shu-508 and Thrombosis

Therapeutic application of ultrasound is a promising tool to develop an alternative or additional treatment modality of acute vessel occlusion. It has previously been shown that ultrasound enhances the effect of pharmacologic thrombolytic agents and has a thrombolytic potential in "stand-alone" therapy. The purpose of this study was to determine, whether the presence of the echo contrast agent Levovist further increases the thrombolytic efficacy of ultrasound.. Thrombolytic efficacy of low-frequency (20.5 kHz) continuous-wave ultrasound was evaluated. Fresh human blood clots (age 3-6 h) were sonicated for 10 min at an intensity of 0.35 W/cm2. The thrombolytic effect of ultrasound alone and in combination with rt-PA (3 micrograms/ml) was assessed with and without addition of Levovist (2 mg/ml). Loss in weight of each blood clot was used to measure the extent of thrombolysis. The number of thrombi in each group was between ten and 18. Experiments were carried out in sodium phosphate buffer, at a temperature of 37 degrees C, in a flow system with a flow rate of 15 ml/min.. The use of ultrasound alone showed a significant thrombolytic effect (41.8% weight loss), as compared to a control group (24.2%). The addition of Levovist further increased thrombolysis to 44.7%, which was not significant. However, in combination with rt-PA, ultrasound-mediated thrombolysis could be significantly increased from 65.8% to 74.2%, when Levovist was added (p < 0.05).. These data show that the thrombolytic efficacy of low-frequency continuous-wave ultrasound in combination with rt-PA is augmented in the presence of Levovist.

Topics: Contrast Media; Drug Synergism; Fibrinolytic Agents; Humans; In Vitro Techniques; Polysaccharides; Thrombosis; Treatment Outcome; Ultrasonic Therapy

Although detecting left ventricular thrombus in anterior myocardial infarction is important for the prevention of embolic events, imaging of apical thrombus is often difficult using conventional echocardiography. We examined whether contrast echocardiography improves sensitivity and specificity in detecting thrombus in the left ventricle in comparison with conventional echocardiography alone in patients with anterior myocardial infarction. Participants in this single-center prospective study comprised 392 patients with anterior myocardial infarction admitted between 2000 and 2006. After conventional echocardiography, all patients underwent contrast echocardiography (left ventricular opacification and myocardial contrast echocardiography) during intravenous drip infusion of contrast media at rest. Left ventricular thrombus was diagnosed based on left ventriculography or multidetector-row computed tomography (MDCT). Mural left ventricular thrombus was confirmed by left ventriculography and/or MDCT in 32 of 393 patients (8 %). Sensitivity and specificity of conventional echocardiography alone were 88 % and 96 %, respectively, compared with 100 % each with contrast echocardiography. Among the 32 patients with left ventricular thrombus, 25 patients (78 %) showed no perfusion in the anterior wall on myocardial contrast echocardiography, even with a four-beat interval. In conclusion, contrast echocardiography offers a clinically feasible and useful method for noninvasively evaluating left ventricular thrombus in anterior myocardial infarction.

Topics: Aged; Anterior Wall Myocardial Infarction; Contrast Media; Feasibility Studies; Female; Heart Diseases; Humans; Infusions, Intravenous; Japan; Male; Multidetector Computed Tomography; Polysaccharides; Predictive Value of Tests; Prospective Studies; Thrombosis; Ultrasonography

To select an appropriate treatment regimen, it is essential to accurately characterize the nature of a thrombus. This study prospectively assessed the ability of contrast-enhanced sonography to differentiate between benign and malignant portal vein thrombosis in a population of high-risk patients.. Fifty-five patients (43 men and 12 women; mean age, 66 years; range, 55-83 years) with thrombi of the portal venous system were examined by power Doppler sonography and contrast-enhanced sonography with the intravenous contrast agent SH U 508A (Levovist; Schering AG, Berlin, Germany). Of the thrombi, 40 were characterized as malignant and 15 as benign. Pulsatile flow in the thrombus on power Doppler sonography and positive enhancement of the thrombus on contrast-enhanced sonography were judged as indications of a malignant thrombus. The sensitivity and specificity of both methods in differentiating the nature of the thrombus were evaluated.. The detection of pulsatile flow in a portal vein thrombus as the criterion for diagnosing malignant portal vein thrombus yielded overall sensitivity of 82.5% and specificity of 100%, whereas positive enhancement of the portal vein thrombus itself as a criterion for diagnosing malignancy yielded overall sensitivity and specificity of 100% for each.. Contrast-enhanced sonography can be helpful in discriminating between benign and malignant portal vein thrombi.

Topics: Aged; Aged, 80 and over; Contrast Media; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Polysaccharides; Portal Vein; Prospective Studies; Risk Factors; Sensitivity and Specificity; Thrombosis; Ultrasonography

The evaluation of diagnostic agents or imaging procedures is governed by the same scientific and regulatory rules as that of other medical products. Receiver operating characteristic (ROC) curves, and especially the area under these ROC curves, are indices for the accuracy of a diagnostic test for continuous as well as ordinal data. The methodology of multivariate rank statistics for the nonparametric Behrens-Fisher problem is used to evaluate the accuracy of a diagnostic test in a complex factorial design with repeated measurements. Hypotheses are formulated by means of relative treatment effects and are tested by a multivariate extension of the Mann-Whitney statistic in a heteroscedastic model. The application of this method is demonstrated by the analysis of a data set from a diagnostic clinical trial.

Topics: Biometry; Clinical Trials as Topic; Confidence Intervals; Contrast Media; Diagnostic Tests, Routine; Humans; Models, Statistical; Multivariate Analysis; Polysaccharides; ROC Curve; Statistics, Nonparametric; Thrombosis; Ultrasonography, Doppler, Color

Low flow velocity within the left atrial appendage, as assessed by transoesophageal echocardiography, is a predictor of thromboembolism and of a low success rate of cardioversion of atrial fibrillation. However, the semi-invasive nature does limit its serial application as a screening technique.. We investigated the value of transthoracic second harmonic echocardiography and pulsed Doppler at baseline and after intravenous contrast injection to visualize the left atrial appendage and assess blood flow velocities within its cavity. We studied 51 consecutive patients undergoing transoesophageal echocardiography. After transoesophageal echocardiography, transthoracic second harmonic imaging was performed and the left atrial appendage was visualized in 46 patients. Interpretable pulsed Doppler tracings of left atrial appendage flow were obtained at baseline in 39 patients and in 45 patients during Levovist administration. The correlations between peak emptying velocity of left atrial appendage as measured by transoesophageal echocardiography and by transthoracic standard and contrast-enhanced Doppler were 0.81 and 0.91, respectively. The agreement between transoesophageal echocardiography and transthoracic contrast-enhanced pulsed Doppler echocardiography in classifying left atrial appendage flow velocity patterns was 93%. Left atrial appendage thrombus was detected by transthoracic second harmonic imaging in only one of the eight patients shown by transoesophageal echocardiography to have a thrombus. However, all but one of the patients with left atrial appendage thrombus and/or spontaneous echocardiographic contrast at transoesophageal echocardiography had <30cm/s left atrial appendage flow velocity by transthoracic Doppler.. This study shows that left atrial appendage can be visualized by transthoracic second harmonic imaging and that the flow velocity within its cavity is reliably measured by pulsed Doppler in a substantial fraction of patients. Contrast enhancement improves the feasibility and the accuracy of transthoracic evaluation of left atrial appendage flow velocity. The practical value of these results in predicting thromboembolic risk and success of cardioversion of atrial fibrillation needs to be proved by prospective studies.

Topics: Aged; Atrial Appendage; Blood Flow Velocity; Contrast Media; Echocardiography; Echocardiography, Doppler, Pulsed; Echocardiography, Transesophageal; Female; Heart Diseases; Humans; Male; Polysaccharides; Thrombosis

A case of a successful systemic thrombolysis of an acute middle carotid artery occlusion is reported. The case underlines the role of contrast-enhanced transcranial color-coded duplex sonography as a noninvasive technique for rapid diagnosis of vessel occlusion in acute stroke. The diagnostic potential of transcranial color-coded duplex sonography for indication and monitoring of intravenous systemic thrombolytic therapy is demonstrated.

Topics: Acute Disease; Brain Ischemia; Carotid Artery Diseases; Cerebral Arteries; Cerebrovascular Circulation; Cerebrovascular Disorders; Contrast Media; Fibrinolytic Agents; Follow-Up Studies; Humans; Image Enhancement; Male; Middle Aged; Polysaccharides; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Ultrasonography, Doppler, Duplex; Ultrasonography, Doppler, Transcranial

The combination of ultrasound (US) exposure and ultrasound contrast agent (UCA) further increases the amount of drug-mediated thrombolysis. The aim of this study was to examine the efficacy of the combination of US and UCA on tissue plasminogen activator (tPA) thrombolysis, and the dependence on the microbubble structure. A catheter-type transducer capable of US emission (10 MHz, spatial peak temporal average intensity = 1.02 W/cm2 and peak negative pressure = 0.33 MPa) in the continuous-wave mode was employed. In 28 artificial white thrombi, serial changes in acoustic properties monitored by echography and histopathology during the tPA-mediated thrombolysis were analyzed. The thrombi were assorted to 4 groups; UCA nontreated (Control), sonicated albumin (A)-, SH-U508A (SH)- and dodecafluoropentane emulsion (DDFP)-treated groups. Persistence of microbubble opacification and thrombus weight were also measured. After the sample was suspended in a beaker with tPA (8000U) and 100 mL of saline, the UCA was administered and the mixture exposed to US for 10 min. Weight reduction of the thrombus was greatest in the DDFP Group (-49 +/- 8%), and that in the A Group (-8 +/- 5%) was not significantly different from that in the Control Group (-5 +/- 1%). The persistence of the microbubbles expressed as the decay of the time-intensity curve, was longest in the DDFP Group. The echo intensity of the superficial layer of the thrombus exposed to US was high and weight loss was marked. Multiple cavity formation was observed histopathologically. The stability of the microbubbles was an important factor of the US and UCA enhancement effect on tPA-mediated thrombolysis. This combination therapy has potential for clinical application in patients with thrombotic arterial and venous occlusion and left arterial thrombus.

Topics: Adult; Albumins; Contrast Media; Fluorocarbons; Humans; In Vitro Techniques; Male; Microspheres; Polysaccharides; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Ultrasonography

Contrast-enhanced 2-dimensional echocardiography without color Doppler did not result in complete filling of the left ventricular cavity in 21 patients studied. However, contrast-enhanced color Doppler was very effective and provided complete opacification of the left ventricular cavity in 20 of these 21 patients.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Volume; Contrast Media; Echocardiography; Echocardiography, Doppler, Color; Female; Heart Diseases; Heart Ventricles; Humans; Image Enhancement; Male; Middle Aged; Mitral Valve Insufficiency; Polysaccharides; Stroke Volume; Thrombosis