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Shi X.,Physical Medicine and Rehabilitation Service | Shi X.,Stanford University | Wang L.,Physical Medicine and Rehabilitation Service | Clark J.D.,Anesthesiology Service | And 2 more authors.
Regulatory Peptides | Year: 2013

Sensory neurons innervating the skin can release neuropeptides that are believed to modulate cellular proliferation, wound healing, pigmentation, and keratinocyte innate immune responses. While the ability of neuropeptides to stimulate keratinocyte production of inflammatory mediators has been demonstrated, there is no information concerning the mechanisms by which neuropeptide activation of keratinocyte cell surface receptors ultimately leads to the up-regulation of mediator production. In this study we used a keratinocyte cell line to identify the presence of substance P (SP) and calcitonin gene-related peptide (CGRP) receptors on keratinocytes and examined the effects of SP and CGRP stimulation on keratinocyte neuropeptide signaling, cell proliferation, and interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and nerve growth factor (NGF) expression. Neuropeptide stimulation caused an up-regulation of neuropeptide receptor expression in keratinocytes and a dramatic increase in keratinocyte secretion of SP and CGRP, suggesting possible autocrine or paracrine stimulatory effects and amplification of neuropeptide signaling. Both SP and CGRP concentration-dependently stimulated cellular proliferation and the expression and secretion of inflammatory cytokines and NGF in keratinocytes. SP also activated all 3 families of mitogen activated protein kinase (MAPK) and nuclear factor κB (NFκB) in keratinocytes, while CGRP only activated p38 and extracellular signal related kinase1/2 (ERK1/2) MAPKs. Neuropeptide stimulated inflammatory mediatory production in keratinocytes was reversed by ERK1/2 and JNK inhibitors. The current study is the first to observe; 1) that CGRP stimulates keratinocyte expression of CGRP and its receptor complex, 2) that SP and CGRP stimulate IL-6 and TNF-α secretion in keratinocytes, 3) that SP activated all three MAPK families and the NFκB transcriptional signaling pathway in keratinocytes, and 4) that SP and CGRP stimulated inflammatory mediator production in keratinocytes is dependent on ERK1/2 and JNK activation. These studies provide evidence suggesting that disruption of ERK1/2 and JNK signaling may potentially be an effective therapy for inflammatory skin diseases and pain syndromes mediated by exaggerated sensory neuron-keratinocyte signaling. © 2013. Source


Hastings R.H.,Anesthesiology Service | Rickard T.C.,University of California at San Diego
Anesthesia and Analgesia | Year: 2015

For the dedicated anesthesiologist, a high level of expertise is needed to deliver good care to patients and to provide excellent service to surgeons, anesthesia colleagues, and others. Expertise helps the anesthesiologist recover from difficult situations and generally makes the practice run more effectively. Expertise also contributes to quality of life through higher self-esteem and long-term career satisfaction. We begin by reviewing the attributes that characterize expert performance and discussing how a specific training format, known as deliberate practice, contributes to acquisition and maintenance of expertise. Deliberate practice involves rehearsal of specific tasks to mastery, ideally under the eye of a mentor to provide feedback. This amounts to an orchestrated effort to improve that enables trainees to progress to expert levels of performance. With few exceptions, people who become recognized experts have pursued deliberate practice on the order of 4 hours per day for 10 to 15 years. In contrast, those who practice their profession in a rote manner see their skills plateau well below the level of top performers. Anesthesiology instruction with attending supervision provides all of the necessary components for deliberate practice, and it can be effective in anesthesia. Using deliberate practice in teaching requires organization in selecting training topics, effort in challenging students to excel, and skill in providing feedback. In this article, we discuss how educational programs can implement deliberate practice in anesthesiology training, review resources for instructors, and suggest how anesthesiologists can continue the practice after residency. Source


Dueck R.,Anesthesiology Service | Dueck R.,University of California at San Diego | Goedje O.,University of Ulm | Clopton P.,Research Service
Journal of Clinical Monitoring and Computing | Year: 2012

The Tensys TL-200® noninvasive beat-to-beat blood pressure (BP) monitor displays continuous radial artery waveform as well as systolic, mean and diastolic BP from a pressure sensor directly over the radial artery at the wrist. It locates the site of maximal radial pulse signal, determines mean BP from maximal pulse waveform amplitude at optimal artery compression and then derives systolic and diastolic BP. We performed a cross-sectional study of TL-200 BP comparisons with contralateral invasive radial artery (A-Line) BP values in 19 subjects during an average 2.5 h of general anesthesia for a wide range of surgical procedures. Two hundred and fifty random sample pairs/patient resulted in 4,747 systolic, mean and diastolic BP pairs for analysis. A-Line BP ranged from 29 mm Hg diastolic to 211 mmHg systolic, and heart rate varied between 38 and 210 beats/min. Bland-Altman analysis showed an average 2.3 mm Hg TL-200 versus A-Line systolic BP bias and limits of agreement (1.96 SD) were ± 15.3 mm Hg. Mean BP showed a 2.3 mm Hg TL-200 bias and ± 11.7 mm Hg limits of agreement, while diastolic BP showed a 1.7 mm Hg bias and ± 12.3 mm Hg limits of agreement. Coefficients of determination for TL-200 and A-Line BP regression were r 2 = 0.86 for systolic, r 2 = 0.86 for mean, and r 2 = 80 for diastolic BP, respectively, with no apparent change in correlation at low or high BP. Bland-Altman analysis suggested satisfactory agreement between TL-200 noninvasive beat-to-beat BP and invasive A-Line BP. Paired TL-200/A-Line BP comparisons showed a high coefficient of determination. © Springer Science+Business Media, LLC 2012. Source


Gelinas C.,McGill University | Gelinas C.,Lady Davis Institute for Medical Research | Puntillo K.,University of California at San Francisco | Joffe A.,University of Washington | And 2 more authors.
Seminars in Respiratory and Critical Care Medicine | Year: 2013

A valid pain assessment is the foundation of adequate pain management. Pain assessment can be challenging, especially in adult intensive care unit (ICU) patients who are unable to self-report. In such situations, relying on observational assessment tools is an alternative strategy. This review describes and analyzes the development and psychometric properties of pain assessment tools developed for use with nonverbal critically ill adults. A total of 32 relevant papers that described the psychometric properties of eight pain assessment tools were included. The scale development process, psychometric properties (i.e., reliability and validity), and feasibility of pain assessment tools were analyzed using a 0 to 20 scoring system. Each pain assessment tool was scored independently by two reviewers. Of the eight behavioral pain scales developed for use in adult ICU patients, the Behavioral Pain Scale (BPS) and the Critical-Care Pain Observation Tool (CPOT) are considered to be the most valid and reliable for this purpose, according to the available evidence. Behavioral pain scales may be viable alternatives to assessing pain in ICU patients who are unable to self-report, but only valid, reliable, and feasible scales should be used for this purpose. © 2013 by Thieme Medical Publishers, Inc. Source


Saugel B.,University of Hamburg | Dueck R.,Anesthesiology Service | Wagner J.Y.,University of California at San Diego
Best Practice and Research: Clinical Anaesthesiology | Year: 2014

Blood pressure is overwhelmingly the most commonly measured parameter for the assessment of haemodynamic stability. In clinical routine in the operating theatre and in the intensive care unit, blood pressure measurements are usually obtained intermittently and non-invasively using oscillometry (upper-arm cuff method) orcontinuously and invasively with an arterial catheter. However, both the oscillometric method and arterial catheter-derived blood pressure measurements have potential limitations. A basic technical understanding of these methods is crucial in order to avoid unreliable blood pressure measurements and consequential treatment errors. In the recent years, technologies for continuous non-invasive blood pressure recording such as the volume clamp method or radial artery applanation tonometry have been developed and validated. The question in which patient groups and clinical settings these technologies should be applied to improve patient safety or outcome has not been definitively answered. In critically ill patients and high-risk surgery patients, further improvement of these technologies is needed before they can be recommended for routine clinical use. © 2014 Elsevier Ltd. All rights reserved. Source

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