Early stages in the self-organization of Si nanopatterns induced by ion bombardment.

We reveal early stages of self-organization of nanopatterns created by 2 keV Cs+ ion-beam irradiation of a Si surface coated with Au and a Ti adhesion layer. After ion-beam etching of the metallic layers, at normal incidence, we first observe distinct transient stages: (I) a dewetting-like pattern of grooves in the Si amorphized layer, sparsely populated with holes, followed by (II) the coexistence of rounded mounds and faceted holes distributed on a flat surface, the latter being an indication of the decisive role played by the crystalline/amorphous interface. Subsequently, the system evolves to stage III, a nanopattern of densely packed nanodots convoluted with a long-wavelength surface corrugation. A momentum-space analysis shows that stages (I) and (II) are identified, respectively, with channel-type and sphere-type quasi order.

Alternative uses of a megavolt tandem accelerator for few-keV studies with ion-source SIMS monitoring.

We increase the versatility of a tandem electrostatic accelerator by implementing simple modifications to the standard operation procedure. While keeping its ability to deliver MeV ion beams, we show that the experimental setup can (i) provide good quality ion beams in the few-keV energy range and (ii) be used to study ion-beam surface modification with simultaneous secondary ion mass spectrometry. This latter task is accomplished without using any chamber connected to the accelerator exit. We perform mass spectrometry of the few-keV anions produced in the ion source by measuring their neutral counterparts at the accelerator exit with energies up to 1.7 MeV. With an additional modification, a high-current few-keV regime is obtained, using the ion source as an irradiation chamber and the accelerator itself only as a mass spectrometer. As an example of application, we prepare a sample for the study of ion-beam assisted dewetting of a thin Au film on a Si substrate.

Frontiers of robotic endoscopic capsules: a review.

Digestive diseases are a major burden for society and healthcare systems, and with an aging population, the importance of their effective management will become critical. Healthcare systems worldwide already struggle to insure quality and affordability of healthcare delivery and this will be a significant challenge in the midterm future. Wireless capsule endoscopy (WCE), introduced in 2000 by Given Imaging Ltd., is an example of disruptive technology and represents an attractive alternative to traditional diagnostic techniques. WCE overcomes conventional endoscopy enabling inspection of the digestive system without discomfort or the need for sedation. Thus, it has the advantage of encouraging patients to undergo gastrointestinal (GI) tract examinations and of facilitating mass screening programmes. With the integration of further capabilities based on microrobotics, e.g. active locomotion and embedded therapeutic modules, WCE could become the key-technology for GI diagnosis and treatment. This review presents a research update on WCE and describes the state-of-the-art of current endoscopic devices with a focus on research-oriented robotic capsule endoscopes enabled by microsystem technologies. The article also presents a visionary perspective on WCE potential for screening, diagnostic and therapeutic endoscopic procedures.

Plasminogen Activator Italian Multicenter Study (PAIMS): comparison of intravenous recombinant single-chain human tissue-type plasminogen activator (rt-PA) with intravenous streptokinase in acute myocardial infarction.

A single chain preparation of recombinant tissue-type plasminogen activator (rt-PA) was compared with intravenous streptokinase to determine coronary thrombolytic efficacy in patients with acute myocardial infarction less than 3 h old. Eighty-six patients were randomly selected to receive the intravenous cumulative dose of 100 mg rt-PA and 85 patients to receive 1.5 million units streptokinase. At 240 min after initiation of the thrombolytic therapy noninvasive signs of sustained reperfusion occurred in 79% of patients in both groups (p = NS). Patency of the infarct-related vessel at follow-up angiography was observed in 81% of patients in the rt-PA group and 74% of patients in the streptokinase group (p = NS). At hospital discharge, compared with admission, echocardiographically determined left ventricular ejection fraction increased from 52 +/- 11% to 56 +/- 10% (p less than 0.01) in the rt-PA group; changes in the streptokinase group (50 +/- 9% to 51 +/- 11%) were not significant. A nadir value of less than 1 g/liter fibrinogen plasma level occurred in 6 patients (7%) receiving rt-PA versus 74 patients (87%) receiving streptokinase (p less than 0.0001). Plasma levels of fibrin(ogen) degradation products were more than doubled in the streptokinase group (p less than 0.01). One patient in the streptokinase group developed a fatal intracranial hemorrhage; five others showed a decline in hemoglobin greater than or equal to 5 g/dl. Other clinical events in the streptokinase-treated group included allergic reactions (four patients) and intrahospital reinfarction (two patients). None of these events occurred in the rt-PA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine reduces transient myocardial ischemia in patients with coronary artery disease: double-blind Circadian Anti-Ischemia Program in Europe (CAPE Trial).

OBJECTIVES: This study was carried out to determine the effect of the once-daily calcium channel blocking agent amlodipine (half-life 35 to 50 h) on the circadian pattern of myocardial ischemia in patients with chronic stable angina. BACKGROUND: Myocardial ischemia during normal daily life, both symptomatic and asymptomatic, has been associated with increased risk of cardiovascular morbidity and mortality, and the circadian pattern parallels that for myocardial infarction and sudden death. METHODS: The Circadian Anti-Ischemia Program in Europe (CAPE) was a large, 10-week international (63 sites), double-blind, parallel study. After a 2-week, single-blind placebo phase, during which stable doses of antianginal treatment were maintained (beta-adrenergic blocking agents in 65% of patients), patients with chronic stable angina with at least three attacks of angina per week, with at least four ischemic episodes or > or = 20 min of ST segment depression in 48 h of Holter monitoring, were randomized to receive treatment with either 5 mg/day of amlodipine or placebo (2:1 randomization). The dose was increased to 10 mg/day after 4 weeks. During week 7 of treatment, 48-h ambulatory ECG monitoring was repeated. RESULTS: Three hundred fifteen of 1,160 patients screened were eligible, and 250 had complete evaluable data. Compared with placebo, amlodipine significantly reduced both the frequency of ST segment depression episodes (60% for amlodipine vs. 44% for placebo, p = 0.025) and total integrated ST ischemic area (62% mm-min vs. 50% mm-min, p = 0.042). Amlodipine reduced ischemia over the 24 h with the intrinsic circadian pattern maintained. In addition, diary data showed a significant reduction in angina (70% for amlodipine vs. 44% for placebo, p = 0.0001) and in nitroglycerin consumption (67% vs. 22%, respectively, p = 0.0006). Amlodipine and placebo demonstrated similar safety profiles (adverse events 17.3% for amlodipine and 13.3% for placebo; discontinuation rates due to adverse events were 2% vs. 4.4%, respectively). CONCLUSIONS: Once-daily amlodipine, when added to background treatment, significantly reduced both symptomatic and asymptomatic ischemic events over 24 h in patients with chronic stable angina.

Favorable effects of flecainide in transvenous internal cardioversion of atrial fibrillation.

OBJECTIVES: The aim of the study was to evaluate the effects of intravenous (IV) flecainide on defibrillation energy requirements in patients treated with low-energy internal atrial cardioversion. BACKGROUND: Internal cardioversion of atrial fibrillation is becoming a more widely accepted therapy for acute episode termination and for implantable atrial defibrillators. METHODS: Twenty-four patients with atrial fibrillation (19 persistent, 5 paroxysmal) underwent elective transvenous cardioversion according to a step-up protocol. After successful conversion in a drug-free state, atrial fibrillation was induced by atrial pacing; IV flecainide (2 mg/kg) was administered and a second threshold was determined. In patients in whom cardioversion in a drug-free state failed notwithstanding a 400- to 550-V shock, a threshold determination was attempted after flecainide. RESULTS: Chronic persistent atrial fibrillation was converted in 13/19 (68%) patients at baseline and in 16/19 (84%) patients after flecainide. Paroxysmal atrial fibrillation was successfully cardioverted in all the patients. A favorable effect of flecainide was observed either in chronic persistent atrial fibrillation (13 patients) or in paroxysmal atrial fibrillation (5 patients) with significant reductions in energy requirements for effective defibrillation (persistent atrial fibrillation: 4.42+/-1.37 to 3.50+/-1.51 J, p < 0.005; paroxysmal atrial fibrillation: 1.68+/-0.29 to 0.84+/-0.26 J, p < 0.01). In 14 patients not requiring sedation, the favorable effects of flecainide on defibrillation threshold resulted in a significant reduction in the scores of shock-induced discomfort (3.71+/-0.83 vs. 4.29+/-0.61, p < 0.005). No ventricular proarrhythmia was observed for any shock. CONCLUSIONS: Intravenous flecainide reduces atrial defibrillation threshold in patients treated with low-energy internal atrial cardioversion. This reduction in threshold results in lower shock-induced discomfort. Additionally, flecainide may increase the procedure success rate in patients with chronic persistent atrial fibrillation.

Serum free light-chain responses after high-dose intravenous melphalan and autologous stem cell transplantation for AL (primary) amyloidosis.

Serum free light-chain (FLC) concentrations were measured by a sensitive nephelometric immunoassay in 66 patients with AL amyloidosis before and after treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). At 1 year after HDM/SCT, 27 patients (41%) achieved a complete hematologic response (CR), that is, disappearance of the monoclonal gammopathy previously evident by immunofixation electrophoresis (IFE) in serum and urine and of plasma cell clonality in the bone marrow. Abnormally elevated FLC levels became normal in 27 patients (41%), and decreased by >90% in 37 (56%). Average improvements in FLC were 94% for patients who achieved a CR and 72% for those who did not (P=0.0001). However, a reduction in FLC of >90% was associated with a similar high likelihood of clinical improvement and prolonged survival, whether or not patients achieved a CR. While CR, as defined by standard criteria, is a more stringent indicator of hematologic response than are decreases in abnormally elevated FLC levels per se, these measures of hematologic response are complementary, and decreases in FLC are more readily detected early after treatment than are the changes in IFE and marrow studies required to determine CR.

Effects of moderate salt restriction on intralymphocytic sodium and pressor response to stress in borderline hypertension.

The effects of a moderate dietary salt restriction on intralymphocytic sodium content and pressor response to stress (mental arithmetic, handgrip, and bicycle exercise) were tested in 25 young subjects with borderline hypertension. The study was performed by a randomized, cross-over, within-patient, experimental design. Diet did not significantly reduce blood pressure at rest but did so significantly in both systolic and diastolic blood pressure during stress and exercise. Variations in diastolic blood pressure induced by stimulation correlated significantly with intralymphocytic sodium content both before and during low-salt diet whereas no correlation was found in the case of systolic blood pressure and heart rate variations. These findings suggest that in young subjects with borderline hypertension, sodium homeostasis and blood pressure regulation are somehow interrelated, and that a moderate dietary salt restriction reduces both intralymphocytic sodium content and pressor response to adrenergic stimulation. This could be useful in preventing the development of sustained hypertension.

Converting enzyme inhibition and heart failure.

Angiotensin converting enzyme inhibitors are known to improve cardiac performance in patients with severe heart failure, and are probably safer and more effective than other vasodilators. Less is known about their effects in mild and moderate heart failure. Results at one year are presented about an ongoing double-blind, placebo-controlled parallel-group study on 94 outpatients in New York Heart Association functional class II and III. After a three-week period during which appropriate doses of digoxin were administered and a stable response to exercise was obtained, diuretic therapy was withdrawn if in use and captopril or placebo treatment was assigned randomly. The assessment of patients was performed by symptom history, clinical examination, New York Heart Association functional class, chest radiograph, 12-lead electrocardiogram, 24-hour Holter monitoring, M-mode echocardiography, and bicycle exercise at the time of random selection and at specified times during a two-year follow-up. Preliminary data after one year suggest that patients receiving placebo may have a greater tendency to need diuretics and may improve New York Heart Association functional class less often than those receiving captopril. No statistically significant treatment differences were found for the noninvasive test results. Detailed analysis suggests that treatment with an angiotensin converting enzyme inhibitor may be more advantageous than that with placebo for some groups of patients. Investigations are under way to determine which patients might benefit most from angiotensin converting enzyme inhibitors.

Clinical results of the Verapamil inHypertension and Atherosclerosis Study. VHAS Investigators.

OBJECTIVE: The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. DESIGN: After a 3-week placebo run-in period, 1414 hypertensive patients [692 men and 722 women, aged 53.2 +/- 7 years, blood pressure 168.9 +/- 10.5/ 102.2 +/- 5.0 mmHg (means +/- SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. RESULTS: After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P < 0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to < or = 90 mmHg or to < or = 95 mmHg with a > or = 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P < 0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P < 0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K < 3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P < 0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). CONCLUSION: Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.

The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness.

BACKGROUND: It is unclear whether the carotid intima-media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principal results of the ultrasound substudy of the randomized, prospective, controlled, Verapamil in Hypertension and Atherosclerosis Study (VHAS). DESIGN AND METHODS: In 498 hypertensive patients in eight Italian centres, randomized to either verapamil (240 mg once a day) or chlorthalidone (25 mg once a day), a B-mode ultrasound scan was performed according to a standardized procedure at baseline and after 3, 12, 24, 36 and 48 months of treatment. The maximum intima-media thicknesses of the far walls of common, bifurcation and internal carotid arteries were measured bilaterally, and the following indices calculated: the mean thickness at the six measured sites, the mean thickness at the common and bifurcation sites and the single maximum thickness. The primary endpoint for treatment efficacy was the slope of the change over 4 years (rate of change, mm/year), corrected by using the initial mean over the six sites (baseline + 3 months) as a covariate (mm/year per mm). The patients were also classified into three strata according to their baseline single maximum thickness: those with normal carotid arteries (single maximum ( 1 mm), those with thickened carotid arteries (single maximum > 1 and < or = 1.5 mm and those with carotid plaques (single maximum > 1.5 mm). RESULTS: Among the 456 patients with satisfactory baseline ultrasound readings, 33% were classified with normal carotid arteries, 27% with thickened carotid arteries and 40% with plaques. In the intention-to-treat population (377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years), the rate of change in the mean thickness at the six sites measured was rather small (0.015 mm/year), but significantly (P < 0.05) smaller in patients with plaques (0.003 mm/year) than in patients with thickened or with normal carotids (0.023 and 0.025 mm/year, respectively). When related to initial values, the rate of change in the mean thickness at the six sites had a negative slope (-0.059 mm/year per mm, P < 0.01). Although rates of change in the carotid intima-media thickness in unstratified patients were not different in those treated with verapamil or with chlorthalidone, when changes in the mean thickness of six sites were related to the initial value, the slope of this relationship was significantly different in the two treatment groups (verapamil -0.082 versus chlorthalidone -0.037 mm/year per mm, P < 0.02). The blood pressure-lowering effect of the two randomized treatments was similar. Taking fatal and nonfatal, major and minor cardiovascular events together, there were 19 events in the verapamil group and 35 in the chlorthalidone group, with a significantly (P < 0.01) greater incidence in patients with plaques, and among patients with plaques in those who were randomized to chlorthalidone (P < 0.05). CONCLUSIONS: In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions. Changes in the carotid intima-media thickness were small in both groups, and the differences between the changes under the two treatments were consequently small, but the observation that these small differences in carotid wall changes were paralleled by differences in the incidence of cardiovascular events (better intima-media thickness regression with verapamil paralleled by a lower cardiovascular event rate) suggests that even small effects on carotid plaques may have clinical and prognostic relevance.

Prevalence of episodes of ST-segment depression among mild-to-moderate hypertensive patients in northern Italy: the Cardioscreening Study.

OBJECTIVES: To assess the prevalence of episodes of ST-segment depression in a population of consecutive patients with mild-to-moderate essential hypertension who are free of clinical signs of coronary artery disease. METHODS: The study involved 28 Italian centers that enrolled 414 hypertensive patients (aged 50-70 years; diastolic blood pressure > or = 95-115 mmHg or systolic blood pressure > or = 150-220 mmHg, or both, 10 days after withdrawal of medications). Silent myocardial ischemia was assessed by means of exercise stress testing and 48 h Holter monitoring. An ischemic episode was defined as a horizontal or downward sloping ST-segment depression > or = 100 microV, occurring 80 ms after the J point, and lasting for at least 1 min. RESULTS: Of the 414 patients enrolled, 411 completed the exercise stress test. During the test significant ST-segment depression occurred for 25 patients (6.1%) and all episodes but one were asymptomatic and not associated with arrhythmias. Of the 396 patients for whom we analyzed a 48 h Holter recording, 43 (10.9%) had at least one episode of ST-segment depression and seven of these had also had one during the exercise stress test The median number of episodes per patient was five (range 1-19), median duration was 9 min (range 1-20 min), and the mean amplitude of the ST-segment depression was 190 +/- 180 microV. None of these episodes was associated with symptoms and all of them occurred under resting condition. Patients with (n = 61) and without (n = 335) ST-segment depression during Holter monitoring or exercise stress testing had similar ages (59 +/- 6 versus 58 +/- 6 years) and did not differ for tobacco smoking, plasma lipid levels, blood pressure values and prevalence of echocardiographic left ventricular hypertrophy (57% of patients had left ventricular mass indexes > or = 134 g/m2 for men and > or = 110 g/m2 for women in both groups). Women had a higher prevalence of ST-segment depression than did men during Holter monitoring [32 of 183 (17.5%) versus 11 of 213 (5.2%)], whereas the prevalences of ischemia during the exercise stress test were similar. Female sex was the only significant factor associated with the occurrence of silent myocardial ischemia [odds ratio 2.56 (95% confidence interval 1.40-4.71)]. CONCLUSIONS: Our results show that 15% of patients with mild-to-moderate hypertension, who are free of clinical signs of coronary artery disease, experience episodes of ST-segment depression during Holter monitoring or exercise stress testing. Most of these episodes are asymptomatic and are not associated with the severity of hypertension, the presence of left ventricular hypertrophy, and other risk factors for coronary artery disease. Episodes of ST-segment depression are more common for women than they are for men, particularly during Holter monitoring. The early detection of silent myocardial ischemia by Holter monitoring or by the exercise stress test might be useful for the identification of hypertensive patients who should be investigated further and administered a more specific treatment.

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis.

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universität München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.

Dipyridamole technetium-99m-2-methoxy isobutyl isonitrile tomoscintigraphic imaging for identifying diseased coronary vessels: comparison with thallium-201 stress-rest study.

A same-day double injection protocol employing 99mTc-methoxyisobutyl isonitrile (MIBI) and myocardial single-photon emission computed tomography (SPECT) for detecting coronary artery disease (CAD) was assessed in 30 patients. SPECT was performed 1 hr after a first injection (250 MBq) of 99mTc-MIBI, given after 0.56 mg/kg dipyridamole (DPD) infusion. Patients were then reinjected at rest (750 MBq) and were reimaged 1 hr later. Within 1 wk, all patients underwent a complete stress-rest SPECT thallium study. Of the 330 myocardial segments evaluated, 25 were judged ischemic by both techniques, while persistent defects were demonstrated in 50 and in 47 with 99mTc-MIBI and 201TI, respectively. Six regions were considered for diseased vessels identification. Sensitivity and specificity for CAD were 100% and 75%, respectively, for both 201TI and 99mTc-MIBI. Sensitivity for identification of diseased vessels by 201TI was 68% for LAD, 89% for RCA, and 80% for LCX as opposed to 75%, 89% and 80%, respectively, by 99mTc-MIBI. Specificity was 93% in both cases for LAD, 73% and 63% for RCA, and 53% and 46% for LCX.

Effects of the early administration of zofenopril on onset and progression of congestive heart failure in patients with anterior wall acute myocardial infarction. The SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation.

Chronic congestive heart failure (CHF) is a common disease responsible for a high mortality and morbidity whose clinical course can be improved by angiotensin-converting-enzyme (ACE) inhibition. However, limited data are available on the effects of ACE inhibitors on the onset and progression of CHF in patients with acute myocardial infarction (AMI). The present study was performed as a substudy of the Survival of Myocardial Infarction Long-term Evaluation trial and involved 1,146 patients with anterior wall AMI not undergoing thrombolysis with the exclusion of patients with prior history or clinical signs of CHF on admission. Patients were randomly allocated to treatment with zofenopril (7.5 to 30 mg twice daily) or placebo for a cumulative period of 6 weeks. The prevalence of CHF, either mild to moderate or severe, has been the main objective and has been evaluated 6 weeks and 1 year after AMI. The overall prevalence of CHF was not reduced by zofenopril after both 6 weeks and 12 months. Conversely the prevalence of severe CHF (1.6% vs 2.6%: risk reduction 55.5%; 95% confidence interval 9 to 63; p = 0.0325) and the combined occurrence of death or severe CHF (4.8% vs 8.2%: risk reduction 59%; 95% confidence interval 11 to 71; p = 0.024) were reduced after 6 weeks of treatment with zofenopril. Moreover, the percentage of patients experiencing a deterioration to severe CHF after 1 year was significantly reduced with zofenopril (11.0% vs 24.3%; p = 0.001). In conclusion, the early administration of zofenopril to patients with AMI attenuates the progression of the clinical symptoms of CHF and its clinical consequences, suggesting that ACE inhibitors should be regarded as a suitable strategy for the prevention and treatment of CHF in patients with AMI.

Early treatment of acute myocardial infarction with angiotensin-converting enzyme inhibition: safety considerations. SMILE pilot study working party.

The use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (AMI) is based on their capacity to limit ventricular enlargement and dysfunction. To date, the safety profile of administration of ACE inhibitors early in the course of AMI has not been established. In-hospital and long-term consequences of treatment with the ACE inhibitor zofenopril initiated within 24 hours of the onset of symptoms were compared with those of standard treatment in an open-label trial involving 204 patients with AMI who were not undergoing thrombolytic treatment. Zofenopril promptly blocked ACE activation. Blockade was almost complete (91 +/- 6%) after 72 hours and paralleled decreases in systolic blood pressure. Systemic blood pressure was acutely reduced by zofenopril, and severe but reversible hypotension occurred in 15% of hospitalized patients and in 3% of those treated over the long term. No adverse clinical or biochemical events were reported during the course of zofenopril therapy. Overall cardiovascular mortality was not significantly reduced by early zofenopril compared with placebo therapy (7.8% vs 10.7% [difference not significant]). The inhospital incidence of acute left ventricular failure and ventricular arrhythmias decreased by 63% and 39%, respectively, among zofenopril-treated patients, who also reported fewer anginal episodes both acutely (68% reduction) and over the long term (56% reduction) and did not require as much drug treatment (i.e., diuretics, digoxin, and/or anti-ischemic agents) during the follow-up phase. Left ventricular size decreased and ejection fraction (EF) increased in patients who received zofenopril, and the improvement was greater among patients with poorer ventricular function (EF less than 40%). Early administration of ACE inhibitors may therefore constitute a safe form of therapy for patients with AMI, particularly when the event is complicated by clinical signs or evidence of ventricular dysfunction.

Results of coronary stenting for unstable versus stable angina pectoris.

Coronary artery stenting has been shown to improve the short- and long-term results of coronary angioplasty in mainly stable patients with 1-vessel disease, but it is uncertain whether its use in an unstable clinical setting may be safe and useful. To evaluate the stenting efficacy in patients with unstable angina, we retrospectively examined our experience with the Palmaz-Schatz balloon expandable stent in 231 consecutive patients. Patients were divided into 2 groups on the basis of symptoms at the time of stent implantation: group U (132 patients) had unstable angina, and group S (99 patients) had stable angina. After stent insertion, patients were treated with anticoagulant or combined antiplatelet therapy. Baseline characteristics of the 2 groups were comparable with the exception of age (higher in the unstable group) and angiographic characteristics of the target lesions (more unfavorable in unstable patients). In both groups, coronary stenting presented a high procedural success rate. Major in-hospital complications occurred in 9 unstable (6.8%) and in 2 stable (2%) patients (p = NS) and were mainly related to subacute stent thrombosis. In both groups, subacute stent thrombosis mostly occurred in patients treated with anticoagulant therapy (7 of 9 unstable patients, 2 of 2 stable patients). At 6-month follow-up, unstable and stable patients had a similar incidence of death (0%), Q-wave myocardial infarction (0%), and need of coronary artery bypass graft (3.2% vs 4%, p = NS), but coronary angioplasty repetition (4.8% vs 14%, p = 0.027) and target vessel revascularization (6.3% vs 17%, p = 0.019) rates were lower in the unstable group. In conclusion, stent insertion increases the short- and midterm coronary angioplasty effectiveness in unstable angina, making it possible to achieve outcomes quite comparable to stable angina. Compared with conventional anticoagulant regimen, combined antiplatelet therapy after placement of coronary stents seems to reduce the incidence of subacute thrombosis also in this clinical setting.

Usefulness of nicorandil in congestive heart failure.

Rest and exercise hemodynamic and hormonal effects of nicorandil, a nicotinamide-nitrate vasodilator, were assessed in 9 patients with New York Heart Association class II or III congestive heart failure (CHF) and left ventricular ejection fraction less than or equal to 40%. Single oral doses of placebo and 40 and 60 mg of nicorandil were given in a double-blind, randomized trial. Hemodynamic measurements were assessed at rest, up to 8 hours after dose and at peak exercise performed on an upright cycloergometer 1 hour after the dose. Forearm blood flow and venous capacitance were measured by plethysmography 45 minutes after dose. Plasma noradrenaline and plasma renin activity were assessed 1 hour and 2 hours after dose, respectively. Data were analyzed by analysis of variance. Peak effects were observed between 30 and 60 minutes after dose. Mean blood pressure decreased from 86 +/- 7 mm Hg after placebo to 78 +/- 7 mm Hg after 40 mg (p less than 0.05) and to 78 +/- 7 mm Hg after 60 mg (p less than 0.05) of nicorandil. Mean pulmonary artery pressure decreased from 24 +/- 11 to 15 +/- 17 mm Hg (p less than 0.05) and to 17 +/- 7 mm Hg (p less than 0.05) and mean pulmonary wedge pressure decreased from 15 +/- 8 to 9 +/- 4 mm Hg (p less than 0.05) and to 10 +/- 5 mm Hg (p less than 0.05). The changes were significant up to 6 to 8 hours after both doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of loading oral flecainide for converting recent-onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension.

Sixty-two patients with recent-onset (less than or equal to 1 week) atrial fibrillation (New York Heart Association functional class 1 and 2) were randomized in a single-blind study to 1 of the following treatment groups: (1) flecainide (300 mg) as a single oral loading dose; or (2) amiodarone (5 mg/kg) as an intravenous bolus, followed by 1.8 g/day; or (3) placebo for the first 8 hours. Twenty-four-hour Holter recording was performed, and conversion to sinus rhythm at 3, 8, 12 and 24 hours was considered as the criterion of efficacy. Conversion to sinus rhythm was achieved within 8 hours (placebo-controlled period) in 20 of 22 patients (91%) treated with flecainide, 7 of 19 (37%) treated with amiodarone (p less than 0.001 vs flecainide), and 10 of 21 (48%) treated with placebo (p less than 0.01 vs flecainide). Resumption of sinus rhythm within 24 hours occurred in 21 of 22 patients (95%) with flecainide and in 17 of 19 (89%) with amiodarone (p = not significant). Mean conversion times were shorter for flecainide (190 +/- 147 minutes) than for amiodarone (705 +/- 418; p less than 0.001). No major side effects occurred. At Holter monitoring, a pause of 9.3 seconds was observed in 1 asymptomatic patient treated with flecainide. Phases of atrial flutter with a ventricular rate less than or equal to 150 beats/min were detected before sinus conversion in 1 patient receiving placebo and in 2 receiving flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)