bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion-Weighted MRI Findings in Patients with Capsular Warning Syndrome
Authors: Staaf Gert , Geijer Bo , Lindgren Arne , Norrving Bo
Published: October 2003

Background and Purpose: The ‘capsular warning syndrome’ (CWS) of recurrent stereotyped episodes of motor or sensory dysfunction is clinically well recognized, and is associated with a high risk of imminent lacunar infarction with permanent deficits resembling those of CWS. However, the pathophysiology of CWS has not been well characterized. We report a clinicoanatomic correlation with MR imaging studies in the acute and chronic phases in patients with CWS. Material and Methods: Between April 1997 and March 2001, we prospectively studied 8 patients, mean age 73.3 years, presenting with 4–17 motor or sensorimotor transient ischemic attacks (TIAs; duration 2–90 min) up to 3 days after onset of the first episode. Four patients were free of symptoms between the attacks and had no residua, whereas 4 patients developed a pure motor or sensorimotor stroke within 1–3 days after symptom onset. Diffusion-weighted echoplanar MRI (DWI) and T2-weighted MRI studies were performed within 1 week after symptom onset and were repeated 1–2 months later. Results: Seven of the 8 patients had an appropriate lesion on DWI in the acute phase. DWI abnormalities in the 3 patients with TIAs were 4–10 mm in diameter and confined to the lateral thalamus or medial globus pallidus without involving the internal capsule, whereas 4 patients who developed a stroke had abnormalities localized to the putamen extending to corona radiata (3 patients), or the pontomesencephalic junction (1 patient). All 6 patients who underwent follow-up MRI had an infarct on T2-weighted images corresponding to, but usually smaller than, the acute phase DWI abnormality. Conclusions: Small infarcts in the basal ganglia or the pons, close to central motor pathways, appear to be the primary lesion in CWS. The pathophysiology of CWS is complex, and may involve hemodynamic mechanisms in penetrating arterial territories, as well as molecular mechanisms, such as peri-infarct depolarizations affecting adjacent motor pathways.
Cerebral Sinus Venous Thrombosis in Two Patients with Spontaneous Intracranial Hypotension
Authors: Berroir Stéphane , Grabli David , Héran Françoise , Bakouche Pierre , Bousser Marie-Germaine
Published: October 2003

We report 2 patients who had clinical and neuroimaging signs of spontaneous intracranial hypotension and who developed cerebral sinus venous thrombosis. This sequence of events – known after dural puncture but not in spontaneous intracranial hypotension – was suggested by the change in the pattern of headache, from a postural to a permanent and increasing one. The diagnostic and therapeutic difficulties that this complication raises are discussed.
Early Functional Recovery and the Fate of the Diffusion/Perfusion Mismatch in Patients with Proximal Middle Cerebral Artery Occlusion
Authors: Singer Oliver C. , du Mesnil de Rochemont Richard , Foerch Christian , Stengel Astrid , Sitzer Matthias , Lanfermann Heiner , Neumann-Haefelin Tobias
Published: October 2003

Background: The relationship between early neurological recovery, time to recanalization and the salvage of hypoperfused, but not diffusion-restricted tissue was investigated. Methods: In 17 patients with acute middle cerebral artery occlusion, a multiparametric stroke MRI protocol was performed <6 h after symptom onset, as well as at day 2 and 7. Recanalization was monitored with transcranial Doppler or with conventional angiography (during local thrombolysis). Functional improvement was defined as a change of ≧4 points on the National Institutes of Health Stroke Scale score. Results: In patients with functional improvement, 78% (median, range 66–95%) of the acute mean transit time (MTT) lesion escaped infarction compared with 28% (median, range –13 to 78%) in patients without neurological improvement (p < 0.01). Similarly, the percentage of tissue with a time-to-peak (TTP) delay of ≧2 s not progressing to infarction was 80 and 4% in the groups with and without improvement, respectively (p < 0.01). Neurological improvement was more frequent in patients with early (≤3 h after presentation) recanalization, due to the salvage of larger areas of initially hypoperfused tissue. Conclusions: The salvage of hypoperfused tissue is a major factor influencing early neurological improvement.
Characteristics of the National Institute of Health Stroke Scale: Results from a Population-Based Stroke Cohort at Baseline and after One Year
Authors: Appelros Peter , Terént Andreas
Published: October 2003

Background: The National Institute of Health Stroke Scale (NIHSS) results at baseline and after 1 year have never before been accounted for within an unselected population-based stroke sample. Neither has it been shown which individual items in the scale are the most important ones for the outcome in terms of death or dependency after 1 year. Methods: The subjects were all patients within a municipality who had their first-ever non-subarachnoidal stroke during 1 year (n = 377). Impairment was evaluated at baseline (within 24–48 h) and after 1 year with the 15-item version of the NIHSS. At the 1-year follow-up, the Modified Rankin Scale was used in order to determine which patients were dependent. Predictors of death and dependency were analysed in logistic regression models. The different NIHSS items, age and gender were used as independent variables. Results: The median NIHSS score was 6 (interquartile range 3–12) at baseline and 1 (interquartile range 0–3) at the 1-year follow-up, when 33% of the patients had died. Of patients scoring less than 4 on baseline NIHSS, 75% were functionally independent after 1 year. Seventeen per cent were functionally dependent and 8% were dead. Independent predictors of death were: age, questions, commands, gaze, alertness and sensation. Independent predictors of dependency were: age, commands, alertness and motor leg. Conclusions: Baseline NIHSS predicts the outcome after 1 year at the group level. Age and any reduction of the level of consciousness on arrival were associated with bad outcome after 1 year.
Complications following Carotid Angioplasty and Carotid Stenting in Patients with Symptomatic Carotid Artery Disease
Authors: McKevitt F.M. , Macdonald S. , Venables G.S. , Cleveland T.J. , Gaines P.A.
Published: October 2003

Background: We review a single centre’s experience of the endovascular treatment of carotid artery disease, present the 30-day and 1-year complication rates and assess whether changes in technique are associated with a change in clinical outcome. Methods: Patients who underwent carotid angioplasty with or without stenting for symptomatic ≧70% carotid artery stenosis secondary to atherosclerosis were included. 333 procedures were performed, i.e. angioplasty alone (86), stent without cerebral protection (150) and stent with cerebral protection (97). Results: At 30 days, the total major disabling stroke and all death rate was 3.0%. For angioplasty alone, this was 2.3%, for stent without cerebral protection 4.0% and for stent with cerebral protection 2.1%. If non-stroke-related deaths were excluded, it was 2.3, 3.3 and 0%, respectively. After 30 days, the 1-year ipsilateral stroke rate was 0.8%. Conclusions: Carotid artery stenting, in particular with a cerebral protection device, is a safe alternative to carotid endarterectomy for the treatment of symptomatic high-grade carotid artery disease.
Aphasia after Stroke: Type, Severity and Prognosis
Authors: Pedersen Palle Møller , Vinter Kirsten , Olsen Tom Skyhøj
Published: October 2003

Aim: To determine the types, severity and evolution of aphasia in unselected, acute stroke patients and evaluate potential predictors for language outcome 1 year after stroke. Methods: 270 acute stroke patients with aphasia (203 with first-ever strokes) were included consecutively and prospectively from three hospitals in Copenhagen, Denmark, and assessed with the Western Aphasia Battery. The assessment was repeated 1 year after stroke. Results: The frequencies of the different types of aphasia in acute first-ever stroke were: global 32%, Broca’s 12%, isolation 2%, transcortical motor 2%, Wernicke’s 16%, transcortical sensory 7%, conduction 5% and anomic 25%. These figures are not substantially different from what has been found in previous studies of more or less selected populations. The type of aphasia always changed to a less severe form during the first year. Nonfluent aphasia could evolve into fluent aphasia (e.g., global to Wernicke’s and Broca’s to anomic), whereas a fluent aphasia never evolved into a nonfluent aphasia. One year after stroke, the following frequencies were found: global 7%, Broca’s 13%, isolation 0%, transcortical motor 1%, Wernicke’s 5%, transcortical sensory 0%, conduction 6% and anomic 29%. The distribution of aphasia types in acute and chronic aphasia is, thus, quite different. The outcome for language function was predicted by initial severity of the aphasia and by the initial stroke severity (assessed by the Scandinavian Stroke Scale), but not by age, sex or type of aphasia. Thus, a scoring of general stroke severity helps to improve the accuracy of the prognosis for the language function. One year after stroke, fluent aphasics were older than nonfluent aphasics, whereas such a difference was not found in the acute phase.
Quality of Life after Treatment of Unruptured Intracranial Aneurysms by Neurosurgical Clipping or by Embolisation with Coils
Authors: Brilstra Eva H. , Rinkel Gabriel J.E. , van der Graaf Yolanda , Sluzewski Menno , Groen Rob J. , Lo Rob T.H. , Tulleken Cornelis A.F.
Published: October 2003

Background: Relatively high rates of complications occur after operation for unruptured intracranial aneurysms. Published data on endovascular treatment suggest lower rates of complications. We measured the impact of treatment of unruptured aneurysms by clipping or coiling on functional health, quality of life, and the level of anxiety and depression. Methods: In three centres, we prospectively collected data on patients with an unruptured aneurysm who were treated by clipping or coiling. Treatment assignment was left to the discretion of the treating physicians. Before, 3 and 12 months after treatment, we used standardised questionnaires to assess functional health (Rankin Scale score), quality of life (SF-36, EuroQol), and the level of anxiety and depression (Hospital Anxiety and Depression Scale). Results: Nineteen patients were treated by coiling and 32 by clipping. In the surgical group, 4 patients (12%) had a permanent complication; 36 of all 37 aneurysms (97%) were successfully clipped. Three months after operation, quality of life was worse than before operation; 12 months after operation, it had improved but had not completely returned to baseline levels. Scores for depression were higher than in the general population. In the endovascular group, no complications with permanent deficits occurred; 16 of 19 aneurysms (84%) were occluded by more than 90%. One patient died from rupture of the previously coiled aneurysm. In the others, quality of life after 3 months and after 1 year was similar to that before treatment. Conclusions: In the short term, operation of patients with an unruptured aneurysm has a considerable impact on functional health and quality of life. After 1 year, recovery occurs but it is incomplete. Coil embolisation does not affect functional health and quality of life.
Does Treatment Modality of Intracranial Ruptured Aneurysms Influence the Incidence of Cerebral Vasospasm and Clinical Outcome?
Authors: Dehdashti Amir R. , Mermillod Bernadette , Rufenacht Daniel A. , Reverdin Alain , de Tribolet Nicolas
Published: October 2003

Background: Cerebral vasospasm is the most common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). This study is designed to determine whether the incidence of symptomatic vasospasm and the overall clinical outcome differ between patients treated with surgical clipping compared with endovascular obliteration of aneurysms. Methods: In this prospective study, 98 patients with aneurysmal SAH were treated. Seventy-two patients underwent surgery and clipping and 26 had coil embolization. The incidence of symptomatic vasospasm, permanent neurologic deficit due to vasospasm and clinical outcome were analyzed. Patients with better clinical and radiological grades (World Federation of Neurological Surgeons grades I–III and Fisher grades I–III) were analyzed separately. Results: Symptomatic vasospasm occurred in 22% of the patients; 25% in the surgical group and 15% in the endovascular group. Nine percent of the patients in the surgical group and 7% in the endovascular group suffered ischemic infarction with permanent neurological deficit. These differences did not reach statistical significance (p = 0.42). For patients with better clinical and radiological grades, no significant difference was found for the rate of symptomatic vasospasm; 23% in the surgical and 12% in the endovascular group (p = 0.49). The overall clinical outcome was comparable in both groups, with no difference in the likelihood of a Glasgow Outcome Scale score of 3 or less (15% in the surgical and 16% in the endovascular group; p = 0.87). The same results for outcome were obtained for the subgroup of patients with better clinical grades on admission. Conclusion: Symptomatic vasospasm and ischemic infarction rate seem comparable in both groups, even for patients with better clinical and radiological admission grades. There is no significant difference in the overall clinical outcome at the long-term follow-up between both groups.
Image Quality of the Temporal Bone Window Examined by Transcranial Doppler Sonography and Correlation with Postmortem Computed Tomography Measurements
Authors: Kollár József , Schulte-Altedorneburg Gernot , Sikula Judit , Fülesdi Béla , Ringelstein E. Bernd , Mehta Vineet , Csiba László , Droste Dirk W.
Published: October 2003

Background and Purpose: The major limitation of native transcranial colour-coded duplex sonography (TCCS) in older stroke patients is the relatively frequent occurrence of an insufficient temporal window. Our goal was to investigate the relationship between the in vivo Doppler ultrasound image quality of the temporal bone, and computed tomography (CT)-determined thickness, density, and homogeneity of cadaver temporal bone. Methods: Thirty-three moribund neurological patients who eventually died were examined by TCCS using the transtemporal approach. The sonographer categorized the quality of the TCCS image (excellent, intermediate, and poor). During autopsy, a rectangular sample of the temporal squama was removed, which corresponded to the area of the in vivo acoustic window. The thickness of the whole temporal bone, cortical, and cancellous (= diploe) bone as well as the density and homogeneity were determined by high-resolution CT. Results: Thirty-seven temporal bones were obtained. The quality of the acoustic window was classified as excellent in 13, intermediate in 6 and poor in 18 cases. A significant correlation between the complete bone thickness, as well as between the absolute thickness of the diploe and the quality of the acoustic window was found: the thinner the bone/diploe, the better the colour Doppler signal. The thickness of the cortical plates and the homogeneity of the bones were identical in the three image quality categories. Conclusion: The transtemporal TCCS image quality depends mainly on the thickness of the cancellous component of the temporal bone.
Cause Is the Main Predictor of Outcome in Patients with Pontine Hemorrhage
Authors: Rabinstein Alejandro A. , Tisch Stephen H. , McClelland Robyn L. , Wijdicks Eelco F.M.
Published: October 2003

Background: Pontine hemorrhages frequently lead to death or severe disability. Predictors of early mortality have been previously described but little is known about the factors influencing long-term disability. Objective: Determine clinical predictors of long-term outcome in a large hospital series of patients with acute pontine hemorrhage. Methods: Review of all patients with acute pontine hemorrhage admitted to a single tertiary center from 1990 to 2002 who underwent a diagnostic workup including brain magnetic resonance imaging (MRI). Long-term outcome was rated using the modified Rankin Scale (mRS) score at the time of the last follow-up. Odds ratios (ORs) for predictive factors were calculated using univariate and multivariable logistic regression analysis. Level of significance was established at p < 0.01. Results: We identified 44 consecutive patients with acute pontine hemorrhage. Twenty-four patients had primary hemorrhages (no cause other than hypertension). Arteriovenous or cavernous malformations were documented by brain MRI in 20 patients. Patients with primary hemorrhages had worse Glasgow Coma Scale sum scores (p = 0.01) and more unfavorable CT patterns (p = 0.005) at presentation. Eighteen percent of the patients died in the hospital. Mean follow-up among survivors was 20 months (range 3–144 months). Twenty-two percent of the patients remained severely disabled (mRS greater than 2) at 3 months and at the time of the last follow-up. All deaths occurred in patients with primary pontine hemorrhage. Poor outcome (death or severe disability) was more frequent in patients with primary hemorrhages when compared with patients harboring cavernous malformations (62 versus 5%; p < 0.01). Primary hemorrhage was the only independent predictor of poor outcome in multivariable regression analysis (OR 12; p = 0.029). Conclusions: Cause is a main predictor of clinical and radiological severity at presentation and outcome in patients with pontine hemorrhage. The first episode of hemorrhage in patients with brainstem cavernous malformations is usually benign. Pontine hemorrhage associated with prior hypertension is much more devastating.
Magnetofection Potentiates Gene Delivery to Cultured Endothelial Cells
Authors: Krötz Florian , Sohn Hae-Young , Gloe Torsten , Plank Christian , Pohl Ulrich
Published: October 2003

Modification of cellular functions by overexpression of genes is increasingly practised for research of signalling pathways, but restricted by limitations of low efficiency. We investigated whether the novel technique of magnetofection (MF) could enhance gene transfer to cultured primary endothelial cells. MF of human umbilical vein endothelial cells (HUVEC) increased transfection efficiency of a luciferase reporter gene up to 360-fold compared to various conventional transfection systems. In contrast, there was only an up to 1.6-fold increase in toxicity caused by MF suggesting that the advantages of MF outbalanced the increase in toxicity. MF efficiently increased transfection efficiency using several commercially available cationic lipid transfection reagents and polyethyleneimine (PEI). Using PEI, even confluent HUVEC could be efficiently transfected to express luciferase activity. Using a green fluorescent protein vector maximum percentages of transfected cells amounted up to 38.7% while PEI without MF resulted in only 1.3% transfected cells. Likewise, in porcine aortic endothelial cells MF increased expression of a luciferase or a β-galactosidase reporter, reaching an efficiency of 37.5% of cells. MF is an effective tool for pDNA transfection of endothelial cells allowing high efficiencies. It may be of great use for investigating protein function in cell culture experiments.
Visualization of Leukocyte Transendothelial and Interstitial Migration Using Reflected Light Oblique Transillumination in Intravital Video Microscopy
Authors: Mempel Thorsten R. , Moser Christian , Hutter Joerg , Kuebler Wolfgang M. , Krombach Fritz
Published: October 2003

Dynamic visualization of the intravascular events leading to the extravasation of leukocytes into tissues by intravital microscopy has significantly expanded our understanding of the underlying molecular processes. In contrast, the detailed observation of leukocyte transendothelial and interstitial migration in vivo has been hampered by the poor image contrast of cells within turbid media that is obtainable by conventional brightfield microscopy. Here we present a microscopic method, termed reflected light oblique transillumination microscopy, that makes use of the optical interference phenomena generated by oblique transillumination to visualize subtle gradients of refractive indices within tissues for enhanced image contrast. Using the mouse cremaster muscle, we demonstrate that this technique makes possible the reliable quantification of extravasated leukocytes as well as the characterization of morphological phenomena of leukocyte transendothelial and interstitial migration.
Vascular Endothelial Growth Factor–Regulated Gene Expression in Endothelial Cells
Authors: Liu Dan , Jia Haiyan , Holmes David Ian Roderick , Stannard Anita , Zachary Ian
Published: October 2003

Objective—

The program of gene expression regulated by vascular endothelial growth factor (VEGF) remains poorly understood. The aim of this study was to identify VEGF-regulated genes in human umbilical vein endothelial cells.

Methods and Results—

VEGF-regulated gene expression was analyzed by screening Affymetrix oligonucleotide arrays and quantitative, real-time, reverse transcription–polymerase chain reaction. The most strongly induced genes were the NR4A nuclear receptor family members Nur77, Nurr1, and Nor1 and the zinc-finger transcription factor Egr3. VEGF also induced rapid expression of Down syndrome candidate region 1, cyclooxygenase-2, tissue factor, stanniocalcin-1, the serine/threonine kinase Cot, and eps15 homology domain-containing protein. VEGF-induced NR4A family and Egr3 expression was blocked by a KDR inhibitor, and placental growth factor and basic fibroblast growth factor weakly increased expression of these genes. Induction of NR4A genes was mediated via intracellular Ca
2+
, protein kinase C- and calcineurin-dependent pathways. VEGF increased protein expression of Nurr1 and Nur77 and decreased Nur77 phosphorylation at the negative regulatory site serine 351.

Conclusions—

VEGF induces expression of NR4A nuclear receptors and Egr3 via KDR and KDR-mediated signaling mechanisms. The genes identified here are novel candidates as key early mediators of VEGF-induced endothelial functions.
Transfer for Primary Angioplasty Versus Immediate Thrombolysis in Acute Myocardial Infarction
Authors: Dalby M. , Bouzamondo A. , Lechat P. , Montalescot G.
Published: October 2003

Background—

The benefit of primary percutaneous coronary intervention (PCI) over thrombolysis has been clearly demonstrated in acute myocardial infarction (AMI). However, the best therapeutic strategy for a patient with AMI presenting to acute care services without catheterization facilities remains under debate. Our objective was to gather all available information from clinical trials comparing transfer of patients experiencing AMI for angioplasty versus immediate thrombolysis.

Methods and Results—

We performed a meta-analysis of all data available from published randomized trials and from presentations in scientific sessions of major cardiology congresses comparing the 2 strategies. The primary end point was the combined criteria (CC) of death/reinfarction/stroke as defined in each trial. Relative risk (RR) evaluated the treatment effect. We identified 6 clinical trials including 3750 patients. Transfer time was always <3 hours. The CC was significantly reduced by 42% (95% confidence interval [CI] 29% to 53%,
P
<0.001) in the group transferred for primary PCI compared with the group receiving on-site thrombolysis. When CC parameters were considered separately, reinfarction was significantly reduced by 68% (95% CI, 34% to 84%;
P
<0.001) and stroke by 56% (95% CI, −15% to 77%;
P
=0.015). There was a trend toward reduction in all-cause mortality of 19% (95% CI, −3% to 36%;
P
=0.08) with transfer for PCI.

Conclusion—

Even when transfer to an angioplasty center is necessary, primary PCI remains superior to immediate thrombolysis. Organization of ambulance systems, prehospital management, and adequate PCI capacity appear now to be the key issues in providing reperfusion therapy for AMI.
Physiological Genomics of Human Arteries
Authors: Durier Séverine , Fassot Céline , Laurent Stéphane , Boutouyrie Pierre , Couetil Jean-Paul , Fine Erika , Lacolley Patrick , Dzau Victor J. , Pratt Richard E.
Published: October 2003

Background—

Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters.

Methods and Results—

In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal–cell membrane–extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell–matrix interactions, or the contractile state of the cell.

Conclusion—

Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.
Impact of Viability, Ischemia, Scar Tissue, and Revascularization on Outcome After Aborted Sudden Death
Authors: van der Burg Alida E. Borger , Bax Jeroen J. , Boersma Eric , Pauwels Ernest K.J. , van der Wall Ernst E. , Schalij Martin J.
Published: October 2003

Background—

Survivors of aborted sudden death attributable to ventricular arrhythmias in the presence of coronary artery disease are at risk for recurrences. The substrate underlying these arrhythmias is not clear, and therefore the relation between ischemia, viability, scar tissue (and revascularization), and the incidence of ventricular arrhythmias (and survival) was studied over up to 3 years.

Methods and Results—

One hundred fifty-three survivors of sudden death underwent stress-rest perfusion imaging. Patients with ischemic/viable myocardium (n=73) were revascularized if possible. Final antiarrhythmic therapy was based on the outcome of electrophysiological testing or left ventricular ejection fraction (LVEF). Implantation of a defibrillator was performed in 112 (72%) patients. During 3-year follow-up, 15 cardiac deaths occurred and 42 (29%) patients had recurrent ventricular arrhythmias. Patients with events (death or recurrence) exhibited more often a severely depressed LVEF (≤30%), more extensive scar tissue, and less ischemic/viable myocardium on perfusion imaging and less frequently underwent revascularization. Multivariate analysis identified extensive scar tissue and LVEF ≤30% as the only predictors of death/recurrent ventricular arrhythmias.

Conclusions—

In patients with aborted sudden death, extensive scar tissue and severely depressed LVEF are the only predictors of death or recurrent ventricular arrhythmias. These patients should be considered for implantation of a defibrillator.
Idiopathic Left Bundle-Branch Block–Shaped Ventricular Tachycardia May Originate Above the Pulmonary Valve
Authors: Timmermans Carl , Rodriguez Luz-Maria , Crijns Harry J.G.M. , Moorman Antoon F.M. , Wellens Hein J.J.
Published: October 2003

Background—

Idiopathic left bundle-branch block (LBBB)–like ventricular tachycardia (VT) is considered to originate in the right ventricular outflow tract (RVOT) or from the aortic root. Both regions are derived from the embryonic outflow tract. We now report that also the pulmonary trunk can give rise to VT, suggesting a common etiology of these tachycardias.

Methods and Results—

We studied 6 patients with symptomatic idiopathic LBBB-VT using electrophysiological mapping techniques. The VT origin was determined by analyzing the electrograms and the angiographic location of the catheter tip at the successful ablation site or the earliest activation site. Eight VTs were induced. Two VTs, with a mean earliest endocardial activation time of −5 and −20 ms and optimal pace mapping, were successfully ablated in the RVOT. In the remaining 6 VTs, the earliest activation site was found in the pulmonary artery, and, at this site, a sharp potential was present −38±12 ms before the QRS in 5 VTs. The mean earliest endocardial activation time in the RVOT was −1±2 ms. Ablation was attempted in 5 of 6 VTs and resulted in an acutely successful procedure. After a mean follow-up of 10±4 months, 1 of 5 patients had a recurrence.

Conclusions—

The site of origin of idiopathic LBBB-VT can be in the root of the pulmonary artery, suggesting a myocardial connection from this site to the RVOT. If no good criteria for ablation in the RVOT are found, detailed mapping of the pulmonary artery should be performed.
Association of Insulin Resistance, Hyperleptinemia, and Impaired Nitric Oxide Release With In-Stent Restenosis in Patients Undergoing Coronary Stenting
Authors: Piatti PierMarco , Di Mario Carlo , Monti Lucilla D. , Fragasso Gabriele , Sgura Fabio , Caumo Andrea , Setola Emanuela , Lucotti Pietro , Galluccio Elena , Ronchi Cristina , Origgi Anna , Zavaroni Ivana , Margonato Alberto , Colombo Antonio
Published: October 2003

Background—

Previously undiagnosed diabetes, impaired glucose tolerance, and insulin resistance are common in patients with acute myocardial infarction and coronary heart disease (CHD) and might be involved in early restenosis after stent implantation. To evaluate whether markers of insulin resistance syndrome, including leptin, and endothelial dysfunction are related to increased rate of early restenosis, we studied nondiabetic patients with CHD after successful coronary stenting.

Methods and Results—

Both patients with CHD undergoing coronary stenting (120 patients) and control subjects (58 patients) were submitted to an oral glucose tolerance test (OGTT). Fasting leptin levels and fasting and postglucose load insulin sensitivity were assessed. Endothelial function was measured by nitrite and nitrate release (NOx) during OGTT. More than 50% of patients treated with stent implantation presented impaired glucose tolerance or type 2 diabetes, which was previously undiagnosed. These patients also had higher glucose, insulin, and leptin levels than control subjects. Among the stented patients, insulin and leptin levels were higher in patients with restenosis than in patients without restenosis. A significant increase in NOx levels was found during OGTT both in patients without restenosis and in control subjects. On the contrary, NOx profiles were blunted in patients with restenosis. At multiple regression analysis, only ΔAUC-NOx areas and insulin sensitivity index showed an independent correlation with the minimal lumen diameter at follow-up.

Conclusions—

We demonstrated that insulin resistance and endothelial dysfunction are independent predictors of early restenosis after coronary stenting.
Endothelial Dysfunction and Cardiovascular Risk Prediction in Peripheral Arterial Disease
Authors: Brevetti Gregorio , Silvestro Antonio , Schiano Vittorio , Chiariello Massimo
Published: October 2003

Background—

Endothelial dysfunction plays a key role in atherogenesis. We prospectively investigated the impact of noninvasive measurement of endothelial function on cardiovascular risk in peripheral arterial disease (PAD). The study was specially aimed at assessing whether brachial artery flow-mediated dilation (FMD) added to the predictive value of ankle-brachial pressure index (ABPI).

Methods and Results—

Of 131 patients monitored for a mean of 23±10 months, 18 had a coronary event, 12 a cerebrovascular event, and 9 a peripheral event. The median FMD was lower in patients with an event than in those without (5.8% versus 7.6%,
P
<0.05), whereas vasodilation to nitroglycerin was similar in the two groups. The cardiovascular event rate was higher in patients with FMD below the median versus those with FMD above the median (
P
<0.001 by log-rank test). In a Cox proportion hazard model, independent predictors of events were FMD below the median (
P
<0.01), ABPI below the median (
P
<0.01), and previous stroke (
P
<0.02). Similar results were obtained when peripheral events were excluded from the analysis. Below-median ABPI and FMD combined was more accurate in predicting risk (relative risk [RR] 13.0; 95% CI, 3.0 to 56.2;
P
<0.01) than ABPI (RR, 6.4; 95% CI, 1.4 to 29.1;
P
<0.02) and FMD (RR, 4.8; 95% CI, 1.1 to 23.3;
P
<0.05) alone.

Conclusions—

A low brachial artery FMD is an independent predictor of cardiovascular risk in patients with PAD and adds to the prognostic value of ABPI, which is currently the most powerful prognostic indicator in PAD.
Feasibility and Short-Term Efficacy of Percutaneous Mitral Annular Reduction for the Therapy of Heart Failure-Induced Mitral Regurgitation
Authors: Kaye David M. , Byrne Melissa , Alferness Clif , Power John
Published: October 2003

Background—

Mitral regurgitation (MR) frequently accompanies congestive heart failure (CHF) and is associated with poorer prognosis and more significantly impaired symptomatic status. Although surgical mitral valve annuloplasty has the potential to offer benefit, concerns about the combined surgical risk and possible effects on ventricular performance have limited progress. We evaluated the feasibility and short-term efficacy of a novel device placed in the coronary sinus to reduce MR in the setting of CHF.

Methods and Results—

CHF and MR were induced in 9 adult sheep by rapid ventricular pacing for 5 to 8 weeks. A mitral annular constraint device was implanted percutaneously through the right internal jugular vein in the coronary sinus and great cardiac vein to create a short-term stable reduction (24.9±2.5%) in the mitral annular septal-lateral dimension as assessed echocardiographically. Right and left heart pressures and cardiac output were determined before and 15 minutes after device implantation. MR extent was examined echocardiographically and expressed as a ratio of left atrial area (MR/LAA). After device placement, MR was substantially reduced from an MR/LAA of 42+6% to 4±3% (
P
<0.01). In association, mean pulmonary wedge pressure was significantly reduced (26±3 to 18±3 mm Hg;
P
<0.01) and mean cardiac output significantly increased (3.4±0.3 to 4.3±0.4 L/min;
P
=0.01).

Conclusions—

In this model of CHF, percutaneous placement of a mitral annular constraint device in the coronary sinus resulted in the short-term elimination or minimization of MR and was accompanied in the short term by favorable hemodynamic effects.
Inflammatory Cytokines Stimulated C-Reactive Protein Production by Human Coronary Artery Smooth Muscle Cells
Authors: Calabró Paolo , Willerson James T. , Yeh Edward T.H.
Published: October 2003

Background—

Serum C-reactive protein (CRP) levels are good predictors of the development of cardiovascular events in apparently healthy men and women. CRP has been believed to be produced exclusively by hepatocytes during the acute-phase response. Several lines of evidence have suggested that atherosclerotic arteries can also produce CRP. However, the cell types that produce CRP locally in the atherosclerotic arterial wall have not been clearly identified.

Methods and Results—

Human coronary artery smooth muscle cells (HCASMCs) and human umbilical vein endothelial cells (HUVECs) were incubated with interleukin-1β (IL-1β), IL-6, their combination, tumor necrosis factor-α (TNF-α), or lipopolysaccharide (LPS) at different concentrations. The supernatants were concentrated and analyzed by a high-sensitivity enzyme-linked immunosorbent assay specific for human CRP. RNA was extracted from the HCASMCs for reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for the CRP. Maximal CRP production was observed in HCASMCs after 48 hours of incubation with the combination of 25 ng/mL of IL-1β and 10 ng/mL of IL-6, whereas incubation with IL-1β or IL-6 alone only modestly induced CRP. Incubation with TNF-α (50 ng/mL) or LPS (1000 EU/mL) resulted in an increase in CRP production comparable to the IL-1β and IL-6 combination. The induction of CRP in HCASMCs was independently confirmed by RT-PCR comparing the relative CRP mRNA levels. The induction of CRP production by HCASMCs was not reproduced in HUVECs, however.

Conclusions—

These results demonstrated that HCASMCs, but not HUVECs, could produce CRP in response to inflammatory cytokines. The locally produced CRP could directly participate in atherogenesis and the development of cardiovascular complications.
Association Between Apolipoprotein E Alleles and Calcific Valvular Heart Disease
Authors: Novaro Gian M. , Sachar Ravish , Pearce Gregory L. , Sprecher Dennis L. , Griffin Brian P.
Published: October 2003

Background—

Studies on apolipoprotein E (apoE) alleles have reported an increased risk of coronary heart disease in patients with the apoE4 allele. Given the risk factor and histological similarities between coronary and calcific valvular heart disease (aortic stenosis [AS] and mitral annular calcification [MAC]), we postulated that apoE alleles might be associated with the development of these valvular lesions.

Methods and Results—

We evaluated the association between apoE alleles and calcific valvular lesions in 802 patients undergoing transthoracic echocardiography using logistic regression analyses. No difference was noted in genotype distribution (
P
=0.59) or prevalence of apoE4 between those with or without MAC (30% versus 27%, respectively;
P
=0.57). Compared with patients without AS, the genotype distribution of patients with AS differed significantly (
P
=0.03), with increasing prevalences of the apoE 4 allele (27% in those without versus 40% in those with AS;
P
=0.01). In multivariate analyses adjusting for age, gender, low-density lipoprotein cholesterol levels, and coronary artery disease, increasing age and the apoE4 allele were significant independent predictors of AS (odds ratio, 1.94; 95% confidence interval, 1.01 to 3.71;
P
=0.046), whereas the apoE4 allele was not predictive of MAC.

Conclusions—

These findings support extension of the importance of the apoE4 allele beyond atherosclerosis and Alzheimer’s disease to calcific AS.
Genetic Determinants of Nonmodulating Hypertension
Authors: Kosachunhanun Natapong , Hunt Steven C. , Hopkins Paul N. , Williams Roger R. , Jeunemaitre Xavier , Corvol Pierre , Ferri Claudio , Mortensen Richard M. , Hollenberg Norman K. , Williams Gordon H.
Published: October 2003

We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C−344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student
t
test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and χ
2
analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235
TT
and angiotensin-converting enzyme
DD
showed further reduction (
P
=0.0377) when compared with angiotensinogen 235
TT
alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 −344
TT
genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235
TT
significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95% confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme
DD
was combined with angiotensinogen 235
TT
, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.
Rho-Associated Protein Kinase Contributes to Early Atherosclerotic Lesion Formation in Mice
Authors: Mallat Ziad , Gojova Andrea , Sauzeau Vincent , Brun Valérie , Silvestre Jean-Sébastien , Esposito Bruno , Merval Régine , Groux Hervé , Loirand Gervaise , Tedgui Alain
Published: October 2003

Members of the Rho family of small GTPases have been recently implicated in inflammatory signaling. We examined the effect of in vivo inhibition of Rho kinase on atherogenesis in mice. Low-density lipoprotein receptor (LDLR) knockout (KO) mice fed a cholate-free high-fat diet received daily intraperitoneal injection of saline (n=8, control group) or Y-27632 (30 mg/kg, n=9), a specific Rho kinase inhibitor. After 9 weeks, Y-27632 treatment resulted in significant in vivo inhibition of Rho kinase activity (
P
=0.004). Body weights, arterial blood pressures, and plasma cholesterol levels were comparable in both groups. Atherosclerotic lesion size in the aortic sinus and thoracic aorta of mice treated with Y-27632 was reduced by respectively 35% and 29% in comparison with the saline-treated animals (
P
=0.006 and
P
=0.03, respectively). This was associated with a significant reduction in T lymphocyte accumulation (
P
=0.035) and expression of p65 subunit of NF-κB within plaques (
P
<0.05). In vitro, treatment with Y-27632 inhibited p65 phosphorylation and degradation of IκBα in mouse peritoneal macrophages and significantly inhibited concanavalin A-induced proliferation of spleen-derived T cells (
P
<0.001). In conclusion, inhibition of Rho kinase significantly limits early atherosclerotic plaque development in the LDLR KO mice. This study identifies Rho kinase inhibitors as potential candidates for the treatment of atherosclerosis.
Wall Mechanics of the Stented Extracranial Carotid Artery
Authors: Vernhet Hélène , Jean Beatrix , Lust Stephan , Laroche Jean Pierre , Bonafé Alain , Sénac Jean Paul , Quéré I. , Dauzat Michel
Published: October 2003

Background and Purpose—

Abrupt compliance changes and concomitant nonlaminar flow patterns may contribute to endothelial dysfunction and subsequent neointimal thickening. The aim of this study was to test the feasibility of wall mechanics measurement using B-mode ultrasound image analysis by dedicated software in the stented human carotid artery.

Methods—

Carotid Wallstents (Schneider) were placed in the extracranial carotid arteries of 15 patients. B-mode ultrasound examination was performed with a 7.5-MHz probe on the carotid artery upstream; at the proximal, mid, and distal stent levels; downstream from the stent; and on the contralateral internal and common carotid arteries. Carotid diameter (d) and systolic diameter changes (Δd) were measured with a dedicated image processing system (IÔ version 3.1, IÔDP), while pulse blood pressure (ΔP) was measured. Diameter compliance (Cd) and distensibility coefficient (DC) were calculated as Cd=2Δd/ΔP and DC=2Δd/ΔP/d and compared between measurement sites.

Results—

The evaluation could be completed in 8 of 15 patients. Compliance was significantly lower at the proximal, mid, and distal stent levels (27.77±1.11, 27.38±1.08, 27.38±1.09×10
−3
mm · kPa
−1
) than upstream (103.3±36.7×10
−3
mm · kPa
−1
), downstream (91.5±41.3×10
−3
mm · kPa
−1
), or on the contralateral internal (87.6±28×10
−3
mm · kPa
−1
) and common (149.3±47.6×10
−3
mm · kPa
−1
) carotid arteries.

Conclusions—

Stenting of the extracranial carotid artery induces a compliance mismatch between the native and the stented artery.
Risk Factors for Death or Stroke After Carotid Endarterectomy
Authors: Tu Jack V. , Wang Hua , Bowyer Beverley , Green Lawrence , Fang Jiming , Kucey Daryl
Published: October 2003

Background and Purpose—

Carotid endarterectomy is an effective method for preventing strokes if patients do not suffer adverse perioperative outcomes. The purpose of this study was to identify preoperative patient risk factors for adverse outcomes (death or nonfatal stroke) after carotid endarterectomy through the use of a large population-based registry from Ontario, Canada.

Methods—

Medical records of all 6038 patients who underwent carotid endarterectomy in Ontario between January 1, 1994, and December 31, 1997, were abstracted from 34 hospitals. Patient characteristics (demographic data, past medical history, neurological symptoms, comorbidities, radiological findings) and 30-day postoperative death or stroke rates were analyzed with logistic regression analysis.

Results—

The overall 30-day death or stroke rate after surgery was 6.0%. A history of transient ischemic attack or stroke (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.39 to 2.20), atrial fibrillation (OR, 1.89; 95% CI, 1.29 to 2.76), contralateral carotid occlusion (OR, 1.72; 95% C.I., 1.25 to 2.38), congestive heart failure (OR, 1.80; 95% CI, 1.15 to 2.81), and diabetes (OR, 1.28; 95% CI, 1.01 to 1.63) were significant independent predictors for 30-day death or stroke. These 5 factors were combined into a simple risk score that can be used to stratify patients into different risk groups for complications after surgery.

Conclusions—

Several patient characteristics predict the development of stroke and death after carotid endarterectomy. These characteristics may help clinicians in patient counseling and contribute to studies “benchmarking” the outcomes of carotid surgery in the community setting.
Toward Ethically Grounded Conflict Interventions: Reevaluating Challenges in the 21st Century
Authors:   Neufeldt,   Fast,   Schirch
Published: October 2003

This article explores the dimensions of ethics and accountability among conflict interveners, proposing an ethical framework that builds upon human rights and moral development. The framework consists of three ethical principles: inherent worth and dignity of individuals; community-defined common good; and authentic relationships. To apply these principles, the authors identify two embedded circles of accountability, which derive from the central parties in an intervention: the intervener and the participant. Dividing these groups into ``sending'' and ``receiving'' communities, this article reviews dimensions of accountability within the process of intervention that are related to each of the ethical principles. In operationalizing these principles, the authors suggest possible ethical responses to the challenges of intervention.
In Different Tongues: Making Room for Cultural Differences in the Negotiated Rulemaking Process
Authors:   Polkinghorn,   Pinto
Published: October 2003

This article explores the ethical impact of cultural recognition within the regulatory negotiation (reg-neg) process as it is currently being used by federal agencies in the United States. The authors use a blend of theory and practice to explore the ethical necessity, feasibility, and practicality of including cultural guidelines within the reg-neg process. Using the findings from extensive prior research on negotiated rulemaking at the U.S. Environmental Protection Agency (EPA) as a foundation, we illustrate the lessons learned from years of regulatory negotiations conducted by the pioneer of reg-neg. We then show how these lessons have been brought under an umbrella of ``cultural recognition'' within the consensus-based regulatory negotiation being used to improve relations between American Indian nations and the U.S. government. We discuss the ethical and practical implications of incorporating cultural sensitivity into the reg-neg process.