withdrawing mechanical ventilation which starts with the first spontaneous breathing trial (SBT). Based on the degree of difficulty and duration, weaning is classified as simple, difficult and prolonged. Prolonged weaning, which includes patients who fail 3 SBTs or are still on mechanical ventilation 7 days after the first SBT, affects a relatively small fraction of mechanically ventilated ICU patients but these, however, requires disproportionate resources. There are several potential causes which can lead to prolonged weaning. It is nonetheless important to understand the problem from the point of view of each individual patient in order to adopt appropriate treatment and define precise prognosis. An otherwise stable patient who remains on mechanical ventilation will be considered for transfer to a specialized weaning unit (SWU). Though there is not a precise definition, SWU can be considered as highly specialized and protected environments for patients requiring mechanical ventilation despite resolution of the acute disorder. Proper staffing, well defined short-term and long-term goals, attention to psychological and social problems represent key determinants of SWU success. Some patients cannot be weaned, either partly or entirely, and may require long-term home mechanical ventilation. In these cases the logistics relating to caregivers and the equipment must be carefully considered and addressed. Copyright © 2014 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  13. Is re-feeding efficiency compromised by prolonged starvation during aestivation in the green striped burrowing frog, Cyclorana alboguttata?

    PubMed

    Cramp, Rebecca L; Franklin, Craig E

    2003-12-01

    We examined several morphological parameters of the gastrointestinal tract, digesta passage rates, and nutrient assimilation efficiencies of Green-striped Burrowing frogs (Cyclorana alboguttata) following prolonged fasting during three months of aestivation and compared these with frogs that had been continuously fed. Whole animal digesta passage rates were significantly reduced following three months aestivation as a result of a decreased digesta evacuation rate from the stomach. Furthermore, food was selectively retained in the small intestine for an increased time following three months of aestivation. Overall digestibility of food and nitrogen, carbon, and energy extraction efficiencies were not significantly different from control values following three months of aestivation. These findings suggest that C. alboguttata employs reduced digesta passage rates so as to maximize nutrient assimilation efficiency following prolonged food deprivation during aestivation.

  14. Effects of cadence on aerobic capacity following a prolonged, varied intensity cycling trial.

    PubMed

    Stebbins, Charles L; Moore, Jesse L; Casazza, Gretchen A

    2014-01-01

    We determined if high cadences, during a prolonged cycling protocol with varying intensities (similar to race situations) decrease performance compared to cycling at a lower, more energetically optimal, cadence. Eight healthy, competitive male road cyclists (35 ± 2 yr) cycled for 180 min at either 80 or 100 rpm (randomized) with varying intensities of power outputs corresponding to 50, 65 and 80% of VO2max. At the end of this cycling period, participants completed a ramped exercise test to exhaustion at their preferred cadence (90 ± 7 rpm). There were no cadence differences in blood glucose, respiratory exchange ratio or rate of perceived exertion. Heart Rate, VO2 and blood lactate were higher at 100 rpm vs. 80 rpm. The total energy cost while cycling during the 65% and 80% VO2max intervals at 100 rpm (15.2 ± 2.7 and 19.1 ± 2.5 kcal∙min(-1), respectively) were higher than at 80 rpm (14.3 ± 2.7 and 18.3± 2.2 kcal∙min(-1), respectively) (p < 0.05). Gross efficiency was higher at 80 rpm vs. 100 rpm during both the 65% (22.8 ± 1.0 vs. 21.3 ± 4.5%) and the 80% (23.1 vs. 22.1 ± 0.9%) exercise intensities (P< 0.05). Maximal power during the performance test (362 ± 38 watts) was greater at 80 rpm than 100 rpm (327 ± 27 watts) (p < 0.05). Findings suggest that in conditions simulating those seen during prolonged competitive cycling, higher cadences (i.e., 100 vs. 80 rpm) are less efficient, resulting in greater energy expenditure and reduced peak power output during maximal performance. Key PointsWhen competitive cyclists perform prolonged exercise that simulates racing conditions (i.e., variable, low-moderate submaximal cycling), a higher cadence results in excess energy expenditure and lower gross efficiency compared to a lower cadence at the same power output.Consequently, maximal power output is reduced during a subsequent exercise bout to exhaustion after using a higher cadence.Selection of a lower, more energetically optimal cadence during prolonged

  15. Effects of prolonged patellar tendon vibration on force steadiness in quadriceps femoris during force-matching task.

    PubMed

    Saito, Akira; Ando, Ryosuke; Akima, Hiroshi

    2016-01-01

    The quadriceps femoris (QF) muscle group plays an essential role in human movement, such as standing, walking and running. The ability to maintain a steady force during physical activity of the human lower limb is important for mobility, postural control and balance. Although prolonged mechanical vibration of the muscle-tendon unit can moderate the efficacy of synaptic input from Ia afferent onto the α-motor neuron pathway, the effect of prolonged tendon vibration on fluctuations of knee extensor force has received little attention. The purpose of the present study was to examine the effects of prolonged patellar tendon vibration on the force steadiness of the QF muscle. Nine healthy men performed a submaximal force-matching task involving isometric knee extension before and after patellar tendon vibration or quiet seated rest (n = 7, control condition) for 30 min. The target force was 2.5, 10 and 30 % of maximal voluntary contraction (MVC). Surface electromyography (EMG) of the four QF synergists was recorded and normalized to EMG amplitude during the MVC. The knee extension force and the EMG amplitude of vastus medialis during the MVC were significantly reduced after the vibration, but did not significantly decrease in the control condition. Fluctuations of force and normalized EMG of individual QF muscles at each submaximal force level did not significantly change after the vibration. We conclude that prolonged patellar tendon vibration does not influence the force steadiness of the QF muscle during an isometric force-matching task.

  16. Effects of prolonged bed rest on the total peripheral resistance baroreflex

    NASA Technical Reports Server (NTRS)

    Xiao, X.; Mukkamala, R.; Sheynberg, N.; Williams, G. H.; Cohen, R. J.; Mark, R. G. (Principal Investigator)

    2002-01-01

    Orthostatic intolerance following prolonged exposure to microgravity continues to be a primary concern of the human space program. Reduced autonomic tone has been demonstrated to contribute to this phenomenon, and the heart rate baroreflex, in particular, has been repeatedly shown to be impaired. However, only the works of Yelle et al. have attempted to address the role of the total peripheral resistance (TPR) baroreflex, a potentially more significant contributor to blood pressure regulation. We applied a previously developed method for estimating the static gains of both the arterial and cardiopulmonary TPR baroreflexes to data obtained before and after 16-day bed rest. Reductions in the estimated static gains of the arterial (statistically significant) and cardiopulmonary TPR baroreflexes were found after bed rest. This study supports the works of Yelle et al, which imply that the TPR baroreflex is reduced after spaceflight.

  17. QT prolongation with antimicrobial agents: understanding the significance.

    PubMed

    Owens, Robert C

    2004-01-01

    Cardiac toxicity has been relatively uncommon within the antimicrobial class of drugs, but well described for antiarrhythmic agents and certain antihistamines. Macrolides, pentamidine and certain antimalarials were traditionally known to cause QT-interval prolongation, and now azole antifungals, fluoroquinolones and ketolides can be added to the list. Over time, advances in preclinical testing methods for QT-interval prolongation and a better understanding of its sequelae, most notably torsades de pointes (TdP), have occurred. This, combined with the fact that five drugs have been removed from the market over the last several years, in part because of QT-interval prolongation-related toxicity, has elevated the urgency surrounding early detection and characterisation methods for evaluating non-antiarrhythmic drug classes. With technological advances and accumulating literature regarding QT prolongation, it is currently difficult or overwhelming for the practising clinician to interpret these data for purposes of formulary review or for individual patient treatment decisions. Certain patients are susceptible to the effects of QT-prolonging drugs. For example, co-variates such as gender, age, electrolyte derangements, structural heart disease, end organ impairment and, perhaps most important, genetic predisposition, underlie most if not all cases of TdP. Between and within classes of drugs there are important differences that contribute to delayed repolarisation (e.g. intrinsic potency to inhibit certain cardiac ion currents or channels, and pharmacokinetics). To this end, a risk stratification scheme may be useful to rank and compare the potential for cardiotoxicity of each drug. It appears that in most published cases of antimicrobial-associated TdP, multiple risk factors are present. Macrolides in general are associated with a greater potential than other antimicrobials for causing TdP from both a pharmacodynamic and pharmacokinetic perspective. The azole

  18. Effect of maintenance tocolysis with nifedipine in established preterm labour on pregnancy prolongation and neonatal outcome.

    PubMed

    Aggarwal, Ajay; Bagga, Rashmi; Girish, Bhavana; Kalra, Jaswinder; Kumar, Praveen

    2017-08-08

    Fifty women with singleton pregnancies between 26(+0/7) and 33(+6/7 )weeks of gestation and arrested preterm labour (PTL) after acute tocolysis were randomised by a computer generated randomisation table into an intervention group (n = 25) who received maintenance tocolysis with tablet nifedipine for 12 days or up to 34 weeks of gestation, whichever was later and a control group (n = 25). The primary outcome was achievement of term gestation and the secondary outcomes were the number of days gained till delivery and neonatal mortality and morbidity. The mean gestation at admission, cervical dilatation and effacement were similar in the two groups (30 + weeks, 2.5 cm, 60%). In the intervention group, 7/25 (28%) and in the control group, 2/25 (8%) delivered at term (p = .066) and pregnancy prolongation of 20 days (IQR 2.5-51) and 14 days (IQR 1-27.5) were achieved, respectively (p = .269). Maintenance tocolysis was given for a median of 14 days (range 3-25.5). Kaplan-Meier analysis showed no statistically significant difference in prolongation of pregnancy between the control and the intervention groups (p = .077). The median number of days of neonatal hospital stay were reduced with maintenance tocolysis, but the difference was not significant (4.0 vs 5.5; p = .608). The mean birth weight was significantly higher in the intervention group (2266 vs 1880 g, p = .044). Among women at a high risk for preterm birth (PTB) due to established PTL as evidenced by a mean cervical dilatation of 2.5 cm and a PTB rate of 92% in the control group, maintenance tocolysis did not prolong the pregnancy or reduce the neonatal hospital stay significantly. Impact statement What is already known on this subject: In women with preterm labour (PTL) the role of maintenance tocolysis following acute tocolysis to reduce recurrent PTL is uncertain. Of the six studies using nifedipine, one reported pregnancy prolongation (26.65 vs 16.14 days, p

  19. Prolonged storage of packed red blood cells for blood transfusion.

    PubMed

    Martí-Carvajal, Arturo J; Simancas-Racines, Daniel; Peña-González, Barbra S

    2015-07-14

    A blood transfusion is an acute intervention, used to address life- and health-threatening conditions on a short-term basis. Packed red blood cells are most often used for blood transfusion. Sometimes blood is transfused after prolonged storage but there is continuing debate as to whether transfusion of 'older' blood is as beneficial as transfusion of 'fresher' blood. To assess the clinical benefits and harms of prolonged storage of packed red blood cells, in comparison with fresh, on recipients of blood transfusion. We ran the search on 1st May 2014. We searched the Cochrane Injuries Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO Host) and two other databases. We also searched clinical trials registers and screened reference lists of the retrieved publications and reviews. We updated this search in June 2015 but these results have not yet been incorporated. Randomised clinical trials including participants assessed as requiring red blood cell transfusion were eligible for inclusion. Prolonged storage was defined as red blood cells stored for ≥ 21 days in a blood bank. We did not apply limits regarding the duration of follow-up, or country where the study took place. We excluded trials where patients received a combination of short- and long-stored blood products, and also trials without a clear definition of prolonged storage. We independently performed study selection, risk of bias assessment and data extraction by at least two review authors. The major outcomes were death from any cause, transfusion-related acute lung injury, and adverse events. We estimated relative risk for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. We identified three randomised clinical trials, involving a total of 120 participants, comparing packed red blood cells with ≥ 21 days storage

  20. Positive effects of Red Bull® Energy Drink on driving performance during prolonged driving.

    PubMed

    Mets, Monique A J; Ketzer, Sander; Blom, Camilla; van Gerven, Maartje H; van Willigenburg, Gitta M; Olivier, Berend; Verster, Joris C

    2011-04-01

    The purpose of this study was to examine if Red Bull® Energy Drink can counteract sleepiness and driving impairment during prolonged driving. Twenty-four healthy volunteers participated in this double-blind placebo-controlled crossover study. After 2 h of highway driving in the STISIM driving simulator, subjects had a 15-min break and consumed Red Bull® Energy Drink (250 ml) or placebo (Red Bull® Energy Drink without the functional ingredients: caffeine, taurine, glucuronolactone, B vitamins (niacin, pantothenic acid, B6, B12), and inositol) before driving for two additional hours. A third condition comprised 4 h of uninterrupted driving. Primary parameter was the standard deviation of lateral position (SDLP), i.e., the weaving of the car. Secondary parameters included SD speed, subjective driving quality, sleepiness, and mental effort to perform the test. No significant differences were observed during the first 2 h of driving. Red Bull® Energy Drink significantly improved driving relative to placebo: SDLP was significantly reduced during the 3rd (p < 0.046) and 4th hour of driving (p < 0.011). Red Bull® Energy Drink significantly reduced the standard deviation of speed (p < 0.004), improved subjective driving quality (p < 0.0001), and reduced mental effort to perform the test (p < 0.024) during the 3rd hour of driving. Subjective sleepiness was significantly decreased during both the 3rd and 4th hour of driving after Red Bull® Energy Drink (p < 0.001 and p < 0.009, respectively). Relative to uninterrupted driving, Red Bull® Energy Drink significantly improved each parameter. Red Bull® Energy Drink significantly improves driving performance and reduces driver sleepiness during prolonged highway driving.

  1. Consecutive days of prolonged tennis match play: performance, physical, and perceptual responses in trained players.

    PubMed

    Gescheit, Danielle T; Cormack, Stuart J; Reid, Machar; Duffield, Rob

    2015-10-01

    To determine how consecutive days of prolonged tennis match play affect performance, physiological, and perceptual responses. Seven well-trained male tennis players completed 4-h tennis matches on 4 consecutive days. Pre- and postmatch measures involved tennis-specific (serve speed and accuracy), physical (20-m sprint, countermovement jump [CMJ], shoulder-rotation maximal voluntary contraction, isometric midthigh pull), perceptual (Training Distress Scale, soreness), and physiological (creatine kinase [CK]) responses. Activity profile was assessed by heart rate, 3D load (accumulated accelerations measured by triaxial accelerometers), and rating of perceived exertion (RPE). Statistical analysis compared within- and between-days values. Changes (± 90% confidence interval [CI]) ≥75% likely to exceed the smallest important effect size (0.2) were considered practically important. 3D load reduced on days 2 to 4 (mean effect size ± 90% CI -1.46 ± 0.40) and effective playing time reduced on days 3 to 4 (-0.37 ± 0.51) compared with day 1. RPE did not differ and total points played only declined on day 3 (-0.38 ± 1.02). Postmatch 20-m sprint (0.79 ± 0.77) and prematch CMJ (-0.43 ± 0.27) performance declined on days 2 to 4 compared with prematch day 1. Although serve velocity was maintained, compromised postmatch serve accuracy was evident compared with prematch day 1 (0.52 ± 0.58). CK increased each day, as did ratings of muscle soreness and fatigue. Players reduced external physical loads, through declines in movement, over 4 consecutive days of prolonged competitive tennis. This may be affected by tactical changes and pacing strategies. Alongside this, impairments in sprinting and jumping ability, perceptual and biochemical markers of muscle damage, and reduced mood states may be a function of neuromuscular and perceptual fatigue.

  2. Unexpected role for perforin in regulating contraction of CD8 and CD4 T cells during prolonged Listeria monocytogenes infection

    PubMed Central

    Schmidt, Nathan W.; Khanolkar, Aaruni; Hancox, Lisa; Heusel, Jonathan W.; Harty, John T.

    2012-01-01

    Summary After infection or vaccination, antigen-specific T cells proliferate then contract in numbers to a memory set point. T cell contraction is observed after both acute and prolonged infections although it is unknown if contraction is regulated similarly in both scenarios. Here, we show that contraction of antigen-specific CD8 and CD4 T cells is markedly reduced in TNF/perforin-double deficient (DKO) mice responding to attenuated Listeria monocytogenes infection. Reduced contraction in DKO mice was associated with delayed clearance of infection and sustained T cell proliferation during the normal contraction interval. Mechanistically, sustained T cell proliferation mapped to prolonged infection in the absence of TNF, however, reduced contraction required the additional absence of perforin since T cells in mice lacking either TNF or perforin (singly-deficient) underwent normal contraction. Thus, while T cell contraction after acute infection is independent of peforin, a perforin-dependent pathway plays a previously unappreciated role to mediate contraction of antigen-specific CD8 and CD4 T cells during a prolonged L. monocytogenes infection. PMID:22161269

  3. Efficacy of metacognitive therapy for prolonged grief disorder: protocol for a randomised controlled trial.

    PubMed

    Wenn, Jenine; O'Connor, Moira; Breen, Lauren J; Kane, Robert T; Rees, Clare S

    2015-12-08

    Studies of effective psychotherapy for individuals suffering from the effects of prolonged grief disorder (PGD) are scarce. This paper describes the protocol for an evaluation of a metacognitive therapy programme designed specifically for PGD, to reduce the psychological distress and loss of functioning resulting from bereavement. The proposed trial comprises three phases. Phase 1 consists of a review of the literature and semistructured interviews with key members of the target population to inform the development of a metacognitive therapy programme for Prolonged Grief. Phase 2 involves a randomised controlled trial to implement and evaluate the programme. Male and female adults (N=34) will be randomly assigned to either a wait list or an intervention group. Measures of PGD, anxiety, depression, rumination, metacognitions and quality of life will be taken pretreatment and posttreatment and at the 3-month and 6-month follow-up. The generalised linear mixed model will be used to assess treatment efficacy. Phase 3 will test the social validity of the programme. This study is the first empirical investigation of the efficacy of a targeted metacognitive treatment programme for PGD. A focus on identifying and changing the metacognitive mechanisms underpinning the development and maintenance of prolonged grief is likely to be beneficial to theory and practice. Ethics approval was obtained from Curtin University Human Research Ethics Committee (Approval number HR 41/2013.) ACTRN12613001270707. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Injectable microparticle-gel system for prolonged and localized lidocaine release. I. In vitro characterization.

    PubMed

    Chen, Pen-Chung; Park, Yoon Jeong; Chang, Li-Chien; Kohane, Daniel S; Bartlett, Robert H; Langer, Robert; Yang, Victor C

    2004-09-01

    Current treatment protocol for postoperative pain is to infuse anesthetic solution around nerves or into the epidural space. This clinical practice is beset by the short duration of the anesthetic effect unless the infusion is continuous. Continuous infusion, however, requires hospitalization of the patients, thereby increasing medical costs. In addition, it also causes systemic accumulation of the drug. We reported herein a novel treatment for the postoperative pain by applying to the surgical site a biodegradable microsphere-gel system for prolonged and localized release of encapsulated anesthetic drugs. This lidocaine-containing biodegradable poly(D,L-lactic acid) (PLA) microsphere system, although being established previously by other investigators, was hindered by a burst release and a followed rapid release of the drug within several hours in vitro. In this article, we demonstrated that by a step-by-step modification of the formulation, prolonged release of lidocaine, up to several days in vitro, could be achieved. Differential scanning calorimetry revealed a lower glass transition temperature for these lidocaine-loaded microspheres comparing to that of lidocaine-free microspheres. This decreased Tg explained for the tendency of the lidocaine-loaded microspheres to physically fuse at higher temperatures. In vitro studies showed that microspheres, when loaded with 35% lidocaine, yielded a threefold increase in the degradation rate. The molecular weight of PLA of the drug-loaded microspheres was reduced by 50% within a period of 1 month. Based on the results (of prolonged lidocaine release and rapid PLA microsphere degradation), this lidocaine-loaded PLA microsphere system could offer a simple solution to the treatment of postoperative pain.

  5. Neurosteroid prolongs GABAA channel deactivation by altering kinetics of desensitized states.

    PubMed

    Zhu, W J; Vicini, S

    1997-06-01

    Fast applications of GABA (1 mM) to nucleated and outside-out patches excised from granule neurons in cerebellar slices from developing rats evoked currents with a double exponential time course reminiscent of that of IPSCs. A neurosteroid 3alpha, 21dihydroxy-5alpha-pregnan-20-one (THDOC) remarkably increased the slow deactivation time constant and slowed down recovery from desensitization, as estimated by paired-pulse GABA applications. THDOC also reduced the amplitude of GABA currents, whereas it failed to affect the fast deactivation component and its relative contribution to peak amplitude. The effects of THDOC on slow deactivation were greater in rats younger than postnatal day 13 (P13) as compared with rats at P30-P35. THDOC failed to alter deactivation of short responses induced by a less-potent agonist taurine at saturating doses. These responses had deactivation kinetics described by a fast single exponential decay, little desensitization, and quick recovery. However, THDOC slowed deactivation if taurine responses were long enough to allow consistent desensitization, suggesting that desensitized states are required for the neurosteroid to modulate GABA responses. In outside-out patches, just as desensitized states prolonged GABA responses by producing reopening of channels activated by brief GABA pulses, THDOC increased the channel open probability by further increasing the number of late channel openings, resulting in a prolongation of the slow deactivation. Our data suggest that neurosteroid potentiates the inhibitory postsynaptic transmission via the prolongation of the slow deactivation and that the alteration of kinetics of entry and exit from desensitized states underlies the allosteric modification of GABAA receptors by neurosteroids.

  6. Prolonged treatment with glucocorticoid dexamethasone suppresses melatonin production by the chick pineal gland and retina.

    PubMed

    Zawilska, Jolanta B; Sadowska, Magdalena

    2002-01-01

    The chick pineal gland and retina synthesize melatonin in a circadian rhythm with high levels during the night. The rhythmic changes in the hormone production result predominantly from the fluctuation in the activity of serotonin N-acetyltransferase (AA-NAT), a penultimate and key regulatory enzyme in melatonin biosynthesis. The aim of this study was to analyze the effects of an acute and prolonged in vivo treatment with a glucocorticoid dexamethasone (4 mg/kg, ip) on the nocturnal increase in AA-NAT activity in chick pineal gland and retina. In acute experiments, dexamethasone (single dose)-injected chicks were killed after 2 h, while in prolonged experiments the glucocorticoid was given once daily for 7 days and the animals were killed 26-32 h after the last injection. Acute administration of dexamethasone did not affect AA-NAT activity in the chick pineal gland and retina. In the pineal glands and retinas of chicks that were treated with dexamethasone for one week and then killed at the end of the light phase of the 12:12 h light-dark cycle, AA-NAT activity was significantly higher than the enzyme activity found in tissues isolated from the vehicle-treated (control) animals. In addition to that, the nocturnal increase in pineal and, to a lower extent, retinal AA-NAT activity was significantly lower in dexamethasone-treated birds when compared with the respective control groups. It is suggested that prolonged treatment of animals with dexamethasone reduces the amplitude of the rhythmic melatonin production, a phenomenon which may affect chronobiological processes being under control of this hormone.

  7. Survival time of cardiac allografts prolonged by isogeneic BMT in mice.

    PubMed

    Chen, Z; Jiang, H; Chen, R; Feng, S; Jin, J; Bi, Y; Yang, H; Chen, J

    2012-08-01

    To find an approach to prolong the survival time of cardiac allografts in a BALB/c-to-C57/BL6 heterotopic heart transplant model and to try to figure out related chemokines and cytokines, isogeneic and allogeneic BM cells were obtained from pregnant C57/BL6 (♀C57/BL6 × ♂BALB/c) and regular BALB/c mice and injected to the half lethally irradiated C57/BL6 mice 1 day before heart transplantation. Recipients were treated with CsA or phosphate-buffered saline for 7 days. Isogeneic BMT (iBMT) from pregnant C57/BL6 mice was observed to significantly prolong the survival of BALB/c allografts and reduce the lymphocyte infiltration. Allogeneic BMT (aBMT) and iBMT both exhibited signicantly less T-cell proliferation reactivity and the similar degree of chimerism. There was no significant difference in these groups of IFN-γ and IL-4 production. The level of chemokine MIG (CXCL9) dramatically decreased in aBMT and iBMT groups compared with the control group. But there were no significant differences between aBMT and iBMT group. IL-17 and RORγ(t) (receptor-related orphan receptor) production were downregulated in iBMT recipients. These results indicate that iBMT can prolong the survival of cardiac allografts. IL-17 production downregulated in iBMT recipients. This means that iBMT may have important therapeutic implications.

  8. Glut4 is upregulated despite decreased insulin signaling during prolonged fasting in northern elephant seal pups.

    PubMed

    Viscarra, Jose A; Vázquez-Medina, José Pablo; Crocker, Daniel E; Ortiz, Rudy M

    2011-01-01

    Postprandial cellular glucose uptake is dependent on an insulin-signaling cascade in muscle and adipose tissue, resulting in the translocation of the insulin-dependent glucose transporter 4 (Glut4) into the plasma membrane. Additionally, extended food deprivation is characterized by suppressed insulin signaling and decreased Glut4 expression. Northern elephant seals are adapted to prolonged fasts characterized by high levels of plasma glucose. To address the hypothesis that the fasting-induced decrease in insulin is associated with reduced insulin signaling in prolonged fasted seals, we compared the adipose protein levels of the cellular insulin-signaling pathway, Glut4 and plasma glucose, insulin, cortisol, and adiponectin concentrations between Early (n = 9; 2-3 wks postweaning) and Late (n = 8; 6-8 wks postweaning) fasted seals. Plasma adiponectin (230 ± 13 vs. 177 ± 11 ng/ml), insulin (2.7 ± 0.4 vs. 1.0 ± 0.1 μU/ml), and glucose (9.8 ± 0.5 vs. 8.0 ± 0.3 mM) decreased, while cortisol (124 ± 6 vs. 257 ± 30 nM) doubled with fasting. Glut4 increased (31%) with fasting despite the significant decreases in the cellular content of phosphatidylinositol 3-kinase as well as phosphorylated insulin receptor, insulin receptor substrate-1, and Akt2. Increased Glut4 may have contributed to the decrease in plasma glucose, but the decrease in insulin and insulin signaling suggests that Glut4 is not insulin-dependent in adipose tissue during prolonged fasting in elephant seals. The reduction of plasma glucose independent of insulin may make these animals an ideal model for the study of insulin resistance.

  9. LONG-TERM BEHAVIORAL EFFECTS IN A RAT MODEL OF PROLONGED POSTNATAL MORPHINE EXPOSURE

    PubMed Central

    Craig, Michael M.; Bajic, Dusica

    2015-01-01

    Prolonged morphine treatment in neonatal pediatric populations is associated with a high incidence of opioid tolerance and dependence. Despite the clinical relevance of this problem, our knowledge of the long-term consequences is sparse. The main objective of this study was to investigate whether prolonged morphine administration in a neonatal rat is associated with long-term behavioral changes in adulthood. Newborn animals received either morphine (10mg/kg) or equal volume of saline subcutaneously twice daily for the first 2 weeks of life. Morphine treated animals underwent 10 days of morphine weaning to reduce the potential for observable physical signs of withdrawal. Animals were subjected to non-stressful testing (locomotor activity recording and a Novel-Object Recognition test) at a young age (PD27-31) or later in adulthood (PD55-56), as well as stressful testing (calibrated forceps test, Hot Plate test, and Forced Swim test) only in adulthood. Analysis revealed that prolonged neonatal morphine exposure resulted in decreased thermal, but not mechanical threshold. Importantly, no differences were found for total locomotor activity (proxy of drug reward/reinforcement behavior), individual Forced Swim test behaviors (proxy of affective processing), or Novel-Object Recognition test. Performance on the Novel-Object Recognition test was compromised in the morphine treated group at the young age, however the effect disappeared in adulthood. These novel results provide insight into the long-term consequences of opioid treatment during an early developmental period and suggest long-term neuroplastic differences in sensory processing related to thermal stimuli. PMID:26214209

  10. Depressive Disorders during Weaning from Prolonged Mechanical Ventilation

    PubMed Central

    Jubran, Amal; Lawm, Gerald; Kelly, Joanne; Duffner, Lisa A.; Gungor, Gokay; Collins, Eileen G.; Lanuza, Dorothy M.; Hoffman, Leslie A.; Tobin, Martin J.

    2010-01-01

    Purpose Patients who require mechanical ventilation are at risk of emotional stress because of total dependence on a machine for breathing. The stress may negatively impact ventilator weaning and survival. The purpose of this study was to determine whether depressive disorders in patients being weaned from prolonged mechanical ventilation are linked to weaning failure and decreased survival. Methods A prospective study of 478 consecutive patients transferred to a long-term acute care hospital for weaning from prolonged ventilation was undertaken. A clinical psychologist conducted a psychiatric interview to assess for the presence of depressive disorders. Results Of the 478 patients, 142 had persistent coma or delirium and were unable to be evaluated for depressive disorders. Of the remaining 336 patients, 142 (42%) were diagnosed with depressive disorders. In multivariate analysis, co-morbidity score (odds ratio [OR], 1.23, p=0.007), functional dependence before the acute illness (OR, 1.70, p=0.03), and history of psychiatric disorders (OR, 3.04, p=0.0001) were independent predictors of depressive disorders. The rate of weaning failure was higher in patients with depressive disorders than in those without such disorders (61% versus 33%, p=0.0001), as was mortality (24% versus 10%, p=0.0008). The presence of depressive disorders was independently associated with mortality (OR, 4.3; p=0.0002); age (OR, 1.06; p=0.001) and co-morbidity score (OR, 1.24; p=0.02) also predicted mortality. Conclusion Depressive disorders were diagnosed in 42% of patients who are being weaned from prolonged ventilation. Patients with depressive disorders were more likely to experience weaning failure and death. PMID:20232042

  11. QT Prolongation and Clinical Outcomes in Patients with Takotsubo Cardiomyopathy.

    PubMed

    Imran, Tasnim F; Rahman, Ifad; Dikdan, Sean; Shah, Rashesh; Niazi, Osama T; Thirunahari, Nandan; Alhaj, Eyad; Klapholz, Marc; Gaziano, J Michael; Djousse, Luc

    2016-06-01

    Takotsubo cardiomyopathy (TCM) has been associated with repolarization abnormalities including QT prolongation and acquired long QT syndrome. However, the association between QT prolongation and clinical outcomes in patients with TCM remains unclear. The aim of this study is to examine the association between QT prolongation and ventricular arrhythmias, cardiogenic shock, and death in patients with TCM. Forty-six patients with TCM met our inclusion criteria in an ongoing prospective cohort database from 2010 to May 2015. We assigned the patients to a long QT group or a normal QT group, and created a composite outcome consisting of ventricular arrhythmias, cardiogenic shock, or death. The mean age of the participants was 59.7 ± 16 years, 67% were women, and 63% had hypertension. Median follow-up time was 3.1 years (interquartile range: 2.0-3.8), with a total of 133.8 person-years. The mean left ventricular ejection fraction at diagnosis was 27.2% ± 1.4%. The mean QTc on diagnosis was 484 ms ± 10.2 ms for men, and 488 ms ± 8.6 ms for women. The long QT group had a 4.1-times higher odds of having the composite clinical outcome as compared to the normal QT group (95% confidence interval: 1.1, 16.1, P = 0.04) after adjusting for age and race in logistic regression. Patients with TCM who have a long QT interval or develop acquired long QT syndrome due to TCM may be more likely to be intubated; require vasopressors; and develop shock, ventricular arrhythmias, and death than those with a normal QT interval. ©2016 Wiley Periodicals, Inc.

  12. Neural compensation within the human triceps surae during prolonged walking.

    PubMed

    Cronin, Neil J; Peltonen, Jussi; Sinkjaer, Thomas; Avela, Janne

    2011-02-01

    During human walking, muscle activation strategies are approximately constant across consecutive steps over a short time, but it is unknown whether they are maintained over a longer duration. Prolonged walking may increase tendinous tissue (TT) compliance, which can influence neural activation, but the neural responses of individual muscles have not been investigated. This study investigated the hypothesis that muscle activity is up- or down-regulated in individual triceps surae muscles during prolonged walking. Thirteen healthy subjects walked on a treadmill for 60 min at 4.5 km/h, while triceps surae muscle activity, maximal muscle compound action potentials, and kinematics were recorded every 5 min, and fascicle lengths were estimated at the beginning and end of the protocol using ultrasound. After 1 h of walking, soleus activity increased by 9.3 ± 0.2% (P < 0.05) and medial gastrocnemius activity decreased by 9.3 ± 0.3% (P < 0.01). Gastrocnemius fascicle length at ground contact shortened by 4.45 ± 0.99% (P < 0.001), whereas soleus fascicle length was unchanged (P = 0.988). Throughout the stance phase, medial gastrocnemius fascicle lengthening decreased by 44 ± 13% (P < 0.001), whereas soleus fascicle lengthening amplitude was unchanged (P = 0.650). The data suggest that a compensatory neural strategy exists between triceps surae muscles and that changes in muscle activation are generally mirrored by changes in muscle fascicle length. These findings also support the notion of muscle-specific changes in TT compliance after prolonged walking and highlight the ability of the CNS to maintain relatively constant movement patterns in spite of neuromechanical changes in individual muscles.

  13. Prolonged parasite clearance in a Chinese splenectomized patient with falciparum malaria imported from Nigeria.

    PubMed

    Zhang, Hong-Wei; Li, San-Jin; Hu, Tao; Yu, Yong-Min; Yang, Cheng-Yun; Zhou, Rui-Min; Liu, Ying; Tang, Jing; Wang, Jing-Jing; Wang, Xiu-Yun; Sun, Yong-Xiang; Feng, Zhan-Chun; Xu, Bian-Li

    2017-04-04

    The spleen plays a pivotal role in the rapid clearance of parasitized red blood cells in patients with falciparum malaria after artemisinin treatment. Prolonged parasite clearance can be found in patients who have had a splenectomy, or those with hemoglobin abnormalities and/or reduced immunity, which are all distinguishable from artemisinin resistance. This paper reports on a case of prolonged parasite clearance in a Chinese splenectomized patient with falciparum malaria imported from Nigeria. A 35-year-old Chinese male suffered 2 days of febrile illness after returning to Zhumadian city of Henan province from Nigeria on October 1, 2014. The main symptoms were febrile, including the highest axillary temperature of 40 °C, headache, and chills. A peripheral blood smear showed parasitemia (53 913 asexual parasites/μl) of Plasmodium falciparum. The patient had not used any chemoprophylaxis against malaria in Nigeria when he worked there as a construction worker between 2009 and 2014. The patient had three episodes of malaria in Nigeria and had a splenectomy due to a traffic accident 8 years ago from the time he was admitted to hospital. The patient was orally administrated a total of 320 mg/2.56 g dihydroartemisinin-piperaquine for 2 days and intravenously administrated a total of 3 000 mg artesunate for 18 days. The axillary temperature of the patient ranged between 37.0 and 37.7 °C from Day 0 to Day 3, and blood microscopy revealed falciparum malaria parasitemia (26 674 asexual parasites/μl) on Day 3. The patient was afebrile on Day 4, falciparum malaria parasitemia was continuously present and then gradually decreased on the next days, and was negative on Day 21. The patient was cured and left hospital on Day 24 after no plasmodium falciparum was found in the blood on Day 21 to Day 23. No mutation was found in the K13 propeller gene when compared with the PF3D7_1343700 K13 propeller gene reference sequence. This is the first reported case in China of

  14. Prolonged acid rain facilitates soil organic carbon accumulation in a mature forest in Southern China.

    PubMed

    Wu, Jianping; Liang, Guohua; Hui, Dafeng; Deng, Qi; Xiong, Xin; Qiu, Qingyan; Liu, Juxiu; Chu, Guowei; Zhou, Guoyi; Zhang, Deqiang

    2016-02-15

    With the continuing increase in anthropogenic activities, acid rain remains a serious environmental threat, especially in the fast developing areas such as southern China. To detect how prolonged deposition of acid rain would influence soil organic carbon accumulation in mature subtropical forests, we conducted a field experiment with simulated acid rain (SAR) treatments in a monsoon evergreen broadleaf forest at Dinghushan National Nature Reserve in southern China. Four levels of SAR treatments were set by irrigating plants with water of different pH values: CK (the control, local lake water, pH ≈ 4.5), T1 (water pH=4.0), T2 (water pH=3.5), and T3 (water pH=3.0). Results showed reduced pH measurements in the topsoil exposed to simulated acid rains due to soil acidification. Soil respiration, soil microbial biomass and litter decomposition rates were significantly decreased by the SAR treatments. As a result, T3 treatment significantly increased the total organic carbon by 24.5% in the topsoil compared to the control. Furthermore, surface soil became more stable as more recalcitrant organic matter was generated under the SAR treatments. Our results suggest that prolonged acid rain exposure may have the potential to facilitate soil organic carbon accumulation in the subtropical forest in southern China. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. A Prolonged NO-Dependent, Opioid-Mediated Antinociceptive Effect of Hyperbaric Oxygen in Mice

    PubMed Central

    Zelinski, Lisa M.; Ohgami, Yusuke; Chung, Eunhee; Shirachi, Donald Y.; Quock, Raymond M.

    2009-01-01

    Hyperbaric oxygen (HBO2) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-min session of HBO2 treatment produced a prolonged antinociceptive effect in mice that persisted for 90 min after cessation of treatment. The HBO2-induced antinociception was significantly attenuated by pretreatment prior to HBO2 exposure with the opioid antagonist naltrexone, the non-specific nitric oxide synthase (NOS)-inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the selective neuronal NOS-inhibitor S-methyl-L-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N5-(1-iminoethyl)-L-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin1-13 but not by rabbit antisera against either β-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 min after HBO2-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 min following HBO2 treatment but prior to nociceptive testing. These findings indicate that the antinociception that persists for 90 min after HBO2 exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO2 treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO2 may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect. PMID:18976963

  16. Prolonged Incubation of Acute Neuronal Tissue for Electrophysiology and Calcium-imaging.

    PubMed

    Cameron, Morven A; Kekesi, Orsolya; Morley, John W; Bellot-Saez, Alba; Kueh, Sindy; Breen, Paul; van Schaik, André; Tapson, Jonathan; Buskila, Yossi

    2017-02-15

    Acute neuronal tissue preparations, brain slices and retinal wholemount, can usually only be maintained for 6 - 8 h following dissection. This limits the experimental time, and increases the number of animals that are utilized per study. This limitation specifically impacts protocols such as calcium imaging that require prolonged pre-incubation with bath-applied dyes. Exponential bacterial growth within 3 - 4 h after slicing is tightly correlated with a decrease in tissue health. This study describes a method for limiting the proliferation of bacteria in acute preparations to maintain viable neuronal tissue for prolonged periods of time (>24 h) without the need for antibiotics, sterile procedures, or tissue culture media containing growth factors. By cycling the extracellular fluid through UV irradiation and keeping the tissue in a custom holding chamber at 15 - 16 °C, the tissue shows no difference in electrophysiological properties, or calcium signaling through intracellular calcium dyes at >24 h postdissection. These methods will not only extend experimental time for those using acute neuronal tissue, but will reduce the number of animals required to complete experimental goals, and will set a gold standard for acute neuronal tissue incubation.

  17. Space physiology VI: exercise, artificial gravity, and countermeasure development for prolonged space flight.

    PubMed

    Hargens, Alan R; Bhattacharya, Roshmi; Schneider, Suzanne M

    2013-09-01

    When applied individually, exercise countermeasures employed to date do not fully protect the cardiovascular and musculoskeletal systems during prolonged spaceflight. Recent ground-based research suggests that it is necessary to perform exercise countermeasures within some form of artificial gravity to prevent microgravity deconditioning. In this regard, it is important to provide normal foot-ward loading and intravascular hydrostatic-pressure gradients to maintain musculoskeletal and cardiovascular function. Aerobic exercise within a centrifuge restores cardiovascular function, while aerobic exercise within lower body negative pressure restores cardiovascular function and helps protect the musculoskeletal system. Resistive exercise with vibration stimulation may increase the effectiveness of resistive exercise by preserving muscle function, allowing lower intensity exercises, and possibly reducing risk of loss of vision during prolonged spaceflight. Inexpensive methods to induce artificial gravity alone (to counteract head-ward fluid shifts) and exercise during artificial gravity (for example, by short-arm centrifuge or exercise within lower body negative pressure) should be developed further and evaluated as multi-system countermeasures.

  18. Rapamycin Prolongs Cardiac Allograft Survival in a Mouse Model by Inducing Myeloid-Derived Suppressor Cells.

    PubMed

    Nakamura, T; Nakao, T; Yoshimura, N; Ashihara, E

    2015-09-01

    Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR inhibitors induce immunosuppression is not fully understood. Myeloid-derived suppressor cells (MDSCs) maintain host immunity; however, the relationship between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine cardiac transplantation model revealed that rapamycin treatment (3 mg/kg, intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of MDSCs and increased their expression of inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed that rapamycin induced the migration of iNOS-expressing MDSCs into the subintimal space within the allograft vessels, resulting in a significant prolongation of graft survival compared with that in the untreated group (67 days vs. 7 days, respectively). These effects were counterbalanced by the administration of an anti-Gr-1, which reduced allograft survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs from rapamycin-treated recipients prolonged allograft survival; this increase was reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathways appear to play an important role in MDSC expansion.

  19. Neoteny, Prolongation of Youth: From Naked Mole Rats to "Naked Apes" (Humans).

    PubMed

    Skulachev, Vladimir P; Holtze, Susanne; Vyssokikh, Mikhail Y; Bakeeva, Lora E; Skulachev, Maxim V; Markov, Alexander V; Hildebrandt, Thomas B; Sadovnichii, Viktor A

    2017-04-01

    It has been suggested that highly social mammals, such as naked mole rats and humans, are long-lived due to neoteny (the prolongation of youth). In both species, aging cannot operate as a mechanism facilitating natural selection because the pressure of this selection is strongly reduced due to 1) a specific social structure where only the "queen" and her "husband(s)" are involved in reproduction (naked mole rats) or 2) substituting fast technological progress for slow biological evolution (humans). Lists of numerous traits of youth that do not disappear with age in naked mole rats and humans are presented and discussed. A high resistance of naked mole rats to cancer, diabetes, cardiovascular and brain diseases, and many infections explains why their mortality rate is very low and almost age-independent and why their lifespan is more than 30 years, versus 3 years in mice. In young humans, curves of mortality versus age start at extremely low values. However, in the elderly, human mortality strongly increases. High mortality rates in other primates are observed at much younger ages than in humans. The inhibition of the aging process in humans by specific drugs seems to be a promising approach to prolong our healthspan. This might be a way to retard aging, which is already partially accomplished via the natural physiological phenomenon neoteny.

  20. Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping.

    PubMed

    Gujjar, Chaitanya Yogananda; Rallabandi, Balaramesha Chary; Gannu, Ramesh; Deulkar, Vallabh Subashrao

    2016-04-01

    Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition. The formulations are evaluated for in vitro drug release in hydrochloric acid alone and with 40% v/v ethanol. The responses, dissolution at 120 min without alcohol (R1) and dissolution at 120 min with alcohol (R2), were statistically evaluated and regression equations are generated. PGA as a hydrophilic polymeric matrix was dumping the dose when dissolutions are carried in 0.1 N hydrochloric acid containing 40% v/v ethanol. ERS addition was giving structural support to the swelling and gelling property of PGA, and thus, was reducing the PGA erosion in dissolution media containing ethanol. Among the formulations, four formulations with diverse composition were meeting the target dissolution (30-40%) in both the conditions. The statistical validity of the mathematical equations was established, and the optimum concentration of the factors was established. Validation of the study with six confirmatory runs indicated high degree of prognostic ability of response surface methodology. Further coating with ReadiLycoat was providing an additional resistance to the alcohol-induced dose dumping. Optimized compositions showed resistance to dose dumping in the presence of alcohol.

  1. Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial.

    PubMed

    Kramer, Michael S; Matush, Lidia; Vanilovich, Irina; Platt, Robert; Bogdanovich, Natalia; Sevkovskaya, Zinaida; Dzikovich, Irina; Shishko, Gyorgy; Mazer, Bruce

    2007-10-20

    To assess whether exclusive and prolonged breast feeding reduces the risk of childhood asthma and allergy by age 6.5 years. Cluster randomised trial. 31 Belarussian maternity hospitals and their affiliated polyclinics. A total of 17,046 mother-infant pairs were enrolled, of whom 13,889 (81.5%) were followed up at age 6.5 years. Breastfeeding promotion intervention modelled on the WHO/UNICEF baby friendly hospital initiative. International study of asthma and allergies in childhood (ISAAC) questionnaire and skin prick tests of five inhalant antigens. The experimental intervention led to a large increase in exclusive breast feeding at 3 months (44.3% v 6.4%; P<0.001) and a significantly higher prevalence of any breast feeding at all ages up to and including 12 months. The experimental group had no reduction in risks of allergic symptoms and diagnoses or positive skin prick tests. In fact, after exclusion of six sites (three experimental and three control) with suspiciously high rates of positive skin prick tests, risks were significantly increased in the experimental group for four of the five antigens. These results do not support a protective effect of prolonged and exclusive breast feeding on asthma or allergy. Current Controlled Trials ISRCTN37687716 [controlled-trials.com].

  2. Prolonged clot lysis time increases the risk of a first but not recurrent venous thrombosis.

    PubMed

    Karasu, Alev; Baglin, Trevor P; Luddington, Roger; Baglin, Caroline A; van Hylckama Vlieg, Astrid

    2016-03-01

    The role of the fibrinolytic system in the development of venous thrombosis (VT) is unclear. We studied the risk of first and recurrent VT associated with reduced fibrinolysis, as measured by clot lysis time (CLT). We also studied the relationship between CLT and thrombin generation to determine if any relationship between CLT and VT was affected by thrombin generation. Analyses were performed in the Thrombophilia Hypercoagulability Environmental risk for Venous Thromboembolism Study, a two-centre population-based case-control study, including 579 patients and 338 controls, with patients followed from the event to determine incidence of recurrent VT. Hypofibrinolysis was associated with a 1·8-fold increased risk of a first VT [95% confidence interval (CI) 1·2-2·7]. Adjustment for sex, age, study location and Endogenous Thrombin Potential (ETP) did not change the result. The risk of VT was 2·9-fold increased when the 90th percentiles of prolonged CLT and high ETP were combined, with the highest risk for unprovoked first events (Odds Ratio = 4·2, 95% CI 1·3-13·5). In the follow-up study the Hazard Ratio for a recurrent VT associated with hypofibrinolysis was 1·5 (95% CI 0·9-2·6). A weak dose response effect was observed in relation to prolongation of CLT and recurrent VT. Although hypofibrinolysis constitutes a risk factor for a first VT, an association with recurrence is, at best, weak.

  3. The differential effects of prolonged exercise upon executive function and cerebral oxygenation.

    PubMed

    Tempest, Gavin D; Davranche, Karen; Brisswalter, Jeanick; Perrey, Stephane; Radel, Rémi

    2017-04-01

    The acute-exercise effects upon cognitive functions are varied and dependent upon exercise duration and intensity, and the type of cognitive tasks assessed. The hypofrontality hypothesis assumes that prolonged exercise, at physiologically challenging intensities, is detrimental to executive functions due to cerebral perturbations (indicated by reduced prefrontal activity). The present study aimed to test this hypothesis by measuring oxygenation in prefrontal and motor regions using near-infrared spectroscopy during two executive tasks (flanker task and 2-back task) performed while cycling for 60min at a very low intensity and an intensity above the ventilatory threshold. Findings revealed that, compared to very low intensity, physiologically challenging exercise (i) shortened reaction time in the flanker task, (ii) impaired performance in the 2-back task, and (iii) initially increased oxygenation in prefrontal, but not motor regions, which then became stable in both regions over time. Therefore, during prolonged exercise, not only is the intensity of exercise assessed important, but also the nature of the cognitive processes involved in the task. In contrast to the hypofrontality hypothesis, no inverse pattern of oxygenation between prefrontal and motor regions was observed, and prefrontal oxygenation was maintained over time. The present results go against the hypofrontality hypothesis.

  4. Evolution of prolonged development: a life table analysis for periodical cicadas.

    PubMed

    Karban, R

    1997-10-01

    According to conventional wisdom, natural selection should favor early reproduction. Prolonged development of 13 and 17 yr has been difficult to explain for periodical cicadas. Earlier, I hypothesized that development may be long for periodical cicadas because fecundity increases as a function of longer development with little increased risk of mortality. In this article, I tested whether the fecundity was greater for 17-yr cicadas than for 13-yr cicadas and estimated the shape of the survivorship curve. A cohort of 17-yr cicadas was followed from 1979 through 1996. Most mortality occurred during the first 2 yr; thereafter mortality was uncommon. Across 17 yr, adult densities increased at five out of seven sites, and in no case did the change exceed three times. Seventeen-year adults had heavier ovaries than did 13-yr adults; this effect was greater for Magicicada cassini (1.80 times) than for Magicicada decim (1.16 times). For M. cassini, the extra fecundity associated with 17-yr development swamped the potential advantages of more frequent reproduction of 13-yr forms under most conditions. For M. decim, realistically low rates of mortality roughly matched the small effect of development on fecundity. Prolonged development in periodical cicadas may be explained adequately by the demographic hypothesis, although it may also reduce predation risk to adults or result from strong selection for large body size.

  5. Plasma protein changes in horse after prolonged physical exercise: a proteomic study.

    PubMed

    Scoppetta, Fausto; Tartaglia, Micaela; Renzone, Giovanni; Avellini, Luca; Gaiti, Alberto; Scaloni, Andrea; Chiaradia, Elisabetta

    2012-07-19

    Physical exercise induces various stress responses and metabolic adaptations that have not yet been completely elucidated. Novel biomarkers are needed in sport veterinary medicine to monitor training levels and to detect subclinical conditions that can develop into exercise-related diseases. In this study, protein modifications in horse plasma induced by prolonged, aerobic physical exercise were investigated by using a proteomic approach based on 2-DE and combined mass spectrometry procedures. Thirty-eight protein spots, associated with expression products of 13 genes, showed significant quantitative changes; spots identified as membrane Cu amine oxidase, α-1 antitrypsin, α-1 antitrypsin-related protein, caeruloplasmin, α-2 macroglobulin and complement factor C4 were augmented in relative abundance after the race, while haptoglobin β chain, apolipoprotein A-I, transthyretin, retinol binding protein 4, fibrinogen γ chain, complement factor B and albumin fragments were reduced. These results indicate that prolonged physical exercise affects plasma proteins involved in pathways related to inflammation, coagulation, immune modulation, oxidant/antioxidant activity and cellular and vascular damage, with consequent effects on whole horse metabolism.

  6. Adaptive prolonged postreproductive life span in killer whales.

    PubMed

    Foster, Emma A; Franks, Daniel W; Mazzi, Sonia; Darden, Safi K; Balcomb, Ken C; Ford, John K B; Croft, Darren P

    2012-09-14

    Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals.

  7. Extracorporeal Free Flap Perfusion in Case of Prolonged Ischemia Time.

    PubMed

    Taeger, C D; Präbst, K; Beier, J P; Meyer, A; Horch, R E

    2016-04-01

    In free flap surgery, a clinically established concept still has to be found for the reduction of ischemia-related cell damage in the case of prolonged ischemia. Although promising results using extracorporeal free flap perfusion in the laboratory have been published in the past, until now this concept has not yet paved its way into clinical routine. This might be due to the complexity of perfusion systems and a lack of standardized tools. Here, we want to present the results of the first extracorporeal free flap perfusion in a clinical setting using a simple approach without the application of a complex perfusion machinery.

  8. Dynamical characterization of the last prolonged solar minima

    NASA Astrophysics Data System (ADS)

    Cionco, Rodolfo Gustavo; Compagnucci, Rosa Hilda

    2012-11-01

    The planetary hypothesis of the solar cycle is an old idea in which the gravitational influence of the planets has a non-negligible effect on the causes of the solar magnetic cycle. The advance of this hypothesis is based on phenomenological correlations between dynamical parameters of the Sun's movement around the barycentre of the Solar System and sunspots time series; and more especially, identifying relationships linking solar barycentric dynamics with prolonged minima (especially Grand Minima events). However, at present there is no clear physical mechanism relating these phenomena. The possible celestial influence on solar cycle modulation is of great importance not only in solar physics but also in Earth sciences, because prolonged solar minima have associated important climatic and telluric variations, in particular, during the Maunder and Dalton Minimum. In this work we looked for a possible causal link in relation with solar barycentric dynamics and prolonged minima events. We searched for particular changes in the Sun's acceleration and concentrated on long-term variations of the solar cycle. We show how the orbital angular momentum of the Sun evolves and how the inclination of the solar barycentric orbit varies during the epochs of orbital retrogressions. In particular, at these moments, the radial component of the Sun's acceleration (i.e., in the barycentre-Sun direction) had an exceptional magnitude. These radial impulses occurred at the very beginning of the Maunder Minimum, during the Dalton Minimum and also at the maximum of cycle 22 before the present extended minimum. We also found a strong correlation between the planetary torque and the observed sunspots international number around that maximum. We apply our results in a novel theory of Sun-planets interaction that it is sensitive to Sun barycentric dynamics and found a very important effect on the Sun's capability of storing hypothetical reservoirs of potential energy that could be released by

  9. How long would SDH/SONET be prolonged?

    NASA Astrophysics Data System (ADS)

    Tao, Zhiyong; Mao, Qian

    2004-04-01

    As we all know, the increasing speed of data traffic is exceeding gradually from voice in today"s communication network. The main reason is the explosive of Internet. The controversy with IP over ATM/SDH/Optical becomes hotter and hotter, Many people in the telecommunication field are doubt: HOW LONG WOULD SDH/SONET BE PROLONGED? WHAT KIND OF SDH EQUIPMENTS COULD BE USED IN THE NETWORK? With the analysis from several aspects: services in the network, new development with SDH technology, market in transport equipment, This paper is considered that the SDH with some new features would be predominant transport technology in the recent years.

  10. Prolonged intermittent renal replacement therapy in the intensive care unit.

    PubMed

    Bellomo, R; Baldwin, I; Fealy, N

    2002-12-01

    To present a review on the use of prolonged intermittent renal replacement therapy in the intensive care patient. Articles and abstracts reporting the use of renal replacement therapy. Standard intermittent haemodialysis (IHD) has significant shortcomings in the treatment of the acute renal failure (ARF) of critical illness. These shortcomings include haemodynamic instability, the need to remove excess fluid over a short period of time, the episodic nature of small solute control, the limited ability to achieve middle molecular weight solute control and the episodic nature of acid-base control. Over the last 20 years, these limitations have stimulated the evolution and increased application of continuous renal replacement therapy (CRRT) which provides major biochemical, biological and physiological advantages compared with IHD, although it remains unclear as to whether such advantages translate into a survival advantage. However, CRRT is technically demanding, requires supervision 24 hr per day and is often associated with the need for continuous anticoagulation, which, in some patients, might be undesirable. In some institutions, CRRT changes the nurse to patient ratio from 1:2 to 1:1, an alteration which has cost implications and might affect resource availability for other patients. Accordingly, techniques which prolong the duration of intermittent therapy and avoid the need for 24 hr treatment may offer "best value" in the management of ARF in the intensive care unit (ICU). These techniques will be referred to as prolonged intermittent renal replacement therapies (PIRRT) in this article. They are characterised by several fundamental principles: 1. Use of a modified or standard dialysis machines, 2. Use of diffusion, convection or any combination of the two, 3. Application of a decreased intensity of solute removal compared with IHD, 4. Extended duration of treatment beyond the typical 3 or 4 hr of standard IHD (hence the term prolonged) but not beyond an 8

  11. Prolonged ictal monoparesis with parietal Periodic Lateralised Epileptiform Discharges (PLEDs).

    PubMed

    Murahara, Takashi; Kinoshita, Masako; Usami, Kiyohide; Matsui, Masashi; Yamashita, Kouhei; Takahashi, Ryosuke; Ikeda, Akio

    2013-06-01

    We report a patient with prolonged monoparesis and parietal periodic lateralised epileptiform discharges (PLEDs). The patient was a 73-year-old man with chronic myelomonocytic leukaemia who developed persisting monoparesis of the right arm, sensory aphasia, and finger agnosia, initially associated with focal clonic seizures. These neurological deficits remained for seven days without subsequent focal clonic seizures. The EEG showed left-sided PLEDs, maximal in the left occipito-parietal area. Ten days later, following phenytoin treatment, these symptoms suddenly improved and parietal PLEDs disappeared. Sustained PLEDs in the left parietal region may have been causally associated with ictal paresis in this patient.

  12. Hemiplegic Migraine Presenting with Prolonged Somnolence: A Case Report

    PubMed Central

    Saleh, Christian; Pierquin, Geneviève; Beyenburg, Stefan

    2016-01-01

    Hemiplegic migraine is a rare and complex disease, characterized by migraine with a reversible motor aura. Hemiplegic migraine can be easily misdiagnosed at its first presentation with an atypical severe form of migraine, a stroke, multiple sclerosis, metabolic disorders, conversion disorder or an epilepsy. We present the case of a young 24-year-old male patient, who since the age of 4 years had been having multiple episodes of migraine associated with hemiparesis, paraesthesia, prolonged somnolence, aphasia and confusion. We review the literature and discuss important diagnostic findings in hemiplegic migraine to help establishing a prompt diagnosis. PMID:27790126

  13. Venlafaxine induced QTc interval prolongation in a therapeutic dose.

    PubMed

    Bavle, Amar

    2015-08-01

    This is the second report of a patient developing severe prolongation of QTc interval with a dose of 300mg/day of venlafaxine; on stopping it, QTc reverted to normalcy. Venlafaxine was restarted and maintained at 150mg/day, with QTc interval remaining normal, indicating, that it has a dose-dependent effect on QTc interval. Venlafaxine was not changed as she had responded best to this drug compared to any other antidepressant. Over 20 years, the only time she had a period of 5 years of remission, was when she was on 75mg of venlafaxine/day. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Aortic root surgery with circulatory arrest: Predictors of prolonged postoperative hospital stay.

    PubMed

    Preventza, Ourania; Coselli, Joseph S; Garcia, Andrea; Akvan, Shahab; Kashyap, Sarang; Simpson, Katherine H; Price, Matt D; de la Cruz, Kim I; Spiliotopoulos, Konstantinos; Cornwell, Lorraine D; Bakaeen, Faisal G; Omer, Shuab; Cooley, Denton A

    2017-03-01

    Little is known about the outcomes of aortic root operations that involve inducing hypothermic circulatory arrest for relatively extensive proximal aortic surgery. We attempted to identify predictors of postoperative hospital length of stay (LOS) and factors that affect postoperative recovery. During 2006-2014, 247 of 265 patients (93.2%) with disease extending into the aortic arch survived aortic root operations (206 elective, 41 urgent/emergent) in which hypothermic circulatory arrest with moderate hypothermia was used. Stepwise multivariate regression analysis was performed to identify predictors of LOS (as a continuous variable) and prolonged LOS (defined as LOS >9 days, the median for the cohort). By this definition, 111 patients (45%) had prolonged LOS and 136 (55%) did not. Preoperative factors that independently predicted longer LOS in the entire cohort included age (P = .0014), redo sternotomy (P = .0047), and intraoperative packed red blood cell (PRBC) transfusion (P = .0007). Redo sternotomy and intraoperative PRBC transfusion also predicted longer LOS in 3 subgroup analyses: one of elective cases, one from which total arch replacement procedures were excluded, and one limited to patients who were discharged home. Age predicted longer LOS in the non-total arch (hemiarch) replacement patients. Ventilator support >48 hours (P < .0001) was associated with longer LOS. Elective aortic valve-sparing root replacement predicted a shorter LOS than valve replacement in multivariate regression analysis (P = .028). In patients undergoing aortic root surgery with hypothermic circulatory arrest for disease extending into the aortic arch, reducing intraoperative PRBC transfusion except when absolutely necessary may reduce postoperative LOS and expedite recovery. Performing aortic valve-sparing root replacement, when feasible, may also reduce LOS. Copyright © 2016 The American Association for Thoracic Surgery. All rights reserved.

  15. Polyvinylpyrrolidone induced artefactual prolongation of activated partial thromboplastin times in intravenous drug users with renal failure.

    PubMed

    Kristoffersen, A H; Bjånes, T K; Jordal, S; Leh, S; Leh, F; Svarstad, E

    2016-05-01

    Essentials Prolonged activated partial thromboplastin times (APTT) were found in drug users with renal failure. An oral methadone solution containing polyvinylpyrrolidone (PVP) had been injected intravenously. Spiking normal plasma with increasing concentrations of PVP resulted in artifically prolonged APTT. APTT prolongation may indicate PVP deposits as underlying cause in patients with renal failure.

  16. Soy phosphatidylinositol containing nanoparticle prolongs hemostatic activity of B-domain deleted Factor VIII in Hemophilia A mice

    PubMed Central

    Shetty, Krithika A.; Kosloski, Matthew P.; Mager, Donald E.; Balu-Iyer, Sathy V.

    2014-01-01

    Factor VIII (FVIII) replacement therapy in Hemophilia A (HA) is complicated by a short half-life and high incidence of inhibitory antibody response against the protein. Phosphatidylinositol (PI) containing lipidic nanoparticles have previously been shown to reduce the immunogenicity and prolong the half-life of full length FVIII. It has not been established whether this prolongation in half-life improves hemostatic efficacy and whether this approach could be extended to the B-domain deleted form of FVIII (BDD FVIII). In the current study, we evaluated the pharmacokinetics (PK), hemostatic efficacy and immunogenicity of BDD FVIII associated with PI nanoparticles (PI-BDD FVIII) in HA mice. Comparative human PK was predicted using an ‘informed scaling’ approach. PI-BDD FVIII showed a ~ 1.5-fold increase in terminal half-life compared to free BDD FVIII following i.v. bolus doses of 40 IU/kg. PI-BDD FVIII treated animals retained hemostatic efficacy longer than the free FVIII treated group in a tail vein transection model of hemostasis. PI association reduced the development of inhibitory and binding antibodies against BDD FVIII after a series of i.v. injections. The combined improvements in circulating half-life and hemostatic efficacy could significantly prolong the time above clinically established therapeutic thresholds of prophylactic FVIII replacement therapy in humans. PMID:24700333

  17. Prolonged fasting impairs neural reactivity to visual stimulation.

    PubMed

    Kohn, N; Wassenberg, A; Toygar, T; Kellermann, T; Weidenfeld, C; Berthold-Losleben, M; Chechko, N; Orfanos, S; Vocke, S; Laoutidis, Z G; Schneider, F; Karges, W; Habel, U

    2016-01-01

    Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

  18. High efficiency holographic Bragg grating with optically prolonged memory

    PubMed Central

    Khoo, Iam Choon; Chen, Chun-Wei; Ho, Tsung-Jui

    2016-01-01

    In this paper, we show that photosensitive azo-dye doped Blue-phase liquid crystals (BPLC) formed by natural molecular self-assembly are capable of high diffraction efficiency holographic recording with memory that can be prolonged from few seconds to several minutes by uniform illumination with the reference beam. Operating in the Bragg regime, we have observed 50 times improvement in the grating diffraction efficiency and shorter recording time compared to previous investigations. The enabling mechanism is BPLC’s lattice distortion and index modulation caused by the action of light on the azo-dopant; upon photo-excitation, the azo-molecules undergo transformation from the oblong-shaped Trans-state to the bent-shaped Cis-state, imparting disorder and also cause the surrounding BPLC molecules to undergo coupled flow & reorientation leading to lattice distortion and index modulation. We also showed that the same mechanism at work here that facilitates lattice distortion can be used to frustrate free relaxation of the lattice distortion, thereby prolonging the lifetime of the written grating, provided the reference beam is kept on after recording. Due to the ease in BPLC fabrication and the availability of azo-dopants with photosensitivity throughout the entire visible spectrum, one can optimize the controlling material and optical parameters to obtain even better performance. PMID:27782197

  19. Caffeine ingestion, affect and perceived exertion during prolonged cycling.

    PubMed

    Backhouse, Susan H; Biddle, Stuart J H; Bishop, Nicolette C; Williams, Clyde

    2011-08-01

    Caffeine's metabolic and performance effects have been widely reported. However, caffeine's effects on affective states during prolonged exercise are unknown. Therefore, this was examined in the present study. Following an overnight fast and in a randomised, double-blind, counterbalanced design, twelve endurance trained male cyclists performed 90 min of exercise at 70% VO(₂ max) 1h after ingesting 6 mg kg⁻¹ BM of caffeine (CAF) or placebo (PLA). Dimensions of affect and perceived exertion were assessed at regular intervals. During exercise, pleasure ratings were better maintained (F(₃,₃₈)=4.99, P < 0.05) in the CAF trial compared to the PLA trial with significantly higher ratings at 15, 30 and 75 min (all P < 0.05). Perceived exertion increased (F(₃,₃₈) = 19.86, P < 0.01) throughout exercise and values, overall, were significantly lower (F(₁,₁₁) = 9.26, P < 0.05) in the CAF trial compared to the PLA trial. Perceived arousal was elevated during exercise but did not differ between trials. Overall, the results suggest that a moderate dose of CAF ingested 1h prior to exercise maintains a more positive subjective experience during prolonged cycling. This observation may partially explain caffeine's ergogenic effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Survey of pertussis in patients with prolonged cough.

    PubMed

    Hu, Jen Jan; Lu, Chun Yi; Chang, Luan Yin; Huang, Chin Hao; Chou, Chen Cheng; Huang, Fu Yuan; Lee, Chin Yun; Huang, Li Min

    2006-02-01

    Pertussis is an acute respiratory tract illness resulting from Bordetella pertussis. Widespread use of pertussis vaccine over the past 50 years has decreased the incidence of pertussis. The incidence of pertussis in adolescents and adults has increased in many areas of the world. This study aimed to evaluate the etiologic role of B. pertussis in patients with prolonged cough in Taiwan. Patients with cough lasting for more than 1 week were recruited. Nasopharyngeal swabs were taken for culture of B. pertussis and detection of nucleic acid of B. pertussis by polymerase chain reaction. Serum samples were collected in a subset of patients for assay of immunoglobulin G and immunoglobulin A antibodies against pertussis toxin. In total, 111 patients were recruited. Thirty-three patients agreed to have their serum samples taken and tested. Eight patients had evidence of acute infection with B. pertussis; among them, 1 was diagnosed by polymerase chain reaction and 7 by serology. Older subjects were more likely to suffer from pertussis than younger subjects. The incidence of pertussis in patients with prolonged cough was 7.2%. However, the rate could have been as high as 21% in those with serum samples tested. We conclude that pertussis is a prevalent disease in Taiwan, especially in adolescents and adults.

  1. Obesity-related changes in prolonged repetitive lifting performance.

    PubMed

    Ghesmaty Sangachin, Mahboobeh; Cavuoto, Lora A

    2016-09-01

    Despite the rising prevalence of obesity, little is known about its moderating effects on injury risk factors, such as fatigue, in occupational settings. This study investigated the effect of obesity, prolonged repetitive lifting and their interaction on lifting performance of 14 participants, 7 obese (mean body mass index (BMI): 33.2 kg m(-2)) and 7 non-obese (mean BMI: 22.2 kg m(-2)) subjects. To present a physically challenging task, subjects performed repetitive lifting for 1 h at 120% of their maximum acceptable weight of lift. Generalized linear mixed models were fit to posture and acceleration data. The obese group bent to a ∼10° lower peak trunk sagittal flexion angle, had 17% lower root mean square (RMS) jerk and took 0.8 s longer per lift. Over time, the obese group increased their trunk transverse and sagittal posterior accelerations while the non-obese maintained theirs. Although the majority of lifting variables were unaffected by BMI or its interaction with prolonged lifting duration, the observed differences, combined with a greater upper body mass, necessitate a more cautious use of existing psychophysical lifting limits for individuals who are obese, particularly when fatigued. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. High efficiency holographic Bragg grating with optically prolonged memory

    NASA Astrophysics Data System (ADS)

    Khoo, Iam Choon; Chen, Chun-Wei; Ho, Tsung-Jui

    2016-10-01

    In this paper, we show that photosensitive azo-dye doped Blue-phase liquid crystals (BPLC) formed by natural molecular self-assembly are capable of high diffraction efficiency holographic recording with memory that can be prolonged from few seconds to several minutes by uniform illumination with the reference beam. Operating in the Bragg regime, we have observed 50 times improvement in the grating diffraction efficiency and shorter recording time compared to previous investigations. The enabling mechanism is BPLC’s lattice distortion and index modulation caused by the action of light on the azo-dopant; upon photo-excitation, the azo-molecules undergo transformation from the oblong-shaped Trans-state to the bent-shaped Cis-state, imparting disorder and also cause the surrounding BPLC molecules to undergo coupled flow & reorientation leading to lattice distortion and index modulation. We also showed that the same mechanism at work here that facilitates lattice distortion can be used to frustrate free relaxation of the lattice distortion, thereby prolonging the lifetime of the written grating, provided the reference beam is kept on after recording. Due to the ease in BPLC fabrication and the availability of azo-dopants with photosensitivity throughout the entire visible spectrum, one can optimize the controlling material and optical parameters to obtain even better performance.

  3. Prolonged paroxysmal sympathetic storming associated with spontaneous subarachnoid hemorrhage.

    PubMed

    Liu, Yan; Jolly, Suneil; Pokala, Krishna

    2013-01-01

    Paroxysmal sympathetic storming (PSS) is a rare disorder characterized by acute onset of nonstimulated tachycardia, hypertension, tachypnea, hyperthermia, external posturing, and diaphoresis. It is most frequently associated with severe traumatic brain injuries and has been reported in intracranial tumors, hydrocephalous, severe hypoxic brain injury, and intracerebral hemorrhage. Although excessive release of catecholamine and therefore increased sympathetic activities have been reported in subarachnoid hemorrhage (SAH), there is no descriptive report of PSS primarily caused by spontaneous SAH up to date. Here, we report a case of prolonged PSS in a patient with spontaneous subarachnoid hemorrhage and consequent vasospasm. The sympathetic storming started shortly after patient was rewarmed from hypothermia protocol and symptoms responded to Labetalol, but intermittent recurrence did not resolve until 3 weeks later with treatment involving Midazolam, Fentanyl, Dexmedetomidine, Propofol, Bromocriptine, and minimizing frequency of neurological and vital checks. In conclusion, prolonged sympathetic storming can also be caused by spontaneous SAH. In this case, vasospasm might be a precipitating factor. Paralytics and hypothermia could mask the manifestations of PSS. The treatment of the refractory case will need both timely adjustment of medications and minimization of exogenous stressors or stimuli.

  4. Influence of a Prolonged Tennis Match Play on Serve Biomechanics.

    PubMed

    Martin, Caroline; Bideau, Benoit; Delamarche, Paul; Kulpa, Richard

    2016-01-01

    The aim of this study was to quantify kinematic, kinetic and performance changes that occur in the serve throughout a prolonged tennis match play. Serves of eight male advanced tennis players were recorded with a motion capture system before, at mid-match, and after a 3-hour tennis match. Before and after each match, electromyographic data of 8 upper limb muscles obtained during isometric maximal voluntary contraction were compared to determine the presence of muscular fatigue. Vertical ground reaction forces, rating of perceived exertion, ball speed, and ball impact height were measured. Kinematic and upper limb kinetic variables were computed. The results show decrease in mean power frequency values for several upper limb muscles that is an indicator of local muscular fatigue. Decreases in serve ball speed, ball impact height, maximal angular velocities and an increase in rating of perceived exertion were also observed between the beginning and the end of the match. With fatigue, the majority of the upper limb joint kinetics decreases at the end of the match. No change in timing of maximal angular velocities was observed between the beginning and the end of the match. A prolonged tennis match play may induce fatigue in upper limb muscles, which decrease performance and cause changes in serve maximal angular velocities and joint kinetics. The consistency in timing of maximal angular velocities suggests that advanced tennis players are able to maintain the temporal pattern of their serve technique, in spite of the muscular fatigue development.

  5. Orchids do not pay costs at emergence for prolonged dormancy.

    PubMed

    Jäkäläniemi, Anne; Crone, Elizabeth E; Närhi, Paavo; Tuomi, Juha

    2011-07-01

    In plants, prolonged dormancy is often considered a response to resource depletion or environmental stress that comes at a fitness cost. However, apparent costs of dormancy could reflect the state in which plants entered dormancy, rather than effects of dormancy per se. We tested this hypothesis for a terrestrial orchid, Epipactis atrorubens, by analyzing differences in vital rates of dormant and emergent plants using generalized linear mixed models, applied to eight years of demographic data. Dormant E. atrorubens plants did not form one homogeneous stage class. Instead, the vital rates of dormant plants mirrored performance of plants in their life stage before dormancy. Plants emerging from dormancy were slightly (albeit only marginally statistically significantly) larger than plants transitioning from the matching aboveground stage class, especially for smaller and younger stage classes. Because small plants were most likely to go dormant, plants emerging from dormancy were also smaller than average, if one were to compare all previously dormant plants to all previously emergent plants. Therefore, misclassifying all dormant plants into a single stage class changes whether we view dormancy as intrinsically costly, in terms of future performance upon emergence. We suggest that prolonged dormancy may be a form of phenotypic plasticity in which plants distribute their performance and reproductive effort through time, rather than a simple stress response.

  6. Moderate superficial hypothermia prolongs bleeding time in humans.

    PubMed

    Romlin, B; Petruson, K; Nilsson, K

    2007-02-01

    In vitro and in vivo studies have shown that mild systemic hypothermia influences platelet adhesion and aggregation and coagulation reactions. We wanted to test the hypothesis that mild local hypothermia in healthy volunteers with preserved core temperature increased bleeding time. A secondary aim was to evaluate if local cooling influenced whole blood coagulation measured by thrombelastograph (TEG) in the same setting. Bleeding time was measured at the left volar forearm at a baseline skin temperature of 32 degrees C and after cooling to 30 degrees C and 28 degrees C in a water bath. Skin temperature was continuously measured by contact thermistors. Measurements of coagulation by TEG were performed at baseline skin temperature before cooling and after cooling to 28 degrees C skin temperature. Tympanic membrane temperature was continuously measured. Compared with baseline, bleeding time was significantly prolonged at 30 degrees C skin temperature and further prolonged at 28 degrees C skin temperature. No significant differences were measured in any of the TEG parameters. During the procedure, tympanic membrane temperature did not change. Lowering the skin temperature from 32 degrees C to 30 degrees C and 28 degrees C with a preserved core temperature more than doubled the bleeding time. Whole blood coagulation measured by TEG was not influenced by the local cooling. In addition to core temperature, local temperature may offer information in understanding the surgical site of bleeding.

  7. Intravenous lipid emulsion prolongs survival in rats intoxicated with digoxin.

    PubMed

    Yurtlu, Bülent Serhan; Özbilgin, Şule; Yurtlu, Derya Arslan; Boztaş, Nilay; Kamacı, Gonca; Akaltun, Mahmut; Hancı, Volkan; Yılmaz, Osman

    2016-06-01

    Intravenous lipid emulsion eliminates the toxicity-related symptoms of several drugs. We hypothesized that intravenous lipid emulsion prolongs the survival time in digoxin-intoxicated rats. Electrocardiograms of 14 anesthesized Wistar rats were monitored. All of the rats received digoxin infusion at a rate of 12 mL/h (0.25 mg/mL). Five minutes after the start of digoxin infusion, animals were treated either with 12.4 mL/kg intravenous lipid emulsion (group L) or saline (group C). The primary outcome variable was time elapsed until asystole development. Cumulative dose of digoxin required to induce asystole was also recorded. Mean time until asystole development in groups C and L were 21.28 ± 8.61 and 32.00 ± 5.41 minutes, respectively (P< .05). The mean lethal doses of digoxin in the groups C and L were 3.97 ± 1.54 and 6.09 ± 0.96 mg/kg, respectively (P< .05). Intravenous lipid emulsion prolonged the time until asystole development and increased cumulative lethal dose in rats intoxicated with digoxin. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Potential risk factors for prolonged recovery following whiplash injury.

    PubMed

    Osti, Orso L; Gun, Richard T; Abraham, George; Pratt, Nicole L; Eckerwall, Goran; Nakamura, Hiroaki

    2005-02-01

    A retrospective analysis of insurance data was made of 600 individuals claiming compensation for whiplash following motor vehicle accidents. Three hundred randomly selected claimants who had settled their injury claims within 9 months of the accident were compared with 300 who had settled more than 24 months after the accident. We compared the two groups to identify possible risk factors for prolonged recovery, for which settlement time greater than 24 months was a marker. Variables considered included demographic factors, type of collision, degree of vehicle damage, workers compensation, prior claim or neck disability, treatment and time to settlement. Consulting a solicitor was associated with a highly significant, four-fold increase of late settlement of the claim. A concurrent workers' compensation claim, prior neck disability and undergoing physiotherapy or chiropractic treatment were weakly associated with late settlement. The degree of damage to the vehicle (as indicated by cost of repairs) was not a significant predictor of late settlement. Late settlement may be the direct effect of legal intervention, independent of the severity of the injury. Whilst the financial benefit to the claimant of consulting a solicitor is apparent, the benefit of prolonged disability is not. It may be to the advantage of both insurers and claimants if those likely to proceed to late settlement could be recognised early and their claims settled expeditiously.

  9. Cyclodextrin modified PLLA parietal reinforcement implant with prolonged antibacterial activity.

    PubMed

    Vermet, G; Degoutin, S; Chai, F; Maton, M; Flores, C; Neut, C; Danjou, P E; Martel, B; Blanchemain, N

    2017-02-12

    The use of textile meshes in hernia repair is widespread in visceral surgery. Though, mesh infection is a complication that may prolong the patient recovery period and consequently presents an impact on public health economy. Such concern can be avoided thanks to a local and extended antibiotic release on the operative site. In recent developments, poly-l-lactic acid (PLLA) has been used in complement of polyethyleneterephthalate (Dacron®) (PET) or polypropylene (PP) yarns in the manufacture of semi-resorbable parietal implants. The goal of the present study consisted in assigning drug reservoir properties and prolonged antibacterial effect to a 100% PLLA knit through its functionalization with a cyclodextrin polymer (polyCD) and activation with ciprofloxacin. The study focused i) on the control of degree of polyCD functionalization of the PLLA support and on its physical and biological characterization by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and cell viability, ii) on the understanding of drug/meshes interaction using mathematic model and iii) on the correlation between drug release studies in phosphate buffer saline (PBS) and microbiological evaluation of meshes and release medium against E. coli and S. aureus. All above mentioned tests highlighted the contribution of polyCD on the improved performances of the resulting antibacterial implantable material.

  10. Effect of Multiparity and Prolonged Lactation on Bone Mineral Density

    PubMed Central

    Natung, Tanie; Barooah, Rituparna; Ahanthem, Santa Singh

    2016-01-01

    Objectives This study was done to determine the effect of multiparity and prolonged lactation on bone mineral density (BMD). Methods This cross-sectional study included 196 perimenopausal and postmenopausal women aged 40 to 60 years old. Age, body mass index (BMI), menopausal status, duration of menopause, parity and total duration of lactation, nutritional history were recorded. Lumbar spine (LS; L2-L4) and femur neck (FN) BMD were measured using dual energy X-ray absorptiometry. Correlation of parity and lactation with BMD were investigated using multiple regression analysis. Results Parity was inversely correlated to BMD for LS (β = −0.266, P = 0.001) and FN (β = −0.380, P = 0.000). This relation remained significant even after adjusting for age, BMI and duration of menopause. Duration of lactation was inversely correlated with BMD for LS (β = −0.271, P = 0.001) but no for FN (β = −0.124, P = 0.130). Conclusions Multiparity and prolonged lactation have negative impact on BMD especially with in a socioeconomic group whose nutritional intake is borderline. Our data support that parity and duration of lactation can be associated with future osteoporosis. PMID:28119896

  11. Prolonged thromboprophylaxis with enoxaparin in early neurological rehabilitation.

    PubMed

    Lang, Alexandra; Kienitz, Carsten; Wetzel, Petra; Rollnik, Jens D

    2011-10-01

    Prevention of venous thromboembolism (VTE) is essential in neurological patients. Little is known about the optimal duration, efficacy, and safety of prolonged off-label use of low-molecular-weight heparin (LMWH). We enrolled n = 1176 early neurological rehabilitation cases in a retrospective study. In most cases (n = 1151, 97.9%), 4000 anti-Xa (activated coagulation factor X [factor Xa]) units enoxaparin were administered, only 25 received 2000 units for approximately 2 months (mean of 57.5 days). In 969 cases, enoxaparin was administered for more than 2 weeks. Incidence of symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) were 0.43% (n = 5) and 1.11% (n = 13), respectively. Hemorrhages during enoxaparin therapy were more frequent. Bleeding occurred in 1.96% (n = 23) of cases, mainly gastrointestinal, urinary tract, and vitreous body bleeding. In short-term (up to 2 weeks) treatment, bleeding and VTE were more frequent than in long-term treatment. Results from this study suggest that prolonged enoxaparin thromboprophylaxis in neurological rehabilitation is safe and effective.

  12. Influence of a Prolonged Tennis Match Play on Serve Biomechanics

    PubMed Central

    Martin, Caroline; Bideau, Benoit; Delamarche, Paul; Kulpa, Richard

    2016-01-01

    The aim of this study was to quantify kinematic, kinetic and performance changes that occur in the serve throughout a prolonged tennis match play. Serves of eight male advanced tennis players were recorded with a motion capture system before, at mid-match, and after a 3-hour tennis match. Before and after each match, electromyographic data of 8 upper limb muscles obtained during isometric maximal voluntary contraction were compared to determine the presence of muscular fatigue. Vertical ground reaction forces, rating of perceived exertion, ball speed, and ball impact height were measured. Kinematic and upper limb kinetic variables were computed. The results show decrease in mean power frequency values for several upper limb muscles that is an indicator of local muscular fatigue. Decreases in serve ball speed, ball impact height, maximal angular velocities and an increase in rating of perceived exertion were also observed between the beginning and the end of the match. With fatigue, the majority of the upper limb joint kinetics decreases at the end of the match. No change in timing of maximal angular velocities was observed between the beginning and the end of the match. A prolonged tennis match play may induce fatigue in upper limb muscles, which decrease performance and cause changes in serve maximal angular velocities and joint kinetics. The consistency in timing of maximal angular velocities suggests that advanced tennis players are able to maintain the temporal pattern of their serve technique, in spite of the muscular fatigue development. PMID:27532421

  13. Simplified methods for the prolonged treatment of fish diseases

    USGS Publications Warehouse

    Fish, F.F.

    1939-01-01

    The prevention or control of epidemics of fish diseases by applying a disinfecting solution in a uniform concentration directly to the water supply of a fish pond or trough for a definite period of time has been exceedingly slow in development. In so far as can be determined, the original idea should be credited to. Marsh and Robinson (1910). In their work on the control of algae in fish ponds by the continuous application of dilute copper sulphate solution, administered to the inflowing water supply by means of a floating syphon, they suggested this method as a possibility in the treatment of fish diseases. Following their work, this commendable idea seems to have remained quite dormant and apparently forgotten until Hess (1930) revived it twenty or more years later. This worker found that a prolonged immersion in a dilute disinfecting bath was more efficacious in remowng fluke parasites from goldfish than was the customary short "hand dip" method. Kingsbury and Embody (1932) later adapted the idea of a prolonged treatment to running water by the use of a float valve for maintaining a constant level in a reservoir, resulting in a constant flow to the pond or trough to be treated. Shortly thereafter, Fish (1933) modified the floating syphon of Marsh and Robinson, as it was a simpler apparatus than that of Kingsbury and Embody.

  14. Prolonged morphine administration alters protein expression in the rat myocardium

    PubMed Central

    2011-01-01

    Background Morphine is used in clinical practice as a highly effective painkiller as well as the drug of choice for treatment of certain heart diseases. However, there is lack of information about its effect on protein expression in the heart. Therefore, here we aimed to identify the presumed alterations in rat myocardial protein levels after prolonged morphine treatment. Methods Morphine was administered to adult male Wistar rats in high doses (10 mg/kg per day) for 10 days. Proteins from the plasma membrane- and mitochondria-enriched fractions or cytosolic proteins isolated from left ventricles were run on 2D gel electrophoresis, scanned and quantified with specific software to reveal differentially expressed proteins. Results Nine proteins were found to show markedly altered expression levels in samples from morphine-treaded rats and these proteins were identified by mass spectrometric analysis. They belong to different cell pathways including signaling, cytoprotective, and structural elements. Conclusions The present identification of several important myocardial proteins altered by prolonged morphine treatment points to global effects of this drug on heart tissue. These findings represent an initial step toward a more complex view on the action of morphine on the heart. PMID:22129148

  15. Design of the INHIBIT trial: preventing inhibitors by avoiding ‘danger’, prolonging half-life and promoting tolerance

    PubMed Central

    Ragni, Margaret V; Malec, Lynn M

    2015-01-01

    Inhibitor formation is among the most serious complications of hemophilia treatment. With the US FDA licensure of the novel long-lasting recombinant factor VIII (FVIII) Fc fusion protein, Eloctate, which prolongs FVIII half-life, we propose an innovative approach to prevent inhibitor formation. In this paper, we describe a multicenter, Phase II, single-arm, 48-week trial, the INHIBIT trial, to determine if Eloctate, begun before a bleed and continued as once weekly prophylaxis, will reduce inhibitor formation in children with hemophilia A. We hypothesize that avoiding ‘danger,’ that is, immune activation by a bleed at first factor exposure and prolonging FVIII half-life will prevent inhibitors and promote FVIII-specific T-cell tolerance. If successful, this approach will suggest a new paradigm in clinical practice. PMID:25374055

  16. The Need for Self-Report Data in the Assessment of Stuttering Therapy Efficacy: Repetitions and Prolongations of Speech. The Stuttering Syndrome

    ERIC Educational Resources Information Center

    Guntupalli, Vijaya K.; Kalinowski, Joseph; Saltuklaroglu, Tim

    2006-01-01

    Background: Bloodstein reviewed hundreds of studies that investigated the efficacy of therapeutic protocols for ameliorating the stuttering syndrome. Surprisingly, almost all were effective in significantly reducing overtly perceptible behaviours such as repetitions and prolongations of speech sounds. These results seem highly improbable…

  17. The Need for Self-Report Data in the Assessment of Stuttering Therapy Efficacy: Repetitions and Prolongations of Speech. The Stuttering Syndrome

    ERIC Educational Resources Information Center

    Guntupalli, Vijaya K.; Kalinowski, Joseph; Saltuklaroglu, Tim

    2006-01-01

    Background: Bloodstein reviewed hundreds of studies that investigated the efficacy of therapeutic protocols for ameliorating the stuttering syndrome. Surprisingly, almost all were effective in significantly reducing overtly perceptible behaviours such as repetitions and prolongations of speech sounds. These results seem highly improbable…

  18. Enhanced cytotoxicity of melphalan by prolonged exposure to nitroimidazoles: the role of endogenous thiols

    SciTech Connect

    Roizin-Towle, L.; Hall, E.J.; Flynn, M.; Biaglow, J.E.; Varnes, M.E.

    1982-01-01

    The present study shows that a prolonged exposure of V-79 cells to a variety of nitroimidazoles (misonidazole, Ro-05-9963, Sr-2508, and MRT1-80) results in an enhanced cytotoxicity when these cells are subsequently exposed to melphalan. This process of enhanced malphalan toxicity occurred only when cells were pretreated with misonidazole under hypoxic conditions, suggesting that nitroreduction is necessary for chemosensitization as it is for increased radiosensitization. Different nitroimidazoles tested vary in the extent to which they sensitize cells to the subsequent action of melphalan. Repair from a misonidazole pretreatment is essentially complete by six hours. This study demonstrated that cysteamine could reduce the cytotoxicity of misonidazole and the enhancement of melphalan toxicity. This was an effect reversible with time and one implying similar mechanisms for the preincubation effect observed in vitro for radiation and chemotherapy agents.

  19. Buoyancy Limitation of Filamentous Cyanobacteria under Prolonged Pressure due to the Gas Vesicles Collapse

    NASA Astrophysics Data System (ADS)

    Abeynayaka, Helayaye Damitha Lakmali; Asaeda, Takashi; Kaneko, Yasuko

    2017-08-01

    Freshwater cyanobacterium Pseudanabaena galeata were cultured in chambers under artificially generated pressures, which correspond to the hydrostatic pressures at deep water. Variations occurred in gas vesicles volume, and buoyancy state of cells under those conditions were analyzed at different time intervals (5 min, 1 day, and 5 days). Variations in gas vesicles morphology of cells were observed by transmission electron microscopy images. Settling velocity ( Vs) of cells which governs the buoyancy was observed with the aid of a modified optical microscope. Moreover, effects of the prolonged pressure on cell ballast composition (protein and polysaccharides) were examined. Elevated pressure conditions reduced the cell ballast and caused a complete disappearance of gas vesicles in Pseudanabaena galeata cells. Hence cyanobacteria cells were not able to float within the study period. Observations and findings of the study indicate the potential application of hydrostatic pressure, which naturally occurred in hypolimnion of lakes, to inhibit the re-suspension of cyanobacteria cells.

  20. Dissemination and implementation of prolonged exposure therapy for posttraumatic stress disorder.

    PubMed

    McLean, Carmen P; Foa, Edna B

    2013-12-01

    Posttraumatic stress disorder (PTSD) is a highly prevalent, often chronic and disabling psychiatric disorder that is associated with significant adverse health and life consequences. Although several evidence-based treatments (EBTs), including Prolonged Exposure therapy (PE), have been found effective and efficacious in reducing PTSD symptomology, the majority of individuals with this disorder receive treatments of unknown efficacy. Thus, it is imperative that EBTs such as PE be made available to PTSD sufferers through widespread dissemination and implementation. We will review some of the efforts to increase the availability of PE and the common barriers to successful dissemination and implementation. We also discuss novel dissemination strategies that are harnessing technology to overcome barriers to dissemination. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Outcomes of Prolonged Laparoscopic Bariatric Operations Compared With Shorter Open Procedures.

    PubMed

    Zettervall, Sara L; Amdur, Richard; Vaziri, Khashayar

    2015-12-01

    Prolonged operative time (ORT) is a drawback of laparoscopic bariatric surgery due to concerns for increased morbidity. This study aims to identify the ORT when open procedures are superior to laparoscopic procedures. Thirty-day outcomes for bariatric procedures in the NSQIP database were analyzed comparing laparoscopic ORT to equal or shorter open ORT. Multivariate regression was utilized to control for patient demographics and comorbidities. Among 48,274 cases, laparoscopic procedures reduced morbidity and mortality compared with open procedures of similar ORT. Laparoscopic procedures ≤3 hours were equal or superior to shorter open procedures. Laparoscopic procedures >6 hours had worse outcomes than open operations <3 hours. Open operations >3 hours had no benefit regardless of ORT. Laparoscopic bariatric operations have less mortality and morbidity compared with open procedures of similar ORT. The advantages of laparoscopic procedures are eliminated when ORT exceeds 6 hours compared with shorter open procedures.

  2. Nullifying tumor efflux by prolonged endolysosome vesicles: development of low dose anticancer-carbon nanotube drug.

    PubMed

    Lee, Yeon Kyung; Choi, Jungil; Wang, Wenping; Lee, Soyoung; Nam, Tae-Hyun; Choi, Wan Sung; Kim, Chang-Joon; Lee, Jong Kwon; Kim, Sang-Hyun; Kang, Sang Soo; Khang, Dongwoo

    2013-10-22

    As the majority of side effects of current chemotherapies stems from toxicity due to excessive dosing of anticancer drugs, minimizing the amount of drug while maximizing drug efficacy is essential to increase the life-quality of chemotherapy patients. This study demonstrated that the intracellular delivery of amide linked doxorubicin on carbon nanotube can nullify the efflux of cancer cells by achieving prolonged endolysosome delivery and can induce burst release of doxorubicin in an acidic hydrolase environment and, ultimately, can reduce the amount of anticancer drug by 10-fold compared to conventional effective drug dose. The clearance of accumulated carbon nanotubes in the liver was observed after 4 weeks, and analysis of liver toxicity markers showed no significant changes in GOT and GPT levels and release of pro-inflammatory cytokines across both short- and long-term periods.

  3. Protective effect of ligustrazine on lumbar intervertebral disc degeneration of rats induced by prolonged upright posture.

    PubMed

    Liang, Qian-Qian; Ding, Dao-Fang; Xi, Zhi-Jie; Chen, Yan; Li, Chen-Guang; Liu, Shu-Fen; Lu, Sheng; Zhao, Yong-Jian; Shi, Qi; Wang, Yong-Jun

    2014-01-01

    Most chronic low back pain is the result of degeneration of the lumbar intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is able to relieve pain, suppress inflammation, and treat osteoarthritis and it has the protective effect on cartilage and chondrocytes. Therefore, we asked whether ligustrazine could reduce intervertebral disc degeneration. To determine the effect of ligustrazine on disc degeneration, we applied a rat model. The intervertebral disc degeneration of the rats was induced by prolonged upright posture. We found that pretreatment with ligustrazine for 1 month recovered the structural distortion of the degenerative disc; inhibited the expression of type X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II collagen; and decreased IL-1 β , cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising agent for treating lumbar intervertebral disc degeneration disease.

  4. Buoyancy Limitation of Filamentous Cyanobacteria under Prolonged Pressure due to the Gas Vesicles Collapse.

    PubMed

    Abeynayaka, Helayaye Damitha Lakmali; Asaeda, Takashi; Kaneko, Yasuko

    2017-08-01

    Freshwater cyanobacterium Pseudanabaena galeata were cultured in chambers under artificially generated pressures, which correspond to the hydrostatic pressures at deep water. Variations occurred in gas vesicles volume, and buoyancy state of cells under those conditions were analyzed at different time intervals (5 min, 1 day, and 5 days). Variations in gas vesicles morphology of cells were observed by transmission electron microscopy images. Settling velocity (Vs) of cells which governs the buoyancy was observed with the aid of a modified optical microscope. Moreover, effects of the prolonged pressure on cell ballast composition (protein and polysaccharides) were examined. Elevated pressure conditions reduced the cell ballast and caused a complete disappearance of gas vesicles in Pseudanabaena galeata cells. Hence cyanobacteria cells were not able to float within the study period. Observations and findings of the study indicate the potential application of hydrostatic pressure, which naturally occurred in hypolimnion of lakes, to inhibit the re-suspension of cyanobacteria cells.

  5. Prolonged Radiant Exposure of the Middle Ear during Transcanal Endoscopic Ear Surgery.

    PubMed

    Shah, Parth V; Kozin, Elliott D; Remenschneider, Aaron K; Dedmon, Matthew M; Nakajima, Hideko Heidi; Cohen, Michael S; Lee, Daniel J

    2015-07-01

    Transcanal endoscopic ear surgery (EES) provides a high-resolution, wide-field view of the middle ear compared with the conventional operating microscope, reducing the need for a postauricular incision or mastoidectomy. Our group has shown in cadaveric human temporal bone studies that radiant energy from the endoscope tip can quickly elevate temperatures of the tympanic cavity. Elevated temperatures of the middle ear are associated with acute auditory brainstem response shifts in animal models. In EES, proposed methods to decrease middle ear temperature include frequent removal of the endoscope and the use of suction to rapidly dissipate heat; however, the routine application of such cooling techniques remains unknown. Herein, we aim to quantify the duration that the tympanic cavity is typically exposed to the endoscope during routine endoscopic middle ear surgery. We find that the tympanic cavity is exposed to the endoscope without a cooling mechanism for a prolonged period of time.

  6. Ion regulatory function of the human kidney in prolonged space flights

    NASA Astrophysics Data System (ADS)

    Grigoriev, A. I.

    Ten cosmonauts, who performed 30-175-day space flights aboard Salyut-4 and Salyut-6, and over 60 test subjects who were exposed to bed rest of up to 182 days and immersion of up to 56 days, were examined. The renal excretion of potassium and calcium increased, reaching a maximum by the 4-6th weeks in prolonged space flights and simulation studies. During the load tests with potassium and calcium salt, excretion postflight was much higher than preflight. During potassium chloride load tests a positive correlation between the blood content of aldosterone and potassium excretion existed, whereas during calcium lactate load tests an increased calcium excretion was accompanied by a decrease in blood parathyroid hormone concentration. The most probable cause of the negative ion balance in weightlessness is the reduced capacity of tissues to retain electrolytes due to the decreased ion pool capacity. Different exercises have been shown to exert a beneficial effect on electrolyte metabolism.

  7. Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people.

    PubMed

    Arbon, Emma L; Knurowska, Malgorzata; Dijk, Derk-Jan

    2015-07-01

    Current pharmacological treatments for insomnia include benzodiazepine and non-benzodiazepine hypnotics targeting γ-aminobutyric acid (GABA)A receptors, as well as agonists of the melatonin receptors MT1 and MT2. Melatonin, temazepam and zolpidem are thought to exert their effect through different mechanisms of action, but whether this leads to differential effects on electroencephalogram (EEG) power spectra during sleep in middle-aged people is currently not known. To establish whether the effects of prolonged-release melatonin (2 mg) on the nocturnal sleep EEG are different to those of temazepam (20 mg) and zolpidem (10 mg). Sixteen healthy men and women aged 55-64 years participated in a double-blind, placebo-controlled, four-way cross-over trial. Nocturnal sleep was assessed with polysomnography and spectral analysis of the EEG. The effects of single oral doses of prolonged-release melatonin, temazepam and zolpidem on EEG slow-wave activity (SWA, 0.75-4.5 Hz) and other frequencies during nocturnal non-rapid eye movement (NREM) sleep were compared. In an entire night analysis prolonged-release melatonin did not affect SWA, whereas temazepam and zolpidem significantly reduced SWA compared with placebo. Temazepam significantly reduced SWA compared with prolonged-release melatonin. Prolonged-release melatonin only reduced SWA during the first third of the night compared with placebo. These data show that the effects of prolonged-release melatonin on the nocturnal sleep EEG are minor and are different from those of temazepam and zolpidem; this is likely due to the different mechanisms of action of the medications.

  8. Arsenic in an Alkaline AMD Treatment Sludge: Characterization and Stability Under Prolonged Anoxic Conditions

    SciTech Connect

    Beauchemin, S.; Fiset, J; Poirier, G; Ablett, J

    2010-01-01

    Lime treatment of acid mine drainage (AMD) generates large volumes of neutralization sludge that are often stored under water covers. The sludge consists mainly of calcite, gypsum and a widespread ferrihydrite-like Fe phase with several associated species of metal(loid) contaminants. The long-term stability of metal(loid)s in this chemically ill-defined material remains unknown. In this study, the stability and speciation of As in AMD sludge subjected to prolonged anoxic conditions is determined. The total As concentration in the sludge is 300 mg kg{sup -1}. In the laboratory, three distinct water cover treatments were imposed on the sludge to induce different redox conditions (100%N{sub 2}, 100%N{sub 2} + glucose, 95%N{sub 2}:5%H{sub 2}). These treatments were compared against a control of oxidized, water-saturated sludge. Electron micro-probe (EMP) analysis and spatially resolved synchrotron X-ray fluorescence (SXRF) results indicate that As is dominantly associated with Fe in the sludge. In all treatments and throughout the experiment, measured concentrations of dissolved As were less than 5 {micro}g L{sup -1}. Dissolved Mn concentration in the N{sub 2} + glucose treatment increased significantly compared to other treatments. Manganese and As K-edge X-ray absorption near edge structure spectroscopy (XANES) analyses showed that Mn was the redox-active element in the solid-phase, while As was stable. Arsenic(V) was still the dominant species in all water-covered sludges after 9 months of anoxic treatments. In contrast, Mn(IV) in the original sludge was partially reduced into Mn(II) in all water-covered sludges. The effect was most pronounced in the N{sub 2} + glucose treatment, suggesting microbial reduction. Micro-scale SXRF and XANES analysis of the treated sludge showed that Mn(II) accumulated in areas already enriched in Fe and As. Overall, the study shows that AMD sludges remain stable under prolonged anoxic conditions. External sources of chemical reductants

  9. Physiological responses of Bos taurus and Bos indicus cattle to prolonged, continuous heat and humidity.

    PubMed

    Beatty, D T; Barnes, A; Taylor, E; Pethick, D; McCarthy, M; Maloney, S K

    2006-04-01

    Two experiments were conducted to investigate the physiological responses of Bos taurus (Angus cross, n = 6) and Bos indicus (Brahman, n = 6) cattle to prolonged heat and humidity, as can occur during live export by sea. Each experiment was carried out in climate-controlled rooms, where heifers were exposed to 15 d of sustained heat and humidity. The treatment was designed to be representative of a long-haul, live-export voyage leaving a southern Australian winter and traveling to a Middle Eastern summer. Wet bulb temperature (WBT) was used to give a combined measure of dry bulb temperature and relative humidity and was increased over several days, culminating in 5 d at 32 degrees C WBT between d 7 and 11. By d 11, the respiratory rate and core body temperature increased (P < 0.001) compared with values at lower ambient temperature on d 1 and 2 when climate-controlled rooms were not operating. Feed intake of Bos taurus was reduced (P < 0.001) by d 11, whereas that of Bos indicus did not change (P = 0.14). Despite no diurnal variation in climatic conditions, core body temperature of both Bos taurus and Bos indicus continued to show a circadian amplitude of approximately 1 degrees C throughout the hottest period. This amplitude increased during the recovery period after heat was removed (up to 1.8 degrees C for Bos indicus and 1.6 degrees C for Bos taurus). Water intake for both Bos taurus and Bos indicus increased when WBT increased (P < 0.01 on d 11). Significant acid-base and blood electrolyte imbalances occurred in both Bos taurus and Bos indicus, with changes in Bos taurus being more substantial and prolonged. The increase in respiratory rate coincided with a decrease in the partial pressures of carbon dioxide and bicarbonate in venous blood. However, during the hottest period, average daily venous blood pH remained unchanged. When the heat load was reduced after d 11, the blood pH decreased, indicating metabolic acidosis. Blood pH declined from 7.44 to 7.36 for

  10. Impact of Prolonged Sitting on Lower and Upper Limb Micro- and Macrovascular Dilator Function

    PubMed Central

    Restaino, Robert M.; Holwerda, Seth W.; Credeur, Daniel P.; Fadel, Paul J.; Padilla, Jaume

    2016-01-01

    Sedentary behavior in the workplace and increased daily sitting time are on the rise; however, studies investigating the impact of sitting on vascular function remain limited. Herein we hypothesized that 6 hours of uninterrupted sitting would impair limb micro- and macrovascular dilator function and this impairment could be improved with a bout of walking. Resting blood flow, reactive hyperemia to 5 min cuff occlusion (microvascular reactivity) and associated FMD (macrovascular reactivity) were assessed in popliteal and brachial arteries of young men at baseline (Pre Sit) and after 6 hours of uninterrupted sitting (Post Sit). Measures were then repeated after a 10 min walk (~1000 steps). Sitting resulted in a marked reduction of resting popliteal artery mean blood flow and mean shear rate (6-hr mean shear rate, −52±8 s−1 vs. Pre Sit, p<0.05). Interestingly, reductions were also found in the brachial artery (6-hr mean shear rate, −169±41 s−1 vs. Pre Sit, p<0.05). Likewise, following 6 hours of sitting, cuff-induced reactive hyperemia was reduced in both the lower leg (−43±7% vs. Pre Sit, p<0.05) and forearm (−31±11% vs. Pre Sit, p<0.05). In contrast, popliteal, but not brachial, artery FMD was blunted with sitting. Notably, lower leg reactive hyperemia and FMD were restored after walking. Collectively, these data suggest that prolonged sitting markedly reduces lower leg micro- and macrovascular dilator function but these impairments can be fully normalized with a short bout of walking. In contrast, upper arm microvascular reactivity is selectively impaired with prolonged sitting and walking does not influence this effect. PMID:25929229

  11. Cigarette smoking following a prolonged mental task exaggerates vasoconstriction in glabrous skin in habitual smokers.

    PubMed

    Uehara, Kouhei; Sone, Ryoko; Yamazaki, Fumio

    2010-12-01

    In the present study, to test the hypothesis that cigarette smoking and physical exercise induce different influences on peripheral vasomotor control after mental stress, we examined the physiological responses, including skin vasomotor responses, to smoking and exercise in six healthy smokers. The smokers performed 2 hr of mental arithmetic tasks (MT) followed by smoking or bicycle exercise (108 +/- 7W) for 10 min or a time control (i.e., rest without smoking) under thermally comfortable conditions (25 degrees C). Skin blood flow (laser-Doppler flowmetry) was monitored at glabrous (palm) and nonglabrous (forearm, forehead) sites. Cutaneous vascular conductance (CVC) was evaluated from the ratio of blood flow to mean arterial pressure (MAP). The prolonged MT increased MAP from 77.7 +/- 2.7 mmHg to 86.0 +/- 3.0 mmHg and reduced CVC in the palm by 27.4 +/- 5.6%, but did not change those in the forearm and forehead. Smoking after MT further decreased CVC in the palm, and the smoking-induced reduction in CVC persisted until 20 min after smoking. Meanwhile, CVC in the forearm and forehead transiently and minimally decreased during smoking. Exercise after MT increased CVC at the three sites, and the exercise-induced elevation of CVC in the palm persisted until 30 min after exercise. In the time control experiments, each variable remained unchanged throughout the recovery period of MT. It was suggested that smoking causes additional vasoconstriction in glabrous skin after prolonged MT, while the exercise-associated vasodilator effect counteracts the vasoconstrictor action of MT. We speculate that long-term mental stress and smoking behavior may synergistically develop chronic stress-induced vascular dysfunction, and the stress-related disorders may be reduced by habitual enforcement of moderate exercise.

  12. Caffeine effects on short-term performance during prolonged exercise in the heat.

    PubMed

    Del Coso, Juan; Estevez, Emma; Mora-Rodriguez, Ricardo

    2008-04-01

    To determine the effect of water, carbohydrate, and caffeine ingestion on fatigue during prolonged exercise in the heat. Seven endurance-trained cyclists (V O2max = 61 +/- 8 mL.kg.min) pedaled for 120 min at 63% V O2max in a hot-dry environment (36 degrees C; 29% humidity), ingesting either no fluid (NF), water (WAT) to replace 97% fluid losses, the same volume of a 6% carbohydrate-electrolyte solution (CES), or each of these treatments along with ingestion of 6 mg of caffeine per kilogram of body weight (NF + CAFF, WAT + CAFF, and CES + CAFF). At regular intervals during exercise, maximal cycling power (PMAX) was measured. Before and after exercise, maximal voluntary contraction (MVC), voluntary activation (VA), and electrically evoked contractile properties of the quadriceps were determined. Without fluid replacement (NF and NF + CAFF), subjects were dehydrated by 3.8 +/- 0.3%, and rectal temperature reached 39.4 +/- 0.3 degrees C, while it was maintained at 38.7 +/- 0.3 degrees C in trials with rehydration (P < 0.05). Trials with caffeine ingestion increased PMAX by 3% above trials without caffeine (P < 0.05). MVC reductions after exercise were larger with NF (-11 +/- 5%) than for the rest of the trials (P < 0.05). MVC was reduced in WAT compared with CES + CAFF (-6 +/- 4 vs 2 +/- 4%; P < 0.05). However, NF + CAFF maintained MVC at the level of the CES trial. VA showed the same treatment response pattern as MVC. There were no differences in electrically evoked contractile properties among trials. During prolonged exercise in the heat, caffeine ingestion (6 mg.kg body weight) maintains MVC and increases PMAX despite dehydration and hyperthermia. When combined with water and carbohydrate, caffeine ingestion increases maximal leg force by increasing VA (i.e., reducing central fatigue).

  13. Interaction of hyperthermia and heart rate on stroke volume during prolonged exercise.

    PubMed

    Trinity, Joel D; Pahnke, Matthew D; Lee, Joshua F; Coyle, Edward F

    2010-09-01

    People who become hyperthermic during exercise display large increases in heart rate (HR) and reductions in stroke volume (SV). It is not clear if the reduction in SV is due primarily to hyperthermia or if it is a secondary effect of an elevation in HR reducing ventricular filling. In the present study, the upward drift of HR during prolonged exercise was prevented by a very small dose of the β1-adrenoreceptor blocker (atenolol; βB), thus allowing SV to be compared at a given HR during normothermia and hyperthermia. Eleven men cycled for 60 min at 57% of peak O2 uptake after receiving placebo control (PL) or a low dose (0.2 mg/kg) of βB. Hyperthermia was induced by reducing heat dissipation during exercise. Four experimental conditions were studied: normothermia-PL, normothermia-βB, hyperthermia-PL, and hyperthermia-βB. Hyperthermia increased skin and core temperature by 4.3 degrees C and 0.8 degrees C (P<0.01), respectively. βB prevented HR elevation with hyperthermia: HR values were similar at minute 60 during normothermia-PL and hyperthermia-βB (155±11 and 154±13 beats/min, respectively, P=0.82). However, SV was increased by 7% during the final 20 min of exercise during hyperthermia-βB compared with normothermia-PL (treatment×time interaction, P=0.03). In conclusion, when matched for HR, mild hyperthermia increased SV during exercise. Furthermore, the reduction in SV throughout prolonged exercise under normothermic and mildly hyperthermic conditions appears to be due to the increase in HR.

  14. Outcomes and predictors of prolonged ventilation in patients undergoing elective coronary surgery†

    PubMed Central

    Saleh, Hesham Z.; Shaw, Matthew; Al-Rawi, Omar; Yates, Jonathan; Pullan, D. Mark; Chalmers, John A.C.; Fabri, Brian M.

    2012-01-01

    OBJECTIVES Despite the seriousness of prolonged mechanical ventilation (PMV) as a postoperative complication, previously proposed risk prediction models were met with limited success. The purpose of this study was to identify perioperative variables associated with PMV in elective primary coronary bypass surgery. PMV was defined as the need for intubation and mechanical ventilation for >72 h, after completion of the operation. METHODS Between April 1997 and September 2010, 10 977 consecutive patients were retrospectively reviewed. A series of two multivariate logistic regression analyses were carried out to identify preoperative predictors of prolonged ventilation and the impact of operative variables. RESULTS PMV occurred in 215 (1.96%) patients; 119 (55.3%) of these underwent tracheostomy. At multivariate analysis, predictors included NYHA higher than class II (odds ratio [OR], 1.77; 95% confidence intervals [CI], 1.34–2.34), renal dialysis (OR, 5.5; 95% CI, 2.08–14.65), age at operation (OR, 1.04; 95% CI, 1.02–1.06), reduced FEV1 (OR, 0.99; 95% CI, 0.98–0.99), body mass index >35 kg/m2 (OR, 1.73; 95% CI, 1.14–2.63). On serial logistic regression analyses, operative variables added little to the discriminatory power of the model. Kaplan–Meier survival curves showed reduced survival among PMV patients (P < 0.001) with an improved survival in the tracheostomy subgroup. CONCLUSIONS PMV after coronary bypass is associated with a reduction in early and mid-term survival. Risk modelling for PMV remains problematic even when examining a more homogenous lower risk group. PMID:22495507

  15. Risk factors for obstetric anal sphincter injury: To prolong or to vacuum?

    PubMed

    Garmi, Gali; Peretz, Hadar; Braverman, Meirav; Berkovich, Ilanit; Molnar, Robert; Salim, Raed

    2016-03-01

    An awareness of risk factors for obstetric anal sphincter injuries (OASIS) is essential in order to reduce the occurrence of the primary event. These risk factors are demographic, obstetric and intrapartum related. We aimed to identify the risk factors for OASIS and to examine how modifiable risk factors may be used in order to reduce the incidence of OASIS. A retrospective, matched case-control study was conducted in the delivery ward of a single university teaching hospital in Israel, using data from January 2004 to July 2012. All singleton vaginal deliveries at term with OASIS were included. The controls included women matched at a ratio of 1:2 based on gestational age and deliveries that occurred immediately before and after the delivery of the women in the study group. Overall, 113 OASIS were identified. Stepwise conditional logistic regression revealed that the first vaginal birth (OR = 7.6; 95% confidence interval (CI), 3.5-16.3; p < 0.001) particularly after a previous caesarean section (OR = 13.6; 95% CI, 4.7-39.3; p < 0.001) and the length of the second stage (OR 1.5; 95% CI, 1.1-2.1, p = 0.045) were the only risk factors for OASIS. Among 24 primiparous women who already had a prolonged second stage, 15 delivered by vacuum extraction and nine spontaneously; OASIS occurred in eight (53%) and three (33%) women, respectively. Multivariate analysis showed that this difference was not significant (OR = 2.3; 95% CI, 0.4-12.7; p = 0.35). The first vaginal birth particularly after a caesarean delivery and the length of the second stage increased the risk of OASIS. Vacuum extraction performed to shorten a prolonged second stage is not necessarily protective. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Reversal of Prolonged Dopamine Inhibition of Dopaminergic Neurons of the Ventral Tegmental Area

    PubMed Central

    Nimitvilai, Sudarat

    2010-01-01

    Drug abuse-induced plasticity of putative dopaminergic (pDAergic) ventral tegmental area (VTA) neurons may play an important role in changes in the mesocorticolimbic system that lead to the development of addiction. In the present study, extracellular recordings were used to examine time-dependent effects of dopamine (DA) on pDAergic VTA neurons in rat brain slices. Administration of DA (2.5–10 μM) for 40 min resulted in inhibition followed by partial or full reversal of that inhibition. The reduced sensitivity to DA inhibition lasted 30 to 90 min after washout of the long-term dopamine administration. The inhibition reversal was not observed with 40-min administration of the D2 agonist quinpirole (25–200 nM), so this phenomenon was not the result of desensitization induced solely by stimulation of D2 DA receptors. Inhibition reversal could be observed with the coapplication of quinpirole and the D1/D5 agonist SKF38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide], suggesting a D1/D5 mechanism for the reversal. Furthermore, D1/D5 antagonists, given in the presence of prolonged DA exposure, prevented the inhibition reversal. Application of 3 μM quinpirole caused desensitization to low quinpirole concentrations that was blocked by a D1/D5 antagonist. These data suggest that coactivation of D1/D5 receptors and D2 receptors in the VTA results in desensitization of autoinhibitory D2 receptors. Prolonged increases in pDAergic tone in the VTA that may occur in vivo with drugs of abuse could reduce the regulation of firing by D2 dopamine receptor activation, producing long-term alteration in information processing related to reward and reinforcement. PMID:20164301

  17. Prolonged mechanical ventilation after CABG: risk factor analysis.

    PubMed

    Gumus, Funda; Polat, Adil; Yektas, Abdulkadir; Totoz, Tolga; Bagci, Murat; Erentug, Vedat; Alagol, Aysin

    2015-02-01

    Prolonged ventilation (PV) after coronary artery bypass graft (CABG) surgery is a common postoperative complication. Preoperative and operative parameters were evaluated in order to identify the patients at risk for prolonged ventilation postoperatively in coronary artery bypass graft (CABG) patients. Retrospective. Research and training hospital, single institution. The authors analyzed the prospectively collected data of 830 on- and off-pump coronary bypass patients. The relationships of PV (>24 hours) with preoperative and operative parameters were evaluated with logistic regression analysis. Forty-six patients (5.6%) required PV postoperatively. Hospital mortality was significantly higher in this group (45.7% v 4.0%; p = 0.0001). Univariate analysis showed that these patients were older (65.6±9.3 v 60.4±9.9; p = 0.001), had higher incidences of cerebrovascular disease (21.7% v 10.5%; p = 0.032), advanced ASA (58.7% v 41.8%; p = 0.026) and NYHA classes (32.6% v 12.2%; p = 0.001), and chronic renal dysfunction (20.0% v 4.0%; p = 0.0001). Concomitant procedures were more commonly performed in these patients (30.4% v 7.8%; p = 0.0001), and total durations of perfusion were longer (147.2±69.1 v 95.7±33.9 minutes; p = 0.0001). In regression analysis, advanced NYHA class (odds ratio = 8.2; 95% CI = 1.5-43.5; p = 0.015), chronic renal dysfunction (odds ratio = 7.7; 95% CI = 1.3-47.6; p = 0.027), and longer perfusion durations (p = 0.012) were found to be independently associated with delayed weaning from the ventilator. Every 1-minute increase over 82.5 minutes of cardiopulmonary bypass increased risk of delayed extubation by 3.5% (95% CI = 0.8%-6.4%). Postoperative prolonged ventilation is associated with advanced NYHA class, chronic renal dysfunction and longer perfusion times in CABG patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The impact of obesity on physiological responses during prolonged exercise.

    PubMed

    Eijsvogels, T M H; Veltmeijer, M T W; Schreuder, T H A; Poelkens, F; Thijssen, D H J; Hopman, M T E

    2011-11-01

    Prolonged, moderate-intensity exercise training is routinely prescribed to subjects with obesity. In the general population, this type of exercise can lead to fluid and sodium imbalance. However, little is known whether obesity alters the risk of fluid and sodium imbalances. This study examined physiological responses, such as core body temperature, fluid and sodium balance, in lean (BMI<25), overweight (2530) subjects during prolonged moderate-intensity exercise. A total of 93 volunteers (24-80 years), stratified for BMI, participated in the Nijmegen Marches and walked 30-50 km at a self-selected pace. Heart rate and core body temperature were recorded every 5 km. Subjects reported fluid intake, while urine output was measured and sweat rate was calculated. Baseline and post-exercise plasma sodium levels were determined, and urinary specific gravity levels were assessed before and after exercise. BMI groups did not differ in training status preceding the experiment. Exercise duration (8 h 41 ± 1 h 36 min) and intensity (72 ± 9% HR(max)) were comparable across groups, whereas obese subjects tended to have a higher maximum core body temperature than lean controls (P=0.06). Obese subjects demonstrated a significantly higher fluid intake (P<0.001) and sweat rate (P<0.001), but lower urine output (P<0.05) compared with lean subjects. In addition, higher urine specific gravity levels were observed in obese versus lean subjects after exercise (P<0.05). Furthermore, plasma-sodium concentration did not change in lean subjects after exercise, whereas plasma-sodium levels increased significantly (P<0.001) in overweight and obese subjects. Also, overweight and obese subjects demonstrated a significantly larger decrease in body mass after exercise than lean controls (P<0.05). Obese subjects demonstrate a larger deviation in markers of fluid and sodium balance than their lean counterparts during prolonged moderate-intensity exercise. These findings

  19. Prolonged Temozolomide Maintenance Therapy in Newly Diagnosed Glioblastoma.

    PubMed

    Skardelly, Marco; Dangel, Elena; Gohde, Julia; Noell, Susan; Behling, Felix; Lepski, Guilherme; Borchers, Christian; Koch, Marilin; Schittenhelm, Jens; Bisdas, Sotirios; Naumann, Aline; Paulsen, Frank; Zips, Daniel; von Hehn, Ulrike; Ritz, Rainer; Tatagiba, Marcos Soares; Tabatabai, Ghazaleh

    2017-05-01

    The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS). In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded. Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, p = .46). Our data do not support a general extension of TMZ maintenance therapy beyond six cycles. The Oncologist 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in

  20. Reducing Dropouts.

    ERIC Educational Resources Information Center

    Timpane, Michael; And Others

    A group of three conference papers, all addressing the subject of effective programs to decrease the number of school dropouts, is presented in this document. The first paper, "Systemic Approaches to Reducing Dropouts" (Michael Timpane), asserts that dropping out is a symptom of failures in the social, economic, and educational systems.…

  1. The biological effect of prolonged radiation and ways of selecting new anti-radiation drugs effective in this kind of radiation injury

    NASA Technical Reports Server (NTRS)

    Rogozkin, V. D.; Chertkov, K. S.; Nikolov, I.

    1974-01-01

    The basic characteristics of prolonged radiation - increased tolerance of radiation injury - are attributed to cellular kinetics; as dose rate is reduced, the population rate is not disturbed, particularly that of stem cells which makes it possible for the organism to tolerate higher radiation loads. It is concluded that this effect makes approved radio protectors, whose effect contains an established cytostatic component, unsuitable for prolonged radiation. It is better to correct the stem pool formation process by either accelerating the proliferation of cells or limiting the effect of stimuli causing cells to lose colony forming properties.

  2. The biological effect of prolonged radiation and ways of selecting new anti-radiation drugs effective in this kind of radiation injury

    NASA Technical Reports Server (NTRS)

    Rogozkin, V. D.; Chertkov, K. S.; Nikolov, I.

    1974-01-01

    The basic characteristics of prolonged radiation - increased tolerance of radiation injury - are attributed to cellular kinetics; as dose rate is reduced, the population rate is not disturbed, particularly that of stem cells which makes it possible for the organism to tolerate higher radiation loads. It is concluded that this effect makes approved radio protectors, whose effect contains an established cytostatic component, unsuitable for prolonged radiation. It is better to correct the stem pool formation process by either accelerating the proliferation of cells or limiting the effect of stimuli causing cells to lose colony forming properties.

  3. Effect of prolonged use of altrenogest on behaviour in mares.

    PubMed

    Hodgson, David; Howe, Stephanie; Jeffcott, Leo; Reid, Stuart; Mellor, Dominic; Higgins, Andrew

    2005-01-01

    Oral administration of altrenogest for oestrus suppression in competition horses is believed to be widespread in some equestrian disciplines, and can be administered continuously for several months during a competition season. To examine whether altrenogest has any anabolic or other potential performance enhancing properties that may give a horse an unfair advantage, we examined the effect of oral altrenogest (0.044 mg/kg), given daily for a period of eight weeks, on social hierarchy, activity budget, body-mass and body condition score of 12 sedentary mares. We concluded that prolonged oral administration of altrenogest at recommended dose rates to sedentary mares resulted in no effect on dominance hierarchies, body mass or condition score.

  4. Effect of prolonged use of altrenogest on behaviour in mares.

    PubMed

    Hodgson, David; Howe, Stephanie; Jeffcott, Leo; Reid, Stuart; Mellor, Dominic; Higgins, Andrew

    2005-05-01

    Oral administration of altrenogest for oestrus suppression in competition horses is believed to be widespread in some equestrian disciplines, and can be administered continuously for several months during a competition season. To examine whether altrenogest has any anabolic or other potential performance enhancing properties that may give a horse an unfair advantage, we examined the effect of oral altrenogest (0.044 mg/kg), given daily for a period of eight weeks, on social hierarchy, activity budget, body-mass and body condition score of 12 sedentary mares. It was concluded that prolonged oral administration of altrenogest at recommended dose rate to sedentary mares had no effect on dominance hierarchies, body-mass or condition score.

  5. Prolonged intensive dominance behavior between gray wolves, Canis lupus

    USGS Publications Warehouse

    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.

  6. Apparent life-threatening prolonged infant apnea in Saskatchewan.

    PubMed Central

    Sunkaran, K; McKenna, A; O'Donnell, M; Ninan, A; Kasian, G; Skwarchuk, J; Bingham, W T

    1989-01-01

    Life-threatening events such as prolonged apnea and severe bradycardia are uncommon in infants. When such events occur in a family, however, the results may be disastrous. Over a period of 3 years ending June 1986, we have looked after 111 such infants aged 4 weeks to 40 weeks with a mean age of 14 weeks (male-female ratio 1.26:1). Of these infants, 33 had an identifiable cause and were treated according to the diagnoses. A structural approach to this problem yielded good results. Only 10 infants were treated with a home monitor (4 prescribed by physician and 6 by parental request). Sleep and pneumogram (polysomnogram) studies showed fewer apneic episodes with advancing age (P less than .01). Giving theophylline seemed to abolish pneumogram abnormalities. No infants died. PMID:2735034

  7. Elevated rates of prolonged grief disorder in African Americans.

    PubMed

    Goldsmith, B; Morrison, R S; Vanderwerker, L C; Prigerson, H G

    2008-01-01