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Search Results: 1 - 10 of 225448 matches for " Lynn R Webster "
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Effects of concurrent intravenous morphine sulfate and naltrexone hydrochloride on end-tidal carbon dioxide
Veeraindar Goli, Lynn R Webster, Michael J Lamson, Jody M Cleveland, Kenneth W Sommerville, Eric Carter
Harm Reduction Journal , 2012, DOI: 10.1186/1477-7517-9-13
Abstract: Single-center, placebo-controlled, double-blind crossover study. Non-dependent male opioid users were randomized to receive single IV doses of placebo, 30 mg morphine alone, and 30 mg morphine + 1.2 mg naltrexone. EtCO2 was measured by noninvasive capnography.Significant differences in EtCO2 least-squares means across all treatments for maximal effect (Emax) and area under the effect curve (AUE0-2, AUE0-8, AUE0-24) were detected (all p ≤ 0.0011). EtCO2 Emax values for morphine + naltrexone were significantly reduced vs morphine alone (42.9 mm Hg vs 47.1 mm Hg, p < 0.0001) and were not significantly different vs placebo (41.9 mm Hg). Median time to reach maximal effect (TEmax) was delayed for morphine + naltrexone vs morphine alone (5.0 h vs 1.0 h).Results provide preliminary evidence that the naltrexone:morphine ratio within MS-sNT is sufficient to significantly reduce EtCO2 when administered intravenously to non-dependent male recreational opioid-users. Further studies with multiple measures of respiratory-function are warranted to determine if risk of respiratory depression is also reduced by naltrexone in the tampered formulation.In the United States in 2007, more than one-third (36%) of all poisoning deaths involved opioid analgesics (drugs usually prescribed to relieve pain) [1]. Since 1999, poisoning deaths in the United States involving opioid analgesics have more than tripled [1,2]; deaths from opioid analgesics have surpassed those from heroin and cocaine [3,4].Although prescription opioids may be formulated for oral use, they are often taken intravenously or intranasally when abused [5,6]. As tolerance to opioid psychoactive effects increases with use over time, the user often progresses from the oral route to the intranasal or intravenous (IV) route to attain greater opioid effects and more rapid onset of action [5,7-10].Respiratory depression is the leading cause of death following opioid overdose [11]. Opioids interact with μ-opioid receptors, reducing
Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia
Lynn R Webster, Marvin Tark, Richard Rauck, Jeffrey K Tobias, Geertrui F Vanhove
BMC Neurology , 2010, DOI: 10.1186/1471-2377-10-92
Abstract: This multicenter, double-blind, controlled study randomized 155 patients 2:1 to receive either NGX-4010 or a 0.04% capsaicin control patch. Patients were at least 18 years old with PHN for at least 3 months, and an average Numeric Pain Rating Scale (NPRS) score of 3 to 9. The primary efficacy endpoint was the percentage change in NPRS score from baseline to weeks 2-8.The mean percent reduction in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 was greater in the NGX-4010 group (36.5%) compared with control (29.9%) although the difference was not significant (p = 0.296). PGIC analysis demonstrated that more NGX-4010 recipients considered themselves improved (much, or very much) compared with control at weeks 8 and 12, but the differences did not reach statistical significance. Post hoc analyses of patients with PHN for at least 6 months showed significantly greater reductions in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 in NGX-4010 patients compared to controls (37.6% versus 23.4%; p = 0.0291). PGIC analysis in this subgroup demonstrated that significantly more NGX-4010 recipients considered themselves much or very much improved compared with control at week 12 (40% versus 20%; p = 0.0403;).Although treatment appeared to be safe and well tolerated, a single 60-minute application of NGX-4010 failed to show efficacy in this study which included patients with PHN for less than 6 months. Large reductions in pain observed among control patients with pain for less than 6 months may have been due to spontaneous resolution of PHN, may have confounded the results of the prespecified analyses, and should be taken into account when designing PHN studies.NCT00068081Postherpetic neuralgia (PHN) is a painful complication of acute herpes zoster (shingles) that is caused by reactivation of the varicella zoster virus usually contracted in childhood. Acute herpes zoster is often very painful. Usually this pain subsides, but
Tolerability of NGX-4010, a capsaicin 8% dermal patch, following pretreatment with lidocaine 2.5%/prilocaine 2.5% cream in patients with post-herpetic neuralgia
Lynn R Webster, Margarita Nunez, Marvin D Tark, Edwin D Dunteman, Biao Lu, Jeffrey K Tobias, Geertrui F Vanhove
BMC Anesthesiology , 2011, DOI: 10.1186/1471-2253-11-25
Abstract: Twenty-four patients with PHN were pretreated with lidocaine 2.5%/prilocaine 2.5% cream for 60 minutes before receiving a single 60-minute application of NGX-4010. Tolerability was assessed by measuring patch application duration, the proportion of patients completing over 90% of the intended treatment duration, application site-related pain using the Numeric Pain Rating Scale (NPRS), and analgesic medication use to relieve such pain. Safety was assessed by monitoring adverse events (AEs) and dermal irritation using dermal assessment scores.The mean treatment duration of NGX-4010 was 60.2 minutes and all patients completed over 90% of the intended patch application duration. Pain during application was transient. A maximum mean change in NPRS score of +3.0 was observed at 55 minutes post-patch application; pain scores gradually declined to near pre-anesthetic levels (+0.71) within 85 minutes of patch removal. Half of the patients received analgesic medication on the day of treatment; by Day 7, no patients required medication. The most common AEs were application site-related pain, erythema, edema, and pruritus. All patients experienced mild dermal irritation 5 minutes after patch removal, which subsequently decreased; at Day 7, no irritation was evident. The maximum recorded dermal assessment score was 2.NGX-4010 was well tolerated following pretreatment with lidocaine 2.5%/prilocaine 2.5% cream in patients with PHN. The tolerability of the patch application appeared comparable with that seen in other studies that used 4% lidocaine cream as the pretreatment anesthetic. This study is registered at http://www.clinicaltrials.gov webcite as number NCT00916942.Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system [1]. Post-herpetic neuralgia (PHN) is a common type of neuropathic pain occurring as a complication of reactivation of the varicella zoster virus (shingles). PHN is caused by damage to the small-diamet
Retroviral expression of a kinase-defective IGF-I receptor suppresses growth and causes apoptosis of CHO and U87 cells in-vivo
B Lynn Seely, Goli Samimi, Nicholas JG Webster
BMC Cancer , 2002, DOI: 10.1186/1471-2407-2-15
Abstract: Dominant negative IGF-I receptors were expressed in CHO and U87 cells by retroviral infection. Cell proliferation, transformation and tumor formation in athymic nude mice were assessed.Inhibition of IGF-IR signaling in a CHO cell model system by expression of a kinase-defective IGF-IR impairs proliferation, transformation and tumor growth. Reduction in tumor growth is associated with an increase in apoptosis in-vivo. The dominant-negative IGF-IRs also prevented growth of U87 PTEN-negative glioblastoma cells when injected into nude mice. Injection of an IGF-IR blocking antibody αIR3 into mice harboring parental U87 tumors inhibits tumor growth and increases apoptosis.Inhibition of an upstream growth factor signal prevents tumor growth of the U87 PTEN-deficient glioma to the same extent as re-introduction of PTEN. This result suggests that growth factor receptor inhibition may be an effective alternative therapy for PTEN-deficient tumors.Phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) is one of the major intracellular second messengers regulating growth, metabolism and vesicular trafficking [for reviews see refs [1-3]]. The level of (PIP3) in the cell is determined by the balance of kinase and phosphatase activity. PI-3Kinase activity is acutely regulated and a number of isoforms have been cloned that are activated in response to various stimuli [4]. The major phosphatidylinositol-3-phosphate phosphatase in cells is the tumor suppressor PTEN [5,6]. This protein has a tonic inhibitory effect on PI-3Kinase signaling by reversing the 3'-phosphorylation. PTEN is altered or deleted in many human cancers [7-10]. In-vitro, cells that are deficient in PTEN show elevated PI-3Kinase signaling [11]. Reintroduction of PTEN in a variety of cancer cells, including glioma, breast, bladder and ovarian cancer cells, causes G1 arrest, inhibits tumorigenesis, and promotes anoikis [12-14]. Mechanistically, Akt activity is decreased, cell motility is decreased, expression of two cyclin-
2-point Correlation Function of HI-selected Galaxies
S. Tantisrisuk,R. Webster
Physics , 2001,
Abstract: The 2-point spatial correlation function (CF), $\xi(s)$, has been used to study the clustering of the galaxies in the preliminary version of the HIPASS Bright Galaxy Catalogue (HIPASS BGC), which includes the 1,000 HI brightest galaxies in the Southern sky. This is the first time the CF has been used to analyse an HI-selected sample. The CF is well described by a power law, $\xi(s)\sim(s/s_0)^{-\gamma}$, with slope $\gamma\sim1.7$ and correlation length $s_0\sim3.55$ $h^{-1}$ Mpc using Peebles estimator. However, when the Hamilton estimator is used, the CF is fit with $\gamma\sim2.19$ and $s_0\sim3.37$ $h^{-1}$ Mpc. Note that, these HI-selected galaxies show less clustering than optically-selected surveys which have a correlation length $s_0\sim$ 5.5 $h^{-1}$ Mpc or larger.
Predicting numerically the large increases in extra pressure drop when boger fluids flow through  [PDF]
H. R. Tamaddon-Jahromi, M. F. Webster, K. Walters
Natural Science (NS) , 2010, DOI: 10.4236/ns.2010.21001
Abstract: Recent numerical studies on pressure-drops in contraction flows have introduced a variety of constitutive models to compare and contrast the competing influences of extensional vis-cosity, normal stress and shear-thinning. Early work on pressure-drops employed the constant viscosity Oldroyd-B and Upper Convected Max- well (UCM) models to represent the behavior of so-called Boger fluids in axisymmetric contrac-tion flows, in (unsuccessful) attempts to predict the very large enhancements that were ob-served experimentally. In more recent studies, other constitutive models have been employed to interpret observed behavior and some pro-gress has been made, although finding a (re-spectable) model to describe observed contrac-tion-flow behavior, even qualitatively, has been frustratingly difficult. With this in mind, the present study discusses the ability of a well- known FENE type model (the so-called FENE- CR model) to describe observed behavior. For various reasons, an axisymmetric (4:1:4) con-traction/expansion geometry, with rounded corners, is singled out for special attention, and a new hybrid finite element/volume algo-rithm is utilized to conduct the modeling, which reflects an incremental pressure-correction time-stepping structure. New to this algo-rithmic formulation are techniques in time discretization, discrete treatment of pressure terms, and compatible stress/velocity-gradient representation. We shall argue that the current simulations for the FENE-CR model have re-sulted in a major improvement in the sort-for agreement between theory and experiment in this important bench-mark problem.
Herbaceous-Layer Community Dynamics along a Harvest-Intensity Gradient after 50 Years of Consistent Management  [PDF]
Marcella A. Campione, Linda M. Nagel, Christopher R. Webster
Open Journal of Forestry (OJF) , 2012, DOI: 10.4236/ojf.2012.23013
Abstract: In 1958, a demonstrational cutting trial totaling 22.2 ha was established in a northern hardwood forest in Alberta, MI. Eight different treatments were installed, including four diameter-limit treatments (56 cm, 41 cm, 30 cm, and 13 cm), three single-tree selection treatments with residual basal areas of 21 m2·ha–1, 16 m2·ha–1, and 11 m2·ha–1, and an uncut control. Within each treatment, a 0.4-ha permanent plot was established and subdivided into 0.04-ha square subplots. Harvests have been implemented every ten years with the most recent harvest occurring during the winter of 2008 - 2009. We quantified ground layer vegetation response before and after the most recent harvest. Nonmetric multidimensional scaling (NMS) ordination showed a very distinct separation between the most intensive management treatment (13-cm diameter-limit treatment) and the uncut control. Compositionally, the diameter-limit treatments moved with greater directionality and magnitude towards the 13-cm diameter-limit treatment following harvest, while compositional change in the residual basal area treatments was less pronounced and lacked strong directionality. Herbaceous species percent cover generally decreased with increasing residual overstory basal area across treatments. Weedy and early successional species were most abundant under lower residual basal area and diameter-limit treatments. Results based on 50 years of continuous management suggest that diameter-limit harvests likely have a greater impact on the herbaceous community than single-tree selection or no management.
Improved Glucose Metabolism In Vitro and In Vivo by an Allosteric Monoclonal Antibody That Increases Insulin Receptor Binding Affinity
John A. Corbin, Vinay Bhaskar, Ira D. Goldfine, Daniel H. Bedinger, Angela Lau, Kristen Michelson, Lisa M. Gross, Betty A. Maddux, Hua F. Kuan, Catarina Tran, Llewelyn Lao, Masahisa Handa, Susan R. Watson, Ajay J. Narasimha, Shirley Zhu, Raphael Levy, Lynn Webster, Sujeewa D. Wijesuriya, Naichi Liu, Xiaorong Wu, David Chemla-Vogel, Steve R. Lee, Steve Wong, Diane Wilcock, Mark L. White
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088684
Abstract: Previously we reported studies of XMetA, an agonist antibody to the insulin receptor (INSR). We have now utilized phage display to identify XMetS, a novel monoclonal antibody to the INSR. Biophysical studies demonstrated that XMetS bound to the human and mouse INSR with picomolar affinity. Unlike monoclonal antibody XMetA, XMetS alone had little or no agonist effect on the INSR. However, XMetS was a strong positive allosteric modulator of the INSR that increased the binding affinity for insulin nearly 20-fold. XMetS potentiated insulin-stimulated INSR signaling ~15-fold or greater including; autophosphorylation of the INSR, phosphorylation of Akt, a major enzyme in the metabolic pathway, and phosphorylation of Erk, a major enzyme in the growth pathway. The enhanced signaling effects of XMetS were more pronounced with Akt than with Erk. In cultured cells, XMetS also enhanced insulin-stimulated glucose transport. In contrast to its effects on the INSR, XMetS did not potentiate IGF-1 activation of the IGF-1 receptor. We studied the effect of XMetS treatment in two mouse models of insulin resistance and diabetes. The first was the diet induced obesity mouse, a hyperinsulinemic, insulin resistant animal, and the second was the multi-low dose streptozotocin/high-fat diet mouse, an insulinopenic, insulin resistant animal. In both models, XMetS normalized fasting blood glucose levels and glucose tolerance. In concert with its ability to potentiate insulin action at the INSR, XMetS reduced insulin and C-peptide levels in both mouse models. XMetS improved the response to exogenous insulin without causing hypoglycemia. These data indicate that an allosteric monoclonal antibody can be generated that markedly enhances the binding affinity of insulin to the INSR. These data also suggest that an INSR monoclonal antibody with these characteristics may have the potential to both improve glucose metabolism in insulinopenic type 2 diabetes mellitus and correct compensatory hyperinsulinism in insulin resistant conditions.
Implementation of Response to Intervention for English Language Learners
Lynn R. Bailey
Christian Perspectives in Education , 2009,
Abstract: Response to Intervention is utilized to provide parents, teachers, and specialists with the data needed to implement and measure the effectiveness of evidence-based instructional and behavioral strategies matched to student needs. English Language Learners are in particular need of research-based instruction paired with progress monitoring as they seek to meet state standards in a new language. Parents, students, and school personnel all benefit from seeing Christ-like consideration for foreigners modeled through Response to Intervention.
Statistical Analysis with Webstat, a Java applet for the World Wide Web
R. Webster West,R. Todd Ogden
Journal of Statistical Software , 1997,
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