Carbon dioxide column angioscopy: a new endovascular imaging technique.

A new angioscopic technique with a CO(2) gas medium for prolonged viewing sessions in the carotid artery is described. A stationary column of CO(2) gas, angled 17-30 degrees subhorizontally and buoyed against a balloon catheter, can be safely maintained. During 10-20-min sessions in dogs, endothelia, thrombi, stent filaments, coils, and an intimal flap were visualized. This technique eliminates the need for continuous saline infusion, which has prevented the application of angioscopy in the carotid artery.

Frequency and predictors for angiographically improved inflow of contrast medium after carotid angioplasty and stenting.

Percutaneous transluminal carotid angioplasty and stenting (PTAS) can result in immediate improvement in cerebral blood flow (CBF) evident through faster transit of contrast medium on angiography. To evaluate frequency and predictors of changes in inflow of contrast medium before and after PTAS, we reviewed 86 patients (mean age 68.6 +/- 9.1 years) treated for symptomatic or asymptomatic carotid stenosis. Clinical data and lesion characteristics were extracted from charts and digital angiograms, respectively. Perfusion change was assessed qualitatively by comparing pre- and poststenting images matched for projection and time from injection. Improved inflow was defined on the basis of spatial or temporal distribution of contrast medium: grade -1: fewer vessels visible after stenting; 0: no change; 1: more distal small arteries visible; 2: time-matched poststenting image showing a capillary blush; 3: time-matched poststenting image showing small veins, 4 time-matched poststenting image showing large veins and sinuses. Faster inflow of contrast medium was observed in 74% of patients (grades 1: 34%,and 4: 4.7%). In linear regression analysis, higher degrees of ipsilateral stenosis were associated with greater changes in inflow of contrast medium (P < 0.05). Right internal carotid lesions were associated with greater change in inflow than left-sided lesions (P < 0.01). In 31 patients (36%) we initially showed contralateral anterior cerebral artery (ACA) filling, and in 39% of these, normal filling was restored after stenting. Lesser contralateral carotid stenosis was associated with crossed ACA filling and with restoration of normal filling pattern after stenting. Faster appearance of a contrast-medium blush is seen in most cases of carotid angioplasty and stenting and depends on the degree of hemodynamic inflow obstruction relieved by stenting.

Role of conventional angiography in evaluation of patients with carotid artery stenosis demonstrated by Doppler ultrasound in general practice.

BACKGROUND AND PURPOSE: Previous studies have suggested that patients with carotid stenosis who are candidates for endarterectomy can be effectively identified on the basis of carotid Doppler ultrasound alone. Before widespread acceptance of this policy, the accuracy of carotid Doppler ultrasound outside selected centers and clinical trials needs to be evaluated. We performed a 12-month prospective study to evaluate the accuracy of Doppler ultrasound in identifying patients for carotid intervention in general practice settings. METHODS: Each patient referred to our endovascular service for diagnostic angiography to evaluate for carotid stenosis was interviewed and examined by a neurologist. Subjects consisted of symptomatic patients with >/=50% stenosis and asymptomatic patients with >/=60% stenosis by Doppler ultrasound. Information pertaining to demographic and cerebrovascular risk factors and the results of the carotid Doppler ultrasound were recorded. The severity of stenosis on angiograms was measured with North American Symptomatic Carotid Endarterectomy Trial criteria by a blinded observer. The results of both studies were compared to determine the relative accuracy of ultrasound results. RESULTS: Of 130 patients (mean age, 69+/-8.8 years) who met Doppler ultrasound criteria, 22 (17%) and 8 patients (6%) were found to have 30% to 49% or <30% stenosis by angiography, respectively. The positive predictive value of carotid Doppler ultrasound for identifying appropriate symptomatic candidates for carotid intervention (angiographic stenosis >/=50%) was 80%, with a false-positive value of 20%. The positive predictive value of carotid Doppler ultrasound for identifying appropriate asymptomatic candidates for carotid intervention (angiographic stenosis >/=60%) was 59%, with a false-positive value of 41%. Carotid endarterectomy or angioplasty and stent placement were undertaken subsequently in 60 (46%) of the patients. In 94 patients who underwent cerebral angiography alone, no complications were observed. CONCLUSIONS: The present accuracy of carotid Doppler ultrasound in general practice does not justify its use as the sole basis of selecting appropriate patients for carotid intervention. Given the relatively low rate of associated morbidity with present day techniques, additional confirmatory studies such as angiography should be performed in every patient before a decision regarding intervention is made.

Carotid endarterectomy: can we select surgical candidates at high risk for stroke and low risk for perioperative complications?

DESPITE EVIDENCE OF the efficacy of carotid endarterectomy from the large randomized multicenter trials completed in the 1990s, the physician who treats patients with carotid artery stenosis still is faced with a difficult management decision. More recently, subgroup analyses have been conducted of asymptomatic and symptomatic patients enrolled in these trials to identify clinical and radiological factors that increase the rates of morbidity and mortality associated with surgery, as well as those that increase the risk of stroke without surgery. Knowledge of these factors is important to recommend the best course of action for the individual patient. In this article, we summarize the conclusions of some of the subgroup analyses from the major carotid endarterectomy trials.

Risk factors for subarachnoid hemorrhage.

OBJECTIVE: Cigarette smoking has been demonstrated to increase the risk of subarachnoid hemorrhage (SAH). Whether cessation of smoking decreases this risk remains unclear. We performed a case-control study to examine the effect of smoking and other known risk factors for cerebrovascular disease on the risk of SAH. METHODS: We reviewed the medical records of all patients with a diagnosis of SAH (n = 323) admitted to Johns Hopkins Hospital between January 1990 and June 1997. Controls matched for age, sex, and ethnicity (n = 969) were selected from a nationally representative sample of the Third National Health and Nutrition Examination Survey. We determined the independent association between smoking (current and previous) and various cerebrovascular risk factors and SAH by use of multivariate logistic regression analysis. A separate analysis was performed to determine associated risk factors for aneurysmal SAH. RESULTS: Of 323 patients admitted with SAH (mean age, 52.7+/-14 yr; 93 were men), 173 (54%) were hypertensive, 149 (46%) were currently smoking, and 125 (39%) were previous smokers. In the multivariate analysis, both previous smoking (odds ratio [OR], 4.5; 95% confidence interval [CI], 3.1-6.5) and current smoking (OR, 5.2; 95% CI, 3.6-7.5) were significantly associated with SAH. Hypertension was also significantly associated with SAH (OR, 2.4; 95% CI, 1.8-3.1). The risk factors for 290 patients with aneurysmal SAH were similar and included hypertension (OR, 2.4; 95% CI, 1.8-3.2), previous smoking (OR, 4.1; 95% CI, 2.7-6.0), and current smoking (OR, 5.4; 95% CI, 3.7-7.8). CONCLUSION: Hypertension and cigarette smoking increase the risk for development of SAH, as found in previous studies. However, the increased risk persists even after cessation of cigarette smoking, which suggests the importance of early abstinence from smoking.

Absence of early proinflammatory cytokine expression in experimental intracerebral hemorrhage.

OBJECTIVE: We sought to analyze the regional concentrations of proinflammatory cytokines in the acute period of intracerebral hemorrhage (ICH) and to test the hypothesis that ICH is associated with the expression of proinflammatory cytokines in the acute period. Although the expression of cytokines and their role in neuronal injury and inflammation is well characterized in cerebral ischemia and head injury, no information exists regarding expression of cytokines in ICH. METHODS: We introduced ICH in eight anesthetized mongrel dogs by autologous blood injection (6 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. Samples of arterial blood and cerebrospinal fluid were collected, and tissue extracts were prepared from different regions of the brain for immunoassay of tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 concentrations in animals with and without ICH. RESULTS: The tumor necrosis factor a levels (+/- standard error) in the cerebrospinal fluid 1 hour after ICH did not differ significantly between the ICH group and the control group (7.1 +/- 1.3 pg/ml versus 10.8 +/- 2.3 pg/ml, P = 0.22). Levels in the perihematoma region in the ICH group (96.6 +/- 3.1 pg/ml) were not significantly different from those in the control group (93.4 +/- 6.7 pg/ml, P = 0.7). IL-6 levels (+/- standard error) in the perihematoma region in the ICH group (116.3 +/- 13.3 pg/ml) did not differ significantly from those in corresponding regions in the control group (122.3 +/- 12.8 pg/ml, P = 0.7). IL-1beta levels were below 5 pg/ml in serum, cerebrospinal fluid, and extracts of different brain regions. CONCLUSION: The early pathophysiology of ICH does not involve significant expression of tumor necrosis factor a either in the perihematoma region or other regions of the brain. The observation suggests that the pathophysiology of ICH in the acute period is different from both cerebral ischemia and traumatic brain injury.

Ineffective secondary prevention in survivors of cardiovascular events in the US population: report from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Survivors of myocardial infarction (MI) or stroke are at high risk for subsequent cardiovascular events. There is limited assessment of the effectiveness of risk factor modification through current secondary preventive strategies in the US population. We determined the adequacy of risk factor modification in 1252 survivors of MI, stroke, or both in a nationally representative sample of US adults and identified factors related to inadequate control of risk factors. METHODS: The adequacy of control for hypertension, diabetes mellitus, cigarette smoking, alcohol use, and hypercholesterolemia was assessed by personal interview, blood pressure measurements, and serum glycosylated hemoglobin and cholesterol levels in 17 752 US adults who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We also evaluated the role of potentially related factors, including age, sex, race/ethnicity, educational attainment, socioeconomic status, and medical insurance status using multivariate logistic regression analysis. RESULTS: Of 738 known hypertensive persons, hypertension was uncontrolled in 388 (53%). Previously undiagnosed hypertension was detected in 138 others (11%). Of 289 diabetic persons, serum glucose control was inadequate in 141. Of 1252 survivors, 225 (18%) were currently smoking, and heavy alcohol use was observed in 56 persons. Hypercholesterolemia was poorly controlled in 185 (46%) of 405 persons with known hypercholesterolemia. Undetected hypercholesterolemia was observed in 160 persons (13%). In the multivariate analysis, high-risk profiles were more likely to be observed in persons aged 46 to 65 years, women, and African Americans. CONCLUSIONS: High prevalence of inadequate secondary prevention was found in a subset of the US population at highest risk for stroke and MI. Considerable efforts are required to effectively implement risk factor modification strategies after MI or stroke, particularly in middle-aged persons, African Americans, and women.

Intra-arterial third-generation recombinant tissue plasminogen activator (reteplase) for acute ischemic stroke.

OBJECTIVE: We prospectively evaluated the safety and recanalization efficacy of intra-arterially administered reteplase, a third-generation recombinant tissue plasminogen activator, for treating ischemic stroke in patients considered poor candidates for intravenously administered alteplase therapy. METHODS: Patients were considered poor candidates for intravenously administered therapy because of severity of neurological deficits, interval from onset of symptoms to presentation of 3 hours or more, or recent major surgery. We administered a maximum total dose of 8 U of reteplase intra-arterially in 1-U increments via superselective catheterization. Adjunctive angioplasty of the occluded artery was performed in seven patients. Angiographic evidence of perfusion and thrombus was graded by use of modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Neurological examinations were performed before and 24 hours and 7 to 10 days after treatment. RESULTS: Sixteen consecutive patients were treated (mean age, 64.1 +/- 16.4 yr; seven were men). Initial National Institutes of Health Stroke Scale scores ranged from 10 to 26. Time from onset of symptoms to treatment ranged from 2 to 9 hours. Occlusion sites were the cervical internal carotid artery (n = 4), intracranial internal carotid artery (n = 4), middle cerebral artery (n = 6), and vertebrobasilar artery (n = 2). Complete or near-complete perfusion (TIMI Grade 3 or 4) was achieved in the arteries in 14 patients (88%), with partial recanalization (TIMI Grade 2) or minimal response (TIMI Grade 1) in the arteries in one patient each. Neurological improvement (defined as decrease of four or more points in National Institutes of Health Stroke Scale score) was observed in 7 (44%) of the 16 patients at 24 hours. Symptomatic intracerebral hemorrhage occurred in one patient; three other patients experienced intracerebral hemorrhages that did not result in neurological worsening. The overall mortality during hospitalization was 56%, related to massive ischemic stroke (n = 7), withdrawal of care at the family's request after the development of aspiration pneumonia and renal failure (n = 1), and a combination of intracerebral hemorrhage and massive ischemic stroke (n = 1). CONCLUSION: In this study, intra-arterially administered reteplase in doses up to 8 U with or without angioplasty resulted in a high rate of recanalization. This strategy should be considered in treating patients considered poor candidates for intravenous thrombolysis.

Cocaine use and hypertension are major risk factors for intracerebral hemorrhage in young African Americans.

OBJECTIVE: To determine the risk factors for intracerebral hemorrhage (ICH) in African Americans aged 18 to 45 years. African Americans are at a higher risk for ICH than Whites, particularly in the younger age groups. However, few data are available regarding the factors that contribute to the high risk of ICH among younger African Americans. DESIGN: A case-control study. SETTINGS: A university-affiliated public hospital. PARTICIPANTS: One hundred and twenty-two African-American patients admitted with non-traumatic ICH to Grady Memorial Hospital (Atlanta, Ga.) and 366 age- and sex matched African-American controls selected from a nationally representative sample of the civilian, non-institutionalized US population. MAIN OUTCOME MEASURE: Association between ICH and various demographic and clinical factors determined by stepwise logistic regression. RESULTS: Cocaine use (OR 6.1, 95% CI 3.3-11.8), hypertension (OR 5.2, 95% CI 3.2-8.7) and alcohol use (OR 1.9, 95% CI 1.1-3.3) were independently associated with increased risk for ICH. CONCLUSIONS: Cocaine use, hypertension and alcohol use contributed to the high risk of ICH observed in younger African Americans. Primary preventive strategies are required to reduce the high frequency of modifiable risk factors predisposing younger African Americans to ICH.

Angioplasty of intracranial occlusion resistant to thrombolysis in acute ischemic stroke.

OBJECTIVE: Thrombolysis has been demonstrated to improve revascularization and outcome in patients with acute ischemic stroke. Many centers now apply thrombolytic therapy locally via intra-arterial infusion. One therapeutic benefit is the ability to cross soft clots with a guidewire and to perform mechanical thrombolysis. In some instances, reopened arteries reocclude as a result of either thrombosis or vasospasm. We report the use of balloon angioplasty during thrombolysis for acute stroke. METHODS: From June 1995 through June 1999, 49 patients underwent intra-arterial therapy for acute stroke. In this group, nine patients (seven men and two women) were treated with balloon angioplasty after inadequate recanalization with thrombolytic infusion. The mean age of these patients was 67.9 years. Nine matched control patients who underwent thrombolysis alone without angioplasty were chosen for comparison. RESULTS: In the group of nine patients who had angioplasty, the mean National Institutes of Health Stroke Scale score at presentation was 21.8 +/- 5.4. Four patients had residual distal occlusion after angioplasty, and one patient had a hemorrhagic conversion. Of the five patients in which recanalization was successful, none had reocclusion of the balloon-dilated vessel. The mean score at 30 days for the five survivors was 12.6 +/- 14.9, for an improvement of 7.0 +/- 14.2. Among the nine control patients, the mean score at presentation was 20.3 +/- 5.2; the mean score at 30 days for the five survivors was 19.4 +/- 7.7, for an improvement of 4.2 +/- 7.8. CONCLUSION: In our experience, balloon angioplasty is a safe, effective adjuvant therapy in patients who are resistant to intra-arterial thrombolysis. The use of balloon angioplasty may prevent reocclusion in a stenotic artery and permit distal infusion of thrombolytic agents.

Superselective intra-arterial carboplatin for treatment of intracranial neoplasms: experience in 100 procedures.

BACKGROUND: The results of animal studies suggest that superselective intra-arterial infusion allows the permeation of a high concentration of chemotherapeutic agents within intracranial neoplasms. In the present report, we review our clinical experience with the 100 intra-arterial infusions of carboplatin in intracranial neoplasms not responsive to other treatment modalities. METHODS: Carboplatin was infused in 100 separate sessions (24 patients) as a mean dose of 286+/-60 mg/m2 (range 34-377 mg/m2). RMP-7, a bradykinin analog, was used as an adjunct in 28 sessions (6 patients). The infusions were performed through superselective microcatheterization of the following arteries: internal carotid (n = 39), middle cerebral (n = 61), posterior cerebral (n = 21) and anterior cerebral (n = 10). The frequency of neurological and non-neurological complications, and survival were recorded. In a subset of 10 patients, tumor volume was measured by serial magnetic resonance images to assess therapeutic response to therapy. RESULTS: The mean age of the patients was 44.5 years (range 26-67 years); 13 were men. The tumors were classified as glioblastoma multiforme (n = 12), metastatic tumor (n = 1), high-grade astrocytoma (n = 6), and anaplastic mixed glioma (n = 5). Follow-up was available for 23 patients (mean 22 months, range 2-69 months). Survival beyond 1 year after initiation of intra-arterial carboplatin therapy was documented in 12 of the 23 patients. A total of 13 neurological complications including seizures (n = 7), transient neurological deficits (n = 5), and ischemic stroke (n = 1) were observed in 100 procedures. A lower frequency of complications occurred in men and in patients who received adjunctive RMP-7. Volumetric analysis of serial magnetic resonance images demonstrated tumor mass reduction in 3 out of 10 patients. An increase in tumor mass ranging from 23% to 230% was observed in the other 7 patients over a period ranging from 2.3 to 37.7 months since initiation of carboplatin therapy. CONCLUSIONS: Superselective intra-arterial administration of carboplatin appears feasible and was associated with predominantly transient neurological complications. The addition of RMP-7 to carboplatin therapy appears to be at least as safe as the administration of carboplatin alone and requires further investigation as a means of chemotherapeutic dose intensification.

Endovascular treatment of intracranial aneurysms by using Guglielmi detachable coils in awake patients: safety and feasibility.

OBJECT: Embolization of intracranial aneurysms performed using Guglielmi detachable coils (GDCs) is performed with the patient in a state of general anesthesia at most centers. Such an approach does not allow intraprocedural evaluation of the patient's neurological status and carries additional risks associated with general anesthesia and mechanical ventilation. At the authors' institution, GDC embolization of intracranial aneurysms is performed in awake patients after administration of sedative and analgesic agents (midazolam, fentanyl, morphine, and/or hydromorphone). To determine the feasibility and safety of this approach, the authors have retrospectively reviewed their clinical experience. METHODS: The authors reviewed the medical records of all patients in whom GDC embolization for the treatment of intracranial aneurysms was undertaken between February 1, 1990 and October 31, 1999. Clinical presentation, medical comorbidities, anesthetic agents used, intraprocedural complications, and final procedural outcome were recorded for each patient. Guglielmi detachable coil embolization was attempted in the awake patient in 150 procedures. Among 92 procedures for unruptured aneurysms, 75 (82%) were completed without complications. Four procedures were completed with complications. Of the 92 procedures, 13 were aborted due to patient uncooperativeness (one patient), complications (three patients), morphological characteristics of the aneurysm or surrounding vessels that made embolization technically difficult (eight patients), or vasospasm (one patient). Among 58 procedures for ruptured aneurysms, the procedure was completed without complication in 48 cases (83%). The procedure was completed with complications in five cases and two patients required induction of general anesthesia during the procedure. Five procedures were aborted because morphological characteristics of the aneurysm or surrounding vessels made embolization technically difficult (two patients) or because of aneurysm rupture (two patients) or the appearance of a transient neurological deficit (one patient). CONCLUSIONS: Embolization of intracranial aneurysms performed using GDCs in the awake patient appears to be safe and feasible and allows intraprocedural evaluation of the patient. Potential advantages, including decreased cardiopulmonary morbidity rates, shorter hospital stay, and lower hospital costs, still require confirmation by a direct comparison with other anesthetic procedures.

Open-label phase I clinical study to assess the safety of intravenous eptifibatide in patients undergoing internal carotid artery angioplasty and stent placement.

OBJECTIVE: Eptifibatide, a competitive platelet glycoprotein IIb-IIIa receptor inhibitor with high selectivity and a short half-life, has been demonstrated to reduce the risk of ischemic events associated with coronary interventions. However, its role in neurointerventional procedures needs to be analyzed. We report the results of an open-label Phase I study to evaluate the safety of the use of eptifibatide during carotid angioplasty and stent placement. METHODS: Each study patient received eptifibatide administered intravenously as a 135-microg/kg single-dose bolus, then a 0.5-microg/kg/min infusion for 20 to 24 hours during carotid angioplasty and stent placement. The primary efficacy end point was the 30-day composite occurrence of death, cerebral infarction, transient ischemic attack, and unplanned or urgent surgical intervention, thrombolysis, or subsequent percutaneous revascularization. The primary safety end point was bleeding. Bleeding complications were classified as major (hemoglobin decrease >5 g/dl), minor (hemoglobin decrease 3-5 g/dl), or insignificant. RESULTS: Ten patients (mean age, 73 yr; four men) were treated by use of the study protocol. One patient developed a minor stroke postprocedurally (National Institutes of Health Stroke Scale score of 21 at 24 h that improved to 1 at 7 d). Three patients underwent scheduled coronary artery bypass graft surgery 4 to 12 days after undergoing carotid angioplasty and stent placement. At 1-month follow-up, no new ischemic events were observed. Major or minor bleeding was not observed in any patient. Insignificant bleeding was observed in two patients. CONCLUSION: The use of eptifibatide as an adjunct to carotid angioplasty and stent placement seems to be safe. Further studies are required to analyze the effectiveness and role of eptifibatide in neurointerventional procedures.

Who should be screened for asymptomatic carotid artery stenosis? Experience from the Western New York Stroke Screening Program.

OBJECTIVE: Identification of significant asymptomatic carotid artery stenosis (ACAS) is important because of the stroke-risk reduction observed with carotid endarterectomy. The authors developed and validated a simple scoring system based on routinely available information to identify persons at high risk for ACAS using data collected during a community health screening program at various sites in western New York. A total of 1331 unselected volunteers without previous stroke, transient ischemic attack, or carotid artery surgery were evaluated by personal interview and duplex ultrasound. The main outcome measure was carotid artery stenosis > 60% by duplex ultrasound. In the derivation set (n = 887), 4 variables were significantly associated with ACAS > 60%: age > 65 years (odds ratio [OR] = 4.1, 95% confidence interval [CI] = 2.6-6.7), current smoking (OR = 2.0, 95% CI = 1.2-3.5), coronary artery disease (OR = 2.4, 95% CI = 1.5-3.9), and hypercholesterolemia (OR = 1.9, 95% CI = 1.2-2.9). Three risk groups (low, intermediate, and high) were defined on the basis of total risk score assigned on the basis of the strength of association. The scheme effectively stratified the validation set (n = 444); the likelihood ratio and posttest probability for ACAS in the high-risk group were 3.0 and 35%, respectively, and in the intermediate and low-risk groups were 1.4 and 20% and 0.4 and 7%, respectively. Routinely available information can be used to identify persons in the community at high risk for ACAS. Doppler ultrasound screening in this subgroup may prove to be cost-effective and have an effect on stroke-free survival.

Treating complex nervous system vascular disorders through a "needle stick": origins, evolution, and future of neuroendovascular therapy.

In the past few decades, dramatic improvements have occurred in the field of neuroendovascular surgery. Endovascular therapy today is a well-established treatment modality for a variety of cerebrovascular and nonvascular central nervous system diseases. The foundation of this spectacular evolution was laid by the efforts of pioneering visionaries who often worked alone and under difficult, almost impossible, conditions. Ongoing device development and refinement have revolutionized the field at a dizzying, exhilarating pace. With a better understanding of the molecular basis of diseases and further advancements in gene therapy, neuroendovascular techniques have an enormous potential for application to the entire spectrum of central nervous system diseases as a minimally invasive vehicle for the delivery of biological factors.

Cocaine use and the likelihood of nonfatal myocardial infarction and stroke: data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Numerous case series have implicated cocaine use as a cause of both myocardial infarction (MI) and stroke on the basis of the temporal relationship between drug use and event onset. Increasing cocaine use in the US population, especially in younger individuals, mandates a more extensive investigation of this relationship. METHODS AND RESULTS: We determined the association of cocaine use with self-reported physician diagnosis of MI or stroke in a nationally representative sample of 10 085 US adults aged 18 to 45 years who participated in the Third National Health and Nutrition Examination Survey. A total of 46 nonfatal MIs and 33 nonfatal strokes were reported. After adjusting for differences in age, sex, race/ethnicity, education, hypertension, diabetes mellitus, cholesterol level, body mass index, and cigarette smoking, persons who reported frequent lifetime cocaine use had a significantly higher likelihood of nonfatal MI than nonusers (odds ratio, 6.9; 95% confidence interval, 1.3 to 58) but not stroke. In this age group, the population-attributable risk percent of frequent cocaine for nonfatal MI was estimated as 25%. CONCLUSION: Regular cocaine use was associated with an increased likelihood of MI in younger patients. Approximately 1 of every 4 nonfatal MIs in persons aged 18 to 45 years was attributable to frequent cocaine use in this survey. Behavior modification by public awareness and education may reduce the cardiovascular morbidity associated with cocaine use.

Quantitative analysis of injured, necrotic, and apoptotic cells in a new experimental model of intracerebral hemorrhage.

OBJECTIVE: To develop a new survival model of intracerebral hemorrhage (ICH) in rabbits and study the patterns of cellular injury in different regions 24 hrs after introduction of hematoma. Quantitation and characterization of injured cells in regions adjacent and distant to the hematoma have not been performed. DESIGN: Prospective case-control study. SUBJECTS: Ten New Zealand rabbits. INTERVENTION: We introduced ICH in six anesthetized New Zealand rabbits by autologous blood injection under arterial pressure in the deep white matter in the frontal lobe. MEASUREMENTS AND MAIN RESULTS: Hematoxylin and eosin staining was performed in six animals with ICH after 24 hrs to quantify intact, injured, and necrotic cells in regions proximal and distant to the hematoma, and the results were compared with four control animals. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed to quantify apoptotic cells in specified regions in five animals with ICH, and the results were compared with four control animals. All cell counts were performed by one investigator who used 100x oil emersion microscopy. The presence of localized hematoma was confirmed in all six animals with blood infusion. Compared with controls, animals with ICH had a significantly higher proportion of swollen cells in both the inner (55.9% +/- 3.0% vs. 26.8% +/- 1.7%; p < .05) and the outer (59.8% +/- 4.6% vs. 27.7% +/- 4.5%; p < .05) rim of the perihematoma region. A small proportion of shrunken dark cells were observed in both the inner (4.0% +/- 1.5%) and the outer (3.6% +/- 1.0%) rim of the perihematoma region. The remaining cells were considered morphologically intact. A large proportion of cells trapped within the matrix of the hematoma were either shrunken dark cells (48.8% +/- 16.4%) or swollen (38.8% +/- 15.1%). In the TUNEL-stained sections, a high burden of apoptotic cells was observed in the matrix of the hematoma (17.5 +/- 6.3 cells per high power field) but not in the perihematoma regions (less than two cells per high power field). CONCLUSIONS: A reproducible model of ICH in rabbits is described. At 24 hrs, the perihematoma region contains relatively large proportions of morphologically intact or reversibly injured (swollen) cells, suggesting the possibility of an extended window for therapeutic intervention.

Angioplasty for cerebral vasospasm from eclampsia.

BACKGROUND: Neurological deterioration in eclampsia is considered to be secondary to cerebral vasospasm. Magnesium sulfate therapy improves symptoms and controls seizures, possibly related to its vasorelaxive effects in spastic arteries. Some cases, however, are refractory to magnesium therapy. To our knowledge, there is no report of angioplasty for vasospasm from eclampsia in the literature. METHODS: A 27-year-old woman presented 10 days postpartum with severe mental status changes and left arm and bilateral leg weakness that were refractory to magnesium therapy. Cerebral angiography demonstrated diffuse, severe vasospasm. We treated her with angioplasty of the bilateral middle and posterior cerebral arteries, basilar artery, and bilateral internal carotid arteries. RESULTS: Angioplasty resulted in excellent angiographic improvement. The patient immediately became responsive and appropriate with improved strength in all extremities. She continued to improve throughout her hospital stay and was discharged 10 days postangioplasty. CONCLUSIONS: Cerebral angioplasty is an effective treatment for vasospasm from eclampsia refractory to magnesium therapy. Angiography should be considered early in the course of neurological deterioration, but delayed therapy may also be effective.

A novel intravascular drug delivery method using endothelial biotinylation and avidin-biotin binding.

In this study, a novel intravascular drug delivery system was developed in which a drug injected from a catheter was fixed to the vasculature of the targeted tissue. Cellular proteins of viable endothelial cells were first biotinylated directly by biotinylation reagents, and then bound by an avidinated drug or, using avidin as a linker, a biotinylated drug. In the initial experiments, we studied in vitro the biotinylation of cultured bovine aortic endothelial cells (BAECs) by applying biotinylation reagents (NHS-LC-biotin or sulfo-NHS-LC-biotin) onto the washed intact BAEC monolayers and showed that the amount of biotin bound to the cells depended on the concentration of the biotinylation reagents applied. The cell-bound biotin decreased with time after the biotinylation. When fluorescein-labeled avidin (FITC-avidin) was applied to the biotinylated BAEC monolayers, the FITC-avidin readily bound to the cells. An LDH-release assay showed that sulfo-NHS-LC-biotin was only slightly cytotoxic to the BAECs and a colony formation assay showed only slight adverse effects of the reagent. In vivo studies were carried out on the renal arteries of normal rabbits. A solution of NHS-LC-biotin was injected through a catheter to one kidney to biotinylate its vasculature and the vehicle to the other as control, followed by a perfusion with saline. Finally, a solution of FITC-avidin was injected to both kidneys that were then reperfused with the blood flow following the withdrawal of the catheters. In the histological sections, more than 85% of glomeruli was stained with fluorescein in the biotinylated kidney, whereas no glomeruli were stained in the control. In the kidneys harvested 2 days after the same procedure, most glomeruli were still brightly stained. In the final experiment, biotinylated kidneys were injected with a solution of avidin, followed by a solution of fluorescein-biotin. Control kidneys had no prior biotinylation but received the same injections of avidin and fluorescein-biotin as above. More than 80% of glomeruli were stained in the biotinylated kidneys but none in the controls. This indicated that biotinylated drugs can be anchored to the biotinylated vasculature through avidin without being flushed away by blood flows. No apparent adverse effect was found in the functions of biotinylated kidneys. We propose that this drug delivery system is feasible for the treatment of some pathological conditions of blood vessels such as microvascular proliferation in malignant tumors and for continuous drug delivery in certain target organs.