Assessment of platelet-derived thrombogenicity with the total thrombus-formation analysis system in coronary artery disease patients receiving antiplatelet therapy.

BACKGROUND: Accurate evaluation of thrombogenicity helps to prevent thrombosis and excessive bleeding. The total thrombus-formation analysis system (T-TAS) was developed for quantitative analysis of platelet thrombus formation by the use of microchips with thrombogenic surfaces (collagen, platelet chip [PL-chip]; collagen plus tissue factor, atherome chip [AR-chip]). We examined the utility of the T-TAS in the assessment of the efficacy of antiplatelet therapy in patients with coronary artery disease (CAD). METHODS AND RESULTS: In this cross-sectional study, 372 consecutive patients admitted to the cardiovascular department were divided into three groups: patients not receiving any antiplatelet therapy (control, n = 56), patients receiving aspirin only (n = 69), and patients receiving aspirin and clopidogrel (n = 149). Blood samples were used for the T-TAS to measure the platelet thrombus-formation area under the curve (AUC) at various shear rates (1500 s(-1) [PL18 -AUC10 ] and 2000 s(-1) [PL24 -AUC10 ] for the PL-chip; 300 s(-1) [AR10 -AUC30 ] for the AR-chip). The on-clopidogrel platelet aggregation was measured by the use of P2Y12 reaction units (PRUs) with the VerifyNow system. The mean PL24 -AUC10 levels were 358 ± 111 (± standard deviation) (95% confidence interval [CI] 328.9-387.1) in the control group, 256 ± 108 (95% CI 230.5-281.5) in the aspirin group, and 113 ± 91 (95% CI 98.4-127.6) in the aspirin/clopidogrel group. In the aspirin/clopidogrel group, the PL24 -AUC10 was higher in poor metabolizers (PMs) with cytochrome P450 2C19(CYP2C19) polymorphisms (152 ± 112, 95% CI 103.4-200.6) than in the non-PM group (87 ± 74, 95% CI 73.8-100.2). CONCLUSIONS: Our findings suggest that the PL24 -AUC10 level measured by the T-TAS is a potentially suitable index for the assessment of antiplatelet therapy in CAD patients.

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.

Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

A novel approach to endoscopic colorectal mucosal resection using a three-channel outer tube and multiple forceps: an experimental assessment.

BACKGROUND AND STUDY AIMS: Colorectal endoscopic mucosal resection (EMR) has limitations both anatomically and technically when it is done using the conventional snare wire method. The aim of this study was to develop a new method and instrument for colorectal EMR. METHODS: A total of 21 EMR procedures were done using ten surgical specimens. Saline was injected into the normal submucosa of freshly resected colorectal specimens to prepare a pseudotumor. EMR was performed experimentally by employing a three-channel outer tube with three forceps and a colonoscope with a needle-type precutting knife. This method was assessed in terms of safety and the size of the resected specimens. RESULTS: Perforation occurred only twice in the initial stage of this study. The size of the specimens resected by EMR was 28-39 mm (long diameter 34.8+/-3.11), by 22-28 mm (short diameter 25.8+/-2.07). CONCLUSION: This method can achieve safety and en bloc mucosal resection to the submucosal layer. This novel approach may be promising for clinical application as a new form of endoscopic surgery.

Quantitative assessment of severity of ventricular septal defect by three-dimensional reconstruction of color Doppler-imaged vena contracta and flow convergence region.

BACKGROUND: The aim of the present study was to investigate the feasibility and potential value of the computer-controlled, 3D, echocardiographic reconstruction of the color Doppler-imaged vena contracta (CDVC) and the flow convergence (FC) region as a means of accurately and quantitatively estimating the severity of a ventricular septal defect (VSD). METHODS AND RESULTS: We performed a 3D reconstruction of the CDVC and the FC region in 19 patients with an isolated VSD using an ultrasound system interfaced with a Tomtec computer. The variable asymmetric geometry of the CDVC and the FC region could be 3D-visualized in all patients. The 3D-measured areas of CDVC correlated well with volumetric measurements of the severity of VSD (r=0.97, P:<0.001). Regression analysis between the shunt flow rate (calculated from the product of the area of CDVC and the continuous Doppler-derived velocity time integral) and the corresponding reference results (calculated by cardiac catheterization) demonstrated a close correlation (r=0.95, P:<0.001). There was also a good correlation between shunt flow rates calculated using the conventional 2D, 1-axis measurement of the FC isovelocity surface area with the hemispheric assumption (r=0.95, P:<0.001); shunt flow rates calculated using 3D, 3-axis measurements of the FC region (r=0.97, P:<0.01); and reference results by cardiac catheterization. However, the 2D method substantially underestimated the actual shunt flow rate. CONCLUSIONS: The 3D reconstruction of the CDVC and the FC region may aid in quantifying the severity of VSD.

[Day surgery for cholecyst lithiasis].

Since 1997, laparoscopic cholecystectomy has been performed as one-day surgery (LC/DS) at our institution. Among the 122 patients enrolled in this program, 97 (80%) were successfully discharged within 24 hours after admission. Discharge was delayed for the other 25 patients, although 12 (48%) of them were discharged on postoperative day (POD) 2 or 3. This study not only verified the efficacy of LC/DS in shortening convalescence and allowing an early resumption of work but also confirmed the safety of LC/DS except in one patient with hemophilia A who required laparotomy for intraabdominal bleeding on POD 13. LC/DS is now the first choice of treatment for cholelithiasis regardless of symptoms. Discharge can be expected within 24 hours after admission in most cases, although the preference of patients should be considered when determining the timing of discharge.

Assessment of global left ventricular function in normal children and in children with dilated cardiomyopathy.

A Doppler index combining systolic and diastolic time intervals (Tei index) has been reported to be useful for assessing global left ventricular (LV) function and predicting clinical outcome in adult patients with LV dysfunction. However, normal values in children and age-related changes in the index have not yet been clarified. The aim of this study was to prospectively determine normal values of the Tei index and the effect of aging on the index in children and to assess the global cardiac function in patients with dilated cardiomyopathy with this index. The subjects included 161 consecutive normal children aged 30 days to 18 years and 5 patients with dilated cardiomyopathy. The Tei index was defined as the sum of the isovolumetric contraction time and the isovolumetric relaxation time divided by the ejection time and was measured from conventional LV outflow and inflow Doppler velocity profiles. The Tei index correlated significantly with the logarithm of age (r = 0.51, P <. 001). The index decreased with aging until 3 years and then did not change after age 3 years. The Tei index in children under age 3 years (0.40 +/- 0.09, n = 80) was significantly higher than that in children ranging in age from 3 to 18 years old (0.33 +/- 0.02, n = 81). The index in patients with dilated cardiomyopathy (0.78 +/- 0. 28) was markedly increased compared with that in normal subjects. Age-related changes in the Tei index may reflect maturational or developmental alterations in the LV properties in infants. The data in this study give basic information for further quantitative assessment of global cardiac function in children with congenital or acquired heart disease.

[A report on medical assistance for patients with cleft lip and palate and technical transfer in Vietnam].

We had participated in the charitable operation for the patients with cleft lip and palate and technical suidance in Vietnam in 1998 for 2 weeks. The project was a part of the activities of the Japanese Cleft Palate Foundation, which were performed as part of the Official Development Assistance (ODA) of Japan, and was aided by state subsidy of the Ministry of Posts and Telecommunications, the Ministry of Foreign Affairs and the Ministry of Education and so on. Our team consisted of members of Tokyo Dental College, Iwate Medical University, Dalhousie University, and our university. The hospital we visited was Odonto-Maxillo-Facial Center in Ho Chi Min City, which had 7 clinical departments, 36 dental units, 60 beds in ward, and 75 doctors in total. This hospital dealt with all kinds of disease in connection with oral and maxillo-facial area including dental caries, periodontal disease, maxillo-facial injuries, and maxillo-facial anomalies. Forty-five patients with cleft lip and palate were operated on during our stay in Vietnam. The age of these patients was higher than that in medical advanced countries because of economic problems and insufficient medical institutions. In some cases, surgery was performed in collaboration with local doctors, which means technical suidance leads to more effective treatment.

Selective high dose gamma-globulin treatment in Kawasaki disease: assessment of clinical aspects and cost effectiveness.

BACKGROUND: High-dose intravenous gamma-globulin (IVGG) plus aspirin (ASA) treatment is effective in preventing coronary artery complications in acute Kawasaki disease (KD). However, gamma-globulin is very expensive, especially in Japan. Furthermore the indication for IVGG treatment and the optimal dose of gamma-globulin remain controversial. OBJECTIVES: To examine these two issues, we used Harada's scoring system to investigate whether a single 2 g/kg dose therapy has any advantage over the 5 day 400 mg/kg per day therapy. METHODS: We studied 203 patients with KD who had no coronary artery complications on admission. Of these, 145 patients scored 4 or more on Harada score within the first 9 days of illness and were treated with IVGG treatment. Using a random number table, 72 patients were selected to receive a single 2 g/kg dose (2 g group), while the remaining 73 patients were treated with 400 mg/kg per day for 5 consecutive days (400 mg group). Those who had a Harada score of three or less received no IVGG (non-IVGG group) treatment (58 patients). RESULTS: The incidence rate of coronary artery complications in the 2 g group was significantly lower than in the 400 mg group. The duration of high fever, positive duration of C-reactive protein and the number of hospital days in the 2 g group were each significantly shorter than in the 400 mg group. The total medical expense in the 2 g group was significantly lower than in the 400 mg group. There were no coronary artery complications in the non-IVGG group. CONCLUSIONS: It was found to be clinically more effective and more cost effective to select a patient by Harada's scoring system and, where a score of four or more was obtained, to administer a single 2 g/kg intravenous dose of gamma-globulin for acute KD.

[Assessment of ischemic heart disease by dipyridamole stress electrocardiographic gated myocardial single photon emission computed tomography with technetium-99m tetrofosmin].

Simultaneous assessment of stress perfusion and rest function is possible with gated single photon emission computed tomography (SPECT) using stress injected technetium-99m (99mTc) tetrofosmin (TF). The feasibility of dipyridamole stress electrocardiographic gated myocardial SPECT (GSPECT) with TF was examined as an alternative to conventional stress/rest imaging. Fifty-one patients underwent stress GSPECT. 740 MBq of TF was administered 3 min after dipyridamole infusion. GSPECT acquisition was performed one hour after the injection. Additional rest SPECT was performed on another day only in patients with abnormal perfusion on stress images. Perfusion and thickening were analyzed visually on 17 segments of the left ventricle. Percentage of wall thickening (%WT) was also calculated in 17 segments of the polar map. Thirty-two of 51 patients (63%) had normal stress perfusion and normal rest thickening. Nineteen of 51 patients (37%) had abnormal perfusion on stress images. Among 157 abnormal perfusion segments of the 19 patients, 139 segments (89%) had thickening and the rest (11%) had no thickening. %WT was higher in the reversible segments with or without thickening. There was better agreement for the identification of normal segments and the presence of reversibility between stress GSPECT and the conventional stress/rest study in patients without previous myocardial infarction than in those with previous myocardial infarction (89% vs 79%). These results suggest that stress GSPECT may substitute for conventional stress/rest perfusion study in patients without previous myocardial infarction, allowing shorter examination time and lower cost. However, stress GSPECT does not replace the need for rest perfusion study in patients with previous myocardial infarction, because of underestimation of viability, but %WT may eliminate this underestimation.

Intravascular ultrasound assessment of regional aortic wall stiffness, distensibility, and compliance in patients with coarctation of the aorta.

BACKGROUND: Impaired aortic pulsatility has been demonstrated by angiography in children and in studies of experimental animals with coarctation of the aorta. OBJECTIVES: The purpose of this study was to assess regional aortic stiffness, distensibility, and compliance before and after balloon dilation in patients with coarctation of the aorta. METHODS AND RESULTS: Intravascular ultrasound examination was performed in 13 pediatric patients with the diagnosis of coarctation of the aorta to yield aortic diameter. Area transverse sections at both systolic and diastolic period were measured at three aortic levels: the proximal, distal, and coarctation segments. Balloon dilation was also performed in eight of 13 patients. By using pressures measured in the same areas, an aortic stiffness index (beta) was calculated as In(Ps/Pd)/(Ds-Dd), where In is natural logarithm, Ps is systolic pressure, Pd is diastolic pressure, Ds is systolic diameter, and Dd is diastolic diameter. Aortic distensibility and an estimation of aortic compliance were also calculated. The beta stiffness index of the coarctation and the proximal segments of the aorta were significantly greater than that of the distal segment of the aorta (p < 0.01). The aortic wall stiffness beta index did not acutely change after successful balloon dilation, but the distensibility and compliance of distal aorta were nonetheless significantly decreased after balloon dilation (p < 0.01, p < 0.05) as a function of changes of pulsatility of flow. CONCLUSIONS: Abnormal proximal aortic stiffness may be a strong contributing factor that promotes the genesis of hypertension in patients with coarctation even after successful repair or balloon angioplasty.

[Assessment of auscultatory blood pressure measurements versus intra-arterial pressure in patients with atrial fibrillation].

The accuracy of auscultatory blood pressure (BP) determination was assessed in patients with chronic atrial fibrillation by performing simultaneous auscultatory BP determination on the upper arm and a direct BP determination on the contralateral arm. The subjects were three hospitalized patients, aged from 52 to 75 years. A Teflon catheter was introduced into the radial artery which was connected to a pressure transducer, and a cuff was twisted around the contralateral upper arm in the supine position. Simultaneous recording of directly determined BP and cuff pressure enabled the comparison of direct BP with auscultatory BP. The appearance of the Korotkoff I sound (systolic BP) and V sound (diastolic BP) was marked on the cuff pressure curve. This maneuver was repeated five times in each patient. The method of Bland and Altman was employed to assess the agreement between auscultatory and direct determinations. The auscultatory method estimated BP with differences of -14.3 to +27.3 mmHg in systolic BP and -12.1 to +11.9 mmHg (+/-2SD) in diastolic BP compared with the direct method. The difference in systolic BP between the auscultatory and the direct methods was greater than that in diastolic BP. Thus, there are unacceptable differences in systolic BP between auscultatory and direct methods that can be attributed to BP fluctuations. The auscultatory method in diastolic BP is more accurate than that in systolic BP and may be more useful in the clinical setting.

Assessment of the accuracy of indirect blood pressure measurements.

This study assessed the accuracy of indirect blood pressure (BP) measurements by simultaneously performing three kinds of indirect BP measurement on the left arm (auscultatory, microphone and oscillometric methods) and a direct BP measurement on the left arm. The subjects were 34 hospitalized patients, ranging in age from 18 to 73 years (average 47.5 years). Highly significant correlations in systolic or diastolic BP between a given pair of the three indirect methods. The indirect methods underestimated systolic BP and overestimated diastolic BP compared with the direct method, with differences of -12.2 +/- 10.5/+4.6 +/- 7.6 (systolic/diastolic BP) with the oscillometric method, -8.1 +/- 9.7/+1.2 +/- 8.9 with the microphone method and -10.6 +/- 8.1/+3.7 +/- 6.5 mmHg with the auscultatory method. The difference in systolic BP between the auscultatory and direct methods was greater and the difference in diastolic BP was smaller in subjects older than 50 years than in those aged 50 years or less (p < 0.001 for systolic BP, p < 0.05 for diastolic BP). The auscultatory method revealed greater systolic BP in subjects with increased carotid arterial wall stiffness assessed by echoarteriography. Thus, it is concluded that there are inherent differences in BP between the indirect and direct methods which can be attributed to the changes in arterial wall physical properties partly due to aging.

[A new protein titrator tape for self-assessment by outpatients with proteinuria].

l- have invented a new dipstick (protein titrator tape) for measuring the volume of protein excreted in the 24-hour urine. The principle of the method is based on the protein error of indicators with the modification of a conventional dipstick test. The dipstick consists of two thick filter papers, containing differently adjusted pH indicators of tetrabromphenol blue, making it possible to detect a wide range of protein concentrations in the urine using a standard color chart that includes twenty color blocks. Two hundred and ninety outpatients had their urine samples assessed with this method as well as with the pyrogallol red test as a comparative study for quantitative measurement of protein concentrations. The new-type dipstick method exhibited good correlation with the results of the pyrogallol red test, especially in the range of protein concentrations from 50 mg/dl to 400 mg/dl, showing the linear equation of "y (Pyrogallol red) = 10.5 + 0.99 x (Dipstick) (r = 0.91, P < 0.01)". Although there was good correlation with the pyrogallol red test at higher concentrations from 400 mg/dl to 1,000 mg/dl, the dipstick method tended to exhibit lower concentrations than those indicated by the counterpart method. The rate of consistency between observers was quite high. This new-type dipstick method will offer a reliable method for patients or their family to assess their protein excretion in the urine every 24 hours at home using a portable urine sampling device.

Intravascular ultrasound of coronary arteries in children. Assessment of the wall morphology and the lumen after Kawasaki disease.

BACKGROUND: The long-term clinical issue in Kawasaki disease (KD) concerns the coronary artery lesion. Two-dimensional echocardiography and coronary angiography are routine examinations to evaluate the coronary lesions; however, these are not adequate to assess the wall morphology of the coronary artery (CA). Intravascular ultrasound imaging (IVUS), a new technology for the evaluation of the coronary artery lumen and wall morphology in vivo, was performed for patients after KD in their long-term follow-up, and we examined the new insights it gave. METHODS AND RESULTS: IVUS was performed during cardiac catheterization in 20 subjects (10 patients after KD who still had coronary aneurysms or regressed coronary aneurysms, 2 after KD who had no coronary abnormal lesion, and 8 control patients with congenital heart disease and normal CA). We evaluated the wall structure at 10 to 15 sites of the CA in each patient. IVUS was performed with a commercially available ultrasound imaging catheter. Four sites of a CA aneurysm in KD demonstrated a markedly dilated lumen without thickened intima. One site of a CA aneurysm with calcification demonstrated an asymmetrical lumen by a dense echo with acoustic shadows. Twenty-two sites of a regressed CA aneurysm demonstrated a marked symmetrical or asymmetrical thickening of the intima with a dense echo, in which the size of the lumen was similar to that at a site near a regressed aneurysm. The sites of angiographically normal CA revealed normal structures and a thin intima in many instances. Nine of 28 sites in KD with a CA abnormal lesion, particularly near a coronary aneurysm or regressed aneurysm, demonstrated a mild thickening of the intima. All the 10 sites in KD without a CA abnormal lesion and all the 25 sites in patients with congenital heart disease with normal CA demonstrated a smooth intima. CONCLUSIONS: This study demonstrated that the site of a regressed coronary aneurysm has a markedly thickened but smooth intima. The sites of angiographically normal CA after KD with or without a coronary lesion demonstrated normal IVUS findings in most instances but in some cases revealed a mild intimal thickening. IVUS is useful to evaluate the CA wall morphology and may contribute to the assessment of long-term CA sequelae and the possible development of arteriosclerotic changes in KD.

The use of the dose-response curve in the assessment of normal and asymptomatic asthmatic patients.

We studied bronchial reactivity, the slope of the dose-response curve to inhaled methacholine, in normal subjects (N), young asthmatics with normal respiratory resistance (Rrs) (YAL), young asthmatics with high Rrs (YAH), and old asthmatics with high Rrs (OAH) by three different methods: linear reactivity (slope of the linear cumulative dose-conductance (Grs = 1/Rrs) curve), timed reactivity (slope of the log concentration-Grs or time-Grs curve), and log reactivity (slope of the log cumulative dose-Grs curve). There were significant differences in linear reactivity between the N and the three asthmatics but no difference among the three asthmatic groups. On the other hand, both timed and log reactivities showed significant differences between the three asthmatic groups. Log and timed reactivities corrected by baseline Grs did not differentiate the YAL from the YAH but showed a significant difference between the YAH and OAH. This study suggests that timed and log reactivities may be better indices of bronchial reactivity than linear reactivity because they differentiate asthmatics, and that bronchial reactivity in asthmatics may be dependent on not only baseline airway caliber in asthmatics but also other factors such as atopic status or age.