When direct measurement of serum low density lipoprotein cholesterol (LDL-c) is not available, it can be estimated from total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-c) by using the formula proposed by Friedewald : LDL-c = TC- [HDL-c + TG/k], k =5 This formula assumes the triglyceride/cholesterol ratio in VLDL to be 5:1. However, it is changeable with serum triglyceride levels, and averaged as 4 among Japanese with triglycerides less than 400 mg/dl. The formula provides a better fit for Japanese people, when k=4, rather than original k=5. In addition, a better estimation is gained, if k is rotated according to the triglyceride levels of individual subjects ; i.e. 3 for those with triglycerides less than 150 mg/dl, 4 for those with triglycerides from 150 to 299 mg/dl, 5 for those with triglycerides from 300 to 400 mg/dl. The percent error of estimation is less than 5% when k=4, and about 1% when variable k is employed for populations of about 1, 000 subjects in number.

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Endomyocardial biopsy was performed on eight children 5 to 12 years old, who were in post myocarditic state. They were evaluated within 2 to 25 months (mean lyr and 1 m) after the onset of the symptoms. Two of the patients developed heart failure and six patients developed other cardiac manifestations such as syncope, palpitation or EG abnormalities at onset. Definite elevation of viral antibody titer was observed in four patients. Radio-nuclide angiography was also performed in all eight patients. An abnormal perfusion area was observed in six patients as a focal hypoperfusion area by Tl-201 myocardial imaging. Ejection fraction was examined by Tc-99m-HSA gated equilibrium ventriculography. LVEF was reduced in 3 patients and RVEF was reduced in 2 patients. Judging from the histopathological findings, these patients were divided into three categories : chronic or smoldering myocarditis (3 patients) ; healing or healed myocarditis (4 patients); and post myocarditic hypertrophy (1 patient). Measurement of left ventricular function was obtained by cardiac catheterization and left ventriculography (LVG), which revealed some abnormal findings such as increased left ventricular mass index, increased left ventricular end diastolic volume index (LVEDVI) and reduced left ventricular ejection fraction (LVEF). Therefore, endomyocardial biopsy findings of pediatric patients in a post myocarditic state reveal certain histopathological abnormalities even in the long-term follow-up period in the absence of cardiac dysfunction.

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Ventricular volume measurements of single ventricle were carried out in 20 patients with or without palliation and in 2 after total correction. In the former 20 patients, 6 had a single left ventricle and 14 a single right ventricle, anatomically. Two having total correction were associated with undivided ventricle. In the 20 patients with or without palliation, ventricular end-diastolic volume ranged from 64 to 206 (115±42) percent of the sum of the normal left and right ventricular volume. Ejection fraction of single ventricle ranged from 0.40 to 0.64 (0.55±0.06). There was no significant difference in ventricular volume and ejection fraction between patients with a single left and right ventricle. There was high correlation of ventricular volume with pulmonary to systemic blood flow ratio (r=0.66, p<0.005). This indicates that systemic-to-pulmonary shunt should increase ventricular volume of single ventricle. In two patients after total correction, total ventricular volume was 136 and 166% of the sum of the normal left and right ventricular volumes. Total ejection fraction was 0.55 and 0.33 in the first and second patient, respectively. The prosthetic ventricular septum bulged toward the right ventricle during systole and this shift made the left ventricular volume increase and ejection fraction decrease. Right-to-left ventricular volume ratio at end-diastole was 0.74 and 0.67 in the first and second patient, respectively. These results suggest that 1) larger ventricular volume than the sum of the normal left and right ventricular volumes would be required for septation of single ventricle, 2) systemic-to-pulmonary shunts would be effective to increase ventricular volume of single ventricle, and 3) single ventricles should be divided into two to make a larger left and a smaller right ventricle, in cases where the right ventricular pressure is lower than the left after septation.

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The present study was designed to investigate the short-term effects of intracerebroventricularly-administered taurine in DOCA-salt hypertensive (DOCA), spontaneously hypertensive (SHR) and their respective normotensive control rats anesthetized with urethane. Blood pressure, heart rate and sympathetic nerve activity were consistently decreased following the injection of taurine 150μg per rat in hypertensive rats as well as in normotensive controls of the two groups. Percent changes from the baselines in blood pressure, heart rate and sympathetic nerve activity were significantly larger in DOCA-salt hypertensive rats than those in sham operated rats. In contrast, percent changes in blood pressure and sympathetic nerve activity were not significantly different between spontaneously hypertensive rats and normotensive wistar kyoto rats. These result show that the responses of blood pressure, heart rate and sympathetic nerve activity to intracerebroventricular taurine are different between spontaneously hypertensive rats and DOCA-salt hypertensive rats. It appears that augmented vasodepressor responses to taurine in DOCA-salt hypertensive rats, compared to spontaneously hypertensive rats, are due to enhanced inhibition of the sympathetic outflow.

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Large cerebral infarctions were caused by atherosclerosis with or without thrombosis in the proximal circumflex (cortical) cerebral arteries. Hypertension, hypercholesterolemia, hypoxidosis, and vasospasm were considered to induce endothelial cell injuries, which might be the primary events not only in atherosclerosis, but also in arteriosclerosis and arteriosis formation. Morphogenesis of atherosclerosis and causes of associated thrombosis were also discussed. Small cerebral infarcts were produced not only by arteriosclerosis, arteriosis, and atherosclerosis, but also by arterionecrosis-derived microaneurysms occluded by thrombi in the distal penetrating (perforating) cerebral arteries. Pathogenesis and morphogenesis of the arterial lesions were discussed. Recent increase of the arterionecrosis occluded by thrombosis in the pathogenesis of small infarcts (lacunes) was noted. The direct cause of hypertensive cerebral hemorrhage was the rupture of arterionecrosis-derived microaneurysms in the distal penetrating cerebral arteries. The primary change of the arterionecrosis was the medial muscle cell necrosis, the causes of which were considered to be hypertension, aging poor diet low in cholesterol, vasospasm and the congenitally poor wall structure of the arteries. The development and healing of experimental arterionecrosis in hypertensive rats were also reported.

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Rheumatic fever (RF) is the common cause of rheumatic heart disease (RHD) in the 5-30 age group and is usually preceded by group A streprococcal pharyngitis. The annual mortality caused by RF and RHD has changed remarkably in Japan between 1960 and 1981 according to the report of the Ministry of Health and Welfare. The annual incidence of RF among schoolchildren as surveyed from pediatric clinics of 20 major hospitals between 1952 and 1980 varied year by year, and is now steadily declining. Follow-up studies of 287 patients with carditis over ten years showed that cardiac murmur disappeared in 44.9% of total patients within 4 years through use of antibiotic prophylaxis. Other patients continued to have cardiac murmur 10 years after the first attack of RF. Valvular involvement due to RF was mostly confined to mitral valve and the appearance of mitral regurgitation was particularly common in schoolchildren. Survey of RHD in schoolchildren showed that mitral regurgitation was the most common anomaly, but the prevalence rate of RHD decreased from 4.6/1000 population in 1958 to 0.14/1000 population in 1981. By contrast, mitral stenosis was predominant in adults, according to the records of patients admitted in three university hospitals. Since socio-economic conditions have improved, and penicillin has been introduced to control group A streptococcus, mortality and morbidity from RF and RHD have remarkably decreased in well developed countries. These factors may have contributed predominantly to the sharp decrease in first and recurrent attack of RF in Japan.

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A rapid diagnostic test for group A streptococci from throat swabs (Culturette Brand 10-Min Strep ID test of Marion Inc.) was performed in 210 patients with acute pharyngitis. This agglutination test is based on the extraction of streptococcal polysaccharide by nitrous acid and observe agglutination with anti-polysaccharidecoated latex suspension. There was a 95.2% total agreement with a standard culture method and agglutination test and specificity of 93.4% sensitivity of 96.0% positive predictive value of 90.5% and negative predictive value of 97.3%. From the results of our study, the agglutination test for group A streptococci is of diagnostic value. This new kit would be most useful in out-patient clinics, especially in a small private medical office without culture facilities.

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The Culturette Brand 10-Minute Group A Strep ID test kit (Marion Scientific, Division of Marion Laboratories, Inc., Kansas City, Mo.) was evaluated for its sensitivity and specificity in identifying the group A streptococci directry form 96 throat swabs, against the conventional culture method and serological grouping test. Our results indicated that the rapid test kit and conventional method are 93.8% accurate ; percent sensitivity and specificity of the rapid test was 80.6% and 100%, respectively. None of the false-positive observed in rapid test kits occured with the heterogeneous microorgainsmus. More than 8 ×10⁴ colony forming unit per swab was required for the positive latex agglutination of the test kit. Since the Culturette method is simple to perform and correctly identifies group A streptococcal antigen, and also required no special instruments, it appears to be applicable in hospital laboratories and outpatients clinics.

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After sensitization by M-protein fraction (MP) of hemolytic streptococci for two generations, Wistar rats were injected with 9 ml/kg of MP on day 9 of gestation (plug day=day 0). The incidence of malformations was about 12% whether anti-MP antibody was positive or not in the maternal sera. The primary malformations were ventricular septal defect, anophthalmia, and microphthalmia. Light microscopic study revealed no myocarditis nor endocarditis in either the maternal or fetal heart. No antinuclear antibody was detected in the maternal sera by the fluorescent antibody technique. No complete heart block was found in the fetus by electrocardiogram. These results were similar to previous findings using a single injection of MP, and therefore further demonstration that the principal factor in the teratogenesis induced by MP administration in the rat is not an inflammation in the fetal organs caused by an autoimmune mechanism but rather yolk sac dysfunction.

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An acquired defect or damage of a subpopulation of suppressor T lymphocytes is reported in connection with autoimmune diseases. In the present study, the role of immunity was examined in 7 patients with dilated cardiomyopathy (DCM). The frequency of lymphocyte subsets using monoclonal antibodies and natural killer (NK) cell activity was evaluated to determine whether DCM patients had lymphocyte abnormalities that would support the hypothesis that the pathological mechanism of DCM is an immune disturbance. The peripheral lymphocyte counts were significantly lower in patients with DCM and higher in patients with ischemic heart disease (IHD) than in normal controls (NC) (p< 0.01). The percentage of T cells, B cells, OKT4 and OKT8 positive cells was not statistically different among the three groups studied here, whereas the percentage of T_γ cells was significantly reduced in DCM patients (p < 0.05). NK cell functional activity as tested in DCM and IHD patients was frequently deficient (22.1 ± 19.3% in DCM, 13.8 ± 3.0% in IHD, 37.4 ± 12.7% in NC). Our results suggest that an imbalance in cellular immune reactions partly explain the pathogenesis of DCM.

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We studied the in vivo effects of eosinophilic cationic protein (ECP) on DBA/2 mice, and compared the cardiac lesions caused by ECP with those caused by encephalomyocarditis (EMC) virus. ECP caused myocarditis in two of five mice (40%), and EMC virus did so in five of five mice (100%). Cardiac lesions of ECP were mild and limited to the right ventricular wall, which differed from those in the mice with EMC virus inoculation, where both the right and left ventricles were involved. This experiment is the first demonstration of the in vivo cardiotoxicity of ECP.

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This light- and electron-microscopic study using monoclonal antibodies provides an immunohistochemical demonstration of lymphocytes in situ in the myocardium in murine coxsackie B3 virus myocarditis. On the 7th and 9th days after virus inoculation, we observed many necrotic cardiocyte foci infiltrated with numerous inflammatory cells including macrophages and T lymphocytes. There were only a few Lyt 1-bearing lymphocytes in this phase of inoculation. On the 14th day there were many Lyt 1-bearing cells among the T cells in the foci. By immuno-electron microscopy, some Lyt 1-bearing T lymphocytes were seen in close contact with macrophages and/or other lymphocytes. These Lyt 1-bearing lymphocytes appeared to represent helper T cells, although Lyt 2.3 + lymphocytes were not examined. It is well known that activation of helper T cells leads to stimulation of B cells and cytotoxic T cells. It is assumed, therefore, that Lyt 1-bearing T lymphocytes that infiltrated into the myocardial foci play an important role in immune responsiveness at this stage of viral myocarditis.

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A 3 year-old Japanese girl had an acute onset associated with vomitting. The electrocardiogram (ECG) indicated changes similar to those of acute myocardial infarction (MI) ; there was no past history of kawasaki disease. Selective coronary angiography taken on the 28th day of illness revealed no abnormality. Thallium 201 scintigraphy was also performed and it revealed that the area of abscent myocardial uptake was in the anterior wall. In serological findings, antibody titers against Coxsackie B-3 virus had risen significantly ; therefore acute myocarditis caused by Coxsackie B-3 virus infection was diagnosed.

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From our study employing serial endomyocardial biopsy in patients with acute viral or idiopathic myocarditis, we were able to construct histopathologic criteria for acute, subacute and convalescent myocarditis. We realize that it is difficult for the inexperienced observed to make an appropriate diagnosis of myocarditis or postmyocarditic changes in patients with dilated cardiomyopathy (DCM). In order to overcome this problem, each finding was graded and the scores obtained were analyzed statistically and compared with those from hypertrophic cardiomyopathy (HCM) and chronic right ventricular overloading (CRVO). The scores were obtained by summing the gradings for each of the following findings : increase of fibrocytes, increase of fibroblasts in the interstitium, hypertrophy of myocytes, fragmentation of muscle bundles, interstitial fibrosis, disarrangement of muscle bundles, abnormal branching, variation in size, increased glycogen deposition in the sarcoplasm, scarcity of myofibrils, and nuclear degeneration of myocytes and endocardial thickening. Since the increase in number of fibrocytes was considered important, its value was doubled. Scores in each group were as follows : convalescent myocarditis : 17.1 ± 4.7 (n=10), DCM : 13.2 ± 3.3 (n=47), HCM : 9.7 ± 2.4 (n=20), CRVO : 7.0± 3.6 (n=21). It was found that the scores for cases with myocarditis in the convalescent stage and in DCM were higher than those found for cases with either HCM and CRVO (p < 0.05). In summary, the high score for postmyocarditis in DCM could suggest that prior myocarditis is an important causative factor of this disease.

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In the annuals of autopsy records in Japan, edited by the Japanese Society of Pathology and covering 20 years, from 1958 to 1977, 377841 autopsy cases are registered with a short summary of the pathology findings. Of these, 434 cases with idiopathic, interstitial, viral, non-specific (NSM) and giant cell (GCM) myocarditis were found. The incidences of NSM and GCM were 0.11 and 0.007%, respectively. The annual incidence of NSM showed periodic fluctuations with in 5-year intervals and increased remarkably after 1974. Incidence of GCM showed a similar fluctuation but with a one to two year delay of peaks. The male to female ratio was 1.2 : 1 and the age distribution had two peaked patterns for both sexes, though these peaks were scattered widely from neonate to elderly patients. The regional distribution of NSM showed a concentration in the middle portion of Honshu and its regional annual incidence had propagation waves from the central area to peripheral areas. The same tendency was observed in GCM cases. Hokkaido was characterized by a low incidence of NSM and no GCM. Complications of myocarditis included pancreatitis, pneumonitis, , interstitial nephritis, meningoencephalitis, hepatitis, hepatic cirrhosis and a considerable incidence of malignancies. Antibiotics, antineoplastic agents, steroids and irradiation therapy were the main forms of treatment applied before or after the start of myocarditis.

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Twenty-three cases of IE, of which 91% had underlying congenital heart diseases were diagnosed by positive blood culture or vegetative lesion detected by 2-D ECHO when a patient revealed clinically suspicious episodes. VSD and TOF were the most common underlying heart diseases. The vegetation was detected successfully by 2-D ECHO in 91% of the cases. The causative organisms were identified in 83% of the cases. Streptococcus viridans and Staphylococcus aureus were the two major organisms detected. Candida albicans was found in 3 postoperative and fatal cases. Embolic complications occurred in 7 cases (30.5%) : five cases of pulmonary infarction and two of cerebral infarction. The overall mortality was 22%. We recommend early surgical intervention whenever a patient reveals a very large vegetation with animated movability, and emphasize the importance of a proper prophylaxic regimen.

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In patients with acquired valvular heart disease detected by group cardiac examinations at school, we analyzed follow-up data obtained during school days as well as after graduation from senior high school. 1) Of the 343 patients followed up after graduation from senior high school up to an age range of 20-38 years (mean : 29.3 years), 18 (5.2%) died, 16 (4.7%) deteriorated, 159 (46.4%) remained unchanged, 40 (11.7%) improved, 18 (5.2%) spontaneously recovered and 30 (9.7%) were treated surgically. 2) Of patients who showed spontaneous recovery after graduation from senior high school, 16 cases (8.4%) had mitral regurgitation and 2 (3.6%) had mitral stenosis-regurgitation. 3) In some patients, the disease type changed many years after graduation from senior high school. In particular, the appearance of stenosal lesions in the mitral or aortic valve was often delayed. 4) The mean annual death rate for patients with acquired valvular heart disease (age range : 6-38 years) between April 1962 and March 1983 was 0.65%. The rate peaked at the 15-17 years age range. In recent years, the fatality rate has been falling and no deaths are seen in younger patients. 5) In the past, the leading cause of death in juvenile patients with acquired valvular heart disease was the recurrence of rheumatic fever. For the past ten years, however, no death attributable to the recurrence of rheumatic fever has been registered.

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A 13-year follow-up study was performed in 301 patients with rheumatic heart disease (RHD). Of these patient, 223 cases, 78 men (average age 59.3 years) and 145 women (average age 60.4 years), survived. Seventy-eight cases including 38 men (mean age of death 72.5 years) and 40 woman (mean age of death 64.8 years) died. RHD consisted of 51% mitral valvular diseases, 40% combined valvular diseases and 9% aortic valvular diseases. The mean mortality for all patients with RHD was 25.9%. Seventy percent of the deaths were due to severe, chronic heart failure, sudden death and cerebral emboli. Atrial fibrillation was observed in 50% of the patients. Cerebral emboli occurred frequently in patients with mitral stenosis (MS), mitral stenoregurgitation (MSR) and combined valvular disease (CVD), which were associated with atrial fibrillation. However, cerebral emboli were rarely found in cases with MSR, CVD and aortic valvular disease with sinus rhythm. The mortality of cardiac surgery was low, 13.3%.

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We analyzed the transient response of oxygen consumption (VO₂) after the sudden termination of exercise. The study population consisted of 20 male athletes (age 13 to 15.9 years) and 87 male patients, 59 of whom (age 4.8 to 17.8 years) were considered to be normal subjects, and 28 of whom (age 6 to 14.8 years) had restricted physical activity because of underlying heart diseases (restricted group). The exercise tests were performed according to Bruce's protocol and terminated at signs of exhaustion. As soon as exercise ceased, the examinee sat on a chair and took rested completely. VO₂ was measured every 30 seconds throughout the test. We characterized the rate of the initial decay of the VO₂ transient as the ratio of the 30 second VO₂ right after the exercise to that at the end of the exercise (Irv). This index did not differ significantly among the groups. On the other hand, Exc, the Irv normalized by the end-exercise VO₂, was a sensitive index for separating the restricted group from the control and athlete groups. Should the Exc remain sensitive enough to quantify exercise capacity regardless of the intensity of the exercise imposed, even the submaximal exercise test should enable us to safely evaluate the exercise capacity of patients with impaired cardiac function.

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To evaluate incidence of serious arrhythmias among school age youths, 24-hour ambulatory ECG monitoring was performed in 100 junior high school students, including 60 subjects with some ECG abnormalities and 40 without. With this monitoring 2 cases with multifocal VPCs and 2 cases with paired VPCs or nonsustained ventricular tachycardia were found ; the case with VT died suddenly after having been lost during careful follow up. It is emphasized from these results that ambulatory ECG monitoring is quite useful in selected cases in this age group and careful follow up of students with advanced grade VPCs is very important.

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The purpose of this study was to determine the prevalence of persistent blood pressure elevation in school children. Mass screening of blood pressure was performed simultaneously with a cardiovascular health check in school children. Forty four hundred and eighty school children were selected as subjects for this study, consisting of 2289 first grade primary school students aged six and seven (group A), ad 2191 second grade junior high school students aged thirteen and fourteen (group B). Of the 4480 students, 4031 were examined at the initial blood pressure screening. Three hundred and sixty students whose systolic and/or diastolic pressures were above the 95th percentile were recalled for a second examination. Three hundred and thirty one students were studied at the 2nd examination, and 69 students were listed for a third survey. 1.7% of the original subjects were examined at the final survey. At the first screening, mean blood pressures were 101.5 ± 8.5 /61.2 ± 6.6 mmHg (mean ± SD) for males and 100.3 ± 8.3 / 60.9 ± 6.5 for females in group A. In group B, blood pressures were 120.2 ± 11.3 / 66.6 ± 7.4 mmHg for males and 117.4 ± 11.2 / 66.9 ± 7.8 mmHg for females. This screening system, if incorporated into the school health program, is an effective and efficient method of screening for persistent blood pressure elevation in school children in Japan.

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Two cohorts of Japanese children were studied longitudinally at 3-year intervals, at ages 6 and 9 years in cohort 1 and 9 and 12 years in cohort 2. There were 252 children in cohort 1 and 235 in cohort 2. The examinations performed were blood pressure, height, weight, skin fold thickness, upper arm length and circumference, ECG, VCG, M-mode echocardiography, serum cholesterol, hemoglobin and urinalysis. The subjects were divided into 5 quintile groups by their systolic blood pressure (SBP) percentiles calculated at each examination. SBP was tracked in each cohort throughout the follow-up period. Percentages remained in the highest SBP quintile group at both examinations were 43.5% (boys) and 59.1% (girls) in cohort 1, and 25.0% (boys) and 56.5% (girls) in cohort 2. The tracking of SBP was defined by body mass (height and weight) in most children. In some children, however, it was not defined by body mass tracking. Left ventricular muscle volume and its index were large in boys in the highest SBP tracking group. This indicates that the cardiac muscle is hypertrophied already, before the development of hypertension.

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Mass screening by ECG for heart diseases in pupils and students was performed in Shimane Prefecture ; all the children had primary screening and were under the supervision of a pediatric cardiologist in all phases, from primary to precise (tertiary) examination. The precise examination was performed with 2D echo, exercise ECG and/or cardiac catheterization when indicated, and an important feature of this mass screening was the ability to carry out an accurate follow-up in all the phases from primary to precise examination. The number of subjects in the primary screening from 1980 to 1984 was 50758 primary school pupils, 44216 junior high school students and 33480 senior high school students ; organic heart diseases not under the supervision of the pediatric cardiologist at the time of mass screening were found in 22 primary school pupils (0.04% of participants in the primary screening), 14 junior high school students (0.03%) and 5 senior high school students (0.01%). Clinically significant arrhythmias without underlying organic heart diseases were discovered by mass screening in 8 primary school pupils (0.02%), 13 junior high school students (0.02%) and 16 senior high school students (0.05%).

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