bluuebunny/crossref_metadata_2025 huggingface dataset:
Termination of refractory ventricular tachycardia by a combination of intravenous sotalol and overdrive ventricular pacing
Authors: Llewellyn M. J. , Ramsdale D. R.
Published: February 2009

Right ventricular overdrive pacing is an effective method for termination of ventricular tachycardia. This may be due to alteration in conduction rate, conduction pathways, or refractory periods of myocardial tissue. The procedure can be facilitated by antiarrhythmic drugs which increase tachycardia cycle length. Sotalol possesses beta‐blocking action, has been shown to increase duration of action potentials and refractory periods throughout myocardial tissue and accessory pathways, and can suppress and prevent recurrent malignant ventricular arrhythmias. We describe two cases with ventricular tachycardia which were terminated transiently by cardioversion, but were resistant to various antiarrhythmic drugs. Right ventricular overdrive pacing was used in both cases, but was only effective after the administration of intravenous sotalol. We conclude that the unique properties of sotalol may make it especially effective in this context. Caution is required because of the hypotensive and negative inotropic actions of beta blockers, and possible acceleration of ventricular tachycardia by overdrive pacing.
Hemodynamic effects of transdermal nitroglycerin in subjects with angina and without congestive heart failure: Comparison between never treated and chronically treated subjects
Authors: Mattioli G. , Tondi S. , Magnavacchi P. , Giulio Zennaro R. , Nardini M.
Published: February 2009

Two groups of patients with angina were studied: Group A, 9 patients not treated previously with nitroderivatives; Group B, 8 patients, treated with transdermally administered nitroderivatives for at least 4 weeks. Hemodynamic parameters did not differ significantly in these groups under baseline conditions; only systolic blood pressure was higher in Group B (165±16 mmHg) than in Group A (144±15 mmHg). Hemodynamic modifications produced by administering nitroglycerin transdermally in these patient groups were evaluated 100 min after the transdermal application. In Group A significant reduction of systolic (144±15 to 126±18 mmHg, p<0.01) and diastolic blood pressure (83.36± to 70.1±13 mmHg, p<0.05), mean right atrial pressure (4.8±2.1 to 3±1.7 mmHg, p<0.005), mean pulmonary arterial pressure (18.6±2.6 to 16.7±2.8 mmHg, p<0.01), and significant increase of heart rate (72±10 to 83.5±12.4 beats/min, p<0.005) were noted. In Group B we noted only a significant reduction in systolic (170±25 to 150.5±16 mmHg, p<0.05) and diastolic blood pressure (88.7±15.5 to 77.5±9.2 mmHg, p<0.05) without other modifications. We conclude that prolonged treatment with adequate doses of transdermal nitroglycerin causes the hemodynamic effects of the medication to dissipate from the venous tone and significant arteriodilative effect to persist.
Acute aortic regurgitation due to spontaneous rupture of a bicuspid aortic valve: Detection by echocardiography
Authors: Ciampricotti R. , El Gamal M. , Mashhour Y. A. S.
Published: February 2009

A 42‐year‐old man was admitted with acute severe aortic regurgitation. There were no signs of a systemic infection. M‐mode and two‐dimensional echocardiography revealed bicuspid aortic valve and echocardiographic features consistent with aortic leaflet rupture. The diagnosis was confirmed at surgery. This report illustrates that spontaneous rupture of a bicuspid aortic valve should be considered in acute aortic regurgitation without infective endocarditis.
Occurrence of anterior st depression in inferior myocardial infarction and relation to clinical outcome
Authors: Herlitz J. , Hjalmarson Å A.
Published: February 2009

In 229 patients admitted to the coronary care unit (CCU) at Sahlgren's Hospital developing inferior myocardial infarction, and with no previous myocardial infarction, the clinical outcome was related to the presence of ST‐segment depression in 16 anterior chest leads. In all, 64% had anterior ST‐segment depression. These patients differed from those not having ST depression in several aspects. They had larger infarcts, as assessed by serum enzyme activity and ECG recording. They were more prone to congestive heart failure and required more treatment for this complication. Their intensity and duration of pain during the first 4 days appeared to be more substantial. During a 5‐year follow‐up, patients with anterior ST depression tended to have a higher mortality. We conclude that among patients with inferior myocardial infarction and no previous infarction, those with anterior ST‐segment depression form a subgroup with a more severe clinical course.
Atrial extension of mitral annular calcification mimicking intracardiac tumor
Authors: Teja K. , Gibson R. S. , Nolan S. P.
Published: February 2009

Liquefaction necrosis of mitral annular calcification occurs in 3% of autopsied cases. The liquified material can spread intramurally in various directions creating suspicious appearing mass lesions on chest x‐ray or echocardiography. An incidential finding of an echogenic left atrial calcified mass in a 57‐year‐old woman was suspected to be an intracardiac tumor for which she underwent exploratory cardiotomy. Instead, culture‐negative liquified pasty material was removed from the posterior left atrial wall adjacent to the calcified mitral annulus. This case illustrates that liquefaction necrosis of mitral annular calcification may spread to contiguous structures and masquerade as an intracardiac tumor. This relatively unknown aspect of mitral annular calcification should be considered in the differential diagnosis of echogenic left atrial mass lesions.
Short‐term reproducibility of dipyridamole‐echocardiography test
Authors: Picano E. , Masini M. , Lattanzi F. , Distante A. , L'Abbate A. , Ciuti M. , Chella P.
Published: February 2009

The aim of this study was to assess the short‐term reproducibility of dipyridamole‐echocardiography test (DET) consisting of two‐dimensional echo monitoring during dipyridamole infusion (up to 0.84 mg/kg in 10 min). The diagnostic end‐point of the test is the detection of new onset or worsening regional asynergy. A group of 87 patients with rest and/or effort angina performed two DETs on two consecutive days. All 60 patients with a positive DET had a positive repeat test, and the 27 negative DETs were also negative on the following day. The timing of the asynergy was also very similar between the two tests, both in patients with angina on effort (r=.93, p<0.01) and at rest (r=.92, p<0.01). In conclusion, DET has a very high short‐term reproducibility regarding the presence and timing of asynergy.
The Role of active myocarditis in the development of heart failure in chronic chagas' disease: A study based on endomyocardial biopsies
Authors: De Higuchi M. Lourdes , Floriano Morais C. De , Pereira Barreto A. C. , Lopes E. A. , Stolf N. , Bellotti G. , Pileggi F.
Published: February 2009

The authors analyze the presence of active myocarditis in endomyocardial biopsies from 38 patients with chronic Chagas' disease diagnosed serologically. The patients were divided into three clinical groups of increasing severity. Group I: 13 patients with normal electrocardiograms, normal chest x‐rays, and no symptoms; Group II: 13 patients with abnormal electrocardiograms and no cardiomegaly; and Group III: 12 patients with abnormal electrocardiograms, cardiomegaly and heart failure. In order to diagnose myocarditis activity, two sets of criteria were used: one mainly observing histopathologic aspects of inflammatory cells aggressing cardiac fibers; and the other counting the mean number of lymphocytes per high power microscopic field. The results of both methods showed a higher incidence of active myocarditis in the clinical group with heart failure. The present report clearly shows the important role played by activity of myocarditis in the development of heart failure in chronic Chagas' disease. Therefore, the possibility of using drugs to control early stages of the activity of the inflammatory process is suggested. On the other hand, endomyocardial biopsy (EMB) seems to be an adequate method to evaluate the intensity of the cardiac inflammatory process in Chagas' heart disease.
Coronary arteritis in nonspecific aortoarteritis
Authors: Bahl V. K. , Dev V. , Narula J. , Mukhopadhyaya S. , Bhatia M. L.
Published: February 2009

Nonostial distal coronary artery involvement in nonspecific aortoarteritis is rare. We report a 35‐year‐old patient with features of nonspecific aortoarteritis who had an inferolateral myocardial infarction and on coronary angiography was shown to have severe disease of the left circumflex artery in its middle third.
Devices external pulse generator: A reliable temporary pacemaker?
Authors: Inoue D. , Katsume H. , Ilichi H. , Ochiai M.
Published: February 2009

Two cases of malfunctioning APC (American Pacemaker Company) Devices pacemakers are reported. Two patients with sick sinus syndrome were temporarily paced using APC Devices pacemaker models EC 4542 and EV 4543 respectively, which showed transient increase (53% and 83% of the preset rate, respectively) in pacing rate. The sudden increase of the pacing rate might be the pacemaker's design to switch to fixed‐rate pacing at nominally 25% higher than the selected rate in the presence of an excessive level of electrical interference. However, the increased rate was much faster than the interference rate. Great caution should be paid when APC Devices pacemaker is to be used.
Sinus arrest associated with clonidine therapy
Authors: Schwartz E. , Friedman E. , Mouallem M. , Farfel Z.
Published: February 2009

A 65‐year‐old male with diabetes, hypertension, and mild renal failure developed dizziness and syncope one week after starting clonidine 0.45 mg/day. A continuous ECG recording revealed sinus bradycardia, nodal rhythm, and multiple episodes of sinus arrest lasting up to 4.5 seconds. Upon discontinuation of clonidine, serial continuous ECG recordings revealed gradual decrease in the number and duration of the sinus arrest episodes, until their complete disappearance shortly after the third day off clonidine. This report shows that clonidine may cause a concentration‐dependent sinus node dysfunction in addition to the atrioventricular (AV) node abnormalities previously ascribed to it.
Morbidity during five years after myocardial infarction and its relation to infarct size
Authors: Herlitz J. , Bengtson A. , HJALMARSON Å. , Karlson B. W.
Published: February 2009

In 809 patients with a recent myocardial infarction, morbidity during 5‐year follow‐up was assessed. The overall 5‐year mortality rate was 33% (39% in patients with larger infarcts and 26% in patients with smaller infarcts) as judged from maximum serum enzyme activity (p<.001). In terms of morbidity, no significant association with estimated infarct size was observed. Patients with smaller infarcts tended to have a higher reinfarction rate and were rehospitalized more often, whereas a similar proportion of patients with large and small infarcts developed stroke. Among survivors, chest pain tended to be more common in patients having smaller infarcts, whereas symptoms of dyspnea and claudicatio intermittens were similar in both groups, as were smoking habits, work capability, and varying forms of medication. We thus conclude that during a 5‐year follow‐up after acute myocardial infarction, mortality, but not morbidity, was related to the original infarct size.
The echo doppler spectrum of valvular abnormalities in the hospitalized octogenarian
Authors: Zavitsanos J. P. , Goldman A. P. , Kotler M. N. , Maze S. S. , Kochar G. , Parry W.
Published: February 2009

Cardiac valves thicken and become more opaque with advancing age. As more individuals live longer and as more treatment modalities such as valvuloplasty evolve, the presence and significance of these valvular abnormalities become important. We retrospectively studied 628 octogenarian patients to try and define further the presence and significance of these abnormalities detected by Doppler echocardiography. A group of 547 patients were suitable for analysis. Age ranged from 80 to 96 years (mean 84.4). The female:male ratio was 1.9:1. Mitral, aortic, and tricuspid regurgitation (MR, AR, and TR) were significant if the jet moved > 2 cm from the plane of the valve away or toward the transducer, depending on transducer position. Mitral regurgitation was detected in 331 patients (60.5%) and was significant in 82 patients (15%). Aortic regurgitation was detected in 276 patients (50.5%) and was significant in 70 patients (12.8%). Tricuspid regurgitation was detected in 131 patients (23.9%) and was significant in 30 patients (5.5%). Regurgitant lesions were detected in two valves in 150 patients (27.4%) three valves in 57 patients (10.4%), in all four valves in 17 patients (3.1%). Aortic stenosis was detected in 160 patients (29.3%). The gradient range was 16‐156 mmHg (mean 47.8). Significant aortic stenosis was present in 70 patients (12.8%) (gradient >50 mmHg), of whom 54 had isolated pure aortic stenosis and 16 had mixed lesion. In 40% of these patients, significant aortic stenosis was an unexpected finding at two‐dimensional echocardiography. Valvular pathology is common in the octogenarian population. It is uncertain to what extent this represents physical adaptation to aging or true pathology, but these findings may have important implications with regard to bacterial endocarditis prophylaxis and potential valvuloplasty in the aged population.
Mechanism of prolongation of pre‐ejection period in the hypertrophied left ventricle with normal systolic function in unanesthetized hypertensive dogs
Authors: Matsuno Y. , Morioka S. , Murakami Y. , Kobayashi S. , Moriyama K.
Published: February 2009

To determine the mechanism for prolongation of pre‐ejection period (PEP) in the hypertensive heart with normal systolic function, cardiac catheterizations, echocardiograms, and electrocardiograms were performed at the baseline period (CS, control stage) and eight weeks (HS, hypertensive stage) after the induction of systemic hypertension by Page's method in unanesthetized dogs. Mean aortic blood pressure increased significantly (96 ± 12 to 137±26 mmHg) (p<0.05). Diastolic aortic pressure also increased significantly (80±12 to 118±24 mmHg) (p<0.01). Left ventricular (LV) PEP of HS was significantly prolonged (72±12 vs. 87±22 ms, CS vs. HS). The ratio of LV pre‐ejection period to ejection time (PEP/ET) also increased significantly (0.33 ±0.04 to 0.42 ±0.07) (p<0.05). LV end‐diastolic wall stress as an index of preload decreased significantly (7.7 ±2.5 vs. 5.9± 1.8 103 dynes/cm2, CS vs. HS). Heart rate, mean velocity of circumferential fiber shortening (VCF) and end‐systolic wall stress of HS did not change. That is, myocardial contractility in the hypertensive heart of HS most likely is not depressed. At autopsy, left ventricle to body weight ratio of HS was significantly (p<0.01) greater than the sham‐operated dogs (5.7±0.8vs. 4.3±0.5 g/kg). From these findings, there are two possible factors responsible for prolongation of PEP of HS. First, elevated diastolic aortic pressure may influence PEP. Second, the prolonged PEP is possibly caused by the decrease of preload. Boudoulas et al. reported that the abnormalities in systolic time intervals (STI) were equivalent in patient subgroups with high and low diastolic arterial pressure within hypertensive groups. Therefore, we conclude that the main factor to prolong PEP in the hypertensive heart with normal systolic function is possibly the decrease of preload rather than the depressed myocardial contractility or elevated diastolic aortic pressure.
Differences in composition of sweat induced by thermal exposure and by running exercise
Authors: Fukumoto T. , Tanaka T. , Fujioka H. , Yoshihara S. , Ochi T. , Kuroiwa A.
Published: February 2009

To determine the differences in sweat composition between sweat induced by thermal stress alone and that induced by physical exercise, seven young healthy men first sat in a hot room and then performed running exercise. A 20‐minute stay in a climate chamber at 40°C resulted in a 5% reduction in body weight. The same body weight loss was induced by running exercise. Both sodium and chloride concentrations were much lower in the sweat induced by thermal exposure than that induced by the running exercise (p<0.01), while urea nitrogen and creatinine concentrations were significantly higher after thermal exposure than after the running exercise (p<0.01). Potassium concentrations did not differ significantly with either procedure. These findings suggest that sweat composition varies with the kind of induction and that more salt seems to be lost through exercise‐induced sweating than by just sitting in a hot environment.
Biphasic response of coronary arterial diameter to intracoronary ergonovine
Authors: Mohri M. , Okamatsu S. , Nakamura M.
Published: February 2009

This report presents a case of paradoxical coronary arterial dilation induced by intracoronary ergonovine. When compared with the control angiogram, the right coronary artery obviously dilated with selective, intracoronary administration of cumulative doses of 5 μg and 15 μg ergonovine without concomitant hemodynamic changes. Additional intracoronary infusion of 35 μg ergonovine into the right coronary artery inversely increased vascular tone of the vessel associated with a focal hyper‐constriction. Such a biphasic response of arterial diameter to intracoronary ergonovine was also observed in the left coronary artery, but the degree of dilation was much smaller.
Quinine overdose: Review of toxicity and treatment
Authors: Goldenberg A. M. , Wexler L. F.
Published: February 2009

Quinine sulfate is a commonly prescribed remedy for idiopathic nocturnal leg cramps and is now available “over the counter.” A 24‐year‐old man ingested 8 g (a commonly dispensed quantity) of quinine sulfate in a suicide attempt. Despite hemoperfusion begun 10 h after ingestion, the patient died. This report reviews the toxic manifestations of quinine and the currently available modes of treatment.
Changes in the levels of plasma atrial natriuretic peptide, hemodynamic measurements, and the levels of vasoactive hormones during the clinical course of congestive heart failure
Authors: Hara H. , Ogihara T. , Nakamaru M. , Rakugi H. , Tateyama H.
Published: February 2009

To investigate the mechanism for the release of human atrial natriuretic peptide (hANP) and the pathophysiological role of hANP in patients with congestive heart failure (CHF), plasma hANP levels in patients with dilated cardiomyopathy (DCM) or acute myocardial infarction (AMI) were determined serially, and the relationship between plasma ANP levels and hemodynamic measurements or various vasoactive hormones was analyzed during the clinical course of congestive heart failure. In 63 patients with either AMI or DCM, plasma hANP, plasma renin activity, aldosterone concentration, and catecholamines were measured over 4 weeks, during the course of CHF. Cardiac catheterization with a Swan‐Ganz catheter was also performed. Plasma hANP in patients with DCM was elevated continuously during the clinical course. Plasma hANP levels in patients with AMI of Groups II and IV of Forrester's class decreased on days 7 and 14 and those in patients with AMI of Group I changed within normal limits. Plasma hANP levels were correlated positively with pulmonary artery pressure and pulmonary capillary wedge pressure in patients with AMI or DCM. Plasma renin activity, noradrenaline, and adrenaline levels were elevated in the acute phase of myocardial infarction and had a tendency to decrease upon improvement in clinical status. Plasma renin activity and noradrenaline level correlated positively with plasma hANP levels. These data indicate that plasma hANP levels are regulated by atrial distension and severity of cardiac impairment, and that plasma hANP and plasma renin activity or catecholamines correlated closely during the clinical course of CHF, indicating that these hormones may be involved in the volume and electrolytes status in CHF.
Day to day reproducibility of doppler sonographic measurements in patients with valvular aortic stenosis
Authors: Siostrzonek P. , Kronik G. , Jung M. , GöSSINGER H. , Schmoliner R. , Zangeneh M. , MöSSLACHER H.
Published: February 2009

High reproducibility of Doppler gradient measurements is necessary for both the reliable noninvasive assessment of the severity of aortic stenosis and for repeated follow‐up examinations in individual patients. We therefore studied day to day reproducibility of Doppler sonographically measured peak pressure drops in 46 patients with valvular aortic stenosis. Clinically stable patients were examined twice within 29 ± 18.2 days by the same examiner. Peak pressure drop (PPD) and peak flow velocity differed between the two examinations by 8.6±7.0 (range 0‐29) mmHg and by 0.25±0.18 (range 0‐0.7) m/s, respectively. Reproducibility was comparable in patients with excellent, good, and moderate quality examinations, but was lower in the 6 patients with poor quality examination. Variability of PPD, but not of peak flow velocity was higher (p<0.05) in patients with severe (PPD >60mmHg) stenosis. Reproducibility was comparable in patients with or without concomitant aortic incompetence and in patients with normal or reduced left ventricular function. Similar reproducibility was obtained in patients with heart rate changes below or above 10 beats/min between the two examinations. It is concluded that good reproducibility of Doppler measurements in patients with aortic stenosis allows reliable noninvasive assessment of the severity of the stenosis. In follow‐up studies of patients with mild to moderate aortic stenosis increases in peak flow velocity in excess of 15% (mean day to day variability+2 SD) are highly indicative of the true progress of the stenosis.
Partial anomalous pulmonary venous drainage and intact atrial septum with mitral stenosis: the paradox of a small shunt
Authors: Dev V. , Narula J. , Tandon R. , Shrivastava S.
Published: February 2009

Clinical, hemodynamic, and angiographic features of 10 patients with partial anomalous pulmonary venous drainage, intact atrial septum, and rheumatic mitral stenosis have been presented. Seventeen patients with this combination of anomalies reported in the literature have also been reviewed. The clinical diagnosis of mitral stenosis was possible in each of our 10 cases. Partial anomalous pulmonary venous drainage and intact atrial septum in addition to mitral stenosis was clinically suspected in only four patients. The findings suggesting additional presence of partial anomalous pulmonary venous drainage and intact atrial septum in a patient with mitral stenosis include: wide variable splitting of the second sound, pulmonary ejection systolic murmur with or without a thrill, and radiological evidence of unilateral increase in pulmonary vascularity or unilateral hilar pulsations. Hemodynamic findings were characterized by a relatively modest left to right shunt (Qp/Qs:2.2±1.4). Elevated pulmonary vascular resistance was found in the anomalously draining as well as the normally draining lung segments (9.1 ±4.9 and 6.5±3.4 units, respectively, t=1.32;NS). The mechanism of the unexpected high resistance in the anomalously draining lung segments permitting only a small left to right shunt is discussed.
Infection risk of cardiac catheterization and arterial angiography with single and multiple use disposable catheters
Authors: Frank U. , Herz L. , Daschner F. D.
Published: February 2009

In a prospective study from November 1986 to June 1987, a cohort of 414 patients underwent cardiac catheterization or angiography with either multiple use or single use disposable catheters: 161 patients were studied with 426 single use catheters, 152 patients with 384 multiple use catheters which were resterilized once or twice, and 101 patients with 325 multiple use catheters reprocessed several times. Postcatheterization temperature did not exceed 38.2°C in any patient, but was greater than 37.4°C in 4‐6% of the patients studied. No significant differences between the three groups with respect to fever could be observed. Infectious complications associated with cardiac catheterization or angiography did not occur in any case. Of 414 patients, 38 (9.2%) developed hematoma at the puncture site. It is concluded that careful cleaning, disinfection, and resterilization of intravascular catheters with ethylene oxide does not increase the risk of infection. With the rising pressure for containment of health care costs, it is likely that the practice of reprocessing and reuse of expensive intravascular catheters will expand further.
Swallowing‐induced arrhythmia
Authors: Matsubara K. , Inoue D. , Morikawa Y. , Shirayama T. , Omori I. , Katsume H. , Nakagawa M.
Published: February 2009

Deglutition tachyarrhythmia, first reported in 1926 by Sakai and Mori, is a rare clinical entity. Vagal reflex has been supposed to be responsible for the induction of the arrhythmia. We have recently studied a patient with swallowing‐induced premature atrial contractions. Atropine sulfate and catecholamine infusion increased the frequency of the arrhythmia, while beta blockade suppressed it. It is suggested that the mechanism of the swallowing‐induced arrhythmia might be related to a sympathetic reflex. As far as we know, there have been few reports in which the sympathetic reflex was proposed to be responsible for the arrhythmia.
Effects of transient increase in intrathoracic pressure on hemodynamic determinants of myocardial oxygen supply and demand
Authors: Pepine C. J. , Nichols W. W.
Published: February 2009

Effects of transient increases in intrathoracic pressure on hemodynamic indexes of myocardial oxygen supply and demand were evaluated in 21 patients with ischemic heart disease. Left ventricular, ascending aortic, and right atrial pressures and electrocardiogram (ECG) were recorded while a Valsalva maneuver was performed during ischemia. Myocardial oxygen demand was assessed from the tension time index (TTI) and cardiac size and potential myocardial oxygen supply were assessed from a diastolic pressure time index (DPTI) and relative changes in supply/demand ratio from DPTI/TTI. During an asymptomatic interval an abrupt but small transient decrease in TTI and cardiac size occurred during phase II (p <0.05) of the Valsalva maneuver. DPTI did not change significantly and DPTI/TTI increased (p<0.05). When Valsalva maneuver was initiated during angina, 16 patients reported prompt and complete relief of angina, and left ventricular end‐diastolic pressure declined following the maneuver. Relief of ischemia occurred uniformly during the latter part of straining (phase II) coincident with the peak reduction in TTI, cardiac size, and increase in DPTI/TTI. These data indicate that a transient increase in intrathoracic pressure results in a decrease in hemodynamic determinants of myocardial oxygen demand and an increase in the myocardial oxygen supply: Demand ratio.
Detection of impaired left ventricular function in coronary artery disease with acceleration index in the first derivative of the transthoracic impedance change
Authors: Feng S. , Okuda N. , Fujinami T. , Takada K. , Nakano S. , Ohte N.
Published: February 2009

In order to detect impaired left ventricular (LV) function in coronary artery disease (CAD) patients using acceleration index (Ac) of impedance cardiography (ICG), exercise ICG was performed in 29 patients with chest pain but without CAD (Group 1) and 21 patients with CAD (Group 2), and their resting values were compared with 30 healthy controls (Group 3). The acceleration index, which reflects indirectly aortic blood flow acceleration, was calculated as the ratio of dZ/dtmax to its accelerating time (AT). At rest, the values for Ac in Groups 1, 2, and 3 were 23±10, 15±6, and 36±13 Ω/s2, respectively. There were significant differences between Group 1 versus 3, 2 versus 3, and 1 versus 2 (all p<0.001). At maximal exercise, Ac showed the largest percent change among the various indices used in this study. An increase of 198% for Group 2 was markedly lower than that of 250% in Group 1 (40±14 vs. 68±24 Ω/s2, p<0.001). With a value of ≤40 Ω/s2, Ac can detect the CAD patients, with a sensitivity of 62% and specificity of 90%, superior to stress ECG using CM5 lead. It is concluded that: (1) Ac is the sole index capable of distinguishing not only between the normals and diseased groups, but also between CAD patients and suspected CAD cases at rest. (2) Ac is a remarkably sensitive index for detecting impaired LV function at maximal exercise. (3) Exercise ICG is useful for predicting CAD from the population predisposing to CAD. As an indicator of acceleration, Ac is the most valuable of its kind in exercise ICG.
Plasma level changes of fibrinopeptide a after uncomplicated coronary angioplasty
Authors: Manolis Antonis S. , Melita‐Manolis Helen , Stefanadis Christodoulos , Toutouzas Pavlos
Published: February 2009

Fibrinopeptide A (FPA) is a small polypeptide cleaved from fibrinogen by thrombin, has a short half‐life, and is considered a sensitive biochemical marker of thrombin activity, fibrin generation, and ongoing thrombosis. Increased plasma levels of FPA have been reported in various procoagulable and thrombotic medical and cardiovascular disorders, including acute myocardial infarction, unstable angina, and sudden cardiac death. However, activation of thrombosis by the arterial injury incurred during coronary angioplasty has not been systematically examined with use of plasma FPA measurements.

To detect and monitor activation of thrombosis by coronary angioplasty, plasma levels of FPA were obtained by venipuncture and measured by radioimmunoassay before, immediately after, 24 to 48 h later, and 1 and 3 months after uncomplicated coronary angioplasty. From December 1990 through June 1991, FPA was measured in 30 patients (28 men and 2 women, aged 54 ± 9 years) with coronary artery disease who were undergoing coronary angioplasty. The mean left ventricular ejection fraction was 55 ± 7%. The dilated vessel was the left anterior descending coronary artery in 20 patients (together with a second vessel in 2), the right coronary artery in 9, and the left circumflex in 1. The procedure was successful and free of major complications in all patients. Before angioplasty the FPA levels averaged 6.50 ± 1.18 ng/ml. Shortly after angioplasty they rose to 20.20 ± 7.91 ng/ml (p = 0.08) despite intravenous heparin. At 24 to 48 h and after heparin had been discontinued for at least 4 h, the mean FPA levels were significantly higher (32.33 ± 10.86 ng/ml) compared with baseline values (p = 0.025 ). At 1 month after the procedure, the FPA levels measured in 22 patients were lower but still elevated (20.25 ± 9.29 ng/ml), albeit nonsignificantly, compared with baseline values, and at 3 months they had fallen to baseline values (4.84 ± 2.20 ng/ml, n = 11). No patient developed restenosis during the study period of 1 to 3 months, during which all patients were receiving aspirin. We conclude that, as reflected by increased FPA levels, angioplasty, most likely due to arterial injury incurred, activates thrombin and generates ongoing coronary thrombosis, which is not suppressed by heparin or aspirin and appears to extend at least through the first month after the procedure.
C‐reactive protein as a risk factor for left ventricular thrombus in patients with acute myocardial infarction
Authors: Çlelik Şüukrü , Baykan Merih , Erdöul Cevdet , Kilinçl Kaǧan , ÖREM Asim , Rem Cihan Ö , Durmus Idotu Smet
Published: February 2009

Background: Elevated C‐reactive protein (CRP) has been found to correlate with higher risk for cardiac events in patients with acute myocardial infarction (AMI). It has been suggested that CRP may be involved in initiation process of coagulation; however, the role of CRP level in the formation of left ventricular (LV) thrombus has not been studied.

Hypothesis: This study investigated whether CRP is a risk factor for LV thrombus in patients with AMI.

Methods: Clinical, echocardiography, and biochemical data were analyzed in 141 consecutive patients (aged 57 ± 13 years; 33 women) with first anterior AMI. Two‐dimensional and Doppler echocardiographic examinations were performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained every day during hospitalization. Serum CRP concentrations were measured by an ultrasensitive immunonephelometry method.

Results: Left ventricular thrombus was detected in 33 (23.4%) patients. Univariate analysis showed that patients with LV thrombus had a higher peak creatine kinase (CK) level (2879 ± 742 vs. 1693 ± 1210 I/U, p = 0.001), higher peak CRP level (14.9 ± 7.1 vs. 9.2 ± 6.8 mg/dl, p = 0.001), higher wall motion score index (1.8 ± 0.2 vs. 1.5 ± 0.3, p = 0.002), higher apical wall motion score index (2.35 ± 0.72 vs. 2.07 ± 0.70, p = 0.001), larger end‐diastolic volume (145.2 ± 43.7 vs. 116.5 ± 44.2 ml, p = 0.002), larger end‐systolic volume (85.4 ± 37.2 vs. 62.9 ± 31.6 ml, p = 0.003), and lower ejection fraction (42.1 ± 12 vs. 47.3 ± 13, p = 0.04). in multivariate analyses, only peak CK level (p = 0.0001), LV apical wall motion score index (p = 0.001), and CRP levels (p = 0.001) were independent predictors of LV thrombus formation.

Conclusions: These results suggest that CRP is a risk factor for LV thrombus in patients with AMI.
Characterization of New PPARγ Agonists: Analysis of Telmisartan’s Structural Components
Authors: Goebel Matthias , Clemenz Markus , Staels Bart , Unger Thomas , Kintscher Ulrich , Gust Ronald
Published: February 2009

Telmisartan was originally designed as an AT1 antagonist but was later also characterized as a selective PPARγ modulator. This study focused on the identification of the essential structural motifs of telmisartan for PPARγ activation activity, elucidating the individual SAR of each different component (shown).

magnified image

In addition to a proven efficacy in lowering blood pressure, the AT1 receptor blocker telmisartan has recently been shown to exert pleiotropic effects as a partial agonist of the nuclear peroxisome proliferator‐activated receptor gamma (PPARγ). Based on these findings and an excellent side‐effect profile, telmisartan may serve as a lead structure for the development of new PPARγ ligands. Therefore, we analyzed the structural components of telmisartan to identify those necessary for PPARγ activation. Synthesized compounds were tested in a differentiation assay using 3T3‐L1 preadipocytes and a luciferase assay with COS‐7 cells transiently transfected with pGal4‐hPPARγDEF, pGal5‐TK‐pGL3 and pRL‐CMV. The data obtained in this structure–activity relationship (SAR) study provide the basis for the development of new PPARγ ligands, which could lead to active compounds with a distinct, beneficial pharmacological profile compared with the existing full agonists. The basic 1‐(biphenyl‐4‐ylmethyl)‐1H‐benzimidazole scaffold of telmisartan was identified as an essential moiety with either a carboxylic acid or tetrazole group at the C‐2 position of the biphenyl. For maximum potency and activity, the alkyl chain in position 2 requires a minimum length of at least two C atoms (ethyl group), while the methyl group at position 4 of the benzimidazole core seems to contribute to partial activity. An additional benzimidazole at position 6 appears to be a further determinant of potency. Similar conclusions can be drawn for the methyl group in position 1.
Synthesis, SAR and Unanticipated Pharmacological Profiles of Analogues of the mGluR5 Ago‐potentiator ADX‐47273
Authors: Engers Darren W. , Rodriguez Alice L. , Williams Richard , Hammond Alexis S. , Venable Daryl , Oluwatola Oluwatomi , Sulikowski Gary A. , Conn P. Jeffrey , Lindsley Craig W.
Published: February 2009

An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago‐potentiator ADX‐47273. This effort identified key substituents in the 3‐position of oxadiazole that engendered either mGluR5 ago‐potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9‐fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.

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DNA Binding Ellipticine Analogues: Synthesis, Biological Evaluation, and Structure–Activity Relationships
Authors: Ferlin Maria Grazia , Marzano Christine , Gandin Valentina , Dall'Acqua Stefano , Dalla Via Lisa
Published: February 2009

Novel angular and branched ellipticine‐correlated anticancer agents were developed. In particular, compound 24, with two basic side chains on opposite sides of the molecule, exhibits cytotoxicity in the nanomolar range, acting as a DNA intercalator and topoisomerase II inhibitor. SAR studies with pyridocarbazole derivatives in comparison with corresponding smaller pyrroloquinolines are discussed.

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In connection with our interest in the synthesis and study of the biological properties of ellipticine analogues as anticancer agents, some 7H‐pyrido[2,3‐c]carbazoles (7H‐PyC) and their corresponding tetrahydro derivatives (7H‐THPyC) were synthesized. A common multistep pathway characterized by conventional reactions involving carbazole Fischer and Conrad–Limpach quinoline syntheses yielded the tetracyclic compounds. With the aim to improve the cytotoxic activity of the new 7H‐PyC derivatives, we provided them with one or two diethylaminoethyl side chains. The new THPyCs, PyCs, and smaller pyrroloquinoline (PQ) derivatives were tested for their in vitro cytotoxic properties against several human tumor cell lines. Most of the compounds tested showed considerable cytotoxic activity, particularly compound 24, which, with two basic alkylamino chains, has IC50 values in the sub‐micromolar range, about one order of magnitude lower than those of the reference compound, ellipticine. Chemosensitivity tests on cisplatin‐, mitoxantrone‐, and multidrug‐resistant (MDR) phenotypes indicated that compound 24 shows no cross‐resistance; this suggests that, besides not being a potential MDR substrate, it might act as a mixed inhibitor of topoisomerases I and II. Flow cytometric and caspase‐3 activation analyses revealed that 24 induces a caspase‐3‐dependent apoptotic cell‐death mechanism. Linear dichroism and unwinding experiments suggested that the most active compounds act as DNA intercalators. For compound 24, an inhibitory concentration‐dependent effect on topoisomerases II and I was demonstrated. Herein we discuss interesting structure–activity relationships with respect to molecular size and planarity, as well as the substitution and position of one side chain on the PyC nucleus, in comparison with corresponding smaller PQs.
Inside Cover: Tritium‐Labeled N1‐[3‐(1H‐imidazol‐4‐yl)propyl]‐N2‐propionylguanidine ([3H]UR‐PI294), a High‐Affinity Histamine H3 and H4 Receptor Radioligand / NG‐Acylated Aminothiazolylpropylguanidines as Potent and Selective Histamine H2 Receptor Agonists (ChemMedChem 2/2009)
Authors: Igel Patrick , Schnell David , Bernhardt Günther , Seifert Roland , Buschauer Armin , Kraus Anja , Ghorai Prasanta , Birnkammer Tobias , Elz Sigurd , Dove Stefan
Published: February 2009

The inside cover picture shows the human histamine H2 receptor and the H2 and H3/H4 receptor‐selective ligands identified. Bioisosteric replacement of the imidazole ring of the NG‐acyl‐imidazolylpropylguanidine with 2‐aminothiazole yielded potent and selective H2 receptor agonists. In contrast, modification of the acyl group gave a high‐affinity H3/H4‐selective tritiated radioligand. For more details, see the Full Papers by A. Buschauer et al. on p. 225 ff and p. 232 ff.

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Predictive value of tumor thickness for cervical lymph‐node involvement in squamous cell carcinoma of the oral cavity
Authors: Huang Shao Hui , Hwang David , Lockwood Gina , Goldstein David P. , O'Sullivan Brian
Published: February 2009

BACKGROUND:

Tumor thickness (TT) appears to be a strong predictor for cervical lymph‐node involvement in squamous cell carcinoma of the oral cavity (OSCC), but a precise clinically optimal TT cutoff point has not been established. To address this question, the authors conducted a meta‐analysis.

METHODS:

All relevant articles were identified from MEDLINE and EMBASE as well as from cross‐referenced publications cited in relevant articles. Lymph‐node involvement was confirmed and identified as positive lymph‐node declaration (PLND) by either pathologic positivity on immediate neck dissection or by neck recurrence identified after follow‐up ≥2 years. Odds ratios (OR) were calculated to quantify the predictive value of TT. Negative predictive values (and the percentage of patients falsely predicted to not have PLND [FN‐PLND]) were compared to determine the optimal TT cutoff point.

RESULTS:

Sixteen studies were selected from 72 potential studies, yielding a pooled total of 1136 patients. Data were examined for the following TT cutoff points: 3 mm (4 studies, 387 patients), 4 mm (9 studies, 778 patients), 5 mm (6 studies, 367 patients), and 6 mm (4 studies, 488 patients). The OR (95% CI) was 7.3 (5.3‐10.1) for the overall group. The proportion of FN‐PLND was 5.3% (95% CI, 2.0‐11.2), 4.5% (2.6‐7.2), 16.6% (11.5‐22.8), and 13.0% (9.7‐16.9) for TT<3, <4, <5, and <6 mm, respectively. There was a statistically significant difference between the 4‐mm and 5‐mm TT cutoff points (P = .007).

CONCLUSIONS:

TT was a strong predictor for cervical lymph‐node involvement. The optimal TT cutoff point was 4 mm. Cancer 2009. © 2009 American Cancer Society.
Bevacizumab for recurrent alkylator‐refractory anaplastic oligodendroglioma
Authors: Chamberlain Marc C. , Johnston Sandra
Published: February 2009

BACKGROUND:

A retrospective evaluation of single agent bevacizumab was carried out in adults with recurrent alkylator‐refractory 1p19q codeleted anaplastic oligodendrogliomas (AO) with an objective of determining progression‐free survival (PFS). There is no standard therapy for alkylator‐resistant AO, and hence a need exists for new therapies.

METHODS:

Twenty‐two patients aged 24 to 60 years with recurrent AO were treated. All patients had previously been treated with surgery, radiotherapy, adjuvant chemotherapy (temozolomide, 17; carmustine wafers, 4; carmustine, 1), and 1 salvage regimen (procarbazine, lomustine, and vincristine, 15; temozolomide, 6; carmustine wafers, 1). Eleven patients underwent repeat surgery. Patients were treated at second recurrence with bevacizumab, once every 2 weeks, defined as a single cycle. Neurological evaluation was performed every 2 weeks, and neuroradiographic assessment was made after the initial 2 cycles of bevacizumab and subsequently after every 4 cycles of bevacizumab.

RESULTS:

A total of 391 cycles of bevacizumab (median, 14.5 cycles; range, 2‐39 cycles) were administered. Bevacizumab‐related toxicity included fatigue (14 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (5; 1 grade 3), deep vein thrombosis (4; 1 grade 3), and wound dehiscence (2; 1 grade 3). Fifteen (68%) patients demonstrated a partial radiographic response, 1 (5.0%) demonstrated stable disease, and 6 (27%) demonstrated progressive disease after 2 cycles of bevacizumab. Time to tumor progression ranged from 1 to 18 months (median, 6.75 months). Survival ranged from 3 to 19 months (median, 8.5 months). Six‐month and 12‐month PFS were 68% and 23%, respectively.

CONCLUSIONS:

Bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent 1p19q codeleted alkylator‐refractory AO. Cancer 2009. © 2009 American Cancer Society.
Interstitial wires releasing diffusing alpha emitters combined with chemotherapy improved local tumor control and survival in squamous cell carcinoma‐bearing mice
Authors: Cooks Tomer , Arazi Lior , Efrati Margalit , Schmidt Michael , Marshak Gideon , Kelson Itzhak , Keisari Yona
Published: February 2009

BACKGROUND:

The objective of this study was to examine the combined effect of diffusing alpha‐emitter radiation therapy (DART) together with the chemotherapeutic agent cisplatin on tumor development.

METHODS:

BALB/c mice bearing squamous cell carcinoma tumors were treated with radium 224 (224Ra‐)–loaded stainless steel wires, releasing short‐lived, alpha‐emitting atoms from their surface. A concomitant regimen of cisplatin doses (5 mg/kg per dose) was given intravenously for the evaluation of the combined effect. Animals were monitored for tumor growth and survival.

RESULTS:

First, the authors observed that alpha particles and cisplatin inhibited SQ2 cell proliferation in vitro and promoted apoptosis. Treatment of tumor‐bearing mice indicated that, when a regimen of 2 separate doses of cisplatin was given concomitantly with a single intratumoral 224Ra‐loaded wire, there was moderate tumor growth inhibition relative to what was observed from each treatment alone. When tumors were treated with 2 radioactive wires positioned near the tumor base and a similar drug administration, the growth arrest effect intensified, and there also was a significant increase in survival rates. The combined treatment reduced both local tumor growth and metastatic spread to the lungs.

CONCLUSIONS:

Antitumor activity and overall survival of metastatic tumor‐bearing mice were improved significantly by the combined treatment. These results highlight the potential benefit of alpha radiation‐based radiotherapy in combination with chemotherapeutic drugs for anticancer treatment. Cancer 2009. © 2009 American Cancer Society.
Optical tools to assess naturalness of cosmetic films
Authors: Maitra Prithwiraj , Balina Angelina , Carlo Steven , Glynn John R.
Published: February 2009

Developing technologies and cosmetic formulations that mimic the optical properties of healthy, youthful skin is a significant challenge and has been one of the recent key areas of focus in the cosmetic industry. A common tool to assess optical properties of cosmetic formulations involves use of spectrophotometer with an integrating sphere to measure transmittance and opacity. Given that the human face is three‐dimensional and contoured, and that the human eye processes information gathered at many angles, adding a measure that capture the angular behavior of light provides cosmetic scientists with an additional valuable tool. Here we describe addition of wide angle transmittance measurement via goniospectrophotometer to the optical tool kit. Results with soft focus materials and commercially available cosmetic products are reported. © 2009 Wiley Periodicals, Inc. Col Res Appl, 34, 170–172, 2009
A spectrophotometric color matching algorithm for precolored fiber blends
Authors: Li Rong , Song Yang , Gu Feng , Pan Wei
Published: February 2009

In this article, a spectrophotometric color matching algorithm based on Stearns‐Noechel model is proposed. This algorithm was run to predict recipes for 48 viscose blends. Color differences between the original blend samples and the calculated were expressed in CIELAB units (10°standard observer). M (the empirical constant in Stearns‐Noechel model) value was determined by median analysis. When M equals to 0.09, the best fit was obtained for three‐components fiber blends. In that case, the maximum color difference is 1.22 CIELAB units and the average computed color difference is 0.56 CIELAB units for 36 three‐components fiber blends under D65 illuminant. When M is from 0.03 to 0.06, the best fit was obtained for four‐components fiber blends. In that case, the maximum color difference is 4.48 CIELAB units and the average computed color difference is 1.02 CIELAB units for 12 four‐components fiber blends under D65 illuminant. It is demonstrated that the algorithm can be used in color matching of fiber blends. © 2009 Wiley Periodicals, Inc. Col Res Appl, 34, 108–114, 2009