UMHS Emergency Medicine | Research Prospectus

As documented in the following pages, progress in all three fronts continues to proceed ahead of expectation, and the clinical and laboratory investigators in the Department look forward to another year of growth in 2001.

In the 1999-2000 academic year, the Department of Emergency Medicine received $1.2M in extramural funding for the conduct of research by its members. This figure brings the cumulative award amount for the past 5 years to $3.6M, making the group one of the most well funded academic departments in the specialty. The composition of the funding base is a healthy mix of federal, private foundation, and industry sponsorship. Sources of revenue have grown to include the National Institute for Alcohol Abuse and Alcoholism, the National Heart, Lung, and Blood Institute, the Centers for Disease Control and Prevention, and the Office of Naval Research. The department’s commitment to clinical trials in the diagnosis and treatment of stroke is responsible for the majority of industrial revenue.

New grants this year include two awards from the United States Department of Health and Human Services to develop new telemedicine and web-based technologies for the provision of emergency medical services to children in the state of Michigan.

*Pending for 2000 include Pfizer Pharmaceuticals and the National Telecommunications and Information Agency.

At the core of the research program in the Department of Emergency Medicine is a commitment to train the next generation of researchers in one of medicine’s youngest specialties. Each year the faculty welcomes research fellows, resident physicians, medical students and undergraduates into their clinical and basic science laboratories as research partners. As Assistant Dean for Student Programs, Dr. Brian Zink is successfully interfacing the Emergency Medicine faculty’s interest in training with the growing number of opportunities available for medical students with a desire to participate in research.

In the past academic year, the University of Michigan became one of several centers nationwide to receive a Clinical Research Curriculum (K30). With this funding, the medical school has assembled a Training Program in Clinical Research. This program specifically targets clinical fellows and junior faculty with an interest in pursuing careers in clinical research. Funding of this project has allowed the fusion of the highly successful Clinical Research Design and Statistical Analysis degree program offered by the School of Public Health with a series of specialized courses on outcomes research, conduct of large-scale clinical trials, and the emerging role of genomics in clinical research. Dr. Younger represents the Department of Emergency Medicine on the faculty advisory committee of this program, and also serves as a research mentor for one of its inaugural fellows.

The departmental commitment to research training extends to junior faculty. Four members have received Masters of Science degrees in Clinical Research Design and Statistical Analysis from the School of Public Health. Two members currently hold Mentored Clinical Scientist Development (K08) Awards from the National Institutes of Health.

Funding for individuals interested in research training are available from a number of sources. For undergraduates at the University of Michigan, several faculty members participate in the Undergraduate Research Opportunity Program (UROP). Two faculty members currently mentor medical students funded through the Summer Research Scholars Program. Last year, the Department was awarded a Resident Research Year grant from the Society of Academic Emergency Medicine, and, through the Emergency Medicine Foundation, is sponsoring a Resident Research Grant recipient during the 2000-2001 academic year. With the support of EMF, Emergency Medicine at Michigan also has had continuous funding for research fellows for the past 5 years. Lastly, Emergency Medicine has sponsored two Robert Wood Johnson Clinical Research Scholars. The table on the following page provides a list of some of the people the Department of Emergency Medicine has had the pleasure to work with over the past few years.

Table 3. Previous Students, Residents, and Postgraduate Fellows trained in the Department of Emergency Medicine

The laboratory at MSRB I, 2522 is a 1,000 sq. ft. facility consisting of an operating suite, an animal preparation room and a blood and tissue analysis room. It also contains office space. The laboratory is equipped to perform large animal surgical experiments with general anesthesia, invasive monitoring and analysis of arterial blood gases, electrolytes, and other biochemical parameters.

Susan A. Stern, M.D., Associate Professor, Emergency Medicine Research Laboratory

The laboratory at Kresge I Building has approximately 800 ft² of space and contains surgical and bench space, a rodent behavioral testing room, small meeting area, and an office for research personnel. The principal missions of the laboratory are 1) investigation of acute brain injury in rodent models and 2) examination of the mechanisms of injury associated with natural venoms. Recent work in the laboratory has focused on the role of hyperbaric oxygenation in ischemic and toxic brain injury, and on the role of adenosine in focal cerebral ischemia. The laboratory is also becoming proficient in the development of purified IgG as an innovative therapy for envenomation injury. The laboratory has 3 independent surgical stations equipped with inhalational anesthesia, surgical microscopes, digital physiologic data aquisition, and a laser Doppler flowmeter. Functional outcomes in spatial learning and memory are measured in a Morris water maze. Digital image acquisition and analysis equipment is available for studies of dermal injury.

The Extracorporeal Life Support (ECLS) Research Laboratory is a collaborative effort between the Departments of Surgery, Pediatrics, and Emergency Medicine and is located in a 1200 sq. ft. facility on the 7^th floor of the Kresge I Research Building. The laboratory’s interest is in the pathophysiology and treatment of acute organ failure. Studies in the treatment of lung injury with extracorporeal devices have been federally funded for over 25 years, and have resulted in the clinical realization of extracorporeal life support as a viable means of supporting neonates, children, and adults with otherwise lethal respiratory failure. Dr. John Younger is one of four faculty within the group, and oversees experiments related to the pathophysiology of acute lung injury and the treatment of respiratory failure with liquid ventilation.

The Medical Readiness Trainer (MRT) Project is an ultramodern platform for comprehensive medical training at all levels of proficiency. The MRT integrates Human Patient Simulators (HPS), state of the art telecommunications, and fully interactive virtual reality (VR). Combining these technologies creates a rich situational environment, which realistically simulates the world of clinical medicine, and most of its challenges and stressors. The revolutionary approach to ultra-long distance teletraining won the MRT members the title of the Laureates of the prestigious Year 2000 Computerworld Smithsonian Institution Collection. The MRT is the subject of continuous attention by the media as an innovative solution to a training dilemma of modern medicine: how to educate providers in a simulated situation prior to an actual patient encounter. The model is now in the process of operational refinement as a training platform for the joint training of medical personnel at the Universities of Michigan and Puerto Rico. The MRT has been noted to have potential application to the Virtual Collaborative Clinics, a cooperative of organizations attempting to develop distance medical applications for use in remote sites such as rural areas and outer space. Other countries, both in Europe and South America are also showing interest in joining a network which, once developed, will provide maximum utilization of scarce and expensive resources: expert teachers and human patient simulators. To this end, the MRT team is committed to developing a robust international training model that achieves the highest standard for continuous clinician training and ensures the foremost patient safety.

Erosion of medical skills caused by inadequate access to refresher training or to infrequent exposure to acute disease are among the most frequently documented causes of adverse medical outcomes reported at those medical facilities without close affiliation to major medical training centers. Despite continuous growth in the use of the Web-based resources as a platform for continuing medical education, their static nature is also their major drawback in training emergency/trauma medicine skills. Contrary to other medical specialties, both emergency and trauma medicine revolve around the crucial factor of time available to determine the nature of the presenting disease, initial stabilization and management, and, finally, the disposition. Furthermore, each acute case requires virtually instantaneous assembly of widely dispersed anatomical, physiological, and pathological facts into a coherent clinical picture that constitutes the basis for all subsequent activities. It is a dynamic environment, where each clinical decision may affect survival of the patient, and where the clinician must be continuously prepared for the sudden emergence of unpredictable events, which may complicate the management even further. Additional layer of difficulty is added by the fact that neither emergency nor trauma medicine are the domains of a solitary practitioner. Instead, both are based on a closely coordinated interaction of medical teams whose communication- and behavioral skills must be continuously practiced and honed in order to guarantee positive outcomes. Clearly, the old fashioned didactic tools – books, computer media, or lectures are inadequate to provide the required level of training. Even interactive Web-based training currently fails to offer the solution in these situations. All of these traditional methods are devoid of providing the trainee with the "real life" stress and urgency of emergency medicine, nor do they provide the required degree of team training and interaction.

The advent of Human Patient Simulators (HPS) eliminated most of the current barriers to training emergency medical personnel. The modern HPS devices are life-size manikins whose complex computer-driven systems reproduce virtually all aspects of the relevant physiology and pathophysiology. HPS units correctly respond to the administered drugs, and display the results on standard vital sign monitors – just as a human patient would. Correct anatomy allows execution of several emergency procedures (eg., intubation, insertion of IV lines, chest tubes, or indwelling catheters). The realism of Human Patient Simulators is enhanced even further amplified by the correct chest and heart sounds, presence of anatomically (and pathophysiologically) correct pulses, modifiable responses of the upper respiratory pathway (eg., laryngospasm), etc. Behaving like a human patient, the simulators allow training under extremely realistic conditions, where inappropriate treatment (procedure or drug) may result in death. Moreover, they also allow team training. Hence, skills can be practiced and honed as many times as required without the patient being endangered. The primary drawback of HPS is their cost. For this reason, HPS systems are available only at the most prestigious medical training centers and their use is extremely restricted.

The Medical Readiness Trainer (MRT) team of the Department of Emergency Medicine at the University of Michigan solved these obstacles by developing a system of HPS remote control, and fusing the remotely controlled simulator with the fully interactive video-teleconferencing Internet-based system. The solutions (shown on the appended photographs and figures) devised by the MRT allow the trainee located virtually anywhere in the world to control the simulator from afar. The trainee can now practice skills of medical management, leadership, and team interaction without having physical access to the simulator, and yet face the same challenges as if the HPS was standing in the same room! Moreover, the MRT solution allows inclusion of an expert teacher as the director of each training exercise irrespectively of the teacher’s location. For example, the simulator may be located in Ann Arbor, MI, the trainees in New Delhi, while the expert teachers instructing on the techniques of airway management may be sitting at his or her office at the Schools of Medicine of the University of Michigan in Ann Arbor. All activities happen in real time, all participants (trainees and teachers) see the same pattern of vital signs on their monitors, and all hear the same dialogue and the same heart sounds. Whenever needed, the teacher can stop the simulator and provide additional instruction, whenever faults are discovered, the same scenario can be run over and over again until full mastery is attained.

While HPS units provide an unprecedented flexibility in training encounters with real patients without risk of injury to the patient, the element of "environmental setting" shown to play an essential role in training of effective medical performance has been always missing. Providers of emergency and trauma medical care work frequently within very stressful and austere environments characterized by a number of stressors that are typically absent in the classical hospital setting. Accident or disaster scenes, sick bays of ships at sea, helicopters, or field hospitals during humanitarian relief operations provide some of the best known examples of such settings. In order to acclimatize medical personnel to such environments, the Medical readiness Trainer Team placed the HPS unit within a virtual reality (VR) environment (CAVE). The CAVE generates appropriate physical surroundings of or the training scenario (eg., ED , a field, a ship at sea, or OR), fills it with pertinent sounds, and can, if required, expose the trainees to entirely unexpected distracting events such as fires, loss of electrical power, earthquakes, sea gales, etc. The MRT is now in the process of devising a system that will allow introduction of olfactory stimuli as well. This addition will provide our students with the "total environmental exposure", and allow practice in a setting as closely resembling that of a real life situation as is possible outside real life activities. Since CAVE environments are quite expensive (from $ 1 million up), very few universities have such facilities (it is estimated that there are 60 CAVES in the world). In order to bypass this limitation, MRT performed a series of successful demonstrations using a portable VR system based on the pioneering computer/optical technology developed jointly by the University of Strathclyde in Scotland and Ethereal Technologies in Ann Arbor. The system, known as VIZ4D allows generation of a 3-dimensional object whose viewing, contrary to the CAVE, does not require special devices (e.g., goggles). VIZ4D-generated image is probably the closest to holographic projection, development of which is still in progress. Combination of HPS, VIZ4D and Internet2 permits linking of all elements of the MRT over very long distances (up to several thousands of miles). This will allow execution of advanced training sessions at locations characterized by less well poorly developed technical/inadequate training facilities such as frequently encountered in rural and remote regions, or poor countries of the Third World.

Currently, the MRT represents arguably one of the best-equipped simulation-based medical training sites in the country. It’s facilities include CAVE and VIZ4D systems, 3 METI Adult Human Patient Simulators and 1 METI Pediatric Human Patient Simulator, and a comprehensive advance computing and telecommunications equipment including Internet2 connectivity, permitting ultra-lomg distance training based on multiple, voice-coordinated video streams and remote control of HPS devices. US Army’s Tank Command in Warren, MI agreed to put at the disposal of the MRT three "HUMVEEs" to be used as field deployable full capacity training stations that will combine all advantages of HPS, VR, and advanced telecommunications and open unprecedented flexibility in providing advanced medical training "anytime, anywhere." Close collaboartion with the University of Puerto Rico School of Medicine (UPRSM, Drs. J. Hawayek and R. Gonzales) allows the MRT to experiment in the environment of foreign language and culture, and in settings of frequently less-than-optimal telecommunication facilities (rural areas of PR) made even more difficult by a very long communication distance over water. Collaboration with UPRSM allowed MRT to develop the fundamental principles governing our approach to ultra-long distance medical education and training.

The Brain Injury Group is a collaborative research group comprised of physicians and research nurses from Emergency Medicine, Neurology, Neurosurgery, Radiology and Anesthesia at the UMMC and St Joseph Mercy Hospital-Ann Arbor. The specific aim of the group is to design and implement internally funded clinical research projects and conduct industry sponsored clinical trials pertaining to the care of adult patients with, or at risk of, stroke. With clinical research infrastructure in place at the University of Michigan Medical Center and St. Joseph Mercy Hospital in Ann Arbor, Hurley Medical Center in Flint, and Foote Memorial Hospital in Jackson, the group has an enrollment base of over 200,000 patients per year in southeastern Michigan.

Specific interests of the group include prevention of stroke through improved management of new-onset atrial fibrillation, a key risk factor in the development of stroke; rapid diagnosis of brain ischemia and injury using new technologies such as xenon computed tomography; rapid return of brain blood flow with angioplastic, thrombolytic and anti-platelet therapies; and a variety of anti-inflammatory techniques to prevent reperfusion injury, such as the blockade of adherence of inflammatory cells at sites of injury within the brain.

Injury is the leading cause of potential years of life lost in the United States, at a cost to society in the hundreds of billions of dollars. The goal of the University of Michigan Injury Research Center (UMIRC) is to decrease injury morbidity and mortality through generating and disseminating knowledge, conducting and promoting education, and informing policy makers. A particular emphasis of the Center is alcohol and other drugs, and their role in kinetic and thermal injury. Other research interests of the Center include: the acute toxic effects of alcohol and other drugs (poisoning or overdose); the effect of age on injury; and gender differences and injury. UMIRC will accomplish its goals through research, education, mentoring programs, and by working with and informing local, state and federal agencies.

The Center is based in the Department of Emergency Medicine and was initiated in July 1997. It is composed of core faculty and associate faculty from the fields of emergency medicine, the behavioral sciences, public health, pediatrics, surgery, and pharmacology. UMIRC is engaged in epidemiological, clinical and laboratory research. Research addresses injury prevention, acute care of the injured patient, and laboratory studies on the pathophysiology of injury. Educational activities include a freshman seminar offered through the College of Literature, Science and the Arts and an Injury Fellowship Program. The Injury Fellowship Program is designed to provide trainees with research expertise in injury control and substance use/abuse, and clinical expertise in the diagnosis and treatment of substance-related injuries. The Center’s multidisciplinary bench-to-bedside approach will result in knowledge that can be used to reduce the burden of this major health problem.

The list of ongoing projects within the Department of Emergency Medicine reflects the broad range of clinical and laboratory interests of the faculty. Funded projects are the result of years of preliminary work and demonstrate the growing expertise of our investigators. Internally funded projects give insight into the various new directions the group is headed. An essential part of the group’s success is its large group of collaborators, shown in table 4. On the following pages are descriptions of some of the work currently being conducted by our faculty.

Reducing death and disability caused by alcohol-related intentional and unintentional injury is a national health status goal. Acute alcohol intoxication is implicated in up to 50% of all injuries. The goal of this research is to test the effectiveness of an innovative, tailored brief intervention system using new technologies to reduce alcohol use and alcohol-related problems among injured hazardous drinkers treated in the ED.

Injury is a major cause of adolescent mortality and morbidity, and alcohol is frequently associated with these injuries. Alcohol programs and messages for adolescents have been delivered in homes, churches, schools, and communities in an effort to develop community-wide norms regarding alcohol use by adolescents. However, interventions to prevent alcohol use/misuse and alcohol related problems are needed for use in the ED. The specific objectives of this project are to develop a computer-based ED intervention to prevent alcohol use/misuse among adolescents and to test the efficacy of this intervention using a randomized controlled trial among injured adolescents presenting to the ED.

The primary goal is to support and facilitate EMS outcomes research and evaluation to be conducted by the broad EMS community. Using an expert panel, the project will identify areas of focus form EMS outcomes, and will develop the tools and methodology to conduct research and evaluation of the effectiveness of out-of-hospital emergency medical care. The project will disseminate the information developed to the broad EMS community, and, in so doing will stimulate EMS outcomes research that will improve the delivery of pre-hospital care.

Increasing Emergency Physicians’ Knowledge of Elder Abuse with an Educational Intervention

Non-accidental injury is an increasingly recognized clinical entity among elderly patients presenting to the Emergency Department. An important barrier to the appropriate care of this disease is a high rate of misdiagnosis. This project will develop and test an education intervention to increase awareness of elder abuse and improve its diagnosis and treatment in the Emergency Department.

Recent studies, using global measures of injury severity, have shown that, contrary to popular opinion, alcohol potentiates injury following a motor vehicle crash (MVC). Using previously collected data with the addition Organ Injury Severity Scaling Scores, the investigators will determine to what degree alcohol potentiates liver and spleen injury in MVC patients. Chronic alcohol use and its interaction with acute alcohol use and crash severity will also be analyzed.

Little is known regarding the acute and chronic drug use characteristics of pedestrians or bicyclists that are involved in motor vehicle crashes. This information is important in developing strategies for prevention of these injuries as well as their effective and efficient treatment. Using prospectively collected data, this study will determine the frequency of acute alcohol and other drug use among non-occupant MVC victims, their chronic alcohol and drug use and the relationship of these characteristics to injury severity, crash characteristics and crash culpability.

Domestic Violence and Alcohol Abuse/Dependence Among Women Admitted to a Trauma Service.

The population of women who sustain a severe injury and are admitted to a general surgery service may highlight a group at high risk for Domestic Violence (DV). Alcohol Abuse/Dependency among victims of DV may also be a significant factor in the injury process. This study is the first to look at DV among admitted female trauma patients and is the first step in developing screening and intervention strategies for DV among admitted trauma patients.

The goal of this preliminary study is to learn more about risk factors for injury and conflict among injured patients in the UM Hurley Emergency Department (ED). The specific aim is to assess health and health habits (including injury, alcohol use, smoking, depressed feelings), disagreements with others, and alcohol and drug experiences among patient seeking treatment at UM Hurley ED for injuries. We hope to use the findings from this study to develop future intervention studies directed at preventing injury and interpersonal conflict.

The use of alcohol and drugs are frequently associated with injury, and injury is a leading cause of death in our society and responsible for more years of productive life lost than cancer or heart disease. The funds from this grant will be used to further develop and refine a course, "Injury Alcohol and Drugs: A Modern Epidemic", UC 151, that has been presented as a first year seminar, to University of Michigan undergraduates, in 1998 and 1999. This course studies how society has addressed the problem of alcohol, drugs and injury through a broad-based approach that includes the medical, behavioral, social and engineering sciences.

Fatigue in Air Medical Helicopter Pilots on Rotating Shift Schedules: Measurement and Characterization

The objective of this project is to quantify the risks of fatigue in emergency helicopter AMS pilots and to determine the shift rotation schedule that minimizes those risks. We are measuring patterns of alertness in on duty pilots with ambulatory electrophysiological and visual monitoring techniques. The amount of sleep obtained off duty during shift rotation related circadian disruptions is determined by actigraphy. Self reported data on shift related effects on the physical and emotional well-being of pilots and their families is also being collected. This project is also developing new methods of measuring performance decrements associated with fatigue; and analyzing characteristics of AMS crash data with respect to circadian rhythms and the newly determined patterns of alertness.

A Multicenter, Open-label, Controlled Clinical Study to Evaluate the Safety and Efficacy of Xenon/CT Quantitative Cerebral Blood Flow for Early Prediction of the Presence and Localization of Cerebral Infarction.

This Phase III study is part of a clinical development plan for the use of Xenon Cerebral Blood Flow Scans (CBF) in stroke. The primary objective of the study is to evaluate the ability of Xenon CBF to predict which regions of the brain will undergo irreversible ischemia and infarction in patients with regions of very low blood flow and to evaluate the safety of Xenon CBF studies in patients with stroke. Information with the ability to discriminate significant areas of low blood flow may possibly predict clinical outcome and assist physicians to determine those patients who are not likely to benefit from t-PA and who need not be exposed to the risk of bleeding associated with t-PA.

A double blind, placebo controlled, multicenter study to evaluate the safety and efficacy of a 72-hour infusion of CP-101, 606 in subjects with acute ischemic stroke in the forebrain.

The purpose of this study is to assess that safety and efficacy of CP101, 606 (an NMDA antagonist) compared to placebo to limit growth of the ischemic tissue volume as measured by diffusion MRI following acute ischemic stroke in the cerebral hemisphere. Secondary purposes are to compare the 48-hour diffusion MR endpoint relative to the conventional 3 months NIH Stroke Scale endpoint and to collect samples for identification and validation of markers of neuronal injury.

Optimizing Resuscitation for the Casualty with Combined Hemorrhagic Shock and Traumatic Brain Injury

The primary objective of this project is to develop an optimal initial resuscitation strategy for the combat casualty with both traumatic brain injury (TBI) and uncontrolled hemorrhage. Specifically, this project 1) compares the effects of standard aggressive resuscitation to those of limited or hypotensive resuscitation, and 2) evaluates the efficacy of small volume infusions of various hypertonic and/or hyperoncotic solutions. Primary outcome measures include 150 minute mortality, intraperitoneal hemorrhage volume, systemic and cerebrovascular hemodynamics, cerebral oxygen kinetics, and traditional and immunohistochemical evaluation of the brain for evidence of early neuronal damage.

Alcohol appears to have a potentiating effect on traumatic brain injury. The experiments focus on alcohol-induced physiological changes in response to injury, and the neurochemical mechanisms responsible for these changes. Using a porcine fluid percussion brain injury model, along with hemorrhagic shock in some animals, early cardiorespiratory changes are monitored, and cerebral parameters such as perfusion pressure, brain tissue oxygen and pH, oxygen saturation, and metabolic rate are determined. Current investigations are exploring opiate receptors, GABA, and glutamate in the model. Recently concluded experiments examined the effects of sodium dichloroacetate. Dr. Schultz is conducting experiments on the effect of traumatic brain injury on the hypothalamic-pituitary-adrenal.

Prolongation of Opportunity for Reperfusion or Neuroprotection After Stroke by Enhanced Cerebral Oxygen Delivery

This objective of this project is to determine if hyperbaric oxygenation (or other methods of enhanced oxygen delivery) can lengthen the window of opportunity for effective treatment of strokes. Treatment of stroke patients with t-PA may be effective for more patients if the ischemic region of brain can be oxygenated during the 60-90 minute interval between the infusion of t-PA and lysis of the clot. Cerebral oxygen delivery can be transiently increased even under very low flow conditions with hyperbaric oxygen therapy or with cell free hemoglobin solutions, both of which rely on plasma rather than blood borne oxygen. We hypothesize that increased oxygen delivery can provide bridging therapy to maintain cerebral oxygenation prior to reperfusion. The project will also explore alternative ways in which oxygen tension may affect ischemic mechanisms.

Loxosceles and Tegenaria spider venoms produce a localized inflammatory lesion that progresses to a black dermonecrotic eschar. Little is known about the mechanisms by which these venoms produce the unusual inflammatory response. Our spider venom research is being done in collaboration with the Pathology Department and is two pronged:

1) In vitro work using human endothelial cell cultures. Endothelial cells are being stimulated with Loxosceles venom with subsequent systematic assays of cytokine secretion by these cells. Extracellular secretion, cell surface expression, and intracellular production of chemokines and other cytokines are being measured using a variety of assay techniques. Similar work will later be done looking at other cell lines found in human skin, such as epidermal cell lines. We will do similar inflammation research with Tegenaria spider venom in the near future.

2) In vivo work using the New Zealand rabbit model. As mechanisms of inflammation become known, we will try to inhibit the dermonecrotic ulcers with antibodies to specific cytokines. We will also investigate ulcer-attenuating effects of fab fragments raised against active components of spider venom. Preliminary work has been successful in attenuating ulcer formation with both IL-8 monoclonal antibodies and antivenom fab fragments. Our aim with this work is to broaden our understanding of mechanisms of inflammation, and through this understanding investigate innovative techniques for the treatment of dermonecrotic arachnidism.

These studies are focused on the pathogenesis of acute lung injury following systemic insults such as acute blood loss, and specifically those processes that mediate neutrophil migration into lung. Current work includes examining the effects of complement activation on the pulmonary and systemic response to acute hemorrhage and the relevance of chemotactic mediators expressed by lung during shock. We are also studying changes in neutrophil migration and activation during exposure to perflubron, a novel perfluorocarbon liquid being considered as a medium for liquid ventilation.

This project will examine pulmonary and systemic physiological responses to lung injury. Specifically, lung function, hemodynamic and oxygen delivery responses will be studies in two rat models. Lung neutrophil content, pulmonary capillary leak and intra-alveolar hemorrhage, changes in the mechanical compliance of the lung, and abnormalities in gas exchange will be assessed in both models of injury. These findings will be compared to studies of systemic injury, including hypotension, metabolic and lactic acidosis, cardiac output, systemic vascular resistance, and oxygen consumption.

The mechanism by which partial liquid ventilation with perfluorocarbon liquids provides protection to the lung remains poorly understood. The hypothesis of this project is that perfluorocarbon liquids in some way interfere with receptor-ligand interactions on the surface of inflammatory cells, either by altering the dissociation constant of this relationship or by promoting the internalization of receptors. Examination of these phenomena should lend greater understanding to the mechanisms of action of liquid ventilation and provide insight into this new technology’s most appropriate application in human respiratory failure.

The number of published reports from the Department of Emergency Medicine continues to increase yearly and is a useful metric for the increasing research productivity of the group. Published work from the Department of Emergency Medicine has now appeared in 36 peer-reviewed journals. In addition, faculty members continue to contribute substantially outside of the University as associate editors and reviewers for leading journals in their fields.

Adams HP, Barnathan E, Bogousslavsky J, Brott T, Fisher M, Furlan AJ, Hacke W, Kappelle J, Kothari R, Leclerc J, Moulin T, Polzer J, Scott PA, and Torner J for The Abciximab in Ischemic Stroke Investigators. Abciximab in Acute Ischemic Stroke. A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study. In press, Stroke.
Aghababian RV, Barsan WG, et al. Research Directions in Emergency Medicine. Annals Emerg Med, 27(3):339-342. J Emerg Med, March 1996. Am J Emerg Med, November 1996, Acad Emerg Med, March 1996, 3(3):274-276.
Alberts MJ, Chaturvedi S, Graham G, Hughes RL, Jamieson DG, Krakowski F, Raps E, Scott PA for the National Acute Stroke Team Group. Acute Stroke Teams: Results of a National Survey. Stroke, 29:11 November 1998, 2318-2320.
Allison EJ, Aghababian RV, Barsan WG, Graff JG, Janiak BD, Kramer DA, Perina DG, Robinson WA, Strange GR . Core content for emergency medicine. Task Force on the Core Content for Emergency Medicine Revision. Annals Emerg Med. 29(6):792-811.
Awad S, Rich P, Kolla S, Younger JG, Reickert CA, Downing VP, Bartlett RH. Characteristics of an albumin dialysate hemodiafiltration system for the clearance of unconjugated bilirubin. ASAIO Journal 1997; 43:M745-M749.
Bartlett RH, Roloff DW, Custer JR, Younger JG, Hirschl RB. Extracorporeal life support: the University of Michigan Experience. JAMA 2000; 283:904-908.
Bickell WH, Stern SA. Fluid replacement for hypotensive injury victims: how, when, and what risks? Current Opinion Anesth 1998; 11: 177-180.
Biros MH, Barsan WG, Lewis RJ, Sanders AB. Supporting emergency medicine research: Developing the infrastructure. Annals Emerg Med, 31(2), 188-196. February, 1998, Acad Emerg Med. 5(2):177-84.
Blaivas M, Hom D, Younger JG. Delayed Partial Airway Obstruction Following Blunt Thyroid Trauma. Amer J Emerg Med 1999; 17:348-50.
Borgialli DA, Hill EM,. Maio RF, Compton CP, Gregor MA. Effects of Alcohol on the Geographic Variation of Driver Fatalities in Motor Vehicle Crashes. Acad Emerg Med; 7:7-13, 2000.
Brent J, Gomez HF, Judson F et al: Botulism from potato salad. Dairy, Food and Environmental Sanitation 1995; 15:420-422
Broderick T, Barsan WG., et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke, 1999;30:905-915.
Brott T, Broderick J, Kothari R, Barsan WG,Tomsick T. Early Hemorrhage Growth in Patients with Intracerebral Hemorrhage. Stroke, 1997:28(1):1-5.
Burney RE, Passini L, Hubert D, Maio RF. Variation in Air Medical Outcomes by Crew Composition: Two-year Follow-up. Annals Emer Med, 1995; 25(2): 187-192.
Carden D, Dronen SC, Gerhig G Zalenski RJ. Funding strategies of emergency medicine research. Acad Emerg Med 1998; 5:168-176.
Chen B, Maio RF, Green PE, Burney RE. Geographic Variation in the Preventable Death Rate from Motor Vehicle Crashes J Trauma, 1995;38(2): 228-232.
Chu K, Gregor MA, Maio RF, Hill E, Swor R. Derivation and Validation of Criteria for Determining the Appropriateness of Non-Emergency Ambulance Transports. Prehospital Emerg Care, 1997;1:219-226.
Chudnofsky CR, Weber JE, Stoyanoff, PJ, et al. Midazolam eliminates serious emergence reactions in adult patients receiving ketamine for conscious sedation in the ED. Acad Emer Med, 2000; 7: 228-235.
Clawson JF, Martin RL, Caddy GA, Maio RF. The Wake Effect-Emergency vehicle-related collisions. Prehospital Disaster Med; 12(4):273-276, 1997.
Cunningham R, Silbergleit R. Viral myocarditis presenting with seizure and EKG findings of acute myocardial infarction in a 14 month old child. In press, Annals Emerg Med.
D. K. J. E. Von Lubitz, J. R. Montgomery, and W. Russell. Medical readiness training - just in time. Navy Medicine, 4: 24 -28, 2000.
D’Onofrio G, Bernstein E, Zink BJ, et al. Patients with alcohol problems in the emergency department, part 2: Intervention and referral. Acad Emerg Med. 1998;5(12): 1210-1217.
D’Onofrio, G, Bernstein E., Zink BJ, et al. Patients with alcohol problems in the emergency department, part 1: Improving detection. Acad Emerg Med. 1998;5(12): 1200-1209
Day SM, Younger JG, Karavite D, Bach D, Armstrong W, Eagle KA. The role of arrhythmias induced during dobutamine echocardiography in perioperative risk assessment. Am J Cardiol 2000; 85:478-483.
Foley D, Younger JG, Pranikoff T, Schreiner RJ, Hirschl RB, Bartlett RH. Report of 100 interhospital patient transports on ECLS. In press, ASAIO Journal.
Gerndt SJ, Conley JL, Lowell MJ, Holmes J, Marsh E, Larin L, Taheri PA, Polley TZ, Rodriguez JL. Prehospital classification combined with an in-hospital trauma radio system response reduces cost and duration of evaluation of the injured patient. Surgery, October 1995, 118 (4): 784-789.
Scott PA, Temovsky CJ, Lawrence K, Gudaitis E, Lowell MJ. Analysis of Canadian population with potential geographic access to intravenous thrombolysis for acute ischemic stroke. Stroke, November 1998, 29 (11): 2304-10.
Armstrong WF, Bach DS, Carey LM, Froehlich J, Lowell MJ, Kazerooni EA. Clinical and echocardiographic findings in patients with suspected acute aortic dissection, American Heart Journal, Dec. 1998, 136(6): 1051-60.
Gomez HF, Johnson R, Guven H, McKinney P, Phillips S, Judson F and Brent J. Adsorption of botulinum toxin to activated charcoal with a mouse bioassay. Ann Emerg Med 1995; 25:818-822 [published erratum appears in Ann Emerg Med 1995; 26:152
Gomez HF, McClafferty HC, Flory D, Brent J and Dart RC. Prevention of gastrointestinal iron absorption via chelation to an orally administered pre-mixed deferoxamine/charcoal slurry. Annals Emerg Med 1997;30:587-92.
Gomez HF, McKinney P, Phillips S, Roberts DV, Brent J and Watson WA. Postmortem acetaminophen pharmacokinetics: An experimental study of site and time-dependent concentration changes. J Forensic Sciences 1995; 40:980-982.
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