bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoantibodies Against Oxidatively Modified Lipoproteins and Progression of Carotid Restenosis After Carotid Endarterectomy
Authors: Meraviglia Maria Vittoria , Maggi Elena , Bellomo Giorgio , Cursi Marco , Fanelli Giovanna , Minicucci Fabio
Published: July 2002

Background

—

The purpose of this study was to determine whether LDL oxidation could play an important pathogenic role in early restenosis after carotid endarterectomy. An immunologic and biochemical study was performed on a group of patients who underwent carotid endarterectomy, and the degree of intima-media thickness was measured 6 months after surgery.

Summary of Report

—

Fifty-two consecutive patients were included in the study. The presence of antibodies against oxidized LDL in the serum at the time of surgery was evaluated and compared with echo Doppler flow imaging 6 months after the operation. A statistically significant correlation was found between the arterial wall thickness at the site of surgery and the absolute value of IgG antibodies against oxidized LDL (
P
<0.012) and IgM immunocomplexes (
P
<0.043).

Conclusions

—

The presence of antibodies against oxidized LDL at the time of surgery seems to predict a greater intima-media wall hyperplasia at 6 months after surgery, usually recognized as early restenosis.
A Prospective Evaluation of the CD14 and CD18 Gene Polymorphisms and Risk of Stroke
Authors: Zee Robert Y.L. , Bates David , Ridker Paul M.
Published: July 2002

Background and Purpose

—

Genetic polymorphisms of the CD14 lipopolysaccharide receptor gene (
CD14
) and the CD18 leukocyte adhesion molecule gene (
CD18
) have recently been hypothesized to be risk factors for atherothrombosis. However, no prospective data on subsequent risk of stroke are available. The present investigation was conducted to examine the possible association between the CD14 C(−260)T and CD18 codon 441 gene polymorphisms and the incidence of stroke in a large, prospective, matched case-control sample from the Physicians’ Health Study.

Methods

—

In the Physicians’ Health Study, 14 916 apparently healthy men were followed over a 12-year period for stroke. Using a nested case-control study design, 338 study participants who developed stroke (cases) and 338 age- and smoking-matched study participants who remained free of reported disease during follow-up (controls) were evaluated. Both polymorphisms were determined by polymerase chain reaction with subsequent and respective restriction fragment length polymorphism gel electrophoresis.

Results

—

All observed genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype distributions of the polymorphisms tested were similar among cases and controls, such that the relative risk of future stroke was 0.87 for
CD14 C(−260)T
(95% CI=0.69 to 1.11;
P
=0.27) and 0.99 for
CD18 codon 441
(95% CI=0.77 to 1.28;
P
=0.96) assuming an additive mode of inheritance. No evidence of association was observed assuming dominant or recessive model, and similar null results were observed in subgroup analysis restricted to thromboembolic events

Conclusions

—

In this large, prospective study, we found little evidence that the two previously described polymorphisms in the CD14 and CD18 genes are associated with risks of future stroke.
Physician Knowledge and Practices in the Evaluation of Coagulopathies in Stroke Patients
Authors: Bushnell Cheryl D. , Goldstein Larry B.
Published: July 2002

Background and Purpose

—

Coagulopathies are a rare cause of ischemic stroke. Prior studies demonstrate that current physician test-ordering practices for the evaluation of these conditions in patients with ischemic stroke is not optimal. We sought to determine neurologists’ views regarding their use of specialized coagulation testing to better understand the possible reasons for these practices.

Methods

—

A survey with multiple-choice and open-ended questions regarding knowledge of and approaches to the evaluation of coagulopathies was sent to a convenience sample of 79 neurologists (26 academic neurology faculty, 24 residents/fellows, and 29 community-based practitioners).

Results

—

Fifty-nine (75%) surveys were completed (response rates: faculty 73%, residents/fellows 88%, and community-based practice 66%). Specialized coagulation tests were reported to infrequently influence stroke patient management (<25% of the time or never for 95% of respondents). Factors reported to increase test-ordering included young patient age (76%), history of thrombosis (46%), history of miscarriages (36%), and having few traditional stroke risk factors (35%). Most (88%) indicated they would order specialized coagulation tests for a hypothetical young patient with no known stroke risk factors. In contrast, only 14% would obtain the tests for a patient having traditional stroke risk factors, and none would order the tests for a stroke patient with atrial fibrillation.

Conclusions

—

Physician-reported practices for obtaining specialized coagulation tests differ from those found in observational studies in which more indiscriminate test ordering was observed. Closing knowledge gaps and improving application of physician’s current knowledge to their test-ordering practices could help to optimize diagnostic testing for coagulopathies in patients with ischemic stroke.
Effects of Induced Hypertension on Intracranial Pressure and Flow Velocities of the Middle Cerebral Arteries in Patients With Large Hemispheric Stroke
Authors: Schwarz Stefan , Georgiadis Dimitrios , Aschoff Alfred , Schwab Stefan
Published: July 2002

Background and Purpose

—

Our aim was to prospectively evaluate the effects of induced arterial hypertension in patients with large ischemic stroke.

Methods

—

A total of 47 monitoring sessions in 19 patients with acute, complete, or subtotal middle cerebral artery (MCA) territory stroke were performed. Intracranial pressure (ICP) was monitored using a parenchymal catheter. Mean arterial blood pressure (MAP), ICP, and peak mean flow velocity of the middle cerebral arteries (V
m
MCA) were continuously recorded. Patients with acute ICP crises were excluded. After obtaining baseline values, MAP was raised by an infusion of norepinephrine to reach an MAP increase of at least 10 mm Hg. After MAP had reached a peak plateau level, the norepinephrine infusion was stopped.

Results

—

Baseline MAP was 83.6±1.6 mm Hg and rose to 108.9±2.0 mm Hg after infusion of norepinephrine. ICP slightly increased from 11.6±0.9 mm Hg to 11.8±0.9 mm Hg (
P
<0.05). Cerebral perfusion pressure rose from baseline 72.2±2 mm Hg to 97±1 mm Hg (
P
<0.0001). V
m
MCA was already higher on the affected side during baseline measurements. At maximum MAP levels, V
m
MCA rose by 25.5±5.5 cm/s on the affected side and by 8.6±1.6cm/s on the contralateral side.

Conclusions

—

In patients with large hemispheric stroke without an acute ICP crisis, induced hypertension enhances cerebral perfusion pressure and augments the V
m
MCA(s), more so on the affected side. The ICP slightly increases; however, this is probably not clinically significant.
Trends in Stroke Prevalence Between 1973 and 1991 in the US Population 25 to 74 Years of Age
Authors: Muntner Paul , Garrett Elizabeth , Klag Michael J. , Coresh Josef
Published: July 2002

Background and Purpose

—

Stroke mortality in the United States has declined since 1900. Primary prevention of stroke incidence did not decline and may have increased during the 1980s, whereas survival after stroke improved substantially during the 1970s and 1980s. The effect of these trends on the prevalence and number of stroke survivors in the United States has not been determined.

Methods

—

The prevalence and number of noninstitutionalized stroke survivors in the United States was estimated through self-report for 3 time periods: 1971–1975, 1976–1980, and 1988–1994, using data from the National Health and Nutrition Examination Surveys (NHANES) I, II, and III, respectively. Prevalence and number of stroke survivors were analyzed by age (25 to 59 and 60 to 74 years), race (non-Hispanic whites/Mexican-Americans and non-Hispanic blacks), and sex. Estimates were limited to the US population ages 25 to 74 years because NHANES I and II did not include persons older than 75 years.

Results

—

The age-, race-, and sex-adjusted prevalence of stroke increased from 1.41% to 1.87% from 1971–1975 to 1988–1994, an average increase of 7.5% (95% confidence interval: −2%, +18%) for each 5-year period during this time. Additionally, during this period, the estimated number of noninstitutionalized stroke survivors increased by 930 000 (95% CI: 300 000 to 1.6 million) from 1.5 million to 2.4 million. Additionally, the average “health in general” among stroke survivors was similar in all 3 periods.

Conclusions

—

These data point to the increasing importance of the care and rehabilitation of stroke survivors.
Early Dramatic Recovery During Intravenous Tissue Plasminogen Activator Infusion
Authors: Felberg Robert A. , Okon Nicholas J. , El-Mitwalli Ashraf , Burgin W. Scott , Grotta James C. , Alexandrov Andrei V.
Published: July 2002

Background and Purpose

—

Acute-stroke patients receiving standard intravenous tissue plasminogen activator (tPA) have been noted to experience early dramatic recoveries. The prevalence, clinical characteristics, and outcome of patients experiencing dramatic recovery is not well described.

Methods

—

We prospectively studied all patients presenting with acute middle cerebral artery (MCA) stroke syndromes and transcranial Doppler (TCD) evidence of an MCA obstruction. All patients received intravenous tPA per the National Institute of Neurological and Communicative Disorders and Stroke protocol, with serial National Institutes of Health Stroke Scale (NIHSS) scores and continuous TCD monitoring. Dramatic recovery was defined as an improvement of ≥10 NIHSS points or a decrease to an NIHSS score of ≤3 by the end of infusion. Outcome at the end of infusion, at 24 hours, and at long-term follow-up were obtained. The timing and pattern of deficit recovery during dramatic recovery was also studied.

Results

—

Dramatic recovery occurred in 22% of all patients. Compared with patients who did not experience dramatic recovery, those patients who did had significantly lower end-infusion NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus median 17 and range 6 to 35 for non–dramatic-recovery patients,
P
<0.01) and 24-hour NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus median 13 and range 2 to 35 for non–dramatic-recovery patients,
P
<0.01). A long-term modified Rankin Score benefit was noted (median 1 and range 0 to 6 for dramatic-recovery patients versus median 4 and range 0 to 6 for non–dramatic-recovery patients,
P
<0.01). Baseline clinical characteristics were similar. The only difference was improved TCD-determined flow values at the end of infusion (normal restoration of flow was 58% in dramatic-recovery patients versus 14% in non–dramatic-recovery patients,
P
<0.01). A characteristic pattern of recovery of deficit was noted.

Conclusions

—

Early dramatic recovery in acute MCA stroke patients treated with intravenous tPA is relatively frequent. The benefit of dramatic recovery is maintained at 24 hours and over the long term. TCD monitoring suggests that dramatic recovery is a result of early restoration of MCA flow during the tPA infusion. The consistent pattern of early clinical recovery may help explain the mechanisms by which thrombolysis improves outcome and could suggest targets for enhancing the therapeutic effect of intravenous tPA.
Global Cerebral Edema After Subarachnoid Hemorrhage
Authors: Claassen Jan , Carhuapoma J. Ricardo , Kreiter Kurt T. , Du Evelyn Y. , Connolly E. Sander , Mayer Stephan A.
Published: July 2002

Background and Purpose

—

Cerebral edema visualized by CT is often seen after subarachnoid hemorrhage (SAH). Inflammatory or circulatory mechanisms have been postulated to explain this radiographic observation after SAH. We sought to determine the frequency, causes, and impact on outcome of early and delayed global cerebral edema after SAH.

Methods

—

We evaluated the presence of global edema on admission and follow-up CT scans in 374 SAH patients admitted within 5 days of onset to our Neurological Intensive Care Unit between July 1996 and February 2001. Using multivariate analysis, we identified predictors of global cerebral edema and evaluated the impact of global edema on outcome 3 months after onset with the modified Rankin Scale.

Results

—

Global edema was present on admission CT scans in 8% (n=29) and developed secondarily in 12% (n=44) of the patients. Global edema on admission was predicted by loss of consciousness at ictus and increasing Hunt-Hess grade. Delayed global edema was predicted by aneurysm size >10 mm, loss of consciousness at ictus, use of vasopressors, and increased SAH sum scores. Thirty-seven percent (n=137) of the patients were dead or severely disabled (modified Rankin Scale 4 to 6) at 3 months. Death or severe disability was predicted by any global edema, aneurysm size >10 mm, loss of consciousness at ictus, increased National Institutes of Health Stroke Scale scores, and older age.

Conclusions

—

Global edema is an independent risk factor for mortality and poor outcome after SAH. Loss of consciousness, which may reflect ictal cerebral circulatory arrest, is a risk factor for admission global edema, and vasopressor-induced hypertension is associated with the development of delayed global edema. Critical care management strategies that minimize edema formation after SAH may improve outcome.
Carotid Artery Wall Thickness in Patients With Obstructive Sleep Apnea Syndrome
Authors: Silvestrini Mauro , Rizzato Barbara , Placidi Fabio , Baruffaldi Roberto , Bianconi Alberto , Diomedi Marina
Published: July 2002

Background and Purpose

—

Epidemiological studies have suggested a pathophysiological link between sleep apnea syndrome and cerebrovascular diseases. The mechanism by which sleep disturbance can affect the predisposition to developing stroke is not clear. The aim of this study was to investigate whether patients with obstructive sleep apnea syndrome have an increase in atherosclerosis indicators at the carotid artery level.

Methods

—

We included 23 male patients with severe obstructive sleep apnea syndrome (respiratory disturbance index >30). Intima-media thickness and the presence of steno-occlusive lesions in the common carotid arteries were investigated with B-mode high-resolution ultrasonography. Results of the ultrasonographic examination were compared with those of a group of 23 subjects without obstructive sleep apnea syndrome who were matched for age and comorbid factors.

Results

—

The intima-media thickness of the common carotid arteries of patients with obstructive sleep apnea syndrome was significantly higher (
P
<0.0001) than that of control subjects (1.429±0.34 versus 0.976±0.17 mm).

Conclusions

—

Results of the present study show that carotid wall thickness is increased in patients with severe sleep apnea syndrome. There is strong evidence that an increase in the thickness of the carotid artery wall is a valid marker of the risk of stroke. For this reason, our finding seems to further strengthen the hypothesis that patients with obstructive sleep apnea syndrome are at risk of developing cerebrovascular diseases regardless of the association with other vascular risk factors.
Association Between Subarachnoid Hemorrhage Outcomes and Number of Cases Treated at California Hospitals
Authors: Bardach Naomi S. , Zhao Shoujun , Gress Daryl R. , Lawton Michael T. , Johnston S. Claiborne
Published: July 2002

Background and Purpose

—

Studies of several complex medical conditions have shown that outcomes are better at hospitals that treat more cases. We tested the hypothesis that patients with subarachnoid hemorrhage treated at high-volume hospitals have better outcomes.

Methods

—

Using a database of all admissions to nonfederal hospitals in California from 1990 to 1999, we obtained discharge abstracts for patients with a primary diagnosis of subarachnoid hemorrhage who were admitted through the emergency department. Hospital volume, defined as the average number of subarachnoid hemorrhage cases admitted each year, was divided into quartiles. Rates of mortality, adverse outcomes (death or discharge to long-term care), length of stay, and hospital charges were computed by univariate analysis and by multivariable general estimating equations, with adjustment for demographic and admission characteristics.

Results

—

A total of 12 804 patients were admitted for subarachnoid hemorrhage through the emergency departments of 390 hospitals. Hospital volumes varied from 0 to 8 cases per year in the first quartile to 19 to 70 cases per year in the fourth quartile. The mortality rate in the lowest volume quartile (49%) was larger than that in the highest volume quartile (32%,
P
<0.001). In multivariable analysis, the difference persisted (odds ratio comparing highest with lowest volume quartiles 0.57, 95% CI 0.48 to 0.67;
P
<0.001). At higher volume hospitals, lengths of stay were longer, and hospital charges were greater in univariate and multivariable models (all
P
<0.001). Only 4.8% of those admitted to hospitals in the lowest volume quartile were transferred to hospitals in the highest quartile.

Conclusions

—

In this study of discharge abstracts in California, hospitals that treated more cases of subarachnoid hemorrhage had substantially lower rates of in-hospital mortality. Few patients with subarachnoid hemorrhage are being transferred to high-volume centers.
Imaging of Distal Internal Carotid Artery by Ultrasonography With a 3.5-MHz Convex Probe
Authors: Todo Kenichi , Watanabe Manabu , Fukunaga Ryuzo , Araki Ken , Yamamoto Shiro , Rai Makiko , Hoshi Taku , Nukata Masaru , Taguchi Akihiko , Kinoshita Naokazu
Published: July 2002

Background and Purpose

—

Conventionally, carotid ultrasonography has been performed with a 7.5-MHz linear probe to evaluate the extracranial internal carotid artery (ICA). However, usually only the carotid bulb or proximal portion of the ICA can be evaluated. We attempted to evaluate the distal extracranial ICA with a 3.5-MHz convex probe.

Methods

—

The subjects were 17 consecutive patients with ICAs free of occlusive disease and 3 other patients with distal extracranial ICA stenosis. Using a 7.5-MHz linear probe and a 3.5-MHz convex probe, we performed long-axis B-mode imaging of the ICAs to evaluate the distance between the distal limit of visualized ICA and the bifurcation of the common carotid artery.

Results

—

The distal limit of the ICA, visualized with a 7.5- or a 3.5-MHz probe, was 31±11 or 57±8 mm distal to the common carotid artery bifurcation, respectively. In the 3 patients with distal extracranial ICA stenosis, the lesion could be successfully diagnosed with only the 3.5-MHz probe.

Conclusions

—

This form of carotid imaging is feasible and may be potentially useful in the evaluation of carotid disease.
Intracerebral Hemorrhages Associated With Neurointerventional Procedures Using a Combination of Antithrombotic Agents Including Abciximab
Authors: Qureshi Adnan I. , Saad Mustafa , Zaidat Osama O. , Suarez Jose I. , Alexander Michael J. , Fareed M. , Suri K. , Ali Zulfiqar , Hopkins L. Nelson
Published: July 2002

Background

—

We report the occurrence of fatal intracerebral hemorrhage associated with using a combination of antithrombotic agents, including abciximab, in patients undergoing neurointerventional procedures.

Summary of Report

—

Seven patients (average age 60, range 46 to 73 years) developed fatal intracerebral hemorrhages associated with neurointerventional procedures and the use of intravenous abciximab. The procedures included angioplasty and stent placement in the cervical internal carotid artery (n=4), angioplasty of the intracranial internal carotid artery (n=1), and angioplasty of the middle cerebral artery (n=2). Clinical deterioration was observed within 1 hour of the procedure in 5 patients and 7 and 8 hours after the procedure, respectively, in the remaining 2 patients. All patients had received heparin and clopidogrel; 6 had also received aspirin.

Conclusions

—

Intracerebral hemorrhages can occur after neurointerventional procedures in patients with recent cerebral ischemic events, particularly when aggressive antithrombotic treatment is used.
Diagnostic Accuracy of Magnetic Resonance Angiography for Cerebral Aneurysms in Correlation With 3D–Digital Subtraction Angiographic Images
Authors: Okahara Mika , Kiyosue Hiro , Yamashita Masanori , Nagatomi Hirohumi , Hata Hiroyuki , Saginoya Toshiyuki , Sagara Yoshiko , Mori Hiromu
Published: July 2002

Background and Purpose

—

We investigated the sensitivity of 3D–time-of flight (3D-TOF) magnetic resonance angiography (MRA) in the detection of cerebral aneurysms with the use of 3D digital subtraction angiography as the gold standard. We also evaluated the effects of location and number of aneurysms (and experience of the reader) on the sensitivity.

Methods

—

3D-TOF MRA was performed in 82 patients with 133 cerebral aneurysms. Each patient underwent rotational angiography. Three-dimensional reconstructed images were obtained from data of the rotational angiography (as the gold standard). A blind study with 4 readers of different experiences was performed to evaluate the diagnostic accuracy of 3D-TOF MRA for cerebral aneurysms.

Results

—

One hundred five (79%) of all 133 aneurysms were detected with MRA by a neuroradiologist, 100 (75%) were detected by an experienced neurosurgeon, 84 (63%) were detected by a general radiologist, and 80 (60%) were detected by a resident neuroradiologist. For each reader, the detectability was lower for small aneurysms (<3 mm in maximum diameter) and/or for those located at the internal carotid artery and anterior cerebral artery. False-positive aneurysms were 29 for the neuroradiologist, 19 for the neurosurgeon, 31 for the general radiologist, and 30 for the resident neuroradiologist; most of the aneurysms were at the internal carotid artery. Causes of the false-positive and false-negative results included complex flow in a tortuous artery and susceptibility artifacts.

Conclusions

—

Although MRA is useful in the diagnosis of cerebral aneurysms, sufficient experience and careful attention are necessary for accurate diagnosis of aneurysms located at the internal carotid and anterior cerebral arteries.
Admission Body Temperature Predicts Long-Term Mortality After Acute Stroke
Authors: Kammersgaard L.P. , Jørgensen H.S. , Rungby J.A. , Reith J. , Nakayama H. , Weber U.J. , Houth J. , Olsen T.S.
Published: July 2002

Background and Purpose

—

Body temperature is considered crucial in the management of acute stroke patients. Recently hypothermia applied as a therapy for stroke has been demonstrated to be feasible and safe in acute stroke patients. In the present study, we investigated the predictive role of admission body temperature to the long-term mortality in stroke patients.

Methods

—

We studied 390 patients with acute stroke admitted within 6 hours from stroke onset. Admission clinical characteristics (age, sex, admission stroke severity, admission blood glucose, cardiovascular risk factor profile, and stroke subtype) were recorded for patients with hypothermia (body temperature ≤37°C) versus patients with hyperthermia (body temperature >37°C). Univariately the mortality rates for all patients were studied by Kaplan-Meier statistics. To find independent predictors of long-term mortality for all patients, Cox proportional-hazards models were built. We included all clinical characteristics and body temperature as a continuous variable.

Results

—

Patients with hyperthermia had more severe strokes and more frequently diabetes, whereas no difference was found for the other clinical characteristics. For all patients mortality rate at 60 months after stroke was higher for patients with hyperthermia (73 per 100 cases versus 59 per 10 cases,
P
=0.001). When body temperature was studied in a multivariate Cox proportional-hazards model, a 1°C increase of admission body temperature independently predicted a 30% relative increase (95% CI, 4% to 57%) in long-term mortality risk. For 3-month survivors we found no association between body temperature and long-term survival when studied in a multivariate Cox proportional hazard model (hazards ratio, 1.11 per 1°C; 95% CI, 0.82 to 1.52).

Conclusion

—

Low body temperature on admission is considered to be an independent predictor of good short-term outcome. The present study suggests that admission body temperature seems to be a major determinant even for long-term mortality after stroke. Hypothermic therapy in the early stage in which body temperature is kept low for a longer period after ictus could be a long-lasting neuroprotective measure.
Risk of Endovascular Treatment of Brain Arteriovenous Malformations
Authors: Hartmann A. , Pile-Spellman J. , Stapf C. , Sciacca R.R. , Faulstich A. , Mohr J.P. , Schumacher H.C. , Mast H.
Published: July 2002

Background and Purpose

—

Independently assessed data on frequency, severity, and determinants of neurological deficits after endovascular treatment of brain arteriovenous malformations (AVMs) are scarce.

Methods

—

From the prospective Columbia AVM Study Project, 233 consecutive patients with brain AVM receiving ≥1 endovascular treatments were analyzed. Neurological impairment was assessed by a neurologist using the Rankin Scale before and after completed endovascular therapy. Multivariate logistic regression models were used to identify demographic, clinical, and morphological predictors of treatment-related neurological deficits. The analysis included the components used in the Spetzler-Martin risk score for AVM surgery (AVM size, venous drainage pattern, and eloquence of AVM location).

Results

—

The 233 patients were treated with 545 endovascular procedures. Mean follow-up time was 9.6 months (SD, 18.1 months). Two hundred patients (86%) experienced no change in neurological status after treatment, and 33 patients (14%) showed treatment-related neurological deficits. Of the latter, 5 (2%) had persistent disabling deficits (Rankin score >2), and 2 (1%) died. Increasing patient age [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 to 1.08], number of embolizations (OR, 1.41; 95% CI, 1.16 to 1.70), and absence of a pretreatment neurological deficit (OR, 4.55; 95% CI, 1.03 to 20.0) were associated with new neurological deficits. None of the morphological AVM characteristics tested predicted treatment complications.

Conclusions

—

From independent neurological assessment and prospective data collection, our findings suggest a low rate of disabling treatment complications in this center for endovascular brain AVM treatment. Risk predictors for endovascular treatment differ from those for AVM surgery.
Response to Intra-Arterial and Combined Intravenous and Intra-Arterial Thrombolytic Therapy in Patients With Distal Internal Carotid Artery Occlusion
Authors: Zaidat Osama O. , Suarez Jose I. , Santillan Concepcion , Sunshine Jeffrey L. , Tarr Robert W. , Paras Vanessa H. , Selman Warren R. , Landis Dennis M.D.
Published: July 2002

Background and Purpose

—

The objective of this study was to determine the clinical features, angiographic findings, and response to treatment with thrombolytic therapy in patients with ischemic stroke caused by acute occlusion of the distal internal carotid artery.

Methods

—

This is a retrospective case series from a prospectively collected stroke database for patients with acute internal carotid occlusion presenting within 6 hours of stroke onset to evaluate safety, feasibility, and response to thrombolytic therapy. The University Hospital–based brain attack database was reviewed over a 5-year period. Demographics, clinical features, stroke mechanisms, severity, imaging findings, type of thrombolysis, treatment responses, mortality, and long-term outcome using modified Rankin Scale and Barthel Index were determined. The short-term outcome was assessed using the National Institutes of Health Stroke Scale (NIHSS). Acute thrombolytic therapy was administered using recombinant tissue plasminogen activator or urokinase given intra-arterially or in combination with intravenous (IV) routes.

Results

—

Two hundred seven patients treated with thrombolysis between 1995 and 2000 were reviewed, and of these, 101 were studied with cerebral angiography. Eighteen patients were identified with acute ischemic stroke and ipsilateral occlusion of the distal internal carotid artery. Time to treatment was the most powerful predictor of response to thrombolytic therapy (
P
<0.001). The response to therapy also correlated well with the severity of the initial clinical deficit as judged by the NIHSS (
P
<0.001). There was no difference in recanalization rate, symptomatic hemorrhage, and NIHSS for IV/intra-arterial (IA) versus IA alone (
P
=NS). Complete angiographic recanalization was accomplished in 80% of those who received combined IV/IA thrombolysis and in 62% of those who received IA therapy (
P
=NS). Those with distal occlusions extending to the middle and anterior cerebral arteries were the least likely to respond to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 20% of the patients receiving IV/IA therapy, and in 15% of the IA only (
P
=NS). At 24 hours, the NIHSS dropped by 3 points in the IA group and 4 points in the IV/IA group (
P
=NS). Mild disability with independence was found in 77% of the survivors at 3-month follow-up. The mortality rate was 50% in this group despite thrombolysis.

Conclusions

—

Thrombolytic therapy using a combination of IV and IA routes and using the IA-only route may be effective in improving outcome for the patients suffering from occlusion of the distal internal carotid artery. Shorter intervals between onset and treatment seem to be correlated with higher rate of recanalization and improved outcome.
Doppler-Derived Myocardial Systolic Strain Rate Is a Strong Index of Left Ventricular Contractility
Authors: Greenberg Neil L. , Firstenberg Michael S. , Castro Peter L. , Main Michael , Travaglini Agnese , Odabashian Jill A. , Drinko Jeanne K. , Rodriguez L. Leonardo , Thomas James D. , Garcia Mario J.
Published: July 2002

Background
—

Myocardial fiber strain is directly related to left ventricular (LV) contractility. Strain rate can be estimated as the spatial derivative of velocities (dV/ds) obtained by tissue Doppler echocardiography (TDE). The purposes of the study were (1) to determine whether TDE-derived strain rate may be used as a noninvasive, quantitative index of contractility and (2) to compare the relative accuracy of systolic strain rate against TDE velocities alone.

Methods and Results
—

TDE color M-mode images of the interventricular septum were recorded from the apical 4-chamber view in 7 closed-chest anesthetized mongrel dogs during 5 different inotropic stages. Simultaneous LV volume and pressure were obtained with a combined conductance–high-fidelity pressure catheter. Peak elastance (E
max
) was determined as the slope of end-systolic pressure-volume relationships during caval occlusion and was used as the gold standard of LV contractility. Peak systolic TDE myocardial velocities (S
m
) and peak (ε′
p
) and mean (ε′
m
) strain rates obtained at the basal septum were compared against E
max
by linear regression. E
max
as well as TDE systolic indices increased during inotropic stimulation with dobutamine and decreased with the infusion of esmolol. A stronger association was found between E
max
and ε′
p
(
r
=0.94,
P
<0.01,
y
=0.29
x
+0.46) and ε′
m
(
r
=0.88,
P
<0.01) than for S
m
(
r
=0.75,
P
<0.01).

Conclusions
—

TDE-derived ε′
p
and ε′
m
are strong noninvasive indices of LV contractility. These indices appear to be more reliable than S
m
, perhaps by eliminating translational artifact.
In Vitro and In Vivo Evaluation of Oral Heparin–Loaded Polymeric Nanoparticles in Rabbits
Authors: Jiao Yuyan , Ubrich Nathalie , Marchand-Arvier Monique , Vigneron Claude , Hoffman Maurice , Lecompte Thomas , Maincent Philippe
Published: July 2002

Background
—

Owing to its short half-life and lack of oral absorption, heparin has to be administered by the parenteral route. An oral heparin formulation, however, would avoid the disadvantages of parenteral injections and would consequently be highly desirable for patients. Polymeric nanoparticles (NPs) prepared with biodegradable poly-ε-caprolactone (PCL) and poly(lactic-
co
-glycolic acid) (PLGA) and nonbiodegradable positively charged polymers (Eudragit RS and RL), used alone or in combination, were evaluated in vitro and in vivo after a single oral administration of heparin-loaded NPs in rabbits.

Methods and Results
—

After oral administration of heparin-loaded NPs in rabbits (600 IU/kg), increases in both anti–factor Xa activity and activated partial thromboplastin time (aPTT) were detected with each formulation. Moreover, the anti-Xa activity was detected for a longer period than when a heparin solution was administered intravenously. A peak concentration of 0.16±0.01 IU/mL and an average aPTT of 24 seconds (2-fold increase) were obtained 7 hours after oral dosing of Eudragit RL/PCL NPs containing heparin, exhibiting an absolute bioavailability of 23%.

Conclusions
—

The significant increases in anti–factor Xa activity and aPTT confirmed the oral absorption in rabbits of heparin released from polymeric NPs.
Assessment of Myocardial Viability With Contrast-Enhanced Magnetic Resonance Imaging
Authors: Klein Christoph , Nekolla Stephan G. , Bengel Frank M. , Momose Mitsuru , Sammer Andrea , Haas Felix , Schnackenburg Bernhard , Delius Wolfram , Mudra Harald , Wolfram Dieter , Schwaiger Markus
Published: July 2002

Background
—

Recent studies indicate that MRI, after administration of gadolinium-diethylenetriamine pentaacetic acid, can identify nonviable areas in dysfunctional myocardium. We compared MRI hyperenhancement with PET as a gold standard for detection and quantification of myocardial scar tissue.

Methods and Results
—

Thirty-one patients with ischemic heart failure (ejection fraction, 28±9%) were imaged with PET and MRI. Scar was defined as regionally increased MRI signal intensity 20 minutes after injection of 0.2 mmol/kg gadolinium-diethylenetriamine pentaacetic acid and as concordantly reduced perfusion and glucose metabolism as defined by PET. Sensitivity and specificity of MRI in identifying patients and segments (n=1023) with matched flow/metabolism defects was 0.96 of 1.0 and 0.86 of 0.94, respectively. Eleven percent of segments defined as viable by PET showed some degree of MRI hyperenhancement. Defect severity score based on visual analysis was 44.3±9.1 for PET and 47.6±11.1 for MRI (
r
=0.91,
P
<0.0001). Quantitatively assessed relative MRI infarct mass correlated well with PET infarct size (
r
=0.81,
P
<0.0001). Furthermore, MRI hyperenhancement was a better predictor of scar tissue than end-diastolic and end-systolic wall thickness or thickening.

Conclusions
—

In severe ischemic heart failure, MRI hyperenhancement as a marker of myocardial scar closely agrees with PET data. Although hyperenhancement correlated with areas of decreased flow and metabolism, it seems to identify scar tissue more frequently than PET, reflecting the higher spatial resolution. Additional functional studies after revascularization are required to define the significance of small islands of scar detected by MRI.
Predicting Death in Patients With Acute Type A Aortic Dissection
Authors: Mehta Rajendra H. , Suzuki Toru , Hagan Peter G. , Bossone Eduardo , Gilon Dan , Llovet Alfredo , Maroto Luis C. , Cooper Jeanna V. , Smith Dean E. , Armstrong William F. , Nienaber Christoph A. , Eagle Kim A.
Published: July 2002

Background
—

Given the high mortality rates in patients with type A aortic dissection, predictive tools to identify patients at increased risk of death are needed to assist clinicians for optimal treatment.

Methods and Results
—

Accordingly, we evaluated 547 patients with this diagnosis enrolled in the International Registry of Acute Aortic Dissection (IRAD) between January 1996 and December 1999. Univariate testing followed by multivariate logistic regression analysis was performed to identify independent predictors of death. In-hospital mortality rate was 32.5% in type A dissection patients. In-hospital complications (neurological deficits, altered mental status, myocardial or mesenteric ischemia, kidney failure, hypotension, cardiac tamponade, and limb ischemia) were increased in patients who died compared with survivors (
P
<0.05 for all). Logistic regression identified the following presenting variables as predictors of death: age ≥70 years (OR, 1.70; 95% CI, 1.05 to 2.77;
P
=0.03), abrupt onset of chest pain (OR 2.60; 95% CI, 1.22 to 5.54;
P
=0.01), hypotension/shock/tamponade (OR, 2.97; 95% CI, 1.83 to 4.81;
P
<0.0001), kidney failure (OR, 4.77; 95% CI, 1.80 to 12.6;
P
=0.002), pulse deficit (OR, 2.03; 95% CI, 1.25 to 3.29,
P
=0.004), and abnormal ECG (OR, 1.77; 95% CI, 1.06 to 2.95;
P
=0.03) (area under receiver operating curve, 0.74; Hosmer-Lemeshow statistic,
P
=0.75).

Conclusions
—

The in-hospital mortality rate in acute type A aortic dissection is high and can be predicted with the use of a clinical model incorporated in a simple risk prediction tool. This tool can be used to educate patients with dissection about their predicted risk and in clinical research for risk adjustment while comparing outcomes of different therapies.
Metavinculin Mutations Alter Actin Interaction in Dilated Cardiomyopathy
Authors: Olson Timothy M. , Illenberger Susanne , Kishimoto Nina Y. , Huttelmaier Stefan , Keating Mark T. , Jockusch Brigitte M.
Published: July 2002

Background
—

Vinculin and its isoform metavinculin are protein components of intercalated discs, structures that anchor thin filaments and transmit contractile force between cardiac myocytes. We tested the hypothesis that heritable dysfunction of metavinculin may contribute to the pathogenesis of dilated cardiomyopathy (DCM).

Methods and Results
—

We performed mutational analyses of the metavinculin-specific exon of
vinculin
in 350 unrelated patients with DCM. One missense mutation (Arg975Trp) and one 3-bp deletion (Leu954del) were identified. These mutations involved conserved amino acids, were absent in 500 control individuals, and significantly altered metavinculin-mediated cross-linking of actin filaments in an in vitro assay. Ultrastructural examination was performed in one patient (Arg975Trp), revealing grossly abnormal intercalated discs. A potential risk-conferring polymorphism (Ala934Val), identified in one DCM patient and one control individual, had a less pronounced effect on actin filament cross-linking.

Conclusions
—

These data provide genetic and functional evidence for
vinculin
as a DCM gene and suggest that metavinculin plays a critical role in cardiac structure and function. Disruption of force transmission at the thin filament-intercalated disc interface is the likely mechanism by which mutations in metavinculin may lead to DCM.
Simvastatin Preserves the Structure of Coronary Adventitial Vasa Vasorum in Experimental Hypercholesterolemia Independent of Lipid Lowering
Authors: Wilson Stephanie H. , Herrmann Joerg , Lerman Lilach O. , Holmes David R. , Napoli Claudio , Ritman Erik L. , Lerman Amir
Published: July 2002

Background
—

Previous studies have demonstrated that experimental hypercholesterolemia leads to neovascularization in the coronary artery vasa vasorum (VV). Recent evidence suggests that HMG-CoA reductase inhibitors (statins) have beneficial effects independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary VV neovascularization, in the absence of cholesterol lowering.

Methods and Results
—

Pigs were randomized to 3 groups fed a normal (N), high cholesterol (HC), or HC+simvastatin (HC+S) diet for 12 weeks. The proximal left anterior descending artery was isolated, scanned with micro-CT, and reconstructed. Quantification of the VV density in serial cross-sections along the vessel was then performed. LDL cholesterol was similarly increased in HC and HC+S compared with N. There was an increase in both VV density (4.7±0.3 versus 2.7±0.2 n/mm
2
;
P
<0.05) and vessel wall area (3.1±0.2 versus 1.8±0.1 mm
2
;
P
<0.05) in HC compared with N. The VV density in HC+S was preserved compared with HC (3.0±0.2 n/mm
2
;
P
<0.05), despite similar increase in vessel wall area compared with N (2.5±0.1 mm
2
;
P
<0.05). Coronary artery tissue expression of VEGF was increased in HC but not in HC+S compared with N. In parallel, immunoreactivity for HIF-1α, VEGF, MMP-2, and MMP-9 was accentuated in the outer media in HC but not in HC+S compared with N.

Conclusions
—

This study demonstrates that simvastatin attenuates hypoxia in the coronary artery wall and VV neovascularization in experimental hypercholesterolemia, despite no change in plasma lipids. These data are consistent with an additional mechanism for the vascular effects of the statins, independent of cholesterol lowering.
Accelerated Cardiomyopathy in Mice With Overexpression of Cardiac G
s
α and a Missense Mutation in the α-Myosin Heavy Chain
Authors: Hardt Stefan E. , Geng Yong-Jian , Montagne Olivier , Asai Kuniya , Hong Chull , Yang Gui Ping , Bishop Sanford P. , Kim Song-Jung , Vatner Dorothy E. , Seidman Christine E. , Seidman J.G. , Homcy Charles J. , Vatner Stephen F.
Published: July 2002

Background

—

To understand further the pathogenesis of familial hypertrophic cardiomyopathy, we determined how the cardiomyopathy induced by an Arg403→Gln missense mutation in the α-myosin heavy chain (403) is affected by chronically enhancing sympathetic drive by mating the mice with those overexpressing G
s
α (G
s
αx403).

Methods and Results

—

Heart rate in 3-month-old conscious mice was elevated similarly (
P
<0.05) in mice overexpressing G
s
α (G
s
α mice; 746±14 bpm) and G
s
αx403 mice (718±19 bpm) compared with littermate wild-type mice (WT; 623±18 bpm) and 403 mice (594±16 bpm). Left ventricular ejection fraction (LVEF), as determined by echocardiography, was enhanced in G
s
αx403 mice (88±1%,
P
<0.001) compared with WT (69±1%), 403 (75±1%), and G
s
α (69±2%) mice. Isolated cardiomyocytes from G
s
αx403 mice also exhibited higher (
P
<0.001) baseline percent contraction (11.9±0.5%) than WT (7.0±0.5%), 403 (5.5±0.5%), and G
s
α (7.8±0.3%) cardiomyocytes. Relaxation of myocytes was impaired in 403 mice compared with WT but enhanced in G
s
α and normalized in G
s
αx403 mice. This was also observed in vivo. In vivo isoproterenol (0.1 μg · kg
−1
· min
−1
) increased LVEF to maximal levels in G
s
αx403 and G
s
α, whereas in 403, the response was attenuated compared with WT. At 10 months of age, G
s
αx403 had significantly depressed LVEF (57±4%). Histopathological examination demonstrated that myocyte hypertrophy and fibrosis were already present in young G
s
αx403 mice and that old animals had severe cardiomyopathy. By 15 months of age, the survival of G
s
αx403 was 0% compared with 100% for WT, 71% for G
s
α, and 100% for 403 mice (
P
<0.05).

Conclusions

—

These results show that the cardiomyopathy developed by G
s
αx403 mice is synergistic rather than additive, most likely owing to the elevated baseline function combined with enhanced responsiveness to sympathetic stimulation.
Insulin Causes Endothelial Dysfunction in Humans
Authors: Arcaro Guido , Cretti Anna , Balzano Sara , Lechi Alessandro , Muggeo Michele , Bonora Enzo , Bonadonna Riccardo C.
Published: July 2002

Background

—

Insulin resistance is often accompanied by hyperinsulinemia and may predispose to atherosclerosis. Endothelium plays a central role in atherogenesis. The in vivo effects of hyperinsulinemia on endothelial function of large conduit arteries are unknown.

Methods and Results

—

Twenty-five healthy subjects were enrolled for study. In study A (n=9), subjects underwent both a time-control saline study and a euglycemic low-dose insulin (insulin ≈110 pmol/L) clamp for 6 hours. Study B (n=5) was identical to study A except that the euglycemic clamp was performed at high physiological insulin concentrations (≈440 pmol/L). In study C (n=7), subjects underwent two 4-hour euglycemic insulin (≈110 pmol/L) clamps with and without the concomitant infusion of an antioxidant (vitamin C). In study D (n=4), two saline time-control studies were performed with and without the concomitant infusion of vitamin C. In all studies, both at baseline and throughout the experimental period, endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-induced) vasodilation was assessed in femoral and brachial arteries by echo Doppler. Both low (study A) and high physiological (study B) hyperinsulinemia abolished endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was unaffected. Vitamin C fully restored insulin-impaired endothelial function without affecting endothelium-independent vasodilation (study C). Vitamin C had no effects on endothelium-dependent or endothelium-independent vasodilation during saline control studies (study D).

Conclusions

—

Modest hyperinsulinemia, mimicking fasting hyperinsulinemia of insulin-resistant states, abrogates endothelium-dependent vasodilation in large conduit arteries, probably by increasing oxidant stress. These data may provide a novel pathophysiological basis to the epidemiological link between hyperinsulinemia/insulin-resistance and atherosclerosis in humans.
Platelet-Derived Growth Factor-AB Limits the Extent of Myocardial Infarction in a Rat Model
Authors: Edelberg Jay M. , Lee Seung H. , Kaur Manmeen , Tang Lilong , Feirt Nikki M. , McCabe Samuel , Bramwell Orville , Wong S. Chiu , Hong Mun K.
Published: July 2002

Background

—

Compared with younger patients, myocardial infarction in the elderly has been associated with less favorable clinical outcomes, which may be attributable to a decline in angiogenic capacity in the aging heart.

Methods and Results

—

To test the hypothesis that the functional phenotype of cardiac microvascular endothelial cells is maintained partly by a cardiac myocyte platelet-derived growth factor (PDGF)-B–induced paracrine pathway, we conducted in vitro studies with murine cardiac cells. These studies demonstrated that unlike young endothelial cells, endothelial cells of the aging heart do not express PDGF-B when cultured in the presence of cardiac myocytes. The functional significance of this endothelial dysregulation was assessed with an ex vivo pinnal cardiac allograft model to demonstrate that senescent cardiac angiogenic activity was depressed (2 of 17 allografts were viable in 18-month-old mice versus 19 of 20 in 3-month-old mice;
P
<0.01). PDGF-AB pretreatment specifically restored the viability of the cardiac allografts in the aging hosts (13 of 13 allografts were viable;
P
<0.01 versus 18-month-old controls). Finally, in vivo studies in rat hearts demonstrated that pretreatment by intramyocardial delivery of PDGF-AB promotes angiogenesis and minimizes the extent of myocardial infarction in the aging hearts after coronary ligation (myocardial infarction size: 10.0±7.0% of left ventricular area in PDGF pretreatment [n=7] versus 17.6±5.6% in control [n=5] groups;
P
<0.03).

Conclusion

—

Aging hearts have impaired angiogenic function as a result of depressed PDGF-B production. Restoration of the dysregulated endothelial PDGF-mediated angiogenic pathway in the aging heart reverses the senescent impairment in cardioprotective angiogenic function and offers a foundation for developing novel therapies for cardiovascular disease in older individuals.