An integrated device for fast and sensitive immunosuppressant detection.

The present paper describes a compact point of care (POC) optical device for therapeutic drug monitoring (TDM). The core of the device is a disposable plastic chip where an immunoassay for the determination of immunosuppressants takes place. The chip is designed in order to have ten parallel microchannels allowing the simultaneous detection of more than one analyte with replicate measurements. The device is equipped with a microfluidic system, which provides sample mixing with the necessary chemicals and pumping samples, reagents and buffers into the measurement chip, and with integrated thin film amorphous silicon photodiodes for the fluorescence detection. Submicrometric fluorescent magnetic particles are used as support in the immunoassay in order to improve the efficiency of the assay. In particular, the magnetic feature is used to concentrate the antibody onto the sensing layer leading to a much faster implementation of the assay, while the fluorescent feature is used to increase the optical signal leading to a larger optical dynamic change and consequently a better sensitivity and a lower limit of detection. The design and development of the whole integrated optical device are here illustrated. In addition, detection of mycophenolic acid and cyclosporine A in spiked solutions and in microdialysate samples from patient blood with the implemented device are reported.

Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients.

Secondary insults can adversely influence outcome following severe traumatic brain injury. Monitoring of cerebral extracellular chemistry with microdialysis has the potential for early detection of metabolic derangements associated with such events. The objective of this study was to determine the relationship between the fundamental biochemical markers and neurological outcome in a large cohort of patients with traumatic brain injury. Prospectively collected observational neuromonitoring data from 223 patients were analysed. Monitoring modalities included digitally recorded intracranial pressure, cerebral perfusion pressure, cerebrovascular pressure reactivity index and microdialysis markers glucose, lactate, pyruvate, glutamate, glycerol and the lactate/pyruvate ratio. Outcome was assessed using the Glasgow Outcome Scale at 6 months post-injury. Patient-averaged values of parameters were used in statistical analysis, which included univariate non-parametric methods and multivariate logistic regression. Monitoring with microdialysis commenced on median (interquartile range) Day 1 (1-2) from injury and median (interquartile range) duration of monitoring was 4 (2-7) days. Averaged over the total monitoring period levels of glutamate (P = 0.048), lactate/pyruvate ratio (P = 0.044), intracranial pressure (P = 0.006) and cerebrovascular pressure reactivity index (P = 0.01) were significantly higher in patients who died. During the initial 72 h of monitoring, median glycerol levels were also higher in the mortality group (P = 0.014) and median lactate/pyruvate ratio (P = 0.026) and lactate (P = 0.033) levels were significantly lower in patients with favourable outcome. In a multivariate logistic regression model (P < 0.0001), which employed data averaged over the whole monitoring period, significant independent positive predictors of mortality were glucose (P = 0.024), lactate/pyruvate ratio (P = 0.016), intracranial pressure (P = 0.029), cerebrovascular pressure reactivity index (P = 0.036) and age (P = 0.003), while pyruvate was a significant independent negative predictor of mortality (P = 0.004). The results of this study suggest that extracellular metabolic markers are independently associated with outcome following traumatic brain injury. Whether treatment-related improvement in biochemistry translates into better outcome remains to be established.

Medical student attitudes before and after participation in rural health fairs.

BACKGROUND: Despite an increased need, residents of rural communities have decreased access to healthcare and oftenpresentuniquehealthcare challenges associated with their rurality. Ensuring medical students receive adequate exposure to these issues is complicated by the urban location of most medical schools. Health fairs (fairs) conducted in rural communities can provide students exposure to ruralhealth;however, it is unknown how participation affects attitudes regarding these issues. MATERIALS AND METHODS: During the 2010-2011 academic year, first-year medical students were surveyed before and after participating in a rural fair regarding the importance of rural health issues, the need for exposure to rural healthcare, their plans to practice in a rural community,andthe educational impact of fairs. RESULTS: Of the 121participating students, 77% and 61% completed pre- and post-fair surveys, respectively. Few had lived in a rural area or planned to practice primary care. Participants strongly agreed that the delivery of healthcare in rural areas was important, and that all physicians should receive rural health training (4.8 and 3.7 out of 5, respectively) despite less than halfplanning to practice in a rural community. After participating in a rural fair, student attitudes were unchanged, although 87% of participants strongly agreed their involvement had contributed to improving patient health and 70% that the fairs provided rural medicine experience. CONCLUSIONS: Among urban medical school students with varied interests in primary care, there was strong interest in volunteering at rural fairs and appreciation for the importance of rural health. Fairs provided interested students with rural medicine experience that reinforced student attitudes regarding rural health. Further, students felt their participation improved patient health.

Improving access to colorectal cancer screening through medical philanthropy: feasibility of a flexible sigmoidoscopy health fair for uninsured patients.

OBJECTIVES: Only half of eligible patients in the United States undergo colorectal cancer (CRC) screening as recommended. Hypothesizing that the medical philanthropy platform may be effective in improving access to CRC screening, we aimed to demonstrate the feasibility of a flexible sigmoidoscopy (FS)-based CRC screening "health fair" for uninsured patients. METHODS: Uninsured patients older than 50 years who had not undergone CRC screening in the preceding 10 years were recruited through local free clinics and health fairs. A standard medical clinic was transformed into a fully functional endoscopy unit. Medicolegal protection for volunteers was obtained through the Florida Department of Health's Volunteer Health Care Provider Program. Unsedated FS with polypectomy was performed. Those with high-risk endoscopic features were given instructions on obtaining a full colonoscopy. RESULTS: Fifty-two patients without access to any form of CRC screening underwent FS. Ninety-four percent had an adequate bowel preparation, although 40% required on-site enema. Eighteen patients had a total of 22 polyps, 4 of which were adenomatous. There were no complications. The total cost of the fair, excluding donated resources such as endoscopes and processors, was $6,531.47, amounting to $126 per patient screened. CONCLUSIONS: Health fair-style CRC screening for uninsured patients is feasible. With improved efficiency, widespread application of CRC screening using the medical philanthropy platform may represent a viable approach to reducing the underuse of CRC screening among the uninsured.

Student-led rural health fairs: attempting to improve medical education and access to health care.

OBJECTIVES: Residents of rural communities, especially in the Southeast, have decreased access to health care. Ensuring medical students receive adequate exposure to their issues is complicated by the urban location of most schools. We describe health fairs conducted in rural communities to suggest how having medical students use screening tools can identify patients with risk factors for disease which can offer students the opportunity to learn about rural health issues through patient counseling. METHODS: The Mitchell Wolfson Sr. Department of Community Service, a University of Miami Miller School of Medicine student-led organization, conducts fairs at four sites throughout the rural Florida Keys. Medical students, under the supervision of attending physicians, offer screening and preventive health services including risk factor screening for cardiovascular disease, ophthalmological exams, dermatologic exams, osteoporosis screening, and female exams with pap smears. These fairs were reviewed. RESULTS: In the past three years, 1694 unique patients were seen. Many lacked a primary care provider (46%) or health insurance (43%) and were provided screening for several disorders including cardiovascular disease risk factors (hypertension, diabetes, dyslipidemia, and obesity). Screening revealed that many patients (41%) had multiple markers of elevated cardiovascular disease risk. This provided experiences to more than 200 students each year. CONCLUSION: Fairs provide medical students exposure to rural health issues through the valuable opportunity of using risk factor screening tools and counseling. This provides valuable information to patients of rural communities. Future research should examine how fairs influence student knowledge and attitudes toward rural health and affect health outcomes.

A combined microdialysis and FDG-PET study of glucose metabolism in head injury.

BACKGROUND: Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Positron emission tomography (PET) establishes metabolism of the whole brain but only for the scan's duration. This study's objective was to apply these techniques together, in patients with traumatic brain injury, to assess the relationship between microdialysis (extracellular glucose, lactate, pyruvate, and the lactate/pyruvate (L/P) ratio as a marker of anaerobic metabolism) and PET parameters of glucose metabolism using the glucose analogue [(18)F]-fluorodeoxyglucose (FDG). In particular, we aimed to determine the fate of glucose in terms of differential metabolism to pyruvate and lactate. MATERIALS AND METHODS: Microdialysis catheters (CMA70 or CMA71) were inserted into the cerebral cortex of 17 patients with major head injury. Microdialysis was performed during FDG-PET scans with regions of interest for PET analysis defined by the location of the gold-tipped microdialysis catheter. Microdialysate analysis was performed on a CMA600 analyser. FINDINGS: There was significant linear relationship between the PET-derived parameter of glucose metabolism (regional cerebral metabolic rate of glucose; CMRglc) and levels of lactate (r = 0.778, p < 0.0001) and pyruvate (r = 0.799, p < 0.0001), but not with the L/P ratio. CONCLUSION: The results suggest that in this population of patients, glucose was metabolised to both lactate and pyruvate, but was not associated with an increase in the L/P ratio. This suggests an increase in glucose metabolism to both lactate and pyruvate, as opposed to a shift towards anaerobic metabolism.

Inflammation in human brain injury: intracerebral concentrations of IL-1alpha, IL-1beta, and their endogenous inhibitor IL-1ra.

Following traumatic brain injury (TBI), cascades of inflammatory processes occur. Laboratory studies implicate the cytokines interleukin-1alpha (IL-1alpha) and IL-1beta in the pathophysiology of TBI and cerebral ischemia, whilst exogenous and endogenous interleukin-1 receptor antagonist (IL-1ra) is neuroprotective. We analyzed IL-1alpha, IL-1beta, and IL-1ra in brain microdialysates (100-kDa membrane) in 15 TBI patients. We also analyzed energy-related molecules (glucose, lactate, pyruvate, glutamate, and the lactate/pyruvate ratio) in these brain microdialysates. Mean of mean (+/-SD) in vitro microdialysis percentage recoveries (extraction efficiencies) were IL-1alpha 19.7+/-7.6%, IL-1beta 23.9+/-10.5%, and IL-1ra 20.9+/-6.3%. In the patients' brain microdialysates, mean of mean cytokine concentrations (not corrected for percentage recovery) were IL-1alpha 5.6+/-14.8 pg/mL, IL-1beta 10.4+/-14.7 pg/mL, and IL-1ra 2796+/-2918 pg/mL. IL-1ra was consistently much higher than IL-1alpha and IL-1beta. There were no significant relationships between IL-1 family cytokines and energy-related molecules. There was a significant correlation between increasing IL-1beta and increasing IL-1ra (Spearman r=0.59, p=0.028). There was also a significant relationship between increasing IL-1ra and decreasing intracranial pressure (Spearman r=-0.57, p=0.041). High concentrations of IL-1ra, and also high IL-1ra/IL-1beta ratio, were associated with better outcome (Mann Whitney, p=0.018 and p=0.0201, respectively), within these 15 patients. It is unclear whether these IL-1ra concentrations are sufficient to antagonize the effects of IL-1beta in vivo. This study demonstrates feasibility of our microdialysis methodology in recovering IL-1 family cytokines for assessing their inter-relationships in the injured human brain, and suggests a neuroprotective role for IL-1ra. It remains to be seen whether exogenous IL-1ra or other agents can be used to manipulate cytokine levels in the brain, for potential therapeutic effect.

Establishing a regional medical campus in southeast Florida: successes and challenges.

In August 2007, the first class of University of Miami Miller School of Medicine (UM) medical students will begin the four-year undergraduate medical education program at the regional medical campus at Florida Atlantic University (FAU) The authors describe how UM and FAU were able to make a successful case to state policymakers for a regional medical campus as a cost-effective approach to expanding undergraduate and graduate medical education opportunities in southeast Florida The authors discuss what motivated UM and FAU to partner to create a regional medical campus, and they describe the challenges that have been encountered since 2004, particularly those relating to delivering a comparable two-year program on two campuses using distance-learning technologies. The opportunities that have resulted from expansion of the regional campus from two to four years are also described, including the development of a new and innovative four-year curriculum emphasizing comprehensive chronic disease management and case-based and patient-centered education using collaborative, small-group student learning communities. UM medical students thus have a choice between two educational tracks. The authors conclude that no significant impediments have resulted from the Florida collaboration between a public and a private university and that the regional medical campus model can serve as a viable option for other states and institutions attempting to expand medical school enrollment and meet physician workforce needs in an efficient and cost-effective manner.

Consensus statement from the 2014 International Microdialysis Forum.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.

Correlation between cerebral blood flow, substrate delivery, and metabolism in head injury: a combined microdialysis and triple oxygen positron emission tomography study.

Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Conversely, positron emission tomography (PET) establishes metabolism of the whole brain, but only for the duration of the scan. The objective of this study was to apply both techniques to head-injured patients simultaneously to assess the relation between microdialysis (glucose, lactate, lactate/pyruvate [L/P] ratio, and glutamate) and PET (cerebral blood flow [CBF], cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen) parameters. Microdialysis catheters were inserted into the frontal cerebral cortex and adipose tissue of the anterior abdominal wall of 17 severely head-injured patients. Microdialysis was performed during PET scans, with regions of interest defined by the location of the microdialysis catheter membrane. An intervention (hyperventilation) was performed in 13 patients. The results showed that combining PET and microdialysis to monitor metabolism in ventilated patients is feasible and safe, although logistically complex. There was a significant relation between the L/P ratio and the OEF (Spearman r = 0.69, P = 0.002). There was no significant relation between CBF and the microdialysis parameters. Moderate short-term hyperventilation appeared to be tolerated in terms of brain chemistry, although no areas were sampled by microdialysis where the OEF exceeded 70%. Hyperventilation causing a reduction of the arterial carbon dioxide tension by 0.9 kPa resulted in a significant elevation of the OEF, in association with a reduction in glucose, but no significant elevation in the L/P ratio or glutamate.

Undergraduate medical education for the 21st century: leadership and teamwork.

BACKGROUND: The health care delivery system is experiencing enormous flux. The knowledge and skills sets required of today's physicians include expertise in competency areas that have not been included in the traditional medical curricula. The Undergraduate Medical Education for the 21st Century (UME-21) project was designed to develop innovative curricula that addressed the training necessary for medical students to gain skills required to provide high-quality, accessible, and affordable care in the modern health care environment. One of the nine UME-21 content areas, leadership and teamwork, has historically received relatively little attention in medical education. METHODS: Each school participating in the UME-21 project submitted a final report that provided information for this descriptive summary of curricular innovations for teaching the concepts of leadership and teamwork to medical students. A classification lexicon for the curricular content and experiences in this content area was derived from these UME-21 project reports. Each school evaluated its curricular innovations independently using a variety of methods, largely descriptive and qualitative in nature. RESULTS: Eight UME-21 schools developed curricula addressing the content area of leadership and teamwork. The majority of these curricula used the clinical care teams in the clinical rotations to demonstrate the principles and importance of leadership and teamwork. Three of the schools implemented didactic sessions and workshops to explicitly address leadership and teamwork. One school used the gross anatomy dissection teams as the "laboratory" for demonstrating this content material. The evaluations of these curricular efforts showed them to be positively regarded by the medical students. Outcomes of measurable changes in competency in this area of expertise were not evaluated. CONCLUSIONS: There is little past experience in teaching leadership and teamwork in medical school. The UME-21 project supported the design and implementation of several curricular innovations in this content area, which were well received by learners. These eight leadership and teamwork curricula are described, a lexicon outlining the specific content that was addressed in this content area is presented, and lessons learned are included in this report. Further efforts to demonstrate the mastery of new skills in this important content area, based on curricula such as these, are needed.

Teaching quality measurement and improvement, cost-effectiveness, and patient satisfaction in undergraduate medical education: the UME-21 experience.

BACKGROUND: The health care system in the United States is changing at an ever-increasing rate. Recent reports by the Institute of Medicine raising concerns regarding rates of medical errors and suggesting the need for reengineering of the health care delivery system have focused attention on the need for quality measurement and improvement. METHODS: We abstracted data from final written reports submitted by 18 Undergraduate Medical Education for the 21st Century (UME-21) schools, as well as other materials available from participating UME-21 schools. Specific curricular innovations developed and implemented were identified. Additionally, senior medical students' responses to the annual Graduation Questionnaire administered by the Association of American Medical Colleges (AAMC) were available for analysis. The change from 1999 to 2001 in the proportion of seniors rating instruction in quality assurance as adequate was compared among four groups of UME-21 schools and the other 107 US medical schools. RESULTS: Eleven of the 18 schools specifically addressed the content areas of quality measurement and improvement, including utilization management (27% of schools), cost-effectiveness (45% of schools), use of clinical practice guidelines (73% of schools), and patient satisfaction assessment (45% of schools). Each school developed unique approaches and educational materials pertinent to the content area. Overall, the percentage of seniors rating the relative amount of instructional time devoted to quality assurance in medicine by their school's curriculum as adequate or better rose from 49% to 66% between 1999 and 2001 at the 11 UME-21 schools that introduced initiatives in quality improvement into their curricula. This change was significantly higher than the pattern at other US medical schools between 1999 and 2001, at which seniors' ratings rose only from 43% to 56%. CONCLUSIONS: Curriculum development and implementation addressing quality improvement in medical practice accelerate improvement of students' perception that their education has adequately addressed this subject area. This article summarizes some of the experiences, curricular approaches, successes, failures, and lessons learned in quality improvement by schools participating in the UME-21 project.

A curriculum in systems-based care: experiential learning changes in student knowledge and attitudes.

BACKGROUND: To provide efficient, quality patient care, physicians must have a fundamental understanding of how the health care delivery system functions and how to appropriately use the various components of this system. As part of the Undergraduate Medical Education for the 21st Century (UME-21) initiative, the University of Miami in partnership with AvMed Health Plans, a nonprofit managed care organization (MCO) developed a longitudinal educational program that prepares all students for medical practice in emerging systems of care. METHODS: The program, which spans the 4-year undergraduate curriculum, incorporates didactic sessions and practical experiences to teach about the clinical, managerial, financial, and ethical aspects of systems-based care. During the third year of medical school, students visit the administrative offices of AvMed Health Plans for a day-long series of presentation-discussions and experiential tours through the various administrative departments. There, they experience first-hand all facets of a systems-based approach to care using evidence-based practice guidelines, utilization review, quality measurement and improvement, and chronic disease management. RESULTS: An attitudinal survey, constructed to evaluate general attitudes toward managing care and MCOs, was administered to students at the beginning of their first, second, and third year and immediately before and after their visit to AvMed during their third year. Using factor analysis, there were no significant differences in students' attitudes at the beginning of the first, second, or third year nor immediately before the seminar day at the MCO. However, the day-long seminar at AvMed did have a favorable effect on attitudes toward systems of care and MCOs in general. In addition, students performed well on post-evaluation knowledge assessments addressing fundamental concepts of systems of care and the function of an MCO in managing the care of its members. The visit to the MCOs (AvMed) offices and the day-long curriculum was replicated at another medical school, with similar effects on students' attitudes. CONCLUSIONS: Medical students have neutral-to-negative opinions of systems of care and MCOs. Early educational experiences such as classroom lectures and panels that address managing care issues have minimal effect on these opinions. However, bringing medical students to an MCO's administrative offices, seeing first-hand how systems of care operate, and having an open dialogue with physician administrators does effect a positive change in medical student opinions of a system in which care is managed. In addition, medical students can gain new knowledge about effective systems-based practice.

Practicing effectively in today's health system: teaching systems-based care.

BACKGROUND AND OBJECTIVES: The Institute of Medicine and the new Accreditation Council for Graduate Medical Education General Essentials have focused attention on the Undergraduate Medical Education for the 21st Century (UME-21) core content area of systems-based care. Through teaching systems-based care, medical students can learn how physicians effectively deliver and coordinate care within the health system. While medical students can be introduced to the organization, financing, and delivery of the health care system through lectures, the principles and practice of systems-based care must be reinforced through structured learning experiences during the clinical (ie, third and fourth) years. The purpose of this article is to define the undergraduate clinical content and experiences in systems-based care offered by the eight UME-21 partner schools. METHODS: The eight partner UME-21 schools exposed third- and fourth-year medical students to a variety of clinical experiences outside the traditional teaching hospital in such settings as physician offices, skilled nursing facilities, the patient's home, hospice, and public health departments. They also taught systems-based care skills such as care coordination, performance assessment, and quality improvement. RESULTS: Based on surveys of graduating students, the UME-21 programs were successful in exposing students to the aforementioned topics, though there was variability among schools. DISCUSSION: The experiences of the UME-21 schools in teaching about systems-based care, as discussed in this paper, may be useful to those involved in medical school curricula planning.

Increasing access to cholesterol screening in rural communities catalyzes cardiovascular disease prevention.

PURPOSE: Despite increasing frequency, little evidence guides cholesterol screening in less traditional health care settings, such as rural health fairs. METHODS: The Miller School of Medicine Department of Community Service (DOCS) is a student-run organization providing free basic health care to underserved South Florida communities. We retrospectively reviewed all new patients seen at 2007 DOCS rural fairs to describe their low-density lipoprotein (LDL) and high-density lipoprotein (HDL) values. In addition, we assessed if patient characteristics were associated with cholesterol abnormalities and whether patients with abnormalities who returned to a subsequent fair in 2008 or 2009 improved their cholesterol. FINDINGS: Of 252 patients, 145 (58%) had an LDL cholesterol over 129 mg/dL and 61 (24%) had an HDL cholesterol below 40 mg/dL or 50 mg/dL for males and females, respectively. Baseline LDL cholesterol was not associated with body-mass index (BMI), age over 60 years, gender, healthy lifestyle habits, or insurance status. Of 36 patients with elevated LDL cholesterol and a follow-up screening, 24 (67%) reduced their LDL cholesterol by at least 16 mg/dL though reductions were not associated with BMI reduction, and 22 (61%) increased their HDL cholesterol by at least 5 mg/dL, trending with BMI reduction. CONCLUSIONS: Cholesterol screening at rural fairs can identify a high proportion of patients with abnormal cholesterol, including those who might not be considered at high risk. Although this may catalyze favorable cholesterol changes, the lack of an association with weight loss suggests patients seek additional medical care, which should be considered before offering cholesterol screening at fairs.

Effect of cerebral perfusion pressure augmentation on regional oxygenation and metabolism after head injury.

OBJECTIVE: In this study we have used O positron emission tomography, brain tissue oxygen monitoring, and cerebral microdialysis to assess the effects of cerebral perfusion pressure augmentation on regional physiology and metabolism in the setting of traumatic brain injury. DESIGN: Prospective interventional study. SETTING: Neurosciences critical care unit of a university hospital. PATIENTS: Eleven acutely head-injured patients requiring norepinephrine to maintain cerebral perfusion pressure. INTERVENTIONS: Using positron emission tomography, we have quantified the response to an increase in cerebral perfusion pressure in a region of interest around a brain tissue oxygen sensor (Neurotrend) and microdialysis catheter. Oxygen extraction fraction and cerebral blood flow were measured with positron emission tomography at a cerebral perfusion pressure of approximately 70 mm Hg and approximately 90 mm Hg using norepinephrine to control cerebral perfusion pressure. All other aspects of physiology were kept stable. MEASUREMENTS AND MAIN RESULTS: Cerebral perfusion pressure augmentation resulted in a significant increase in brain tissue oxygen (17 +/- 8 vs. 22 +/- 8 mm Hg; 2.2 +/- 1.0 vs. 2.9 +/- 1.0 kPa, p < .001) and cerebral blood flow (27.5 +/- 5.1 vs. 29.7 +/- 6.0 mL/100 mL/min, p < .05) and a significant decrease in oxygen extraction fraction (33.4 +/- 5.9 vs. 30.3 +/- 4.6 %, p < .05). There were no significant changes in any of the microdialysis variables (glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol). There was a significant linear relationship between brain tissue oxygen and oxygen extraction fraction (r = .21, p < .05); the brain tissue oxygen value associated with an oxygen extraction fraction of 40% (the mean value for oxygen extraction fraction in normal controls) was 14 mm Hg (1.8 kPa). The cerebral perfusion pressure intervention resulted in a greater percentage increase in brain tissue oxygen than the percentage decrease in oxygen extraction fraction; this suggests that the oxygen gradients between the vascular and tissue compartments were reduced by the cerebral perfusion pressure intervention. CONCLUSIONS: Cerebral perfusion pressure augmentation significantly increased levels of brain tissue oxygen and significantly reduced regional oxygen extraction fraction. However, these changes did not translate into predictable changes in regional chemistry. Our results suggest that the ischemic level of brain tissue oxygen may lie at a level below 14 mm Hg (1.8 kPa); however, the data do not allow us to be more specific.