Bio

Clinical Focus


  • Anesthesia
  • Critical Care Medicine
  • Cardiac and Thoracic Anesthesia

Academic Appointments


Professional Education


  • Internship:Santa Clara Valley Medical Center (1996) CA
  • Fellowship:Stanford University School of Medicine (2000) CA
  • Residency:Stanford University School of Medicine (1999) CA
  • Board Certification: Anesthesia, American Board of Anesthesiology (2000)
  • Board Certification: Critical Care Medicine, American Board of Anesthesiology (2001)
  • Medical Education:University of Maryland (1995) MD
  • MD, University of Maryland, Medicine (1995)
  • PhD, University of Maryland, Physiology (1993)

Community and International Work


  • Anesthesia outreach in developing countries, Mexico

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Research & Scholarship

Current Research and Scholarly Interests


1 Critical Care Education

One of my interests centers on the use of patient simulation as an educational and training tool in critical care. The Palo Alto VA is the Mecca of Patient Simulation; high performance simulation and a curriculum on anesthesia crisis management were invented by David Gaba and colleagues in the Department of Anesthesia. As part of the VA ICU rotation, we run monthly classes on Crisis Resource Management in Critical Care in a brand new facility that is a virtual copy of an adult ICU, complete with two computer - controlled patients. Human patient simulation offers an ever-changing laboratory for developing and testing educational methods as well as participating in our current strength - critical care team training. Research projects currently center on implementing a performance assessment tool to evaluate whether classroom instruction improves management of simulated patient emergencies, examination of team communication during simulated emergencies, and assessment of resuscitation quality following a new critical care skills course.

2 Medical Emergency Teams
Medical Emergency Teams (or METs for short) are groups that perform rapid assessment and stabilization of patients in response to signs of clinical deterioration. They have arisen in response to data demonstrating that many opportunities to reverse clinical decline are not acted upon in a time frame that would prevent further deterioration, or progression to cardiac arrest. I have implemented a MET at the VA Palo Alto and am looking at the clinical impact of this intervention; I have also developed programs for team training and technical skill development applicable to MET operation.

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • An institution-wide approach to redesigning management of cardiopulmonary arrests The joint commission journal of patient safety Lighthall, G., Mayette M, Harrison TK 2013; 39 (4): 157-166
  • Introduction of a Rapid Response System at a United States Veterans Affairs Hospital Reduced Cardiac Arrests ANESTHESIA AND ANALGESIA Lighthall, G. K., Parast, L. M., Rapoport, L., Wagner, T. H. 2010; 111 (3): 679-686

    Abstract

    We sought to determine the impact of a rapid response system on cardiac arrest rates and mortality in a United States veteran population.We describe a prospective analysis of cardiac arrests in 9 months before and 27 months after institution of a rapid response system, and retrospective analysis of mortality 3.5 years before the intervention and 27 months after the intervention. The study included all inpatients from a university-affiliated United States Veterans Affairs Medical Center, before and after implementation of a rapid response system, including an educational program, patient calling criteria, and a physician-led medical emergency team. Primary end points were hospital-wide cardiac arrests and mortality rates normalized to hospital discharges. Comparisons of event rates between various time points during the implementation process were made by analysis of variance.Three hundred seventy-eight calls were made to the medical emergency team in the time period studied. Compared with preintervention time points, cardiac arrests were reduced by 57%, amounting to a reduction of 5.6 cardiac arrests per 1000 hospital discharges (P < 0.01). Mortality was reduced during the intervention, but this was attributable to a natural decrease occurring over all phases of the study.A significant reduction in the rate of cardiac arrests was realized with this intervention, as well as a trend toward lower mortality. We estimate that 51 arrests were prevented in the timeframe studied. Our results suggest that further reductions in morbidity can be realized by expansion of rapid response systems throughout the Veterans Affairs network.

    View details for DOI 10.1213/ANE.0b013e3181e9c3f3

    View details for Web of Science ID 000281150100015

    View details for PubMedID 20624835

  • Using in situ simulation to improve in-hospital cardiopulmonary resuscitation. Joint Commission journal on quality and patient safety / Joint Commission Resources Lighthall, G. K., Poon, T., Harrison, T. K. 2010; 36 (5): 209-216

    Abstract

    There is widespread recognition that the conduct of cardiac resuscitation is problematic. In situ simulation has been used to train and evaluate cardiac arrest teams' performance in the hospital setting, but in work at a university-affiliated, tertiary care facility, the simulated cardiac arrests were used to understand how well health care providers and their environment function during arrests, with the goal of a rapid intervention to correct problem areas. Latent conditions--innate, mostly hidden, workplace factors--can have a large detrimental impact on resuscitation efforts.Observations from a series of unannounced simulated cardiac arrests undertaken at diverse locations within a university-affiliated, tertiary care hospital were a component of an ongoing initiative to improve performance of emergency cardiovascular care.Fourteen cardiac arrest simulations revealed 24 hazardous findings, approximately two thirds of which had a high likelihood of compromising patient survival if they had occurred during an actual cardiac arrest. Categories of problems included active errors by teams and individuals and systemic or latent errors of the environment. Because the simulations were designed with the goal of discovering and documenting errors, most errors led to further actions, policies, and procedures that were rapidly adopted by the medical center to prevent their recurrence.In situ simulation of cardiac arrests elicits lifelike behaviors and allows engagement of all personnel and resources applicable to real arrests. This method allowed for remedial plans to be developed before further harm could occur. Accordingly, in situ simulation of high-risk events may be a useful, efficient technique that complements existing quality assurance processes in hospitals.

    View details for PubMedID 20480753

  • Abnormal vital signs are associated with an increased risk for critical events in US veteran inpatients RESUSCITATION Lighthall, G. K., Markar, S., Hsiung, R. 2009; 80 (11): 1264-1269

    Abstract

    Establish the frequency of abnormal vital signs in medical and surgical ward patients; study their association with "critical events," which for the purposes of this study, were mortality, cardiac arrests and unplanned ICU transfers.Four-month prospective, observational cohort study; University-affiliated US Veteran's hospital. Vital signs from all regular ward medical and surgical inpatients were recorded over the study period and compared with records of cardiac arrests, mortality and ICU admissions.Using the Hospital's Medical Emergency Team criteria to define normal/abnormal thresholds for vital signs, abnormal vital signs (VS(MET)) were found in 16% of patients; of these; 35% experienced a critical event vs. 2.5% in the patients with normal vital signs (OR 21, 95% CI 12-35, p<0.001). The sensitivity of VS(MET) to predict a critical event was 0.72 and the positive predictive value was 0.35; sensitivity decreased to 0.28 and positive predictive value increased to 0.78 for patients that had two different VS(MET). Survival was significantly lower in both medical and surgical patients with VS(MET) at both 30 days and at 1 year following discharge (p<0.02). Both medical and surgical patients with VS(MET) had twice the length of stay of patients with normal vitals (3 vs. 7 days; p<0.001).Even single recordings of VS(MET) signaled increased risk for critical events in hospital ward patients. Use of vital signs as criteria for additional patient assessment and possible ICU admission appears justified. Development of abnormal vitals during hospitalization may signify impaired physiologic reserve that places a patient at higher risk for mortality after discharge.

    View details for DOI 10.1016/j.resuscitation.2009.08.012

    View details for Web of Science ID 000272009600011

    View details for PubMedID 19744762

  • Evaluating the management of septic shock using patient simulation CRITICAL CARE MEDICINE Ottestad, E., Boulet, J. R., Lighthall, G. K. 2007; 35 (3): 769-775

    Abstract

    Develop a scoring system that can assess the management of septic shock by individuals and teams.Retrospective review of videotapes of critical care house staff managing a standardized simulation of septic shock.Academic medical center; videotapes were made in a recreated intensive care unit environment using a high-fidelity patient simulator.Residents in medicine, surgery, and anesthesiology who had participated in the intensive care unit rotation.The septic patient was managed by the intensive care unit team in a graded manner with interns present for the first 10 mins and more senior-level help arriving after 10 mins. The intern was graded separately for the first 10 mins, and the team was graded for the entire 35-min performance.Both technical and nontechnical scoring systems were developed to rate the management of septic shock. Technical scores are based on guidelines and principles of managing septic shock. Team leadership, communication, contingency planning, and resource utilization were addressed by the nontechnical rating. Technical scores were calculated for both interns and teams; nontechnical scores applied only to the team. Of 16 technical checklist items, interns completed a mean of 7 with a range of 1.5-11. Team technical ratings had a mean of 9.3 with a range of 3.3-13. Nontechnical scores showed similar intergroup variability with a mean of 26 and a range of 10-35. Technical and nontechnical scores showed a modest correlation (r = .40, p = .05). Interrater reliabilities for intern and team technical scores were both r = .96 and for nontechnical scores r = .88.Objective measures of both knowledge-based and behavioral skills pertinent to the management of septic shock were made. Scores identified both adequate and poor levels of performance. Such assessments can be used to benchmark clinical skills of individuals and groups over time and may allow the identification of interventions that improve clinical effectiveness in sepsis management.

    View details for DOI 10.1097/01.CCM.0000256849.75799.20

    View details for Web of Science ID 000244470800011

    View details for PubMedID 17235260

  • Use of a fully simulated intensive care unit environment for critical event management training for internal medicine residents CRITICAL CARE MEDICINE Lighthall, G. K., Barr, J., Howard, S. K., Gellar, E., Sowb, Y., Bertacini, E., Gaba, D. 2003; 31 (10): 2437-2443
  • Percutaneous tracheostomy at the bedside: 13 tips for improving safety and success. Journal of intensive care medicine Maxwell, B. G., Ganaway, T., Lighthall, G. K. 2014; 29 (2): 110-115

    Abstract

    We have developed a set of routines and practices in the course of performing a large series (n = 70) of percutaneous dilational tracheostomy (PDT). The 13 tips discussed in this review fall into 4 categories. System factors that facilitate training, patient safety, and avoidance of crises including the use of appropriate personnel, importance of timing, use of premedication, and the utility and content of a preprocedure briefing. Suggestions to prevent loss of the airway include tips on airway assessment, preparation of airway equipment, and use of exchange catheter techniques. Strategies to avoid and manage both microvascular and large-vessel bleeding are discussed. We also discuss the management of common postprocedure problems including tracheostomy tube obstruction, malposition requiring tube exchange or replacement, and air leak. The practical considerations for successful execution of PDT involve common sense, thorough planning, and structured approaches to prevent adverse effects if the procedure does not go as smoothly as expected. These strategies will aid anesthesiologists and intensivists in improving their comfort level, safety, and competence in performing this beside procedure.

    View details for DOI 10.1177/0885066613487305

    View details for PubMedID 23753248

  • The pharmacology of airway management in critical care. Journal of intensive care medicine Consilvio, C., Kuschner, W. G., Lighthall, G. K. 2012; 27 (5): 298-305

    Abstract

    This review provides an update on the pharmacology of airway management, emphasizing medications and management strategies widely used in an intensive care unit setting. Induction agents, muscle relaxants, opioids, sedative-hypnotics, and adjunctive agents are reviewed in the context of emergent airway management. Throughout this review, we emphasize the utility of considering a broad set of pharmacologic agents and approaches for airway management of the critically ill patient.

    View details for DOI 10.1177/0885066611402154

    View details for PubMedID 21436166

  • Generation of early warnings with smart monitors: The future is all about getting back to the basics! CRITICAL CARE MEDICINE Lighthall, G. K. 2012; 40 (8): 2509-2511

    View details for DOI 10.1097/CCM.0b013e31825adc46

    View details for Web of Science ID 000306604900041

    View details for PubMedID 22809927

  • The evolving role of preoperative testing in vascular surgery patients: can a little knowledge be dangerous? Seminars in cardiothoracic and vascular anesthesia Verduzco, L. A., Lighthall, G. K. 2011; 15 (3): 75-84

    Abstract

    It has been traditionally recommended that candidates for vascular surgery receive noninvasive stress perfusion testing risk stratification to help decide which patients may benefit from coronary artery revascularization. Recent clinical trials have contested the efficacy of revascularization in this population as well as the information yield of noninvasive testing. This article reviews a number of these studies that are likely to change our beliefs regarding testing and subsequent interventions as well as evolving role of medical therapy in patients undergoing vascular surgery.

    View details for DOI 10.1177/1089253211416517

    View details for PubMedID 21859808

  • Use of physiologic reasoning to diagnose and manage shock States. Critical care research and practice Lighthall, G. 2011; 2011: 105348-?

    Abstract

    Shock states are defined by stereotypic changes in well-known physiologic parameters. While these well-known changes provide a convenient entry point into further evaluation of patients in shock or at risk for shock, use of such physiologic evaluation is not commonly seen in clinical medicine. A formal description of physiologic reasoning in the diagnosis of shock states is presented in this paper. Included with this conceptual framework is a discussion of key tests or findings that can be used to differentiate between possible diagnoses, and the pairing of treatment strategies to distinct classes of physiologic abnormalities. It is hoped that the methodology presented here will demonstrate the primacy of physiologic reasoning in the diagnosis and treatment of hemodynamic instability. Advantages of this method are speed and accuracy, efficient use of resources, and mitigation against sources of medical errors.

    View details for DOI 10.1155/2011/105348

    View details for PubMedID 21845222

  • Perioperative intravascular fluid assessment and monitoring: a narrative review of established and emerging techniques. Anesthesiology research and practice Singh, S., Kuschner, W. G., Lighthall, G. 2011; 2011: 231493-?

    Abstract

    Accurate assessments of intravascular fluid status are an essential part of perioperative care and necessary in the management of the hemodynamically unstable patient. Goal-directed fluid management can facilitate resuscitation of the hypovolemic patient, reduce the risk of fluid overload, reduce the risk of the injudicious use of vasopressors and inotropes, and improve clinical outcomes. In this paper, we discuss the strengths and limitations of a spectrum of noninvasive and invasive techniques for assessing and monitoring intravascular volume status and fluid responsiveness in the perioperative and critically ill patient.

    View details for DOI 10.1155/2011/231493

    View details for PubMedID 21785588

  • "Identifying the hospitalised patient in crisis"-A consensus conference on the afferent limb of Rapid Response Systems RESUSCITATION DeVita, M. A., Smith, G. B., Adam, S. K., Adams-Pizarro, I., Buist, M., Bellomo, R., Bonello, R., Cerchiari, E., Farlow, B., Goldsmith, D., Haskell, H., Hillman, K., Howell, M., Hravnak, M., Hunt, E. A., Hvarfner, A., Kellett, J., Lighthall, G. K., Lippert, A., Lippert, F. K., Mahroof, R., Myers, J. S., Rosen, M., Reynolds, S., Rotondi, A., Rubulotta, F., Winters, B. 2010; 81 (4): 375-382

    Abstract

    Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patient deterioration or a clear description of what constitutes patient monitoring.A consensus conference of international experts in safety, RRS, healthcare technology, education, and risk prediction was convened to review current knowledge and opinion on clinical monitoring. Using established consensus procedures, four topic areas were addressed: (1) To what extent do physiologic abnormalities predict risk for patient deterioration? (2) Do workload changes and their potential stresses on the healthcare environment increase patient risk in a predictable manner? (3) What are the characteristics of an "ideal" monitoring system, and to what extent does currently available technology meet this need? and (4) How can monitoring be categorized to facilitate comparing systems?The major findings include: (1) vital sign aberrations predict risk, (2) monitoring patients more effectively may improve outcome, although some risk is random, (3) the workload implications of monitoring on the clinical workforce have not been explored, but are amenable to study and should be investigated, (4) the characteristics of an ideal monitoring system are identifiable, and it is possible to categorize monitoring modalities. It may also be possible to describe monitoring levels, and a system is proposed.

    View details for DOI 10.1016/j.resuscitation.2009.12.008

    View details for Web of Science ID 000276707200003

    View details for PubMedID 20149516

  • A Controllable Patient Monitor for Classroom Video Projectors SIMULATION IN HEALTHCARE Lighthall, G. K., Harrison, T. K. 2010; 5 (1): 58-60

    Abstract

    Moderate capability simulators such as Laerdal's SimMan allow for the operator to control the vital signs presented on the monitor. However, the presence of the mannequin simulator may not always be needed to achieve specific teaching goals. In this report, we describe the use of the SimMan software to generate, control, and project vital signs on a projector screen, with an appearance identical to that of its normal companion monitor.We connected a laptop computer running Laerdal's SimMan software to a video projection system through a VGA or S-video connection and were able to create a controllable monitor that could be used for tabletop simulation sessions.We were able to create an interactive and dynamic patient monitor that could be projected to a large group to facilitate tabletop simulation utilizing the Laerdal SimMan software and an external projection screen setup.Laerdal SimMan software can be used to create a dynamic and interactive presentation tool for classroom learning.

    View details for DOI 10.1097/SIH.0b013e3181b5c3e6

    View details for Web of Science ID 000276077900012

    View details for PubMedID 20383093

  • Using the rapid response system to provide better oversight of patient care processes. Joint Commission journal on quality and patient safety / Joint Commission Resources Moore, M. S., Howard, S. K., Lighthall, G. 2007; 33 (11): 695-?

    Abstract

    The cross-disciplinary nature of patient care and medical emergency teams allows for identification of systemwide problems that might otherwise be perceived as isolated events.

    View details for PubMedID 18074718

  • The use of clinical simulation systems to train critical care physicians. Journal of intensive care medicine Lighthall, G. K., Barr, J. 2007; 22 (5): 257-269

    Abstract

    Intensive care units are complex and dynamic clinical environments in which the delivery of appropriate and timely care to critically ill patients depends on the integrated and efficient actions of providers with specialized training. The use of realistic clinical simulator systems can help to facilitate and standardize the training of critical-care physicians, nurses, respiratory therapists, and pharmacists without having the training process jeopardize the well-being of patients. In this article, we review the current state of the art of patient simulator systems and their applications to critical-care medicine, and we offer some examples and recommendations on how to integrate simulator systems into critical-care training.

    View details for PubMedID 17895484

  • Genetic variants of the P-glycoprotein gene Abcb1b modulate opioid-induced hyperalgesia, tolerance and dependence PHARMACOGENETICS AND GENOMICS Liang, D., Liao, G., Lighthall, G. K., Peltz, G., Clark, D. J. 2006; 16 (11): 825-835

    Abstract

    Opioid-induced hyperalgesia (OIH) is a state of paradoxically increased nociceptive sensitivity seen in both humans and rodents following the resolution of the acute opioid antinociceptive effects or during periods of chronic opioid administration. Using the power of genetic analysis, we hoped to discover novel mechanisms modulating this trait.The degree of opioid-induced hyperalgesia displayed in response to a thermal stimulus applied to the hind paw was measured in 16 strains of inbred mice after 4 days of morphine administration. The degree of thermal sensitization was then used in a recently developed in silico haplotypic mapping algorithm along with a haplotypic map constructed from a database containing 209,000 single nucleotide polymorphisms.Analysis of the data resulted in the identification of several haplotype blocks strongly associated with the thermal opioid-induced hyperalgesia trait. The most strongly associated block was located within the Abcb1b P-glycoprotein drug transporter gene. Experiments using the P-glycoprotein inhibitor cyclosporine A and P-glycoprotein null mutant mice supported the hypothesis that a functional association exists between P-glycoprotein transporters and opioid-induced hyperalgesia. The observation of a correlation between morphine brain concentrations and the development of opioid-induced hyperalgesia was consistent with this hypothesis as well. In addition, P-glycoprotein gene deletion and pharmacological inhibition altered morphine ED50, tolerance and physical dependence.We conclude that the use of haplotypic mapping to identify novel mechanisms controlling complex traits is a viable approach. Variants of the Abcb1b gene may explain some portion of the interstrain differences in OIH and perhaps other consequences of chronic opioid administration.

    View details for Web of Science ID 000241971500008

    View details for PubMedID 17047491

  • Findings of the First Consensus Conference on Medical Emergency Teams CRITICAL CARE MEDICINE DeVita, M. A., Bellomo, R., Hillman, K., Kellum, J., Rotondi, A., Teres, D., Auerbach, A., Chen, W., Duncan, K., Kenward, G., Bell, M., Buist, M., Chen, J., Bion, J., Kirby, A., Lighthall, G., Ovreveit, J., Braithwaite, R. S., Gosbee, J., Milbrandt, E., Peberdy, M., Savitz, L., Young, L., Galhotra, S. 2006; 34 (9): 2463-2478

    Abstract

    Studies have established that physiologic instability and services mismatching precede adverse events in hospitalized patients. In response to these considerations, the concept of a Rapid Response System (RRS) has emerged. The responding team is commonly known as a medical emergency team (MET), rapid response team (RRT), or critical care outreach (CCO). Studies show that an RRS may improve outcome, but questions remain regarding the benefit, design elements, and advisability of implementing a MET system.In June 2005 an International Conference on Medical Emergency Teams (ICMET) included experts in patient safety, hospital medicine, critical care medicine, and METs. Seven of 25 had no experience with an RRS, and the remainder had experience with one of the three major forms of RRS. After preconference telephone and e-mail conversations by the panelists in which questions to be discussed were characterized, literature reviewed, and preliminary answers created, the panelists convened for 2 days to create a consensus document. Four major content areas were addressed: What is a MET response? Is there a MET syndrome? What are barriers to METS? How should outcome be measured? Panelists considered whether all hospitals should implement an RRS.Patients needing an RRS intervention are suddenly critically ill and have a mismatch of resources to needs. Hospitals should implement an RRS, which consists of four elements: an afferent, "crisis detection" and "response triggering" mechanism; an efferent, predetermined rapid response team; a governance/administrative structure to supply and organize resources; and a mechanism to evaluate crisis antecedents and promote hospital process improvement to prevent future events.

    View details for DOI 10.1097/01.CCM.0000235743.38172.6E

    View details for Web of Science ID 000240010400027

    View details for PubMedID 16878033

  • The value of simulation training during anesthesia residency ANESTHESIOLOGY Lighthall, G. K. 2006; 105 (2): 433-433

    View details for Web of Science ID 000239411600036

    View details for PubMedID 16871088

  • An interchangeable Mapleson A-E breathing system is practical and cost effective ACTA ANAESTHESIOLOGICA SCANDINAVICA Robinson, M., Lighthall, G. K. 2006; 50 (1): 45-49

    Abstract

    In locations where oxygen and anesthesia gas supplies are limited, and where circle systems are not practical, means to reduce fresh gas flow during maintenance of inhalational anesthesia are of potential value. We investigated whether a common transport breathing apparatus could be modified to allow interchange between Mapleson D (Map-D) and Mapleson A (Map A) configurations.A common Map-D transport system was converted to a Map-A system by switching positions of the exhaust valve and the elbow connector where fresh gas is delivered; these two breathing systems were compared in this study. The key question was whether rebreathing of CO2 could be eliminated at a lower fresh gas flow rate (FGF) with the Map-A design. A structured protocol was followed.A mean decrease in FGF of 2.8 l/min was seen with the Map-A apparatus when compared with the Map-D (P=0.003). With no significant differences in physiologic or anesthetic variables, FGF/V(E) was significantly lower with the Mapleson A configuration than with the Mapleson D system design (1.1 vs. 1.8; P=0.007). The extent to which FGF could be lowered when switching between Mapleson D and A systems correlated strongly with the patients' respiratory rate while under anesthesia (r=0.45, P<0.01).Cost and resource savings can be realized through the use of a breathing system modification that achieves appropriate ventilation at lower fresh gas flows.

    View details for DOI 10.1111/j.1399-6576.2005.00848.x

    View details for Web of Science ID 000235005500007

    View details for PubMedID 16451150

  • Fluid management in hospitalized patients. Comprehensive therapy Meinke, L., Lighthall, G. K. 2005; 31 (3): 209-223

    Abstract

    Intravenous fluid administration is critical to the care of hospitalized patients. Despite the lack of a clear consensus on fluid administration, one may use the principles in this article to develop an organized framework for patient care.

    View details for PubMedID 16110129

  • Alterations in spinal cord gene expression after hindpaw formalin injection JOURNAL OF NEUROSCIENCE RESEARCH Li, X. Q., Lighthall, G., Liang, D. Y., Clark, J. D. 2004; 78 (4): 533-541

    Abstract

    Heme oxygenase type 2 (HO-2) is an enzyme that uses heme as a substrate to produce iron, biliverdin, and carbon monoxide (CO). This enzyme participates in regulation of nociceptive signal transmission in spinal cord tissue. We set out to identify genes undergoing alterations in expression in a model of inflammatory pain and to determine whether HO-2 participates in that regulation. After the hindpaw injection of formalin in mice, we measured changes in expression of immediate early genes including c-fos, c-jun, jun B, nerve growth factor induced genes (NGFI-A and NGFI-B) and activity-related cytoskeletal protein (ARC) using real-time PCR. The mRNA corresponding to these genes increased in abundance in the first hour after formalin injection and then slowly declined. Changes in the abundance of prodynorphin, extracellular signal related kinases (ERK1 and ERK2) and N-methyl-D-aspartate (NMDA) receptor R1 subunit mRNA generally peaked between 8 and 12 hr after formalin injection. In HO-2 null mutant mice, the enhancement of expression was less for all genes studied. We went on to quantify gene expression in superficial dorsal horn tissue using laser capture microdissection followed by RNA amplification and real-time PCR. The results confirmed that the changes in gene expression were occurring in regions of the spinal cord involved in nociceptive processing. We conclude that the hindpaw injection of formalin leads to enhanced early and late expression of many genes in spinal cord dorsal horn tissue, and that this enhancement of expression relies to a degree on the presence of HO-2.

    View details for DOI 10.1002/jnr.20274

    View details for Web of Science ID 000225008400009

    View details for PubMedID 15389827

  • Identification of salt-sensitive genes in the kidneys of Dahl rats JOURNAL OF HYPERTENSION Lighthall, G. L., Hamilton, B. P., Hamlyn, J. M. 2004; 22 (8): 1487-1494

    Abstract

    Inherited differences in renal function underlie the effect of high salt diets on blood pressure in Dahl rats. We probed the kidneys of inbred Dahl SS/Jr and SR/Jr for anonymous and candidate genes whose expression was regulated by dietary sodium.mRNA quantitation of both candidate genes implicated in sodium excretion and anonymous gene products found by differential hybridization in the kidneys of salt-resistant (SR) and salt sensitive (SS) inbred Dahl rats on high and low salt diets for 21 days.Differential screening revealed a cDNA clone (H1) that showed increased dietary salt-dependent expression only in SS rats. Sequencing of the H1 cDNA showed it was the Dahl rat homologue to a perchloric acid soluble protein expressed in liver and kidney. Among candidate genes, transcript levels of arginosuccinate synthetase (AS) and arginosuccinate lyase (AL) were higher in SS on low salt diets, and AS mRNA increased in response to a high salt diet in SR. Renal mRNA for the ANP-A and the vasopressin type II receptors did not differ by strain or dietary conditions.Three new salt-sensitive genes were detected in the kidneys of inbred Dahl rats. Two genes encode enzymes in the biosynthesis of L-arginine. The upregulation of these genes by dietary salt indicates increased demand and biosynthesis of L-arginine in Dahl SS rats. A third gene encodes a small acid-soluble protein thought to influence the transcription/translation of numerous genes. Further studies will be needed to determine the nature of the association of these genes with salt-sensitivity and blood pressure.

    View details for DOI 10.1097/01.hjh.0000133719.94075.e2

    View details for Web of Science ID 000222982600012

    View details for PubMedID 15257170

  • Correction of intraoperative coagulopathy in a patient with neurofibromatosis type I with intravenous desmopressin (DDAVP) INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Lighthall, G. K., Morgan, C., Cohen, S. E. 2004; 13 (3): 174-177

    Abstract

    A patient with the genetic condition neurofibromatosis type I and no known coagulopathy undergoing cesarean delivery, had diffuse uterine and surgical site bleeding that was not correctable by oxytocin, methylergonovine and PGF2 alpha. Despite good uterine tone, hemorrhage continued from the uterus and the surrounding tissues, persisting even after surgical ligation of the uterine arteries. With no change in her condition, which was behaving clinically as a coagulopathy, an infusion of desmopressin acetate (DDAVP) was begun. The patient's bleeding promptly resolved shortly after infusion of this agent. A review of relevant literature suggests that platelet reactivity of patients with neurofibromatosis type 1 is attenuated in some in vitro conditions. Thus, there may be some theoretical basis for using DDAVP in patients with neurofibromatosis type 1 who have bleeding problems with no other known source, such as in the case presented here.

    View details for DOI 10.1016/j.ijoa.2004.01.008

    View details for Web of Science ID 000222738700008

    View details for PubMedID 15321397

  • Asystole during successive electroconvulsive therapy sessions: A report of two cases JOURNAL OF CLINICAL ANESTHESIA Robinson, M., Lighthall, G. 2004; 16 (3): 210-213

    Abstract

    Intense vagal discharge often follows stimulus application during electroconvulsive therapy (ECT). Related periods of asystole during ECT have been reported sporadically in psychiatric journals, but to date not in the anesthesia literature. We report here two cases of prolonged asystole that occurred in our facility in spite of the fact that published suggestions for its prevention were followed. With careful monitoring of these patients--including echocardiography for one patient--we document the onset of asystole at the exact time of ECT stimulus application. With these data, we discuss why asystole is likely to result from a direct central pathway rather than via a baroreceptor reflex, and discuss a neuroanatomic pathway potentially responsible for our findings. We also demonstrate that high-dose atropine (0.8 mg) can effectively prevent most cases of asystole in susceptible patients, and that administration of esmolol following cessation of seizures effectively reduces the elevated heart rate without causing asystole or bradycardia.

    View details for DOI 10.1016/j.jclinane.2003.07.009

    View details for Web of Science ID 000222422600010

    View details for PubMedID 15217662

  • Dexmedetomidine fails to cause hyperalgesia after cessation of chronic administration ANESTHESIA AND ANALGESIA Davies, M. F., Haimor, F., Lighthall, G., Clark, J. D. 2003; 96 (1): 195-200

    Abstract

    Hyperalgesia occurring after the cessation of chronic opioid administration occurs in humans and has been modeled in rodents with chronic systemic and intrathecal administration paradigms. It is, however, unclear if this type of postanalgesic hyperalgesia is unique to opioids. The alpha(2)-adrenergic receptor agonist, dexmedetomidine (Dex), is similar to opioids in that it is an analgesic that interacts with cell-surface receptors linked to the inhibition of adenylate cyclase and the modulation of ion channel activity. In these studies, we first constructed antinociceptive dose-response curves for Dex and morphine (MSO4). The 50% effective doses for Dex and MSO4 administered intraperitoneally to C57Bl/6 mice were 75 micro g/kg and 5.2 mg/kg, respectively. Using equally effective doses, we treated separate groups of mice with twice-daily injections of Dex or MSO4 for 5 days. Tolerance to these drugs was documented after this period. In the 16-72 h after cessation of administration, MSO4-treated mice demonstrated both thermal hyperalgesia and mechanical allodynia. However, the Dex-treated mice showed no changes in their thermal or mechanical withdrawal thresholds. We conclude that using this experimental paradigm, opioids but not an alpha(2)-adrenergic agonist, cause hyperalgesia and allodynia after cessation of chronic administration.The cessation of the administration of opioids is associated with hyperalgesia in both humans and other animals. However, antinociceptive dexmedetomidine does not seem to be associated with this type of hyperalgesia syndrome during periods of abstinence.

    View details for DOI 10.1213/01.ANE.0000038086.81696.9C

    View details for Web of Science ID 000180169700041

    View details for PubMedID 12505952

  • Heme oxygenase type 2 modulates molecular changes during chronic behavioral and exposure to morphine NEUROSCIENCE Liang, D., Li, X., Lighthall, G., Clark, J. D. 2003; 121 (4): 999-1005

    Abstract

    The heme oxygenase (HO) enzyme system has been shown to participate in nociceptive signaling in a number of different models of pain. In these experiments we investigated the role of the HO type 2 (HO-2) isozyme in tolerance to the analgesic effects of morphine, and the hyperalgesia and allodynia which are measurable upon cessation of administration. Wild type C57Bl/6 wild type mice or HO-2 null mutants in that background strain were treated with morphine for 5 days. The morphine administration protocol consisted of either twice daily repeated s.c. boluses of 15 mg/kg or s.c. implantation of a morphine pellet. At the end of the treatment period wild type mice treated by either protocol exhibited tolerance, but the HO-2 null mutants did not. The HO-2 null mutants also exhibited less mechanical allodynia following cessation of morphine administration, though only modest differences in thermal hyperalgesia were noted. There was no correlation between the degree of tolerance obtained in the bolus and pellet protocols and the degree of hyperalgesia and allodynia observed after cessation of morphine administration in the wild type mice. Our final experiments analyzed increases in expression of mRNA for nitric oxide synthase type 1, N-methyl-D-aspartate (NMDA) receptor NMDAR1 subunit and prodynorphin in spinal cord tissue. In pellet-treated mice two- to three-fold increases were observed in the abundance of these species, but very little change was observed in the null-mutant mice. Taken together our results indicate that HO-2 participates in the acquisition of opioid tolerance, the expression of mechanical allodynia after cessation of opioid administration and in gene regulation occurring in the setting of treatment with morphine. Furthermore, these studies suggest that the mechanisms underlying analgesic tolerance and opioid-induced hypersensitivity are at least somewhat distinct.

    View details for DOI 10.1016/S0306-4522(03)00483-4

    View details for Web of Science ID 000186469800020

    View details for PubMedID 14580950

  • An improved method for topical cerebral cooling during deep hypothermic circulatory arrest JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Lighthall, G. K., Cartwright, C. R., Haddow, G. R. 2000; 120 (2): 403-404

    View details for Web of Science ID 000088733700028

    View details for PubMedID 10917961

  • A comparison of the onset and clinical duration of high doses of cisatracurium and rocuronium JOURNAL OF CLINICAL ANESTHESIA Lighthall, G. K., Jamieson, M. A., Katolik, J., Brock-Utne, J. G. 1999; 11 (3): 220-225

    Abstract

    To determine the onset and clinical duration of cisatracurium and rocuronium in equipotent doses in balanced opioid/isoflurane anesthesia.Randomized, controlled study.University hospital.40 healthy patients scheduled for elective surgery.Patients underwent anesthesia induction with thiopental or propofol with a cisatracurium intubating dose of either 0.15 or 0.2 mg/kg or a rocuronium dose of either 0.9 or 1.2 mg/kg. These doses correspond to three and four times the ED95 dose.The onset time and time to 25% recovery of baseline first twitch in a train-of-four were determined using an accelerometric sensor. Rocuronium had a faster onset time that cisatracurium at equipotent doses (3 x ED95: 134 vs. 220 sec respectively, and at 4 x ED95: 95 vs. 162 sec). Recovery tended to be faster, but not statistically different for cisatracurium compared to rocuronium.With equipotent intubating doses of rocuronium and cisatracurium, rocuronium produces a more rapid onset of muscle relaxation. The data suggest a tendency toward more rapid clinical recovery of cisatracurium compared to equipotent doses of rocuronium, although these differences were not statistically significant.

    View details for Web of Science ID 000081512700008

    View details for PubMedID 10434218

  • THE CHROMOSOMES OF LEISHMANIA PARASITOLOGY TODAY Lighthall, G. K., GIANNINI, S. H. 1992; 8 (6): 192-199

    Abstract

    Chromosome size polymorphisms occur in Leishmania such that each strain of a given species has a distinctive molecular karyotype. Despite this variability, the chromosomal similarities among closely related strains of Leishmania are sufficiently characteristic to permit classification of unidentified clinical isolates. Mechanisms generating chromosome size polymorphisms are related to chromosomal evolution. In this review, Geoffrey Lighthall and Suzanne Giannini explain that the chromosomal profiles of members of different species may be diverging from a conserved 'consensus' karyotype at different rates, and present a current understanding of the genomic organization of Leishmania with emphasis on chromosomal elements.

    View details for Web of Science ID A1992HW56100005

    View details for PubMedID 15463615

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