PubMed Health⌕ Search

Biomedical subjects

B L Gewertz

Publications and source records attributed to B L Gewertz.

At least 19 recordsLinked to original sources

Estimating the contemporary in-hospital costs of carotid endarterectomy.

Carotid endarterectomy (CEA) is the treatment of choice for symptomatic carotid stenosis and selective asymptomatic lesions. Alternative approaches have recently been championed under the guise of increased efficacy and decreased cost. The purpose of this study was to determine the results and in-hospital costs of CEA in a university hospital in the modern era. A retrospective chart review was undertaken for all patients undergoing CEA between January 1995 and December 1997. This corresponded to the implementation of a clinical path and extended efforts toward cost reduction. Patients undergoing combined CEA and cardiopulmonary bypass were excluded (n = 3). Cost was analyzed by the hospital Office of Program Planning using TSI (Transition Systems, Inc.) software. Direct costs are related to the utilization of clinical resources and are therefore manageable by clinicians (bed, room, supplies, nursing staff, OR staff, radiology, pharmacy, etc.). Total costs additionally include administration and overhead costs not directly chargeable to patient accounts. The results of this study showed that CEA can be safely performed with brief hospital stays and reasonable hospital costs. Results of alternative interventions for the treatment of carotid stenosis should be compared to these contemporary data.

Adult↗

Effective hemodynamic diameter: an intrinsic property of vein grafts with predictive value for patency.

INTRODUCTION: Conduit size and quality are major determinants of the long-term success of infrainguinal autologous vein grafting. However, accurate measurement of the internal diameter of vein grafts is difficult given their variable wall thickness and taper. The purpose of this study was to define the "effective" internal diameter of a vein graft according to its hemodynamic properties and to determine its significance for graft patency. METHODS: Sixty infrainguinal bypass grafts performed on 57 patients were evaluated intraoperatively. Proximal and distal graft pressure and blood flow (Q(meas)) were measured with fluid-filled catheter transduction and ultrasonic transit-time flowimetry, respectively, after unclamping. Waveforms were recorded digitally at 200 Hz under baseline conditions and after stimulation with 60 mg of papaverine. According to Fourier transformation of the measured pressure gradient (DeltaP), the Womersley solution for fluid flow in a straight rigid tube was used to calculate theoretical flow waveforms (Q(calc)) for a range of graft diameters. The theoretical waveforms were then compared with the measured flow waveforms and the best-fit diameter chosen as the "effective hemodynamic diameter" (EHD). Only grafts in which the correlation coefficient of Q(calc) versus Q(meas) was more than 0.90 were accepted (n = 47) to assure validity of the hemodynamic model. After a mean follow-up of 12.5 months (range, 0.1-43.9 months), patency was determined by the life table method. Hemodynamic and clinical variables were tabulated, and their effect on patency determined the use of univariate and multivariate Cox regression. RESULTS: Mean EHD was 4.1 +/- 0.1 mm with a range of 2.5 to 5.7 mm. Administration of papaverine caused profound changes in DeltaP (+78% +/- 17%) and Q(meas) (+71% +/- 12%) as expected, but had no effect on EHD (+0.05% +/- 0.1%). Univariate regression identified five variables associated with decreased secondary patency (P <.10): low EHD, conduit source other than the greater saphenous vein, high baseline DeltaP(mean), female sex, and redo operation. Of these, only low EHD was significant after multivariate analysis (P =.03). Patency of small diameter grafts (EHD < 3.6 mm; n = 11) was compared with patency of larger grafts (EHD > 3.6 mm; n = 36) to test a frequently espoused clinical guideline. Grafts with an EHD less than 3.6 mm exhibited significantly lower secondary patency compared with larger grafts (P =.0001). The positive and negative predictive values for an EHD less than 3.6 mm for secondary graft failure for grafts with at least 1 year follow-up were 86% and 88%, respectively. CONCLUSION: An EHD is a unique parameter that quantifies conduit size and has a significant impact on vein graft patency. An EHD less than 3.6 mm portends graft failure.

Aged↗

Measuring faculty effort and contributions in medical education.

A national panel on medical education was appointed as a component of the AAMC's Mission-based Management Program and charged with developing a metrics system for measuring medical school faculty effort and contributions to a school's education mission. The panel first defined important variables to be considered in creating such a system: the education programs in which medical school faculty participate; the categories of education work that may be performed in each program (teaching, development of education products, administration and service, and scholarship in education); and the array of specific education activities that faculty could perform in each of these work areas. The panel based the system on a relative value scale, since this approach does not equate faculty performance solely to the time expended by a faculty member in pursuit of a specific activity. Also, a four-step process to create relative value units (RVUs) for education activities was developed. This process incorporates quantitative and qualitative measures of faculty activity and also can measure and value the distribution of faculty effort relative to a school's education mission. When adapted to the education mission and culture of an individual school, the proposed metrics system can provide critical information that will assist the school's leadership in evaluating and rewarding faculty performance in education and will support a mission-based management strategy in the school.

Education, Medical↗

Decrease in mucosal alkaline phosphatase: a potential marker of intestinal reperfusion injury.

Intestinal ischemia necessitates rapid re-establishment of blood flow to prevent irreversible anoxic tissue damage. However, reperfusion results in additional injury as a consequence of the generation of oxygen free radicals. To date, no clear-cut marker to differentiate between ischemia versus reperfusion injury is available. In this regard, previous studies from our laboratory utilizing a rat in vitro lipid peroxidation model demonstrated that the generation of free radicals resulted in the inactivation of only the intestinal brush border alkaline phosphatase enzyme, with no effect on other membrane-bound digestive enzymes. Current studies were designed to assess the possibility of alkaline phosphatase being a specific marker of the reperfusion injury in canine and human ex vivo ischemia/reperfusion models. Small bowels harvested from canines and organ donors were subjected to ischemia followed by reperfusion. Brush border membrane enzymes, alkaline phosphatase, sucrase, maltase, and gamma-glutamyl transpeptidase were assayed in mucosal extracts from intestines with ischemia versus reperfusion. In both experimental models, there was no change in any enzyme activity with warm ischemia alone. In contrast, alkaline phosphatase activity was significantly decreased in both the canine and human reperfusion models, with no change in specific activities of sucrase, maltase, and gamma-glutamyl transpeptidase. Our data indicate that the alkaline phosphatase enzyme activity may represent a potential marker of intestinal reperfusion injury and may permit quantitative assessments of therapeutic interventions in human intestinal reperfusion injury.

Alkaline Phosphatase↗

Endothelial permeability and IL-6 production during hypoxia: role of ROS in signal transduction.

Prolonged hypoxia produces reversible changes in endothelial permeability, but the mechanisms involved are not fully known. Previous studies have implicated reactive oxygen species (ROS) and cytokines in the regulation of permeability. We tested whether prolonged hypoxia alters permeability to increasing ROS generation, which amplifies cytokine production. Human umbilical vein endothelial cell (HUVEC) monolayers were exposed to hypoxia while secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-6, and IL-8 was measured. IL-6 and IL-8 secretion increased fourfold over 24 h in a pattern corresponding to changes in HUVEC permeability measured by transendothelial electrical resistance (TEER). Addition of exogenous IL-6 to normoxic HUVEC monolayers caused time-dependent changes in TEER that mimicked the hypoxic response. An antibody to IL-6 significantly attenuated the hypoxia-induced changes in TEER (86 +/- 4 vs. 63 +/- 3% with hypoxia alone at 18 h), whereas treatment with anti-IL-8 had no effect. To determine the role of hypoxia-induced ROS on this response, HUVEC monolayers were incubated with the antioxidants ebselen (50 microM) and N-acetyl-L-cysteine (NAC, 1 mM) before hypoxia. Antioxidants attenuated hypoxia-induced IL-6 secretion (13 +/- 2 pg/ml with ebselen and 19 +/- 3 pg/ml with NAC vs. 140 +/- 15 pg/ml with hypoxia). Ebselen and NAC prevented changes in TEER during hypoxia (94 +/- 2% with ebselen and 90 +/- 6% with NAC vs. 63 +/- 3% with hypoxia at 18 h). N-nitro-L-arginine (500 microM) did not decrease hypoxia-induced changes in dichlorofluorescin fluorescence, IL-6 secretion, or TEER. Thus ROS generated during hypoxia act as signaling elements, regulating secretion of the proinflammatory cytokines that lead to alterations of endothelial permeability.

Antibodies↗

Assessing outcomes, costs, and benefits of emerging technology for minimally invasive saphenous vein in situ distal arterial bypasses.

BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion has recently been approved for use. Despite the attractiveness of this approach (2 short incisions), benefits such as lower morbidity and shorter hospitalizations remain undocumented. To justify wide acceptance, minimally invasive surgical techniques must match conventional procedures in durability and cost while enhancing patient comfort. Often such comparisons are difficult during the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes of the MIAB procedures with a concurrent group of patients undergoing conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING: University medical center. PATIENT: The first 20 consecutive MIAB procedures in 19 patients performed between August 1, 1995, and July 31, 1997, were compared with 19 contemporaneous consecutive conventional in situ bypass procedures performed at the same institution. MAIN OUTCOME MEASURES: Operative time, postoperative length of stay, hospital costs, complications, primary assisted and secondary patency, limb salvage, and survival. RESULTS: The patient groups were comparable with respect to age, sex, incidence of smoking, coronary artery disease, hypertension, diabetes, renal failure, cerebrovascular disease, indication, and distal anastomosis level. The median operative time was significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and intraoperative completion arteriography more frequently showed retained arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median postoperative length of stay and total cost were 6.5 days and $18,000 for the MIAB group and 8 days and $27,800 for the conventional group (P > or = .05). There were no significant differences in major complications (10% in the MIAB group vs 11% in the conventional group), wound complications (10% vs 11%, respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%, respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively), limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing the MIAB procedure avoided lengthy vein exposure incisions without sacrificing short-term results. There was a trend toward decreased hospital stay and cost, which may be further realized as the clinical experience broadens. Although longer follow-up and larger cohorts will always be required to define durability, immediate access to outcomes and costs on small numbers of patients facilitates the early assessment of emerging technology.

Adult↗

Serum proteins facilitate neutrophil induction of endothelial leukocyte adhesion molecule 1.

BACKGROUND: Although the individual actions of neutrophils and serum proteins such as complement in acute inflammation are well characterized, less is known about their effects in combination. We investigated the combined effects of neutrophil contact and active serum proteins on the expression of endothelial leukocyte adhesion molecule 1 (ELAM-1). METHODS: Confluent monolayers of human umbilical vein endothelial cells were incubated with neutrophils in the presence and absence of fresh human serum. Flow cytometry was used to assess expression of endothelial intercellular adhesion molecule 1 (ICAM-1) and ELAM-1. In addition, neutrophils were retained in a semipermeable insert, which allowed their secretions to contact the endothelium but restricted neutrophil-endothelial contact. RESULTS: ELAM-1 expression was significantly increased on the cells coincubated with neutrophils and fresh human serum (25.8%; p < 0.001). There was no significant change in ELAM-1 expression on endothelial cells incubated with fresh human serum alone (3.9%; p > 0.01) or in those incubated with neutrophils and heat-inactivated serum (9.3%; p > 0.01). In the absence of neutrophil contact, ELAM-1 expression was increased only in the presence of fresh human serum (9.6%; p < 0.05). CONCLUSIONS: These findings suggest that serum proteins may potentiate the volume or potency of neutrophil-derived diffusable mediators of ELAM-1 expression. These effects are eliminated with the heat inactivation of serum proteins, implicating a heat sensitive mediator such as the complement cascade.

Blood Physiological Phenomena↗

Improving perioperative management of carotid endarterectomy.

Multiple components of the perioperative course of patients who undergo carotid endarterectomy must be tightly controlled in order to maintain an acceptably low complication rate. These factors include appropriate patient selection, routine assessment of cardiac risk factors, precise control of blood pressure intraoperatively and postoperatively, meticulous surgical technique and reliable monitoring for intraoperative cerebral ischemia. This discussion focuses on the vascular practice patterns at the University of Chicago and emphasizes intraoperative management and the safe utilization of intraluminal shunts.

Brain Ischemia↗

Prolonged hypoxia alters endothelial barrier function.

BACKGROUND: It is well recognized that hypoxia/reoxygenation and exposure to inflammatory mediators such as cytokines and neutrophils alter the barrier function of the vascular endothelium. The experiments we conducted tested whether hypoxia alone could produce changes in permeability and whether a prolonged period of hypoxia alters the surface expression of cell adhesion molecules. METHODS: Endothelial cells were cultured from human umbilical vein endothelial cells (HUVECs). Hypoxia was created by isolating the cells in a chamber through which 1% 02, 5% CO2, and 94% N2 were insufflated (30 min at 1/min). Oxygen tension was measured through oxygen-quenching phosphorescence. Hypoxia was maintained for 24 hours. Changes in endothelial permeability were measured by transendothelial electrical resistance (TEER). Endothelial leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression were assessed by flow cytometry (mean +/ standard error of the mean [SEM]. RESULTS: Exposure of endothelial cells to hypoxia resulted in increased permeability between 6 and 24 hours, with the greatest decrease in TEER at 18 hours (63% +/ 3%; P < .05). Prolonged hypoxia produced no change in the surface expression of ELAM-1 or ICAM-1. CONCLUSIONS: Hypoxia alone produced a significant reversible alteration in endothelial permeability. However, this change was observed only under severe hypoxic conditions (eg, below 20 mm Hg); higher oxygen tensions (25 and 35 mm Hg) had no significant effect. Unlike observations made after cytokine exposure, hypoxic breakdown of endothelial barrier function was unassociated with up-regulation of either ELAM-1 or ICAM-1.

Cell Hypoxia↗

Current results of surgical therapy for chronic mesenteric ischemia.

BACKGROUND: Although recognition of chronic mesenteric ischemia has increased in recent years, this disorder has continued to present diagnostic and therapeutic challenges. OBJECTIVE: To examine the modern results of surgical revascularization for chronic mesenteric ischemia. DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: The management of 24 consecutive patients (mean +/- SEM age, 58 +/- 3 years; 5 men, 19 women) who were undergoing surgical treatment of chronic mesenteric ischemia between 1986 and 1996 was reviewed. INTERVENTION: Surgical mesenteric revascularization. MAIN OUTCOME MEASURES: Postoperative course, long-term graft patency rate, and long-term symptom-free survival rate. RESULTS: The most frequent presenting symptoms were postprandial abdominal pain (18 patients [75%]) and weight loss (14 patients [58%]). Less specific complaints included nausea and vomiting (8 patients [33%]), diarrhea (7 patients [29%]), and constipation (4 patients [17%]). Atherosclerotic risk factors were common, including tobacco use (20 patients [83%]), coronary artery disease (10 patients [42%]), and hypertension (10 patients [42%]). The cause was identified as atherosclerosis in 21 patients, median arcuate ligament compression in 2 patients who were monozygotic twins, and Takayasu arteritis in 1 patient. Lesions were localized to all 3 major visceral vessels (celiac artery, superior mesenteric artery [SMA], and inferior mesenteric artery) in 8 patients, celiac artery and SMA in 13, SMA alone in 2, and SMA and inferior mesenteric artery in 1. Seventeen patients underwent antegrade reconstructions from the supraceliac aorta to the SMA and/or celiac artery; 7 patients underwent revascularization by use of a retrograde bypass that originated from the infrarenal aorta or a prosthetic graft. There were no perioperative deaths although 1 patient died in the hospital 6 weeks after early graft failure and sepsis (overall in-hospital mortality, 4%). Follow-up ranged from 3 months to 10 years (median, 2.4 years). The mean +/- SEM 5-year primary graft patency rate, as objectively documented by use of contrast angiography or duplex scanning in 19 of 24 patients, was 78% +/- 11%. Primary failure was documented in 3 patients (at 3 weeks, 5 months, and 7 months). Two patients required a thrombectomy; 1 of these patients subsequently died of an intestinal infarction. The mean +/- SEM 5-year survival rate by use of life-table analysis was 71% +/- 11%. No patient with a patent graft experienced a symptomatic recurrence. CONCLUSIONS: Chronic mesenteric ischemia is usually a manifestation of advanced systemic atherosclerosis. Symptoms almost always reflect midgut ischemia in the distribution of the SMA. An antegrade bypass from the supraceliac aorta can be performed with acceptable operative morbidity and is currently the preferred reconstructive technique. Surgical revascularization affords long-term symptom-free survival in a majority of patients with chronic mesenteric ischemia.

Adult↗

TNF-alpha and IL-1 upregulate membrane-bound and soluble E-selectin through a common pathway.

BACKGROUND: Endothelial cell adhesion molecules such as E-selectin promote the capture of neutrophils (PMN) in the microcirculation and initiate the inflammatory response. In contrast, when "shed" into the microcirculation, soluble E-selectin can bind PMN in the blood stream, reducing the number available for adhesion to injured tissue. These experiments were designed to better characterize the molecular response to cytokines and the balance between cell surface (bound) and soluble (unbound) E-selectin. METHODS: Cultured human umbilical veins, exposed to human recombinant TNF-alpha or IL-1 (10 pg/ml), were analyzed for E-selectin mRNA induction (Northern blot), E-selectin cell surface expression (flow cytometry), and sE-selectin release (ELISA). Transcriptional regulation was analyzed via Raf kinase dominant negative gene transfection. RESULTS: E-selectin mRNA expression was markedly increased at 2 h and sustained through 8 h. No further induction was noted at 12 h. Upregulation of cell surface E-selectin was noted (mean fluorescence) as early as 2 h for TNF-alpha (baseline, 12.28 +/- 1.32; TNF-alpha, 23.03 +/- 1.81) or 4 h for IL-1 (baseline, 12.28 +/- 1.32; IL-1, 70.00 +/- 3.04) with maximum expression at 6 h (TNF-alpha, 118.8+/-15; IL-1, 94.11 +/- 9. 34). Expression returned to baseline levels by 24 h. Soluble E-selectin (ng/ml) assays demonstrated later increases beginning at 12 h (TNF-alpha, 0.313 +/- 0.077; IL-1, 0.159 +/- 0.075) and continuing through 24 h (TNF-alpha, 0.340 +/- 0.062; IL-1, 0.157 +/- 0.030). Transfection of endothelial cells with Raf kinase 301 dominant negative gene resulted in proportionate decreases in the peak expression in both surface (bound) E-selectin (TNF-alpha, 51. 7%; IL-1, 29.6%) and sE-selectin (TNF-alpha, 49.2%; IL-1, 34.5%). CONCLUSION: The temporal sequence of late decreases in cell surface E-selectin accompanied by increases in soluble E-selectin indicates that the source of E-selectin in the microcirculation is shed receptors rather than synthesis of a different type of receptor. Enhancement of such "shedding" may decrease PMN adhesion to injured tissue and have therapeutic potential.

Cell Adhesion↗

Loss of endothelial barrier function requires neutrophil adhesion.

BACKGROUND: The inflammatory response is characterized by cytokine-induced up-regulation of endothelial adhesion molecules followed by polymorphonuclear neutrophil (PMN) adhesion and breakdown of tight junctions between cells. The purpose of this investigation was to determine whether PMN adhesion is an essential element in the alteration of endothelial permeability or whether cytokines alone can produce this change. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to formylated met-leu-phe-activated PMNs. In a second series of experiments, PMNs were contained in a microporous membrane that allowed passage of secreted cytokines but not cells. Permeability was quantified by using transendothelial electrical resistance (TEER, ohm.cm2,) whereas expressions of two cell adhesion molecules (endothelial leukocyte adhesion molecule-1 [ELAM-1] and intercellular adhesion molecule-1 [ICAM-1]) were measured by flow cytometry (% shift). Cytokine production was monitored with enzyme-linked immunosorbant assays (picograms per milliliter). RESULTS: Stimulated PMNs secreted comparable amounts of cytokines whether allowed access to HUVECs or trapped in a microporous membrane (interleukin-1 alpha, 5.88 +/- 2.38 versus 3.65 +/- 1.84 pg/ml; tumor necrosis factor-alpha, 10.27 +/- 3.21 versus 6.61 +/- 1.82 pg/ml). Up-regulation of ELAM-1 and ICAM-1 was observed whether PMNs were free or restricted (52.97% +/- 2.14% versus 75.32% +/- 4.19% and 71.66% +/- 7.37% versus 73.66% +/- 4.32%, respectively). TEER was unchanged in controls and when PMNs were membrane restricted. In contrast, TEER decreased precipitously (51% +/- 5.9% of control, p < 0.05) if PMNs were allowed access to HUVECs. CONCLUSIONS: Cytokine secretion by PMNs is independent of endothelial contact and is sufficient to upregulate adhesion molecules. However, PMN adhesion is essential for the loss of endothelial barrier function, which leads to diapedesis of activated PMNs and eventual tissue injury.

Cell Adhesion↗

Acute mesenteric ischemia.

The morbidity and mortality of acute mesenteric ischemia have remained high over the past 30 years despite heightened sensitivity to the diagnosis. Because the duration of the ischemic episode is the most significant determinant of outcome, an aggressive diagnostic and treatment protocol must be maintained. Although this stance may precipitate a number of negative angiographic studies, such an approach is the only opportunity for salvage in these critically ill patients.

Acute Disease↗

Chronic mesenteric ischemia. Clinical presentation and diagnosis.

Owing to a heightened awareness of the disease as well as improved diagnostic tests, chronic mesenteric ischemia is now recognized as a more common cause of abdominal pain. The classic symptoms of postprandial abdominal pain with weight loss are evident in the majority of proven cases; most patients also have other evidence of advanced atherosclerotic vascular disease. Several new diagnostic techniques are being developed and tested, most notably color duplex imaging, although angiography still remains the diagnostic gold standard. It is hoped that better noninvasive testing may eventually eliminate the need for angiography, as well as lead to a more expedient diagnosis of chronic mesenteric ischemia.

Chronic Disease↗

Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis.

PURPOSE: The structural features that underlie carotid plaque disruption and symptoms are largely unknown. We have previously shown that the chemical composition and structural complexity of critical carotid stenoses are related to plaque size regardless of symptoms. To further determine whether the spatial distribution of individual plaque components in relation to the lumen corresponds to symptomatic outcome, we evaluated 99 carotid endarterectomy plaques. METHODS: Indications for operation were symptomatic disease in 59 instances (including hemispheric transient ischemic attack in 29, stroke in 19, and amaurosis fugax in 11) and angiographic asymptomatic stenosis > 75% in 40. Plaques removed after remote symptoms beyond 6 months were excluded. Histologic sections from the most stenotic region of the plaque were examined using computer-assisted morphometric analysis. The percent area of plaque cross-section occupied by necrotic lipid core with or without associated plaque hematoma, by calcification, as well as the distance from the lumen or fibrous cap of each of these features, were determined. The presence of foam cells, macrophages, and inflammatory cell collections within, on, or just beneath the fibrous cap was taken as an additional indication of plaque neoformation. RESULTS: The mean percent angiographic stenosis was 82% +/- 11% and 79% +/- 13% for the asymptomatic and symptomatic groups, respectively (p > 0.05). The necrotic core was twice as close to the lumen in symptomatic plaques when compared with asymptomatic plaques (0.27 +/- 0.3 mm vs 0.5 +/- 0.5 mm; p < 0.01). The percent area of necrotic core or calcification was similar for both groups (22% vs 26% and 7% vs 6%, respectively). There was no significant relationship to symptom production of either the distance of calcification from the lumen or of the percent area occupied by the lipid necrotic core or calcification. The number of macrophages infiltrating the region of the fibrous cap was three times greater in the symptomatic plaques compared with the asymptomatic plaques (1114 +/- 1104 vs 385 +/- 622, respectively, p < 0.009). Regions of fibrous cap disruption or ulceration were more commonly observed in the symptomatic plaques than in the asymptomatic plaques (32% vs 20%). None of the demographic or clinical atherosclerosis risk factors distinguished between symptomatic and asymptomatic plaques. CONCLUSIONS: These findings indicate that proximity of plaque necrotic core to the lumen and cellular indicators of plaque neoformation or inflammatory reaction about the fibrous cap are associated with clinical ischemic events. The morphologic complexity of carotid stenoses does not appear to determine symptomatic outcome but rather the topography of individual plaque components in relation to the fibrous cap and the lumen. Imaging techniques that precisely resolve the position of the necrotic core and evidence of inflammatory reactions within carotid plaques should help identify high-risk stenoses before disruption and symptomatic carotid disease.

Aged↗