Yani Liu

Correlation of Carotid Plaque Neovascularization Detected by Using Contrast-enhanced US with Clinical Symptoms

PURPOSE To determine the correlation between the degree of plaque enhancement with contrast agent microbubbles and clinical symptoms in patients with carotid atherosclerotic plaque. MATERIALS AND METHODS The study was approved by the hospital ethical committee, and informed consent was obtained from all patients. One hundred four patients (83 men: mean age, 64 years +/- 9 [standard deviation]; 21 women: mean age, 61 years +/- 10) with carotid plaques were studied with standard and contrast material-enhanced ultrasonography (US). Contrast enhancement in the plaque was evaluated with visual interpretation and quantitative analysis. RESULTS Among the 104 patients, 35 (34%) had transient ischemic attack and/or cerebrovascular ischemic stroke. Plaque enhancement was found in 28 (80%) of 35 symptomatic patients and in 21 (30%) of 69 asymptomatic patients (P < .001). Enhanced intensity in the plaque (13.9 dB +/- 6.4) and the ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery (0.54 +/- 0.23) in symptomatic patients were significantly greater than those in asymptomatic patients (8.8 dB +/- 5.2 [P < .001] and 0.33 +/- 0.19 [P < .001], respectively). Sensitivity and specificity were 74% and 62%, respectively, for enhanced intensity in the plaque (cutoff value, 10.0 dB) and 74% and 75%, respectively, for ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery (cutoff value, 0.46). CONCLUSION Symptomatic patients had more intense contrast agent enhancement in the plaque than asymptomatic patients, suggesting that contrast-enhanced carotid US may be used for plaque risk stratification.

Use of Carotid Plaque Neovascularization at Contrast-enhanced US to Predict Coronary Events in Patients with Coronary Artery Disease.

PURPOSE To determine whether carotid plaque neovascularization as assessed with contrast-enhanced ultrasonography (US) can help predict future coronary events in patients with stable coronary artery disease (CAD). MATERIALS AND METHODS The study was approved by the hospital ethics committee, and informed consent was obtained from all patients. Three hundred twelve consecutive patients (228 men; mean age, 63 years ± 9; age range, 42-88 years) with both CAD and at least one carotid plaque thicker than 2.0 mm underwent both standard and contrast-enhanced carotid US. Patients with stable CAD were followed up for 8-47 months (mean, 33 months ± 9) or until a coronary event occurred. Statistical analysis was performed with the Student t test, χ(2) analysis, Kaplan-Meier method, and Cox proportional hazards regression models. RESULTS Contrast material enhancement of plaque was seen in 42 of 51 patients (82%) with acute coronary syndrome (ACS) and 114 of 261 patients (43.7%) with stable CAD (P < .001). Coronary events occurred during the follow-up period in 24 of 111 patients (21.6%) with contrast material enhancement of plaque and only seven of 137 patients (5.1%) without enhancement (P< .001). In 248 patients with stable CAD and follow-up, Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with contrast material enhancement of plaque than in those without contrast material enhancement (P < .001). The presence of contrast material enhancement of plaque was a significant and independent predictor of future coronary events in patients with stable CAD (odds ratio: 3.90; 95% confidence interval: 1.60, 9.46; P = .003). CONCLUSION Contrast material enhancement of plaque is more common in patients with ACS than in those with stable CAD and is a significant and independent predictor of future coronary events in patients with stable CAD, suggesting that noninvasive contrast-enhanced carotid US may be used as a method for risk stratification of patients with stable CAD.

Evaluation of short-axis and long-axis myocardial function with two-dimensional strain echocardiography in patients with different degrees of coronary artery stenosis.

This study was designed to characterize the changes in the peak systolic longitudinal, circumferential and radial strains by using 2-D strain echocardiography in patients with coronary artery stenosis without segmental wall motion abnormalities on conventional 2-D echocardiography. 2D strain echocardiography was performed in 44 patients with different degrees of coronary artery stenosis. Myocardial longitudinal, circumferential and radial strain profiles were obtained and peak systolic strain values were measured. The peak systolic longitudinal strain was significantly reduced in myocardial segments subtended by coronary arteries with greater than 75% stenosis when compared with those subtended by coronary artery with less than 75% stenosis and those in control. Sensitivity and specificity were 74% and 72%, respectively, for peak systolic longitudinal strain to predict segments subtended by coronary arteries with greater than 75% stenosis (cutoff value--17.7%; area under the receiver operating characteristic curve, 0.825). There were no significant differences in circumferential and radial strains among myocardial segments subtended by coronary arteries with greater than 75% stenosis and those with less than 75% stenosis and in control. In conclusion, our study suggests that analysis of long-axis cardiac function by using the 2-D strain echocardiography may help to identify the myocardial segments subtended by coronary arteries with severe stenosis.

Evaluation of subtle myocardial noncompaction by contrast echocardiography in patients with hypertrophic cardiomyopathy and its relationship with regional ventricular systolic dysfunction.

Ourstudy was undertaken to analyze the impact of subtle noncompaction of the left ventricle on regional left ventricular function in patients with hypertrophic cardiomyopathy.

Rapid and accurate quantification of right ventricular volume and stroke volume by real-time 3-dimensional triplane echocardiography.

Previous studies have demonstrated that 3‐Dimensional (3‐D) echocardiography can determine right ventricular (RV) volume accurately. However, this technique has not been feasible in everyday clinical practice because of the necessity of time‐consuming off‐line processes.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Parathyroid Hormone (1–34) in Healthy Chinese Subjects

BACKGROUND The recombinant human parathyroid hormone (1-34) (rhPTH[1-34]) teriparatide is the first anabolic agent approved by the US Food and Drug Administration for the treatment of osteoporosis in men and women. This study was conducted to provide support for marketing authorization of an agent biosimilar to teriparatide in China. OBJECTIVE The main aim of the present study was to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic parameters of rhPTH(1-34) after single and multiple subcutaneous doses in healthy Chinese subjects. METHODS Two open-label, randomized, single-center, dose-escalation studies were performed. In study 1, subjects were randomized to receive a single dose of rhPTH(1-34) (10, 20, 30, 40, 50, or 60 μg) or a multiple dose of rhPTH(1-34) (10 and 20 μg once daily for 7 consecutive days) to determine the safety profile and tolerability, as reflected by the incidence, intensity, and seriousness of the observed adverse events. In study 2, a single dose of rhPTH(1-34) (10, 20, or 40 μg) and a multiple dose of rhPTH(1-34) (20 μg) were administrated subcutaneously to investigate the pharmacokinetic and pharmacodynamic parameters. RESULTS Forty-two subjects completed study 1, and 30 subjects completed study 2. rhPTH(1-34) was well tolerated during the investigated single (10-60 μg) and multiple (10-20 μg once daily for 7 consecutive days) dose ranges. The most generally reported adverse events were erythema at the injection site and gastrointestinal reactions. After single and multiple subcutaneous administration of rhPTH(1-34), the drug was rapidly absorbed, with a Tmax of 20 to 30 minutes, and rapidly cleared from the plasma, with a t½ of 47.2 to 60.6 minutes. The mean Cmax, AUC0-t, and AUC0-∞ increased in proportion to the doses, whereas the t½, total clearance, and Tmax values were independent of the administered dose. No significant differences in pharmacokinetic parameters were noted by sex except for Tmax in the 10-μg and 20-μg single-dose groups. Compared with the baseline levels, no significant changes or dose-related significant effects were observed in serum calcium and phosphate levels. CONCLUSIONS All rhPTH(1-34) doses appeared to be well tolerated in the population studied. Linear pharmacokinetic characteristics were displayed in the dose range studied. Chinese ClinicalTrials.gov identifier: ChiCTR-ONC-12002874.

Value of quantitative tissue velocity imaging in the detection of regional myocardial function in dogs with acute subendocardial ischemia.

This study evaluated the application of quantitative tissue velocity imaging (QTVI) in assessing regional myocardial systolic and diastolic functions in dogs with acute subendocardial ischemia. Animal models of subendocardial ischemia were established by injecting microspheres (about 300 μm in diameter) into the proximal end of left circumflex coronary artery in 11 hybrid dogs through cannulation. Before and after embolization, two-dimensional echocardiography, QTVI and real-time myocardial contrast echocardiography (RT-MCE) via intravenous infusion of self-made microbubbles, were performed, respectively. The systolic segmental wall thickening and subendocardial myocardial longitudinal velocities of risk segments before and after embolization were compared by using paired t analysis. The regional myocardial video intensity versus contrast time could be fitted to an exponential function: y=A·(1-exp−β·t), in which the product of A and β provides a measure of myocardial blood flow. RT-MCE showed that subendocardial normalized A·β was decreased markedly from 0.99±0.19 to 0.35±0.11 (P<0.05) in 28 left ventricular (LV) myocardial segments after embolization, including 6 basal and 9 middle segments of lateral wall (LW), 8 middle segments of posterior wall (PW) and 5 middle segments of inferior wall (IW). However, there was no statistically significant difference in subepicardial layer before and after embolization. Accordingly, the ratio of A·β of subendocardial myocardium to subepicardial myocardium in these segments was significantly decreased from 1.10±0.10 to 0.31±0.07 (P<0.05). Although the systolic wall thickening did not change 5 min after the embolization in these ischemic segments (29%±3% vs 31%±5%, P>0.05), the longitudinal peak systolic velocities (Vs) and early-diastolic peak velocities (Ve) recorded by QTVI were declined significantly (P<0.05). Moreover, the subendocardial velocity curves during isovolumic relaxation predominantly showed positive waves, whereas they mainly showed negative waves before the embolization. This study demonstrates that QTVI can more sensitively and accurately detect abnormal regional myocardial function and post-systolic systole caused by acute subendocardial ischemia.SummaryThis study evaluated the application of quantitative tissue velocity imaging (QTVI) in assessing regional myocardial systolic and diastolic functions in dogs with acute subendocardial ischemia. Animal models of subendocardial ischemia were established by injecting microspheres (about 300 μm in diameter) into the proximal end of left circumflex coronary artery in 11 hybrid dogs through cannulation. Before and after embolization, two-dimensional echocardiography, QTVI and real-time myocardial contrast echocardiography (RT-MCE) via intravenous infusion of self-made microbubbles, were performed, respectively. The systolic segmental wall thickening and subendocardial myocardial longitudinal velocities of risk segments before and after embolization were compared by using paired t analysis. The regional myocardial video intensity versus contrast time could be fitted to an exponential function: y=A·(1-exp−β·t), in which the product of A and β provides a measure of myocardial blood flow. RT-MCE showed that subendocardial normalized A·β was decreased markedly from 0.99±0.19 to 0.35±0.11 (P<0.05) in 28 left ventricular (LV) myocardial segments after embolization, including 6 basal and 9 middle segments of lateral wall (LW), 8 middle segments of posterior wall (PW) and 5 middle segments of inferior wall (IW). However, there was no statistically significant difference in subepicardial layer before and after embolization. Accordingly, the ratio of A·β of subendocardial myocardium to subepicardial myocardium in these segments was significantly decreased from 1.10±0.10 to 0.31±0.07 (P<0.05). Although the systolic wall thickening did not change 5 min after the embolization in these ischemic segments (29%±3% vs 31%±5%, P>0.05), the longitudinal peak systolic velocities (Vs) and early-diastolic peak velocities (Ve) recorded by QTVI were declined significantly (P<0.05). Moreover, the subendocardial velocity curves during isovolumic relaxation predominantly showed positive waves, whereas they mainly showed negative waves before the embolization. This study demonstrates that QTVI can more sensitively and accurately detect abnormal regional myocardial function and post-systolic systole caused by acute subendocardial ischemia.

Usefulness of Contrast Perfusion Echocardiography for Differential Diagnosis of Cardiac Masses

The aim of this study was to assess the usefulness of contrast perfusion echocardiography in the differential diagnosis of different types of cardiac masses. Conventional echocardiography and contrast perfusion echocardiography were performed in 72 patients with cardiac masses. The degree of contrast enhancement of the mass and an adjacent section of myocardium after injection of contrast agent was determined by visual inspection and quantitative time-signal intensity curve analysis. The difference in maximal steady-state pixel intensity between the mass and the adjacent myocardium (ΔAmass-myocardium) was calculated. All masses had a pathologic diagnosis or resolved after anticoagulation. All 16 cardiac masses without enhancement on visual inspection were confirmed to be cardiac thrombi. Twenty-four masses with incomplete enhancement on visual inspection were recognized as benign tumors with validation methods. Of the 32 cardiac masses with complete enhancement, 30 were confirmed as malignant tumors and two as benign tumors with validation methods. The sensitivity and specificity of ΔAmass-myocardium in differentiating thrombi from tumors were 93% and 100%, respectively, and 100% and 97% in differentiating malignant tumors from benign tumors and thrombi. Both visual and quantitative assessment of degree of enhancement of cardiac masses in relation to the adjacent myocardium during contrast perfusion echocardiography had high diagnostic accuracy for differentiation of a thrombus from a tumor or a benign tumor from a malignant tumor.

A simple and sensitive liquid chromatographic technique for the determination of cefotetan disodium in human plasma and its application in a pharmacokinetic study

A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT), a semi-synthetic cephamycin antibiotic, in human plasma. CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid. Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80, v/v) at a flow rate of 1.0 mL/min. The column effluent was monitored by UV detection at 300 nm. The column temperature was maintained at 40°C. This method demonstrated good linearity in the range of 0.525–300.0 μg/mL, with correlation coefficients greater than 0.99. The limit of quantification (LOQ) was 0.525 μg/mL in human plasma. Intra- and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD). The accuracy, when expressed by the bias, ranged from 0.57% to 4.04%. The mean extraction recovery of CTT was higher than 40.94%. The method was found to be precise, accurate, and specific for CTT quantitative analysis, and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.SummaryA simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT), a semi-synthetic cephamycin antibiotic, in human plasma. CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid. Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80, v/v) at a flow rate of 1.0 mL/min. The column effluent was monitored by UV detection at 300 nm. The column temperature was maintained at 40°C. This method demonstrated good linearity in the range of 0.525–300.0 μg/mL, with correlation coefficients greater than 0.99. The limit of quantification (LOQ) was 0.525 μg/mL in human plasma. Intra- and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD). The accuracy, when expressed by the bias, ranged from 0.57% to 4.04%. The mean extraction recovery of CTT was higher than 40.94%. The method was found to be precise, accurate, and specific for CTT quantitative analysis, and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.

The therapeutic effect of bevacizumab on plaque neovascularization in a rabbit model of atherosclerosis during contrast-enhanced ultrasonography.

The purpose of the study was to assess the therapeutic effect of the angiogenesis inhibitor bevacizumab on plaques of various stages in rabbit models using contrast-enhanced ultrasonography (CEUS). Abdominal aortic atherosclerosis was induced in 55 rabbits. Thirty-six randomly selected rabbits were divided into 2 groups according to the timing of the bevacizumab injection: an early-stage plaque group (Group ESP) and a later-stage plaque group (Group LSP). The remainder were considered the control group. Standard ultrasonography and CEUS imaging of the abdominal aorta were performed. The animals were euthanized after CEUS, and plaque specimens were harvested for histological staining of CD31. The control group exhibited a substantially higher enhanced intensity, a higher ratio of enhanced intensity in the plaque to that in the lumen, and an increased number of CD31-positive microvessels in the plaque sections than Groups ESP and LSP (P < 0.05 for all). A higher enhanced intensity (P = 0.044), a higher ratio of enhanced intensity in the plaque to that in the lumen (P = 0.023) and more CD31-positive microvessels in the plaque sections (P = 0.006) were found in Group LSP than in Group ESP. Bevacizumab demonstrated more advanced inhibition of neovascularization in early-stage plaques in rabbits.