Magnetoliposomes as model for signal transmission.

Liposomes containing magnetic nanoparticles (magnetoliposomes) have been extensively explored for targeted drug delivery. However, the magnetic effect of nanoparticles movement is also an attractive choice for the conduction of signals in communication systems at the nanoscale level because of the simple manipulation and efficient control. Here, we propose a model for the transmission of electrical and luminous signals taking advantage of magnetophoresis. The study involved three steps. Firstly, magnetite was synthesized and incorporated into fusogenic large unilamellar vesicles (LUVs) previously associated with a fluorescent label. Secondly, the fluorescent magnetite-containing LUVs delivered their contents to the giant unilamellar vesicles (GUVs), which were corroborated by magnetophoresis and fluorescence microscopy. In the third step, magnetophoresis of magnetic vesicles was used for the conduction of the luminous signal from a capillary to an optical fibre connected to a fluorescence detector. Also, the magnetophoresis effects on subsequent transmission of the electrochemical signal were demonstrated using magnetite associated with CTAB micelles modified with ferrocene. We glimpse that these magnetic supramolecular systems can be applied in micro- and nanoscale communication systems.

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial.

BACKGROUND: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. OBJECTIVE: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. PATIENTS AND METHODS: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. RESULTS: The primary efficacy endpoint of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischemic events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). CONCLUSIONS: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemic events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.

Peroxisomes exist in growth cones and move anterogradely and retrogradely in neurites of PC12D cells.

Localization and movement of peroxisomes have been investigated in neurites of a subline of PC12 pheochromocytoma cells (PC12D cells). The cells were transfected with a construct encoding the green fluorescent protein and bearing the C-terminal peroxisomal targeting signal 1 SKL motif (-Ser-Lys-Leu-COOH). Peroxisomes were detected as green punctate fluorescent signals. Many peroxisomes were observed in neurites of PC12D cells, especially in neural terminal-like structures, growth cones, varicosities, and branch points. Growth cones containing many peroxisomes were active, since they extended several long filopodias. Existence of peroxisomes in growth cones and neuronal terminal-like structures suggests that peroxisomes might have some role in neuronal extension and nerve terminal functioning. Peroxisomal motility was analyzed by time-lapse imaging using a fluorescence microscope at 25 degrees C. Peroxisomes were transported bidirectionally in neurites, i.e., through anterograde and retrograde transport. This result suggests that peroxisomes move to growth cones and neural terminals from the PC12D cell body, play some role in these parts, and go back to cell body.

Heart disease in Friedreich's ataxia: observation of a case for half a century.

A case of Friedreich's ataxia was followed for 47 years, beginning in 1930; this patient had an abnormal electrocardiogram (flat or inverted T waves in leads II and III with prolonged QT interval) from the very beginning of the onset of neurological symptoms. Cardiac and neurological disturbances progressed slowly but steadily, and the patient died suddenly at the age of 67. The autopsy revealed typical findings of Friedreich's ataxia and hypertrophic cardiomyopathy with thickened left ventricular wall and myocardial fiber disarray. To the authors' knowledge, this is the longest continuous follow-up study of Friedreich's ataxia, and it will provide invaluable information on the natural history and development of the cardiac and neurological disorders in this condition.

Ethnicity and long-term outcome after an acute coronary event. Multicenter Myocardial Ischemia Research Group.

BACKGROUND: The role of ethnicity on the long-term outcome after myocardial infarction is not fully understood. METHODS AND RESULTS: We analyzed the data from the Multicenter Study of Myocardial Ischemia in North America and Japan. We enrolled patients after acute myocardial infarction (MI) or unstable angina, with follow-up for 6 to 43 months, an average of 26 months. Among patients enrolled, there were 627 white, 158 black, and 109 Asian patients. Unadjusted cardiac events (cardiac death or nonfatal MI) were more frequent in black patients than in the other 2 ethnic groups (12% in blacks, 6. 4% in whites, 4.0% in Asians, P =.022). Although insulin-dependent diabetes, history of hypertension, and female sex were most frequent in black subjects, coronary angioplasty and thrombolysis at index event were done equally. After adjusting for several covariates, Cox analyses revealed that the black group was significantly associated with cardiac events (hazard ratio 6.5, P =.002). Subgroup analyses showed that the event rate among patients who had a higher educational level (6.1% in whites, 5.9% in blacks, and 7.0% in Asian, P =.94) or who were in a professional occupational class (5.7% in whites, 4.0% in blacks, and 4.8% in Asians, P = 1.0) was not different among the 3 ethnic groups. CONCLUSIONS: Blacks have an increased rate of cardiac events after MI, and a lower socioeconomic status may contribute to the adverse outcome in this ethnic group.

Long-term nitrate use may be deleterious in ischemic heart disease: A study using the databases from two large-scale postinfarction studies. Multicenter Myocardial Ischemia Research Group.

BACKGROUND: Secondary coronary prevention studies have generally focused on specific medications, often to the exclusion of commonly used therapies. To date, long-term nitrate use has not been investigated in large-scale clinical trials. METHODS AND RESULTS: We examined the relation between long-acting nitrates given during the chronic phase of the disease and the outcome. We analyzed data prospectively acquired in a large, observational study involving 1042 patients enrolled for the Multicenter Study of Myocardial Ischemia (MSMI) in North America, Israel, and Japan as well as 1779 patients enrolled for the Multicenter Diltiazem Post Infarction Trial (MDPIT). The Cox analyses with all the variables retained revealed that nitrates were associated with a significantly increased mortality risk (MSMI: hazard ratio 3.78, P =.011; MDPIT: hazard ratio 1.61, P =.019) in patients who had recovered from an acute coronary event. The analyses with the propensity score method on the MSMI and the MSMI databases also showed that the risk for cardiac death with use of nitrates was increased in most of the 5 subclasses according to the score. CONCLUSION: These analyses raise concern about the potential adverse effects of long-acting nitrate therapy in chronic coronary disease.

From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future.

A progression from viral myocarditis to dilated cardiomyopathy has long been hypothesized, but the actual extent of this progression has been uncertain. However, a causal link between viral myocarditis and dilated cardiomyopathy has become more evident than before with the tremendous developments in the molecular analyses of autopsy and endomyocardial biopsy specimens, new techniques of viral gene amplification, and modern immunology. The persistence of viral RNA in the myocardium beyond 90 days after inoculation, confirmed by the method of polymerase chain reaction, has given us new insights into the pathogenesis of dilated cardiomyopathy. Moreover, new knowledge of T-cell-mediated immune responses in murine viral myocarditis has contributed a great deal to the understanding of the mechanisms of ongoing disease processes. Apoptotic cell death may provide the third concept to explain the pathogenesis of dilated cardiomyopathy, in addition to persistent viral RNA in the heart tissue and an immune system-mediated mechanism. Beneficial effects of alpha1-adrenergic blocking agents, carteolol, verapamil, and ACE inhibitors have been shown clinically and experimentally in the treatment of viral myocarditis and dilated cardiomyopathy. Antiviral agents should be more extensively investigated for clinical use. The rather discouraging results obtained to date with immunosuppressive agents in the treatment of viral myocarditis indicated the importance of sparing neutralizing antibody production, which may be controlled by B cells, and raised the possibility of promising developments in immunomodulating therapy.

Mesangiolytic glomerulopathy in severe congestive heart failure.

To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

Intraoperative ultrasonography versus cholangiography during laparoscopic cholecystectomy: a prospective comparative study.

BACKGROUND: The purpose of this study was to compare the functional utility of intraoperative ultrasonography (IOUS) and cholangiography (IOC) during a laparoscopic cholecystectomy for the treatment of gallstone disease. STUDY DESIGN: A prospective study comparing IOUS and IOC was carried out in 65 patients. Intraoperative ultrasonography was conducted first using a 7.5-MHz linear array probe. After IOUS, IOC was then conducted in all patients. The respective usefulness of IOUS and IOC in the identification of gallstones, detection of hepatobiliary structures, and demonstration of congenital anomalies was then compared. RESULTS: Intraoperative ultrasonography was successful in all 65 patients, and IOC was successful only in 54. The time required for IOUS was significantly shorter (p < 0.0001) than for IOC. Intraoperative ultrasonography imaged the hepatic ducts and their confluence, the common hepatic duct, the common bile duct, and the ampulla of Vater in 97, 100, 97, and 51% of cases, respectively. Intraoperative cholangiography, on the other hand, depicted these structures in 85, 89, 100, and 94% of cases, respectively. Intraoperative ultrasonography demonstrated the cystic duct and its confluence in 94% of cases. Biliary anomalies were identified by IOUS in 12 patients and by IOC in 13. Intraoperative ultrasonography could detect the hilar vascular structures in most patients and visualized anomalies of the hepatic arteries in 5 patients. In this series, 5 patients had choledocholithiasis. The sensitivities, specificities, positive and negative predictive values, and accuracies in identifying these bile duct stones were 80, 98, 80, 98, and 97% by IOUS, and 80, 97, 67, 98, and 95% by IOC, respectively. CONCLUSIONS: Intraoperative ultrasonography is superior to cholangiography with respect to its safety, shorter examination period, and ease of administration in all patients. In addition, IOUS is also better for identifying subtle anatomic detail. Intraoperative ultrasonography compares favorably with IOC in terms of utility in exploring bile ducts for stones. Intraoperative ultrasonography is an effective procedure for biliary exploration during a laparoscopic cholecystectomy.

A prospective, randomized, double-blind multicenter trial of a single bolus injection of the novel modified t-PA E6010 in the treatment of acute myocardial infarction: comparison with native t-PA. E6010 Study Group.

OBJECTIVES: This prospective, randomized, double-blind multicenter trial evaluated the efficacy and safety of a single bolus injection of the novel modified tissue-type plasminogen activator (t-PA) E6010 in the treatment of acute myocardial infarction compared with that of native t-PA. BACKGROUND: E6010 is a novel modified t-PA with a prolonged half-life (t1/2 alpha > or = 23 min) compared with native t-PA (t1/2 alpha = 4 min). E6010 can be administered in patients as a single intravenous bolus injection, and early recanalization can be expected. METHODS: The efficacy of E6010 was compared with that of native t-PA in 199 patients with acute myocardial infarction who were treated within 6 h of onset in a prospective, randomized, double-blind multicenter trial. Patients were given either 0.22 mg/kg body weight of E6010 intravenously over 2 min or native t-PA (tisokinase) 28.8 mg or 14.4 million IU (10% of the total dose over 1 to 2 min, the remainder infused over 60 min). RESULTS: The primary end point was the recanalization rate of the infarct-related coronary artery at 60 min after the start of treatment. Time to reperfusion was shorter in the E6010 group than in the native t-PA group. Thrombolysis in Myocardial Infarction flow grade 2 or 3 recanalization at 15, 30, 45 and 60 min after administration was observed in 37%, 62%, 74% and 79% (95% confidence interval [CI] 70% to 87%) of the E6010-treated patients and in 14%, 32%, 50% and 65% (95% CI 55% to 74%) of native t-PA-treated patients, respectively (p = 0.032 at 60 min). CONCLUSIONS: The present study indicates that, compared with native t-PA, a single bolus injection of E6010 over 2 min produces a higher rate of early recanalization of the infarct-related coronary artery without fatal bleeding complications.

Determining the optimum dose for the intravenous administration of nicardipine in the treatment of acute heart failure--a multicenter study. The Nicardipine Heart Failure Study Group.

Nicardipine is a potent arteriolar vasodilator with a negligible negative inotropic effect. Although intravenous administration of this drug has been reported to be effective in the treatment of heart failure, the optimal dose by this route is not clear. This study was designed to determine the optimum dose for the intravenous infusion of nicardipine in the treatment of heart failure. In Trial 1, nicardipine was administered intravenously at a dose of 0.5 microgram/kg per min to 14 patients with acute heart failure. The dose was increased to 1.0 microgram/kg per min in 13 cases with marked improvement at 2 h. In Trial 2, nicardipine was administered in a double-blind manner to 53 patients at 3 different rates of infusion for 2 h: 1.0 (Group 1, n = 19), 2.0 (Group 2, n = 15), and 3.0 (Group 3, n = 19) micrograms/kg per min. Neither heart rate nor mean right atrial pressure changed in any of the 3 groups. Favorable hemodynamic effects were evident in all groups beginning 30 min after the start of infusion, with an increase in cardiac index (control vs 2 h after infusion, L/min per m2) (Group 1: 2.2 +/- 0.4 vs 3.1 +/- 0.8, Group 2: 2.2 +/- 0.4 vs 2.9 +/- 0.5, Group 3: 2.3 +/- 0.3 vs 3.1 +/- 0.7, all p < 0.01 compared to the control) and a decrease in diastolic pulmonary artery pressure (Group 1: 26 +/- 10 vs 19 +/- 7, Group 2: 27 +/- 10 vs 20 +/- 8, Group 3: 26 +/- 7 vs 18 +/- 5 mmHg, all p < 0.01). The decrease in systolic pressure was greatest in Group 3 (Group 1: 141 +/- 31 vs 119 +/- 18, Group 2: 149 +/- 25 vs 118 +/- 17, Group 3; 147 +/- 27 vs 107 +/- 14 mmHg, all p < 0.01 compared to control, and p < 0.05 between Groups 1 and 3). The intravenous drip infusion of nicardipine is effective in the treatment of heart failure by inducing an increase in cardiac output and a decrease in pulmonary artery wedge pressure. The optimal dose in this study was 1.0 microgram/kg per min.

Angina pectoris after recovery from an acute coronary event--the role of psychological factors in Japanese vs North American patients.

To determine whether specific psychological characteristics are associated with angina pectoris in clinically stable patients 1 to 6 months after recovery from an acute coronary event, a battery of tests was administered to 92 Japanese and 646 North American participants (22% females) in the Multicenter Study of Myocardial Ischemia. Of these 738 patients, 541 had originally suffered acute myocardial infarction, 188 had unstable angina, and 9 were admitted for other acute ischemic events. At the time of enrollment, an average of 2.7 months after the index event, 205 patients reported having had anginal symptoms during the preceding months. Compared to those who did not report angina, these patients scored higher on a modified Autonomic Perception Questionnaire (p = 0.04) and lower on the Internal Health Locus of Control Scale (p = 0.004). These differences were generalized across the Japanese and North American cohorts. These results indicate that in these patients, angina pectoris was associated with an increased awareness of a wide range of physical symptoms and a decreased sense of personal control over one's own health and prognosis.

Fatal diffuse alveolar damage from bird fanciers' lung.

A 68-year-old man, who had continuing exposure to budgerigars, developed fatal acute respiratory failure following years of slowly progressive pulmonary deterioration. His lung function was characterized first by mild airflow obstruction and later by progressive loss of lung volume. Computed tomography showed progressive development of pulmonary fibrosis and honeycombing. His serum disclosed precipitins to pigeon antigen. During his final illness his chest radiograph showed widespread patchy consolidation. At autopsy, his lungs revealed left lower lobe bronchopneumonia, fibrosis and honeycombing at the bases and widespread evidence of diffuse alveolar damage with organized exudate in some alveoli. To our knowledge, this is the second reported fatality due to acute alveolar injury in bird fanciers' lung.

Differential effects of beta-blockers in patients after recovery from myocardial infarction and after recovery from unstable angina. Multicenter Myocardial Ischemia Research Group.

We examined the effect of beta-blockers on outcome in patients enrolled in the Multicenter Study of Myocardial Ischemia. We started prospective enrollment of patients after an acute coronary event (acute myocardial infarction [MI] or unstable angina) in North America, Israel, and Japan from mid-1988, and followed-up the 1042 patients for 6-43 months (average, 26 months); 47.2% of the patients were receiving beta-blockers at baseline. Overall, beta-blockers were associated with neutral effects on the chronic outcome: the cardiac event (cardiac death or recurrent nonfatal MI) rate was 6.8% for patients on beta-blockers and 7.5% for those who were not on beta-blockers (P = 0.72). However, a significant interaction (P = 0.018) was found between event type and the use of beta-blockers in regard to the cardiac event rate. That is, beta-blockers were associated with a lower risk of the cardiac event for patients whose index event type was MI (risk ratio, 0.59) in contrast to those whose index event was unstable angina (risk ratio, 1.92). The chronic use of beta-blockers in patients recovered from unstable angina may be associated with an increase in risk.

Patients' expectations of information provided at cancer hospitals in Japan.

In order to survey patients' views on disease and treatment information that should be provided at hospitals, an anonymous self-administered questionnaire was distributed to patients at Aichi Cancer Center Hospital in 1995. All eligible first-visit outpatients (97 persons), randomly selected revisit outpatients (99 persons; about one in ten refused), and all except six eligible inpatients in good condition at discharge (97 persons) responded. Out of 293 patients (115 males, 174 females and 4 unspecified), 74% answered that they wanted to be informed of their diagnosis irrespective of circumstances, 20% answered that they would want to be informed only in certain circumstances, and 2% did not want to be informed at all. There were no significant differences in response among the three sources of patients. Inpatients wanted more (81%) to be explained about recommended therapy than either first-visit outpatients (67%) or revisit outpatients (67%). The majority considered that about a 30-minute explanation was needed using pamphlet-like written materials or video. When asked what information was needed when choosing a cancer hospital, 71% specified information on the specialty of the hospital, 57% the content of the care provided, 23% the name and specialty of the doctors, 20% the waiting period before scheduled admission, 13% the average admission period, 11% the number of patients with the same disease, 10% the waiting time at the outpatient clinic, 6% the meal menu, and 4% the number of private wards. Forty-three percent wanted an information service covering all hospitals in the region through an information center. The results revealed that patients at this cancer hospital required information on their disease, treatment, and hospital specialty.

Effect of ebselen on bovine and rat nitric oxide synthase activity is modified by thiols.

The inhibition of nitric oxide synthase (NOS) by ebselen, 2-phenyl-1,2-benzisoselenazole-3(2H)-one, was reversed by the addition of 10(-5) M dithiothreitol, suggesting that ebselen reacts with a critical thiol group of NOS in the inhibitory mechanism. In the presence of 10(-4) to 10(-3)M dithiothreitol, ebselen dose-dependently enhanced NOS activity, implicating another interaction of ebselen with NOS under these conditions. Thus, the effect of ebselen on the NOS activity is modified by thiols.

Comparison between Japan and North America in the post-hospital course after recovery from an acute coronary event.

We compared the post-hospital prognosis after an acute coronary event (acute myocardial infarction and unstable angina) in 106 patients in Japan vs. 789 patients in North America who were prospectively enrolled in the Multicenter Study of Myocardial Ischemia and were followed-up for an average of 26 months per patients. Risk factors more frequent in Japan were older age, males and smoking at enrollment, but the rest of many risk factors were similar. After adjusting for differences in clinical and medication variables, Cox analyses indicated patients in North America had a significantly greater risk of experiencing a primary end-point (cardiac death, non-fatal myocardial infarction or unstable angina) than patients in Japan (hazard ratio [North America:Japan] = 3.1, P = 0.003). There was a non-significant trend in the restricted end-points (cardiac death or non-fatal myocardial infarction) with North America having more frequent events than Japan (hazard ratio = 2.2, P = 0.12). The long-term outcome after recovery from an acute coronary event is more favorable in Japan than in North America, mostly due to a reduction in subsequent hospitalization for unstable angina. The reason for these findings cannot be explained by differences in the measured risk factors or medications.

Liver specific kynurenine(alanine):glyoxylate aminotransferase was expressed in kidney cell line.

Kynurenine (Alanine); glyoxylate aminotransferase (AGT) expression plasmid in the COS-7 was constructed. pGV-C was used as a expression vector which contains SV-40 promoter and enhancer. pGV-C and human AGT clone, H1-2, were digested by Hind III/Sma I separately. The AGT fragment was inserted into the digested pGV-C large fragment, The constructed plasmid was named as pGV-AGT. The constructed plasmid was transfected to COS-7 cultured cell by electroporation. The best electroporation condition was checked.

A SP1 binding site in the GC-rich region is essential for a core promoter activity of the human endothelial nitric oxide synthase gene.

Endothelial nitric oxide synthase (eNOS) is an important oxygenase which catalyzes the conversion of L-arginine to L-citrulline to form nitric oxide (NO), a potent important factor for vasodilation and inhibition of platelet aggregation. We have analyzed characteristics of the promoter region of the human eNOS gene using the transient expression in human endothelial cells of CAT constructs with a series of 5'-deletion mutants. The 5'-flanking region between -116 and -98, which contains a putative consensus sequence for binding of transcription factor Sp1, is essential to direct a basal promoter activity. Gel mobility shift analysis involving anti-Sp1 antibody and competitor DNAs disrupted at the binding site for Sp1 reveals that Sp1 or its closely related protein(s) binds to the consensus sequence located between -104 and -96. These results indicate that the Sp1 site is essential for a core promoter activity of the human eNOS gene.

Long-term prognosis after thrombolytic therapy for acute myocardial infarction.

In order to clarify the relationship between the patency of the infarcted arteries and subsequent long-term prognosis after thrombolytic therapy, we evaluated 116 patients with acute myocardial infarction treated with intracoronary (112 patients) or intravenous (four patients) urokinase. Patients treated with angioplasty after thrombolysis were excluded. The infarcted vessel was recanalized in 52 patients (patent group) and was not in the remaining 64 patients (occluded group). Five-year and 8-year follow up was conducted in 91% and 81% of the patients, respectively. The 1-, 5- and 8-year survival rate for the patent and occluded group was 91.8 and 80.9%, 80.8 and 79.2%, and 75.9 and 75.6%, respectively. The survival rate in the patent group tended to be higher than that in the occluded group up to 4 years. However, after 5 years, both groups showed similar survival rates. Therefore, reopening of the infarcted arteries with thrombolysis was not an independent predictor for late cardiac death (Cox regression analysis).