Increased expression and plasma levels of myeloperoxidase are closely related to the presence of angiographically-detected complex lesion morphology in unstable angina.

BACKGROUND: Myeloperoxidase (MPO) is a leucocyte enzyme that catalyses the formation of a number of reactive oxidant species. OBJECTIVE: The purpose of this study is to evaluate the relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP) and MPO levels. PATIENTS AND DESIGN: Plasma MPO levels on admission were measured in 236 patients with UAP, 146 with SAP and 85 control subjects using an ELISA kit. The angiographic morphology of the culprit lesion was classified into two types, simple or complex, based on the Ambrose classification. In addition, 61 atherectomy specimens obtained from a different cohort of patients with UAP and SAP were studied immunohistochemically for MPO. RESULTS: Median (IQR) plasma MPO levels in patients with UAP with a complex lesion were significantly higher than in patients with a simple lesion (41.9 (21.7­73.7) ng/ml vs 20.5 (15.9­27.9) ng/ml, p<0.0001), but there was no significant difference between the two groups in patients with SAP. On multivariate analysis, raised plasma MPO levels and Braunwald class III were independent factors for angiographically-detected complex lesions (adjusted OR 12.49, 95% CI 3.24 to 48.17, p=0.0002). In the atherectomy specimens the number of MPO-positive cells in patients with UAP with complex lesions was significantly higher (p<0.0005) than in patients with simple lesions. Moreover, in this cohort, plasma MPO levels were positively correlated with the number of MPO-positive cells in atherectomy specimens (R=0.42, p=0.024). CONCLUSIONS: This study shows that increased expression and plasma MPO levels are closely related to the presence of angiographically-detected complex lesion morphology in patients with UAP.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals.

BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. OBJECTIVE: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). METHODS: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. RESULTS: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months' supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). CONCLUSION: Three months' supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

Early detection of cardiac involvement in patients with sarcoidosis by a non-invasive method with ultrasonic tissue characterisation.

OBJECTIVES: To clarify the value of cycle dependent variation of myocardial integrated backscatter (CV-IB) analysis, which non-invasively measures acoustic properties of the myocardium, for early detection of cardiac involvement in patients with sarcoidosis. METHODS: The study population consisted of 22 consecutive patients with biopsy proven sarcoidosis who did not have any abnormal findings on conventional two dimensional echocardiogram. Cardiac sarcoidosis was diagnosed by radionuclide testing including thallium-201 scintigraphy, gallium-67 scintigraphy, and cardiac fluorine-18-deoxyglucose positron emission tomography. The magnitude and delay of the CV-IB were analysed in the basal mid septum and the basal mid posterior wall of the left ventricle of all patients. RESULTS: The patients were divided into two groups: 8 patients with cardiac involvement and 14 patients without cardiac involvement. In the basal septum, a major reduction in the magnitude (mean (SD) 1.8 (4.4) v 6.6 (1.3), p = 0.012) and an increase in the time delay (1.3 (0.5) v 1.0 (0.1), p = 0.038) of CV-IB were observed in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. The sensitivity for detecting cardiac involvement was such that the magnitude of CV-IB in the basal septum discriminated 75% of patients with cardiac sarcoidosis from those with non-cardiac sarcoidosis, whereas two dimensional echocardiographic parameters did not discriminate between these two groups. CONCLUSIONS: The CV-IB is decreased in the basal septum in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. Analysis of CV-IB may be a useful method to detect early myocardial involvement in patients with sarcoidosis.

Coronary flow velocity analysis during short term follow up after coronary reperfusion: use of transthoracic Doppler echocardiography to predict regional wall motion recovery in patients with acute myocardial infarction.

BACKGROUND: A recent study using a Doppler guide wire showed that coronary flow velocity measurements immediately after coronary reperfusion were useful in predicting recovery of regional left ventricular function. The value of coronary flow velocity analyses during follow up after reperfusion has not been established in the clinical setting. OBJECTIVE: To evaluate coronary flow velocity measurements in predicting recovery of regional left ventricular function during short term follow up after acute anterior myocardial infarction, using transthoracic Doppler echocardiography (TTDE). METHODS: 30 consecutive patients with anterior acute myocardial infarction were studied. They all underwent successful coronary angioplasty for lesions in the left anterior descending coronary artery (LAD). Using TTDE, coronary flow velocity in the LAD was recorded on days 1 and 3, and at one and two weeks after reperfusion. Regional wall motion was analysed by the wall motion score index (WMSI), calculated as an average of segmental scores in the LAD territory before reperfusion and one month after the infarction. RESULTS: Deceleration time of diastolic flow velocity (DDT) in patients with viable myocardium (WMSI in LAD territory at one month, < 2.0) was significantly longer after recanalisation than in patients without viable myocardium (WMSI in LAD territory at one month, > 2.0): 657 (226) v 271 (117) ms on day 1, p < 0.001; 732 (219) v 373 (217) ms on day 3, p < 0.01; and 903 (107) v 577 (300) ms at one week, p < 0.01. However, the difference at two weeks (991 (75) v 795 (281) ms) was not significant. For the prediction of viable myocardium, DDT > 600 ms had a sensitivity of 78% and a specificity of 92% on day 1, and a sensitivity of 78% and a specificity of 84% on day 3. At one and two weeks, DDT > 600 ms was sensitive (100% and 100%, respectively) but less specific (46% and 26%, respectively) for predicting viable myocardium. CONCLUSIONS: Non-invasive assessment of coronary flow velocity using TTDE within three days of successful coronary angioplasty in patients with anterior acute myocardial infarction is useful in predicting recovery of regional left ventricular function.

Assessment of myocardial perfusion abnormalities by intravenous myocardial contrast echocardiography with harmonic power Doppler imaging: comparison with positron emission tomography.

BACKGROUND: Intravenous myocardial contrast echocardiography with harmonic power Doppler imaging (HPDI) enables assessment of myocardial perfusion. Its accuracy in comparison with positron emission tomography (PET), which is one of the most reliable clinical gold standards for myocardial perfusion, remains to be determined. OBJECTIVE: To assess the ability of HPDI to identify myocardial perfusion abnormalities, using PET as a gold standard. METHODS: 23 patients with myocardial infarction underwent HPDI. Images were obtained from the apical two and four chamber views at pulsing intervals of one to eight cardiac cycles with continuous infusion of Levovist (Schering, Germany). PET was done within two weeks of HPDI. The left ventricle was divided into 12 segments and myocardial opacification by HPDI and uptake of NH(3) by PET in each segment was graded as normal, mildly reduced, or severely reduced. RESULTS: Of the 276 segments examined, adequate image quality was obtained in 226 (82%) by HPDI; 50 segments were excluded because of inadequate image quality. There were more exclusions in the basal segments than in the mid or apical segments (p < 0.0001). Of the 226 segments analysed, overall concordance between HPDI and PET was 82% (chi = 0.70). In the apex, more segments were overestimated by HPDI than were underestimated (chi(2) = 6.25, p = 0.012). CONCLUSIONS: HPDI and PET gave similar results in the assessment of myocardial perfusion abnormalities. However, poor image quality in the basal segments and overestimation of perfusion in the apical segments are current limitations of HPDI.

Automated quantification of aortic regurgitant volume and regurgitant fraction using the digital colour Doppler velocity profile integration method in patients with aortic regurgitation.

BACKGROUND: The recently introduced automated cardiac flow measurement (ACM) technique provides a quick and an accurate automated calculation of stroke volume and cardiac output. This is obtained by spatio-temporal integration of digital Doppler velocity profile data. OBJECTIVE: To evaluate the use of the ACM method in the non-invasive assessment of aortic regurgitant volume and per cent regurgitant fraction (%RF) in patients with aortic regurgitation. METHODS: Aortic outflow volume and mitral inflow volume were calculated by the ACM method in 22 patients with isolated aortic regurgitation. Aortic regurgitant volume and %RF were calculated using the following equations: aortic regurgitant volume = [aortic outflow volume] - [mitral inflow volume]; %RF = [aortic regurgitant volume]/[aortic outflow volume] x 100. The results were compared with those obtained using pulsed Doppler cross sectional echocardiography (PD-2D). RESULTS: Aortic regurgitant volumes measured by the ACM method showed a good correlation with the PD-2D measurements (r = 0.95, y = 0.9x + 3.9, SEE = 8.6 ml); the mean (SD) difference between the two methods was -1.5 (8.5) ml. %RF estimated by the ACM method also correlated well with the values obtained by the PD-2D method (r = 0.91, y = 0.9x + 4.9, SEE = 6.0%); the mean difference between the two methods was -1.5 (6.0)%. Total time required for aortic regurgitant volume (for one cardiac cycle) by the ACM method was significantly shorter than by the PD-2D method (130 (16) v 230 (32) s, p < 0.01). CONCLUSIONS: The newly developed the ACM method is quick and accurate in the automated assessment of aortic regurgitant volume and per cent regurgitant fraction in patients with isolated aortic regurgitation.

Changes in transmural distribution of myocardial perfusion assessed by quantitative intravenous myocardial contrast echocardiography in humans.

OBJECTIVE: To clarify whether changes in transmural distribution of myocardial perfusion under significant coronary artery stenosis can be assessed by quantitative intravenous myocardial contrast echocardiography (MCE) in humans. METHODS: 31 patients underwent dipyridamole stress MCE and quantitative coronary angiography. Intravenous MCE was performed by continuous infusion of Levovist. Images were obtained from the apical four chamber view with alternating pulsing intervals both at rest and after dipyridamole infusion. Images were analysed offline by placing regions of interest over both endocardial and epicardial sides of the mid-septum. The background subtracted intensity versus pulsing interval plots were fitted to an exponential function, y = A (1 - e(-betat)), where A is plateau level and beta is rate of rise. RESULTS: Of the 31 patients, 16 had significant stenosis (> 70%) in the left anterior descending artery (group A) and 15 did not (group B). At rest, there were no differences in the A endocardial to epicardial ratio (A-EER) and beta-EER between the two groups (mean (SD) 1.2 (0.6) v 1.2 (0.8) and 1.2 (0.7) v 1.1 (0.6), respectively, NS). During hyperaemia, beta-EER in group A was significantly lower than that in group B (1.0 (0.5) v 1.4 (0.5), p < 0.05) and A-EER did not differ between the two groups (1.0 (0.5) v 1.2 (0.4), NS). CONCLUSIONS: Changes in transmural distribution of myocardial perfusion under significant coronary artery stenosis can be assessed by quantitative intravenous MCE in humans.

Non-invasive automated assessment of the ratio of pulmonary to systemic flow in patients with atrial septal defects by the colour Doppler velocity profile integration method.

BACKGROUND: The recent introduction of the automated cardiac flow measurement (ACM) method, using spatiotemporal integration of the Doppler velocity profile, provides a quick and accurate automated calculation of cardiac output. OBJECTIVE: To evaluate the ACM method against oximetry during cardiac catheterisation for estimating the Qp/Qs (pulmonary to systemic flow) ratio in patients with an atrial septal defect. METHODS: Left and right ventricular stroke volume (LVSV, RVSV) were calculated by ACM in 22 patients with an atrial septal defect who underwent cardiac catheterisation and in 11 patients without heart disease (control group). With ACM, the Qp/Qs ratio was estimated from RVSV divided by LVSV. In the patients with an atrial septal defect, the Qp/Qs ratio was assessed by oximetry at the time of cardiac catheterisation. RESULTS: There was a good correlation between LVSV and RVSV obtained by ACM in the control group (r = 0.98, y = 0.97x + 0.25, SEE = 2.9 ml). The mean difference between LVSV and RVSV by ACM was -1.25 (2.76) ml. The Qp/Qs ratio obtained by ACM in the control group was 0.98 (0.06). The Qp/Qs ratio in patients with an atrial septal defect was significantly higher than in the control group (3.11 (1.20), p < 0.001). ACM determination of the Qp/Qs ratio correlated well with oximetry determination (r = 0.86, y = 0.75x + 0.55, SEE = 0.64). The mean difference between ACM and oximetry for the measurement of the Qp/Qs ratio was -0.28 (0.69). CONCLUSIONS: The newly developed ACM method is clinically useful for non-invasive automated estimations of the Qp/Qs ratio in patients with an atrial septal defect.

Modulation of coronary flow velocity reserve by gender, menstrual cycle and hormone replacement therapy.

OBJECTIVES: The purpose of this study was twofold: 1) to examine the relationship between menstrual cycle and coronary flow velocity reserve (CFVR) in young healthy women, and 2) to evaluate the effect of hormone replacement therapy by estrogen on CFVR in postmenopausal women, using transthoracic color Doppler echocardiography (TTCDE). BACKGROUND: Although the incidence of cardiovascular disease is lower in women before menopause compared with men, postmenopausal women have an incidence of coronary artery disease similar to that of men of the same age. This is mainly dependent upon estrogen deficiency. However, no clinical report has yet examined the effect of estrogen on CFVR, which is one index of coronary microcirculation. METHODS: We examined 15 male and both 15 premenopausal and 10 postmenopausal female healthy volunteers. We measured coronary flow velocity of the left anterior descending coronary artery at baseline and hyperemic conditions during adenosine triphosphate infusion by TTCDE and determined CFVR. Each premenopausal woman was studied two times (menstrual [M] and follicular [F] phases) in one menstrual cycle. Fifteen men were also studied at a time corresponding to women's menstrual cycle. The postmenopausal women were studied before and two hours after oral administration of conjugated estrogen (CE). RESULTS: Serum 17beta-estradiol level in premenopausal women increased in the F phase and decreased to the same levels as in men, as in the M phase and as in postmenopausal women (123 +/- 9 pg/ml vs. 28 +/- 6 pg/ml, 25 +/- 9 pg/ml and 19 +/- 11 pg/ml; p < 0.0001, respectively). The CFVR increased in the F phase compared with that in the M phase (4.8 +/- 0.4 vs. 3.7 +/- 0.8, p < 0.0001). We found that CFVR in men remained unchanged (3.7 +/- 0.6 vs. 3.8 +/- 0.5). After CE administration, CFVR increased compared with baseline in postmenopausal women (4.1 +/- 0.8 vs. 3.4 +/- 0.8, p < 0.005). CONCLUSIONS: In premenopausal women, CFVR determined by TTCDE varied during the menstrual cycle, and in postmenopausal women, CFVR increased after acute estrogen replacement.

Assessment of left ventricular systolic function using contrast two-dimensional echocardiography with a high-frequency transducer in the awake murine model of myocardial infarction.

The estimation of global left ventricular function using M-mode echocardiography has technical limitations in the murine model of myocardial infarction (MI), but the recent improvements in 2-dimensional (2-D) echocardiography using a high-frequency transducer provide more accessible images. Furthermore, intravenous injection of contrast agent has the additional benefit of enhancing the endocardial border in the murine heart. The present study was designed to evaluate the value of 2-D echocardiography with intravenous injection of contrast agent in the assessment of global systolic function of the murine heart with MI. Two-dimensional and M-mode echocardiography without and with intravenous injection of contrast agent (Optison, 0.1-0.15 ml) were performed in 76 awake mice 2 days before and 2 days after left coronary artery ligation. Fractional shortening (FS) was calculated from the end-diastolic and end-systolic diameters on M-mode echocardiography, and fractional area change (FAC) from the end-diastolic and end-systolic areas on 2-D echocardiography. Both FS and FAC were compared with the areas of hypoperfusion observed in the pathological samples. The use of contrast agent improved the number of hearts that could be evaluated by both the M-mode and 2-D method (M-mode: non-contrast 87% vs contrast 99%, p<0.01; 2-D: non-contrast 26% vs contrast 89%, p<0.001). FAC from the 2-D method correlated better with the region of hypoperfusion in the pathological samples than did FS from the M-mode method (FAC: r=0.84 vs FS: r=0.51). In conclusion, FAC obtained from 2-D contrast echocardiography is useful for noninvasive assessment of global systolic function in infarcted murine hearts and can be used to serially assess systolic function in various models of the murine heart.

[Three-dimensional transesophageal echocardiographic measurement of left ventricular volumes using the average rotation method: comparison with the disk summation method].

OBJECTIVES: Three-dimensional(3-D) echocardiography accurately calculates left ventricular volumes without geometric assumptions. Conventional 3-D echocardiography using the disk summation method is limited in practical use because of the long analysis time. This study validated the average rotation method for rapid and accurate left ventricular volume measurement compared with the conventional disk summation method. METHODS: 3-D data acquisition using multiplane transesophageal echocardiography was performed in 13 patients. Left ventricular volumes and ejection fraction were calculated by the disk summation method with 20 parallel short-axis tomograms and by the average rotation method with 3, 6, 9 and 12 apical long-axis tomograms. RESULTS: 3-D left ventricular volumes and ejection fraction by the average rotation method in each subgroup of slice resolution had excellent correlation and close limits of agreement with those by the disk summation method. Intraobserver variability and interobserver variability were < or = 11%. With the use of three component tomograms, analysis time required for left ventricular volume measurement by the average rotation method was < or = 2 min. CONCLUSIONS: Transesophageal 3-D echocardiography using the average rotation method is a clinically useful tool for accurate and rapid measurement of left ventricular volume and function.

Noninvasive estimation of coronary flow reserve by transthoracic Doppler echocardiography with a high-frequency transducer.

Recent technological advances in transthoracic Doppler echocardiography (TTDE) provide visualization of the coronary blood flow signal and noninvasive analysis of coronary flow reserve with a high frequency transducer. Coronary flow velocity and coronary flow reserve measured by TTDE were compared with those measured by a Doppler guide wire. Values of mean coronary flow velocity and coronary flow reserve measured by TTDE were closely correlated with values measured by the invasive Doppler guide wire (r = 0.97, y = 0.94x + 0.40; r = 0.94, y = 0.95x + 0.21, respectively). This noninvasive technique was applied to patients who underwent coronary angiography to evaluate coronary artery disease. There was a significant difference in coronary flow reserve measured by TTDE between patients with and without significant left anterior descending coronary artery stenosis (% diameter stenosis > 70%) (1.5 +/- 0.2 vs 2.6 +/- 0.4, p < 0.001). Coronary flow reserve < 2.0 obtained by TTDE had a high sensitivity (92%) and a high specificity (86%) for the presence of significant left anterior descending coronary artery stenosis. TTDE with a high-frequency transducer can be applied to noninvasive estimation of coronary flow reserve in the clinical setting, and is useful in noninvasive diagnosis of significant coronary stenosis in patients with coronary artery disease.

Assessment of left ventricular function by real-time 3-dimensional echocardiography compared with conventional noninvasive methods.

Quantitative assessment of left ventricular ejection fraction is an essential component of cardiac evaluation. We performed real-time 3-dimensional echocardiography in 56 consecutive patients who underwent multigated radionuclide angiography. Thirteen patients were excluded for the following reasons: 5 for large size of left ventricle required for image acquisition, 5 for suboptimal image quality in real-time 3-dimensional echocardiography, and 3 for atrial fibrillation. Finally, we compared left ventricular ejection fraction assessed by real-time 3-dimensional echocardiography and conventional 2-dimensional echocardiography with that obtained by multigated radionuclide angiography in 43 patients. Left ventricular ejection fraction was determined by real-time 3-dimensional echocardiography with the use of parallel plane-disks and sector plane-disks summation methods. A good correlation was obtained between both real-time 3-dimensional echocardiography methods and multigated radionuclide angiography (r = 0.87 and 0.90, standard error of estimate = 3.7% and 4.2%), whereas the relation between the 2-dimensional echocardiography method and radionuclide angiography demonstrated a significant departure from the line of identity (P <.001). In addition, interobserver variability was significantly lower (P <.05) for the real-time 3-dimensional echocardiography methods than that by the 2-dimensional echocardiography method. Real-time 3-dimensional echocardiography may be used for quantification of left ventricular function as an alternative to conventional methods in patients with adequate image quality.

Anesthetic inhibition in ischemic and nonischemic murine heart: comparison with conscious echocardiographic approach.

It is well known that the level of anesthesia obtained by intraperitoneal injection is variable and may alter cardiac function. In this study, we compared the effects of different anesthetics on cardiac function with the conscious state using high-resolution two-dimensional echocardiography in nonischemic and ischemic mice. Eighty-four mice were tested before and after surgery with ligation of the coronary artery. All 84 mice were studied in the conscious state and under high-dose intraperitoneal anesthesia. Twenty-two of 84 mice were studied under low-dose intraperitoneal anesthesia. Another 22 mice were also studied under gas anesthesia and spontaneous breathing. Experiments in the conscious state were performed by two investigators before the administration of anesthesia: one investigator held the animal and the transducer and the other operated the ultrasound equipment. Left ventricular systolic function was measured, and measurements obtained after surgery were compared with infarcted areas assessed by histological staining. Results showed that both high- and low-dose intraperitoneal anesthesia significantly reduced heart rates and left ventricular contractility in both pre- and postsurgical mice as opposed to conscious mice (P < 0.01). There were significantly higher correlation coefficients between mean fractional area change (FAC) and infarcted area in conscious state compared with high-dose intraperitoneal anesthesia (P < 0.05). The correlation coefficient between FAC and infarcted area during gas anesthesia was also significantly higher compared with high-dose intraperitoneal anesthesia (P < 0.05). In conclusion, conscious experiments or the use of gas anesthesia is preferred for echocardiographic assessment of cardiac function in mice because intraperitoneal injection significantly induces a significant reduction in heart rate and left ventricular systolic function.

Assessment of segmental wall motion abnormalities using contrast two-dimensional echocardiography in awake mice.

Murine models of cardiac disease are becoming an important tool for studying pathophysiological processes. Development of methods to accurately assess ventricular function are therefore important. The purpose of this study was to evaluate the feasibility of echocardiographic assessment of segmental wall motion abnormalities in a murine model of myocardial infarction. Two-dimensional contrast (C+) and noncontrast (C-) echocardiography were performed in 76 awake mice 2 days before and 2 days after left coronary ligation. The short-axis images obtained with two-dimensional echocardiography and corresponding postmortem cross-sectional histological samples stained with Evans blue dye were each divided into 16 segments, and all matched segments were examined for correlation between wall motion abnormalities and myocardial hypoperfusion. With the use of contrast enhancement, the number of visualized segments was significantly increased (base: C- 86%, C+ 98%; midpapillary: C- 57%, C+ 89%; apex: C- 30%, C+ 74%). Agreement between echocardiographically assessed regional wall motion abnormalities and pathologically determined hypoperfusion in basal, midpapillary, and apical levels were 90%, 93%, and 93%, respectively. Agreement between echocardiographically normal wall motion and pathologically normal findings in basal, midpapillary, and apical levels were 99%, 88%, and 71%, respectively. Thus echocardiographic assessment of segmental wall motion in awake mice was feasible and the accuracy was improved with the use of a contrast agent.

Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo.

Eugeniin exhibits antiviral activity against acyclovir and phosphonoacetic acid (PAA)-resistant herpes simplex virus type 1 (HSV-1) as well as the wild-type HSV-1 in vitro. In this study, we characterized the biological activity of eugeniin in cutaneously HSV-1-infected mice and its interaction with HSV-1 DNA polymerase. The oral and intraperitoneal administrations of eugeniin at 0.3 mg/kg showed similar therapeutic efficacy in retarding the development of skin lesions of HSV-1-infected mice. The two routes of administration at 6 or 50 mg/kg significantly prolonged the mean survival times and/or reduced mortality without toxicity. The oral administration of eugeniin at 50 mg/kg reduced virus yields in the skin and brain of infected mice. Thus, the therapeutic efficacy of oral administration at the various doses of eugeniin was similar to that of intraperitoneal administration, suggesting that the oral bioavailability of eugeniin was high with respect to absorption. Furthermore, the anti-HSV-1 activity of eugeniin was characterized by isobolograms analyzing its combined effects with acyclovir or PAA in HSV-1-infected Vero cells. Eugeniin enhanced the anti-HSV-1 activity of acyclovir but was suggested to be antagonistic with PAA. The interaction of eugeniin and PAA on the activity of partially purified HSV-1 DNA polymerase suggested that eugeniin interacted with the polymerase in the vicinity of PAA-binding site. Thus, eugeniin showed different anti-HSV-1 action from acyclovir and PAA and therapeutic anti-HSV-1 activity in mice.

Cyst of the ligamentum flavum.

We report the case of a patient with sciatica resulting from a cyst of the ligamentum flavum.

Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus: a serial intravascular ultrasound study.

OBJECTIVES: The aim of the present study was to determine whether troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus (NIDDM). BACKGROUND: Increased in-stent restenosis in patients with diabetes mellitus is due to accelerated neointimal tissue proliferation after coronary stent implantation. Troglitazone inhibits intimal hyperplasia in experimental animal models. METHODS: We studied 62 stented lesions in 52 patients with plasma glucose levels (PG) > or = 11.1 mmol/liter at 2 h after 75 g oral glucose load. The study patients were randomized into two groups: the troglitazone group of 25 patients with 29 stents, who were treated with 400 mg of troglitazone, and the control group of 27 patients with 33 stents. All patients underwent oral glucose tolerance tests before and after their six-month treatment period. The sum of PG (sum of PG) and the sum of insulin levels (sum of IRI) were measured. Serial (postintervention and at six-month follow-up) intravascular ultrasound studies were performed. Cross-sectional images within stents were taken at every 1 mm, using an automatic pullback. Stent areas (SA), lumen areas (LA), and intimal areas (IA = SA - LA) were measured and averaged over a number of selected image slices. The intimal index was calculated as intimal index = averaged IA/averaged SA x 100%. RESULTS: There were no differences between the two groups before treatment in sum of PG (31.35 +/- 3.07 mmol/liter vs. 32.89 +/- 4.87 mmol/liter, respectively, p = 0.2998) and sum of IRI (219.6 +/- 106.2 mU/liter vs. 209.2 +/- 91.6 mU/liter, respectively, p = 0.8934). However, reductions in sum of PG at the six-month follow-up in the troglitazone group were significantly greater than those in the control group (-21.4 +/- 8.8% vs. -4.5 +/- 7.4%, respectively, p < 0.0001). Likewise, decreases in sum of IRI were greater in the troglitazone-treated group (-31.4 +/- 17.9% vs. -1.9 +/- 15.1%, respectively, p < 0.0001). Although, there were no differences between the two groups in SA at postintervention (7.4 +/- 2.2 mm2 vs. 7.3 +/- 1.7 mm2, respectively, p = 0.9482) and at follow-up (7.3 +/- 2.3 mm2 vs. 7.3 +/- 1.8 mm2, respectively, p = 0.2307), the LA at follow-up in the troglitazone group was significantly greater than that in the control group (5.3 +/- 1.7 mm2 vs. 3.7 +/- 1.7 mm2, respectively, p = 0.0002). The IA at follow-up in the troglitazone group was significantly smaller than that in the control group (2.0 +/- 0.9 mm2 vs. 3.5 +/- 1.8 mm2, respectively, p < 0.0001). This was also true for intimal index (27.1 +/- 11.5% vs. 49.0 +/- 14.4%, respectively, p < 0.0001). CONCLUSIONS: Serial intravascular ultrasound assessment shows that administration of troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with NIDDM.