bluuebunny/crossref_metadata_2025 huggingface dataset:
The yield of head‐up tilt testing is not significantly increased by repeating the baseline test
Authors: Pavri Behzad B. , Ruskin Jeremy N. , Brooks Ross
Published: August 2009

Background and hypothesis: Head‐up tilt is widely used in evaluating patients with syncope. Data suggest that baseline tilt without isoproterenol is associated with few ≤ 10%) positive results in normals. However, there is considerable day‐today variability in patients with syncope, resulting in low reproducibility. We hypothesized that repeating the baseline tilt would increase the total number of positive responses.

Methods: In all, 193 patients with syncope of unknown etiology prospectively underwent serial baseline tilt (Tilt‐1 and Tilt‐2) at 70° for 25 min on two consecutive days.

Results: Of 193 patients, 39(20%) had a positive Tilt‐1. Of these, 19 had a positive Tilt‐2, (positive concordance rate: 19/39 = 49%). Of 154 patients with a negative Tilt‐1, 145 had a negative Tilt‐2 (negative concordance rate: 142/151=94%). Only 9 of 154 patients (6%) with a negative Tilt‐1 had a positive Tilt‐2. Thus, the yield increased from 20% (39/193) after Tilt‐1, and to 25% (48/193) after Tilt‐1 plus Tilt‐2, p = NS.

Conclusions: (1) Reproducibility of a positive Tilt‐1 is moderate. (2) Reproducibility of a negative Tilt‐1 is high. (3) Repetition of tilt in patients with a negative Tilt‐1 does not significantly increase the number of positive results.
Cost‐effective management of chronic stable angina
Authors: O'Rourke Robert A.
Published: August 2009

In certain patients with stable angina who are at moderate to high risk, coronary bypass surgery or coronary angioplasty are the therapeutic options of choice. However, in selected other patients the use of anti‐ischemic drug therapy and secondary prevention reduce episodes of myocardial ischemia and result in a good long‐term prognosis. Factors affecting management include the extent of coronary disease, the magnitude of cardiac symptoms, the severity of myocardial ischemia and of left ventricular function. Based upon these and other clinical characteristics, patients can be divided into low‐, moderate‐, or high‐risk categories for morbidity and mortality. Patients at high risk are more likely to be selected for myocardial revascularization and patients at low risk are often treated with medical therapy, at least initially. Based on the available cost‐effectiveness data, medical therapy or coronary angioplasty are the preferred initial strategies for low‐risk coronary disease, whereas coronary bypass surgery (CABG) is recommended for many high‐risk patients, particularly for those with triple‐vessel disease and impaired left ventricular function or ischemia at a low workload. CABG is cost‐effective for patients with severe angina and left main coronary artery disease and also for patients with mild angina and triple‐vessel disease. Coronary angioplasty is cost‐effective for patients with severe angina, and single‐ or multivessel disease. In patients with lesser symptoms and mild coronary disease, the cost effectiveness of myocardial revascularization therapy is less likely to be as good as it is in patients with more extensive disease and severe symptoms.
Chronotropic incompetence—Part II: Clinical implications
Authors: Camm A. John , Fei Lü
Published: August 2009

The definition of chronotropic incompetence as inadequate chronotropic response to metabolic demand is, in theory, quite satisfactory. However, the method used in clinical practice for determination of chronotropic incompetence is far from established. The determination of chronotropic incompetence has important diagnostic, therapeutic, and prognostic implications although the exact mechanism underlying chronotropic incompetence is at present unclear. From a pacing viewpoint, chronotropic incompetence is clinically relevant only when there is a functional improvement associated with rate‐responsive pacing. Rate‐responsive pacing has improved the physiologic approach to artificial pacing.
Nonatherosclerotic causes of coronary artery narrowing—Part I
Authors: Waller Bruce F. , Fry Edward T. A. , Hermiller James B. , Peters Thomas , Slack John D.
Published: August 2009

Approximately 5% of patients with acute myocardial infarction do not have atherosclerotic coronary artery disease but have other causes for their luminal narrowing. The first part of this three‐part review of nonatherosclerotic causes of coronary narrowing focuses on congenital coronary artery anomalies, coronary fistula, and high take‐off position of coronary ostia.
Uncommon etiologies of atrial fibrillation
Authors: Raggi Paolo , Vasavada Balendu C. , Parente Thomas , Prasada Sudhir , Sacchi Terrence J.
Published: August 2009

A newly diagnosed atrial fibrillation warrants a full investigation of the etiopathogenesis of this common arrhythmia. In the adult population, the most frequently associated conditions are systemic hypertension, coronary artery disease, mitral valvulopathy, congestive heart failure, and hyperthyroidism. Nevertheless, more infrequent and even rare, yet correctable, etiologies should not be overlooked. We describe three patients who presented to our hospital with a first episode of atrial fibrillation and who subsequently were demonstrated to have very unusual cardiovascular pathologies subtending this common arrhythmia. In all three cases, transesophageal echocardiography was instrumental in reaching an accurate diagnosis that was later confirmed at surgery.
Constrictive pericarditis causing extrinsic mitral stenosis and a left heart mass
Authors: Pai Ramdas G. , Wong Sammy , Tarazi Riyad
Published: August 2009

Constrictive pericarditis is a fibrotic process involving both layers of the pericardium and is known to give rise to obstruction to blood flow in the right heart. We report a patient with constrictive pericarditis who had echocardiographic features of mitral stenosis caused by a fibrocalcific mass lesion involving the mitral annulus with infiltration into the base of the posterior mitral leaflet. To our knowledge, this has not been reported in the literature.
Electrocardiographic evidence of ischemia during ventricular paced rhythms
Authors: Diaz Claro F. , Ganim Mazen S. , Ellestad Myrvin H.
Published: August 2009

Exercise‐induced electrocardiographic (ECG) changes are the most widely recognized noninvasive means for detecting myocardial ischemia. The specificity of these changes depends on the normalcy of the resting ECG. Right ventricular pacing produces major QRS and ST‐T changes very similar to those of complete left bundle‐branch block. They alter the resting ECG such that ischemic changes are considerably difficult to detect. Because of these resting abnormalities, ECG changes during treadmill exercise testing usually do not facilitate the diagnosis of ischemia or coronary artery disease. The following are two cases of ischemic ECG changes that occurred during right ventricular pacing. To our knowledge, there have been no reports of the classic ECG changes of ST‐segment depression suggestive of ischemia which occurred during right ventricular pacing and which were discemible from the resting ECG changes.
Monocyte‐endothelial cell interaction in atherogenesis and thrombosis
Authors: Ikeda Uichi , Takahashi Masafumi , Shimada Kazuyuki
Published: August 2009

Cellular interactions between leukocytes and the endothelium are critical events in vascular biology, such as atherosclerosis and acute coronary syndrome. When monocytes and endothelial cells are activated via direct cell‐cell interaction, both types of cells express several biologically active molecules such as adhesion molecules, cytokines, coagulation and fibrinolytic factors, metalloproteinases, and vasoactive substances. All of these molecules could contribute to atherogenesis and thrombosis.
Impact of chronic patency of infarct‐related coronary artery on prevalence of myocardial ischemia during the pharmacologic and exercise stress test
Authors: Lu Chunzeng , Marzilli Mario , Distante Alessandro , Wang Yanjun , De Nes Maurizio , Marraccini Paolo , L'Abbate Antonio
Published: August 2009

Background: Even late restoration of anterograde coronary flow may have beneficial effects on left ventricular function, electrophysiology, and survival in postinfarction patients.

Hypothesis: The patency or occlusion of an infarct‐related coronary artery in the chronic phase may also be associated with myocardial ischemia provoked by pharmacologic and physiologic stress tests.

Methods: High‐dose dipyridamole echocardiography test (DET) (up to 0.84 mg/kg over 10 min), exercise electrocardiography (EET), and coronary angiographic data in a group of 127 in‐hospital patients who had survived an acute myocardial infarction were analyzed. Patients who had only angiographic evidence of infarct‐related single artery disease (≥50% luminal diameter reduction) and no previous revascularization were enrolled in the study. DET and EET were performed (DET in all, EET in 118 patients) within 5 days before coronary angiography. Fifty‐seven patients had total occluded infarct arteries (Group 1) with various degrees of collateral circulation (2.6±1.1 collateral score, by a 3 grading system), whereas the other 70 patients had patent infarct arteries (Group 2) with significant residual stenoses (82±13% diameter reduction).

Results: The prevalence of rest angina or effort angina and topography of the infarct‐related coronary artery did not differ between the two groups (all p = NS). There were more patients with Q wave in Group 1 than in Group 2 (72 vs. 57%, p = 0.08) compared with non‐Q wave infarction (Group 1 = 28 vs. Group 2 = 43%, p = 0.08). Ischemia in the infarct‐related artery territory detected by DET (defined as new wall motion dyssynergy or marked worsening of resting hypokinesia) was 61% in Group 1 and 41% in Group 2 (p = 0.025). EET was positive in 26 of 54 (48%) Group 1 and in 21 of 64 (33%) Group 2 patients (p = 0.09).

Conclusions: Patients with occluded infarct‐related arteries have a higher prevalence of ischemia during DET and EET regardless of the presence of collateral flow. These results suggest that the presence of partial anterograde flow in the prolonged period could have a favorable influence on prevalence of residual ischemia in these patients.
Costs and outcomes of patients admitted with chest pain and essentially normal electrocardiograms
Authors: McCullough Peter A. , Ayad Osama , O'Neill William W. , Goldstein James A.
Published: August 2009

Background: Although inroads have been made in the outpatient evaluation of chest pain, the majority of hospitals in the United States do not have chest pain centers and the direct costs associated with hospital admissions in low‐risk patients is unknown.

Hypothesis: The study was undertaken to evaluate the cost and outcomes of admission to the hospital for patients with acute chest pain and essentially normal electrocardiograms (ECGs).

Methods: For that purpose, we reviewed 1,670 patients presenting to our emergency department with chest pain over a 5‐month period in 1994. Of these, 567 [34.0%, confidence interval (CI) 95%, 31.7–36.3%] patients were considered to be low risk by ECG criteria alone.

Results: Complete clinical and financial data were available in 445 cases of which 152 had a previous history of coronary artery disease (CAD) and 31 (7.0%, CI95%, 4.9‐9.6%) were ultimately proven to have acute myocardial infarction (AMI). There were no deaths. All patients initially underwent noninvasive evaluation, and an additional 177 (39.8%) underwent subsequent cardiac catheterization. Of those, 107 (60.5%) had significant CAD (at least one vessel>70% stenosis). We assumed an expected mortality rate of 1% in the AMI group based on previously reported series with all the mortalities preventable by hospitalization. This yielded a valuation of $1.7 million dollars per life saved. Sensitivity analysis revealed the practice of admission and in‐patient evaluation for this group of patients was cost ineffective at all assumption levels.

Conclusion: The practice of hospital admission for patients with chest pain and essentially normal ECGs is not cost favorable, and all hospital facilities should consider outpatient chest pain evaluation strategies.
Acute changes of left atrial distensibility in congestive heart failure
Authors: Dernellis John M. , Vyssoulis Gregory P. , Zacharoulis Apostolos A. , Toutouzas Pavlos K.
Published: August 2009

Background: Investigations of the left atrial (LA) distensibility have revealed that it plays a major role in atrial function; however, LA distensibility has not as yet been studied in congestive heart failure (CHF).

Hypothesis: The study was undertaken to determine the effects of acute administration of esmolol, isosorbide dinitrate, dobutamine, and normal saline infusion on LA dimension, pressure, and distensibility.

Methods: The study included 23 patients with CHF (18 with ischemic heart disease and 5 with idiopathic dilated cardiomypathy). Left atrial diameters (D) and pressures (P) were recorded at rest and thereafter during acute tests. P and D data during the ascending limb of the V loop were fitted to the exponential function P = b·ead, where a is the passive elastic chamber stiffness constant and b is the elastic constant. The instantaneous diastolic LA distensibility (IDLAD) was calculated as 1/(dP/dD)= 1/a·P.

Results: The constant, a, increased significantly after normal saline and esmolol infusion (p<0.001), while it significantly decreased after isosorbide dinitrate (p <0.001) and dobutamine administration (p <0.05) compared with baseline. Instantaneous diastolic LA distensibility (in mm/Hg) was 0.16 at baseline; it significantly increased after isosorbide dinitrate (0.32) and dobutamine (0.24) administration, while it significantly decreased after normal saline (0.11) and esmolol (0.12) infusion (p <0.001 for all).

Conclusion: In CHF, LA distensibility may acutely increase with vasodilators or inotropics or may decrease with beta blockade or volume loading.
Effect of spinal cord stimulation on heart rate variability and myocardial ischemia in patients with chronic intractable angina pectoris—A prospective ambulatory electrocardiographic study
Authors: Hautvast Raymond W. M. , Brouwer Jan , Dejongste Mike J. L. , Lie K. I.
Published: August 2009

Background and hypothesis: Spinal cord stimulation is an effective treatment for chronic refractory angina pectoris. Its efficacy is related to an anti‐ischemic action, possibly as a result of modulation of the autonomic nervous system. Therefore, the influence of spinal cord stimulation on the autonomic nervous system and myocardial ischemia was prospectively studied in 19 consecutive patients with intractable angina pectoris.

Methods: Patients were included when demonstrating > 0.1 m V STsegment depression on the exercise electrocardiogram (ECG) during two separate treadmill tests. After enrollment, heart rate variability together with ischemic indices were studied with 48 h ambulatory ECG monitoring. Assessments were made at baseline and after 6 weeks of spinal cord stimulation therapy.

Results: After 6 weeks, no significant changes in heart rate variability were detected. However, ischemic indices on the ambulatory ECG, as well as anginal attacks and consumption of sublingual nitrate tablets, were significantly decreased.

Conclusion: Autonomic modulation assessable with heart rate variability analysis may not be the explanatory mechanism of action for the decrease of anginal attacks and ischemia, exerted by spinal cord stimulation used as an adjuvant therapy in patients with chronic intractable angina pectoris.
Immunosuppressive therapy for peripartum‐type spontaneous coronary artery dissection: Case report and review
Authors: Kolle Patrick T. , Cliffe Charles M. , Ridley David J.
Published: August 2009

Background: A 35‐year‐old postpartum woman presented with myocardial infarction (MI) due to spontaneous coronary artery dissection (SCAD). In addition to conventional medical therapy, she was treated with immunosuppressive agents (prednisone and cytoxan) because of five noncontiguous coronary dissections, surgical inoperability, and postinfarction angina. Repeat angiography 94 days later demonstrated angiographically normal vessels.

Methods: A literature review of 42 additional cases of peripartum SCAD was performed, and the results were compared with this patient.

Results: Mortality was 48.8% (21/43). Sudden cardiac death was the initial presentation in 27.9% (12/43) of cases. The left coronary artery was involved in 78.6% (44/56) of dissections with left main segment dissection in 10 cases. In women who survived > 24 h post infarction, recurrent MI, usually due to a second coronary dissection, occurred in 20.8% (5/24). Histopathologic studies have often shown periadventitial inflammation (80%, 16/20), in which eosinophils predominate (68.8%, 11/16), and may be linked to the medial degeneration often found in these cases.

Conclusions: The common observation of eosinophilic periadventitial inflammation suggests a role in the pathophysiology of this rare, yet serious condition. Aggressive immunosuppressive therapy in this case of multivessel dissection resulted in spontaneous angiographic healing of all lesions.
A Case of giant cell myocarditis and malignant thymoma: A postmortem diagnosis by needle biopsy
Authors: Kilgallen Clive M. , Salomon Robert N. , Jackson Elizabeth , Surks Howard K. , Bankoff Mark
Published: August 2009

This paper reports a case of fulminant giant cell myocarditis arising in association with a malignant thymoma causing death in a 46‐year‐old woman. Although the diagnosis was suspected in life, postmortem examination was required for confirmation of giant cell myocarditis. Consent was obtained only for percutaneous needle biopsy of the heart. In order to respect the family's wishes and harvest sufficient diagnostic myocardium, a simple needle‐based biopsy technique was devised. A bone marrow trephine needle was attached to a 20 ml syringe and, with suction, multiple passes were used to fill 15 tissue cassettes. The cores were placed immediately in formalin and B5 fixatives. High‐quality tissue preservation was obtained without crush artefact. Immunohistochemical studies of the biopsy tissue confirmed that the giant cells were of macrophage derivation.
Torsade de Pointes Secondary to d, I‐Sotalol after Catheter Ablation of Incessant Atrioventricular Reentrant Tachycardia—Evidence for a Significant Contribution of the “Cardiac Memory”
Authors: Haverkamp W. , Hördt M. , Breithardt G. , Borggrefe M.
Published: August 2009

Radiofrequency catheter ablation of a right septal accessory pathway was performed in a 66‐year‐old patient with incessant orthodromic atrioventricular reentrant tachycardia. Intravenous administration of flecainide, ajmaline, verapamil, and d, l‐sotalol had been ineffective in controlling the tachycardia. After the ablation procedure, precordial T‐wave inversion was observed during sinus rhythm. These repolarization abnormalities persisted and were suggested to represent “cardiac memory”. Three days later, atrial fibrillation with a fast ventricular response developed and oral d, l‐sotalol, which had been well tolerated previously on a long‐term basis, was started again. However, at this time, and in the presence of the persisting repolarization abnormalities, the T waves became deeper and broader within a few hours after the introduction of d, l‐sotalol. Marked QT prolongatio that was paralleled by the occurrence of repeated episodes of torsade de pointes developed. Serum electrolytes were nomal. Direct current cardioversion was necessary due to the degeneration of torsade de pointes into ventricular fibrillation. Further sustained arrhythmia episodes were suppressed by temporary endocardial ventricular pacing. The patient recovered without any sequela. This case demonstrates that replarization abnormalities after catheter ablation, which may be due, at least in part, to the “cardiac memory,” are not always benign but may contribute significantly to proarrhythmia.
Long‐term patency (9½ years) and atherosclerosis of a polytetrafluoroethylene (Gortex®) coronary artery bypass graft
Authors: Vlay Stephen C. , Malik Amir Z.
Published: August 2009

The patency of a polytetrafluoroethylene (Gortex®) graft 9½ years after coronary artery bypass graft surgery (CABG) is demonstrated. While this material is not commonly used as a conduit because of limited success in the past, this case demonstrates that, given the right circumstances, longterm patency is possible. Since available conduits for CABG are quite often limited, viable alternatives may be lifesaving and require further evaluation. In addition to mechanical considerations such as size, length, and material, anticoagulation and strict management of hyperlipidemia may be critical.
End organ protection by calcium‐channel blockers
Authors: Tzivoni Dan
Published: August 2009

In recent years, much attention has been given to end organ protection by antihypertensive, anti‐heart failure, and anti‐ischemic medications. This review describes the available information on end organ protection by calcium‐channel blockers (CCBs). In normotensive patients and patients with hypertension treated with long‐acting dihydropyridines, medial thickness was thinner than in patients treated with atenolol or in untreated hypertensive patients. Long‐term treatment was associated with significant reduction in left ventricular mass. Calcium‐channel blockers also improved endothelial‐dependent relaxation and reversed the vasoconstrictive response to nitric oxide inhibitors. In diabetic patients. CCBs were effective in preserving kidney function and microalbuminurea. The combination of angiotensin‐converting enzyme (ACE) inhibitors and CCBs was more effective than ACE inhibitors alone in preserving kidney function. In animal experiments, CCBs prevented development of coronary atheroschlerosis; however, in humans only limited data are available on their antiatherogenic effect. Some studies suggest that CCBs exert antiplatelets properties and may therefore be beneficial in patients with coronary artery disease.
Prognosis following acute myocardial infarction in patients with ST‐T abnormalities on electrocardiograms obtained before myocardial infarction
Authors: Ando Hiromi , Yotsukura Masayuki , Sakata Konomi , Yoshino Hideaki , Ishikawa Kyozo
Published: August 2009

Background: Many studies have examined the relationship between prognosis after myocardial infarction (MI) and electrocardiographic (ECG) findings at the time of or after the onset of MI. However, little work has been done concerning the association between ECG findings obtained before the onset of MI (pre‐MI) and the prognosis after MI.

Hypothesis: The study was undertaken to determine whether ST‐T segment and T‐wave morphology on pre‐MIECGs provides useful information for prognosis after acute MI.

Methods: Pre‐MIECGs of 212 patients recorded within the 6‐month period before MI were studied for the presence of high‐voltage R waves, ST‐segment depression, and negative T waves. The Kaplan‐Meier method and multivariate analysis were used to determine the relationship between these ECG findings and in‐hospital cardiac death.

Results: In‐hospital cardiac death occurred in 32 (15.1%) patients. The in‐hospital mortality rate was 38.5% (5/13) for the patients with high‐voltage R waves, 54.5% (6/11) for patients with ST‐segment depression, and 45.6% (15/33) for patients with negative T waves. The in‐hospital mortality rate was 13.6% (27/199) for patients without high‐voltage R waves, 12.9% (26/201) for patients without ST‐segment depression, and 9.5% (17/179) for those without negative T waves. Multivariate analysis identified age and negative T waves as independent risk factors for cardiac death, with a hazard ratio for negative T waves of 3.1.
Intervention to improve adherence to ACC/AHA recommended adjunctive medications for the management of patients with an acute myocardial infarction
Authors: Axtell Sandra S. , Ludwig Elizabeth , Lopez‐Candales A.
Published: August 2009

Background: The most recent published guidelines regarding management of patients surviving an acute myocardial infarction (AMI) advocate the administration of aspirin (ASA), beta blockers (BB), and angiotensin‐converting enzyme inhibitors (ACEi) and discourages the use of calcium‐channel blockers (CCB). Previous data collected in our region from the National Registry (NR) showed a dismal compliance with these guidelines. In an attempt to increase physician awareness and to optimize implementation of recommended guidelines, a cardiac and pharmacy steering committee was created.

Methods: The pharmacist assigned to the project identified all patients admitted with an AMI using troponin‐I and creatine kinase‐MB (CK‐MB) reports. The pharmacist then contacted physicians to make recommendations if an adjunctive medication was not prescribed for a patient with no apparent contraindications. Administration rates for ASA, BB, ACEi, and CCB were then assessed and compared with the previously obtained baseline data from the NR.

Results: At admission, the use of ASA increased from 70 to 72%, BB from 45 to 72%, and ACEi from 12 to 44%. In terms of medications at discharge, ASA use increased from 74 to 88%. BB from 55 to 76%, and ACEi from 30 to 40%. In addition, the prescription rates for CCB at discharge decreased from 36 to 21%.

Conclusions: An interdisciplinary approach for disease management is an effective method for improving adherence to treatment guidelines simply with pharmacy intervention. the percentage of patients receiving the recommended adjunctive medications increased significantly. We propose that these guidelines should be periodically inserviced to physicians. Furthermore, patient counseling sessions should also be instituted to help reinforce the importance of compliance with the medications after discharge, as well as lipid management and smoking cessation.
Reduced incidence of clinical restenosis with newer generation stents, stent oversizing, and high‐pressure deployment: Single‐operator experience
Authors: Manolis Antonis S.
Published: August 2009

Background: Over the last 4 years, several newer generation stents have become available, promising to change the scenery of coronary angioplasty (PTCA) with its attendant restenosis rate.

Hypothesis: The aim of this study was to review prospectively the results of a single operator adopting a uniform approach with approximately 0.5 mm stent oversizing and high‐pressure (≥ 12‐16 bar) deployment and compare them with conventional PTCA in a series of 244 consecutive patients.

Methods: The study included 203 men and 41 women, aged 59 ± 11 years, who presented with stable angina and/or positive exercise testing (n = 75), unstable angina (n = 161), or acute myocardial infarction (n = 8). Dilated vessels included the left anterior descending artery (n = 139), the right coronary artery (n = 86), the left circumflex artery (n = 47), the ramus branch (n = 4), or venous grafts (n = 2). Stents were implanted for dissection, suboptimal PTCA result, and electively. Two groups were compared: 83 patients who underwent balloon PTCA alone and 161 patients who also received stent(s).

Results: The two groups had similar demographics, age (58 ± 10 vs. 59 ± 11 years), initial vessel stenosis (92 ± 7 vs. 93 ± 6%), and left ventricular ejection fraction (51 ± 9 vs. 51 ± 8%). Procedural success was also similar (97.6 vs. 99.4%), but as expected the residual stenosis was much lower in the stent group (≤ 0 vs. 17%). The following stents were employed: J & J (n = 1), NIR (n = 117), ACS (n = 59), AVE (n = 9), Inflow GoldFlex (n = 9), Crossflex (n = 5), Wictor (n = 1), Jostent (n = 16), R stent (n = 9), Seaquence (n = 2) and Wallstent (n = 1). Single stents were used in 118 patients, two stents in 31 patients, three in 6 patients, and four in 6 patients. There was one in‐hospital death at 3 days unrelated to the procedure. There were no events of subacute stent thrombosis; all patients in the stent group received combined therapy with aspirin and ticlopidine, the latter for 1 month. During 18 ± 14 months, the clinical rèstenosis rate was significantly lower in the stent group (6.9%) than in the PTCA group (28.4%) (p = 0.001).

Conclusion: In a series of 244 consecutive patients, newer generation stents and a consistent approach of stent oversizing and high‐pressure stent deployment by a single operator resulted in high procedural success (99%), lack of stent thrombosis (0%), and a very low clinical restenosis rate (7%).
Accelerated dobutamine stress testing: Safety and feasibility in patients with known or suspected coronary artery disease
Authors: Lu David , Little Raymond , Malik Qudsia , Fernicola Daniel J. , Greenberg Michael D. , Weissman Neil J.
Published: August 2009

Background: Dobutamine pharmodynamics require approximately 10 min to reach steady state. Despite this, standard dobutamine stress echo typically uses 3‐min stages of advancing dobutamine doses because of safety concerns.

Hypothesis: In patients with a high pretest probability of coronary artery disease (CAD), a continuous infusion of high‐dose dobutamine is a feasible and safe method for performing a dobutamine stress test.

Methods: Forty‐seven consecutive patients (mean age 64 ± 11 years) with 3.0 ± 1.4 cardiac risk factors underwent dobutamine stress testing utilizing a single, high‐dose (40 mcg/kg/min), continuous dobutamine infusion. The 40 mcg/kg/min infusion was continued for up to 10 min or until a test end‐point had been reached. If a test endpoint was not achieved, atropine (up to 1.0 mg) was added.

Results: Heart rate rose from 71 ± 12 to 137 ± 18 beats/min at peak (p< 0.0001) with a concomitant change in systolic blood pressure (143 ± 35 vs. 167 ± 38 mmHg; p = 0.001) but no change in diastolic blood pressure (74 ± 19 vs. 75 ± 18 mmHg; p = NS). Target heart rate was achieved in 20 of 47 (43%) patients with accelerated dobutamine alone and in 34 of 47 (72%) with the addition of atropine. An average of 11.6 ± 3.7 min was required to obtain target heart rate. Subjective sensations from the dobutamine occurred in 49% of patients (palpitations 21%, nausea 6%, chest pain 6%, headache 6%, dizziness 13%), mild arrhythmia in 48% of patients (ventricular premature beats 38%, supraventricular tachycardia 10%), and one patient had nonsustained ventricular tachycardia.

Conclusion: A single, high‐dose (40 mcg/kg/min) dobutamine‐atropine protocol provides an efficient means of performing dobutamine stress echocardiography with a similar symptom profile as conventional dobutamine infusion protocols in patients with a high pretest probability of CAD. Randomized, controlled studies will be necessary to assess the sensitivity and specificity of this accelerated dobutamine echo protocol.
Sleep‐disordered breathing in patients referred for angina evaluation—association with left ventricular dysfunction
Authors: Sanner Bernd M. , Konermann Martin , Doberauer Claus , Weiss Thomas , Zidek Walter
Published: August 2009

Background: Clinical observations have linked sleep‐disordered breathing to cardiovascular morbidity and mortality, and especially to coronary artery disease.

Hypothesis: The study was undertaken to determine the prevalence of sleep‐disordered breathing in consecutive patients referred for angina evaluation, and analyzed the parameters influencing the severity of sleep‐disordered breathing.

Methods: In all, 68 consecutive patients (53 men, 15 women, aged 63.4 ± 10.0 years) referred for angina evaluation were studied. Coronary angiography, selective left ventriculography, and a polygraphic study with a validated six‐channel monitoring device were performed. Full‐night polysomnography was used to reevaluate patients with an apnea/hypopnea index ≥ 10/h. Results: Sleep‐disordered breathing as defined by an apnea/hypopnea index > 10/h was found in 30.9% of patients; its prevalence was not increased in patients with and without coronary artery disease (26.5 vs. 42.1%). Multiple stepwise linear regression analysis revealed that the severity of sleep‐disordered breathing was significantly and independently associated with left ventricular ejection fraction (r = −0.38; p = 0.002), but not with age, body mass index, gender, diabetes mellitus, hypertension, hyperuricemia, hypercholesterolemia, smoking habits, or coronary artery disease. In this group of patients, multiple logistic regression analysis could not demonstrate sleep‐disordered breathing to be an independent predictor of coronary artery disease.

Conclusions: Sleep‐disordered breathing is common in patients referred for angina evaluation. The degree of sleep‐disordered breathing is mainly determined by the extent of left ventricular dysfunction.
Oral antidiabetic treatment in patients with coronary disease: Time‐related increased mortality on combined glyburide/metformin therapy over a 7.7‐year follow‐up
Authors: Fisman Enriqe Z. , Tenenbaum Alexander , Adler Yehuda , Motro Michael , Boyko Valentina , Benderly Michal , Friedensohn Aharon , Kohanovski Mira , Rotzak Rene , Schneider Hanan , Behar Solomon
Published: August 2009

Background: A sulfonylurea —usually glyburide—plus metformin constitute the most widely used oral antihyperglycemic combination in clinical practice. Both medications present undesirable cardiovascular effects. The issue whether the adverse effects of each of these pharmacologic agents may be additive and detrimental to the prognosis for coronary patients has not yet been specifically addressed.

Hypothesis: This study was designed to examine the survival in type 2 diabetics with proven coronary artery disease (CAD) receiving a combined glyburide/metformin antihyperglycemic treatment over a long‐term follow‐up period.

Methods: The study sample comprised 2,275 diabetic patients, aged 45–74 years, with proven CAD, who were screened but not included in the bezafibrate infarction prevention study. In addition. 9,047 nondiabetic patients with CAD represented a reference group. Diabetics were divided into four groups on the basis of their therapeutic regimen: diet alone (n = 990), glyburide (n = 953), metformin (n = 79), and a combination of the latter two (n = 253).

Results: The diabetic groups presented similar clinical characteristics upon recruitment. Crude mortality rate after a 7.7‐year follow‐up was lower in nondiabetics (14 vs. 31.6%, p<0.001). Among diabetics, 720 patients died: 260 on diet (mortality 26.3%). 324 on glyburide (34%), 25 on metformin alone (31.6%), and 111 patients (43.9%) on combined treatment (p<0.000001). Time‐related mortality was almost equal for patients on metformin and on combined therapy over an intermediate follow‐up period of 4 years (survival rates 0.80 and 0.79, respectively). The group on combined treatment presented the worst prognosis over the long‐term follow‐up, with a time‐related survival rate of 0.59 after 7 years, versus 0.68 and 0.70 for glyburide and metformin, respectively. After adjustment to variables for prognosis, the use of the combined treatment was associated with an increased hazard ratio (HR) for all‐cause mortality of 1.53 (95% confidence interval [CI] 1.20–1.96), whereas glyburide and metformin alone yielded HR 1.22 (95% CI 1.02–1.45) and HR 1.26 (95% CI 0.81–1.96), respectively.

Conclusions: We conclude that after a 7.7‐year follow‐up, monotherapy with either glyburide or metformin in diabetic patients with CAD yielded a similar outcome and was associated with a modest increase in mortality. However, time‐related mortality was markedly increased when a combined glyburide/metformin treatment was used.
Effects of stent coating on platelets and endothelial cells after intracoronary stent implantation
Authors: Atalar Enver , Aytemir Kudret , Aksöyek Serdar , Övünç Kenan , Oto Ali , özmen Frhan , Haznedaro ǧlu Ibrahim
Published: August 2009

Background: Adhesion molecules are known to be important in the regulation of endothelial cell and platelet functions. Increased platelets P‐selectin expression is a marker of stent thrombosis after uncoated stent placement.

Hypothesis: The aim of this study was to compare the effects of intracoronary placement of phosphorylcholine (PC)‐coated, versus heparin‐coated, versus uncoated stents on platelets and endothelial activity.

Methods: Thirty patients (age 55 ± 10, 27 men) with significant proximal left anterior descending coronary artery stenoses were randomized to elective implantation of PC‐coated. versus heparin‐coated. versus uncoated stents. Following stent placement, intravenous heparin and aspirin plus ticlopidine were administered. Venous plasma soluble E‐selectin, sP‐sclectin, and intercellular adhesion molecule‐1 levels were measured before the procedure and 24 and 48 h thereafter as markers of platelet and endothelial cell activation. Patients were excluded if they had a disease known to influence platelet and endothelial cell function.

Results: Plasma sP‐selectin levels decreased significantly after implantation of PC‐ and heparin‐coated stents (p = 0.04), hut remained unchanged in patients randomized to uncoated stents. Plasma sE‐selectin levels increased significantly after uncoated stent placement (p = 0.04) and remained unchanged after coated stent implantation.

Conclusion: In patients treated with combined antiplatelet therapy, implantation of PC‐ and heparin‐coated stents decreased platelet activity without activating endothelial cells, whereas placement of uncoated stents led to endothelial activation without changing platelet activity. These results suggest that PC‐coated and heparin‐coated stents may be advantageous in limiting thrombotic complications.
Birthdays of retinal amacrine cell subtypes are systematically related to their molecular identity and soma position
Authors: Voinescu P. Emanuela , Kay Jeremy N. , Sanes Joshua R.
Published: August 2009

The mammalian retina contains six major cell types, several of which are divided into multiple molecularly and morphologically distinct subtypes. To understand how subtype diversity arises during development, we focused on amacrine interneurons in the mouse retina; ∼30 amacrine subtypes have been identified in mammals. We used antibody markers to identify the two main amacrine subsets—GABAergic and glycinergic—and further subdivided these groups into smaller subsets based on expression of neurotransmitter and transcription factor markers. We then used bromodeoxyuridine (BrdU) labeling to see whether amacrine subsets are born (become postmitotic) at different times, as is the case for lamina‐specified subsets of cortical projection neurons. We found that GABAergic amacrines are generated on average 2–3 days before glycinergic amacrines. Moreover, subsets of GABAergic amacrines are born at distinct times. We also found a strong correlation between amacrine cell birthday and soma position in the mature retina, another point of similarity with cortical projection neurons. This relationship raised the possibility that amacrine subtype identity is determined by signals that uncommitted cells receive after they migrate to their destinations. However, cells labeled with BrdU in vivo, then dissociated and allowed to develop in vitro, acquired the amacrine subtype‐specific markers appropriate for their birthdays, supporting the idea that they become specified near the time and place of their birth. Together, our results suggest that the birthdays of amacrine cells independently specify their destinations and subtype identities. J. Comp. Neurol. 517:737–750, 2009. © 2009 Wiley‐Liss, Inc.
Differential expression patterns and developmental roles of duplicated scinderin‐like genes in zebrafish
Authors: Jia Sujuan , Nakaya Naoki , Piatigorsky Joram
Published: August 2009

Scinderin, the closest homologue of the actin‐severing protein, gelsolin, has two similar paralogs (Scinla and Scinlb) in zebrafish. Scinla is abundant in the adult cornea; Scinlb comprises considerably less corneal protein. Here, we show that scinla is expressed in the nose, lens, brain, cornea and annular ligament of the iridocorneal angle; by contrast, scinlb is expressed in the hatching gland, floor plate, notochord, otic vesicle, brain, pharynx, cartilage, swim bladder and cornea. Activity of scinla and scinlb promoter fragments driving the EGFP reporter gene in transgenic zebrafish resembled scinla or scinlb expression. Previously, we showed that reduction of scinla by injection of antisense morpholino oligonucleotides ventralized embryos; here, specific reduction of scinlb expression led to subtle brain abnormalities associated with increased cell death, decreased shhb expression in the floor plate, and slightly reduced eye distance. Thus, scinla and scinlb have different expression patterns and developmental roles during zebrafish development. Developmental Dynamics 238:2633–2640, 2009. Published 2009 Wiley‐Liss, Inc.
Expanding the scope of CE reactor to ssDNA‐binding protein–ssDNA complexes as exemplified for a tool for direct measurement of dissociation kinetics of biomolecular complexes
Authors: Takahashi Toru , Ohtsuka Kei‐ichirou , Tomiya Yoriyuki , Iki Nobuhiko , Hoshino Hitoshi
Published: August 2009

CE reactor (CER), which was developed as a tool for direct measurement of the dissociation kinetics of metal complexes, was successfully applied to the complexes ofEscherichia colissDNA‐binding protein (SSB) with ssDNA. The basic concept of CER is the application of CE separation process as a dissociation kinetic reactor for the complex, and the observation of the on‐capillary dissociation reaction profile of the complex as the decrease of the peak height of the complex with increase of the migration time. The peak height of [SSB‐ssDNA] decreases as the migration time increases since the degree of the decrease of [SSB‐ssDNA] through the on‐capillary dissociation reaction is proportional to the degree of the decrease of the peak height of [SSB‐ssDNA]. The dissociation degree‐time profiles for the complexes are quantitatively described by analyzing a set of electropherograms with different migration times. Dissociation rate constants of [SSB‐ssDNA] consisting of 20‐mer, 25‐mer and 31‐mer ssDNA were directly determined to be 3.99×10−4, 4.82×10−4and 1.50×10−3/s, respectively. CER is a concise and effective tool for dissociation kinetic analysis of biomolecular complexes.
The consistency of pressure‐gradient approximations used in multi‐dimensional shock hydrodynamics
Authors: Christon Mark A.
Published: August 2009

This paper presents a study of the consistency properties of the pressure‐gradient approximation used in multi‐dimensional finite‐element shock hydrodynamics codes today. In specific, consideration is given to the so‐called ‘bent‐element blues’ problem associated with the pressure‐gradient approximation when using the Q1Q0 element. On arbitrary grids comprised of distorted elements, the piecewise‐constant representation of the pressure field leads to a low‐order pressure‐gradient approximation at the global (nodal) level. This results in spurious nodal forces that are not aligned with the pressure gradient. There are several side‐effects of this behavior that include (a) incorrectly exciting physical modes in problems that exhibit unstable behavior, e.g. Rayleigh–Taylor problems (both magnetic and hydrodynamic), (b) potentially seeding hourglass modes, and (c) exhibiting non‐stationary behavior for steady‐state problems. A series of commonly used pressure‐gradient approximations are reviewed and evaluated based on linear consistency—the ability of the approximation to annihilate constant terms and exactly reproduce a linear gradient. The deeper theoretical issues associated with the proper selection of function spaces for the finite‐element hydro formulation are not discussed here. There are two gradient approximations that use piecewise‐constant data and deliver a consistent pressure‐gradient approximation on arbitrary grids. The first is the well‐known least‐squares gradient construction, and the second is a corrected gradient approximation that imposes linear consistency at the (global) nodal level. At the time of this writing, the corrected gradient approximation appears to be the most viable candidate for resolving the consistency issues associated with the Q1Q0 element technology. Copyright © 2009 John Wiley & Sons, Ltd.
A study of gridless method with dynamic clouds of points for solving unsteady CFD problems in aerodynamics
Authors: Wang Hong , Chen Hong‐Quan , Periaux Jacques
Published: August 2009

When solving unsteady computational fluid dynamics problems in aerodynamics with a gridless method, a cloud of points is usually required to be regenerated due to its accommodation to moving boundaries. In order to handle this problem conveniently, a fast dynamic cloud method based on Delaunay graph mapping strategy is proposed in this paper. A dynamic cloud method makes use of algebraic mapping principles and therefore points can be accurately redistributed in the flow field without any iteration. In this way, the structure of the gridless clouds is not necessarily changed so that the clouds regeneration can be avoided successfully. The spatial derivatives of the mathematical modeling of the flow are directly determined by using weighted least‐squares method in each cloud of points, and then numerical fluxes can be obtained. A dual time‐stepping method is further implemented to advance the two‐dimensional Euler equations in arbitrary Lagarangian–Eulerian formulation in time. Finally, unsteady transonic flows over two different oscillating airfoils are simulated with the above method and results obtained are in good agreement with the experimental data. Copyright © 2009 John Wiley & Sons, Ltd.
Option pricing under Markov‐switching GARCH processes
Authors: Chen Chao‐Chun , Hung Ming‐Yang
Published: August 2009

This study proposes an N ‐state Markov‐switching general autoregressive conditionally heteroskedastic (MS‐GARCH) option model and develops a new lattice algorithm to price derivatives under this framework. The MS‐GARCH option model allows volatility dynamics switching between different GARCH processes with a hidden Markov chain, thus exhibiting high flexibility in capturing the dynamics of financial variables. To measure the pricing performance of the MS‐GARCH lattice algorithm, we investigate the convergence of European option prices produced on the new lattice to their true values as conducted by the simulation. These results are very satisfactory. The empirical evidence also suggests that the MS‐GARCH model performs well in fitting the data in‐sample and one‐week‐ahead out‐of‐sample prediction. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 30:444–464, 2010
Slug is a downstream mediator of transforming growth factor‐β1‐induced matrix metalloproteinase‐9 expression and invasion of oral cancer cells
Authors: Joseph Mathew J. , Dangi‐Garimella Surabhi , Shields Mario A. , Diamond Michelle E. , Sun Limin , Koblinski Jennifer E. , Munshi Hidayatullah G.
Published: August 2009

Members of Snail family of transcription factors play an important role in oral cancer progression by inducing epithelial–mesenchymal transition, by promoting invasion and by increasing matrix metalloproteinase (MMP) expression. Although Snail (Snai1) is the best characterized and the most extensively studied member of this family, the role and regulation of Slug (Snai2) in oral cancer progression is less well understood. In this report, we show that transforming growth factor‐β1 (TGF‐β1) increases Slug levels in tert‐immortalized oral keratinocytes and in malignant oral squamous cell carcinoma (OSCC) cells. Inhibiting ERK1/2 signaling, but not PI3‐kinase signaling, blocked TGF‐β1‐induced Slug expression in the malignant UMSCC1 cells. To further examine the role of Slug in OSCC progression, we generated UMSCC1 cells with inducible expression of Slug protein. Induction of Slug in UMSCC1 cells did not repress E‐cadherin levels or regulate individual movement of UMSCC1 cells. Instead, Slug enhanced cohort migration and Matrigel invasion by UMSCC1 cells. Slug increased MMP‐9 levels and MMP‐9‐specific siRNA blocked Slug‐induced Matrigel invasion. Interestingly, Slug‐specific siRNA attenuated TGF‐β1‐induced MMP‐9 expression and Matrigel invasion. These data demonstrate that TGF‐β1 increases Slug via ERK1/2 signaling, and thereby contributes to OSCC progression. J. Cell. Biochem. 108: 726–736, 2009. © 2009 Wiley‐Liss, Inc.