[A new autonomic functional test using digital analysis of digital plethysmography].
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Biomedical subjects
Publications and source records attributed to H Toshima.
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There is increasing interest in the notion that some patients with hypertrophic cardiomyopathy (HCM) progress to morphological and functional manifestations similar to those of dilated cardiomyopathy (DCM). From 165 consecutive patients with HCM, 20 patients with left ventricular dilatation (left ventricular end-diastolic diameter greater than or equal to 50 mm) were selected and designated as dilated HCM. The diagnosis of HCM was established in these patients either by detection of the classical form of HCM in family members, with 2-dimensional echocardiographic evidence of asymmetric septal hypertrophy (ASH; septal thickness greater than or equal to 15 mm and a ratio of septal to posterior wall thickness greater than or equal to 1.3); or by demonstrating myocardial fiber disarray in autopsy or biopsy samples. The clinical manifestations of these patients with dilated HCM were then compared with those of other forms of HCM without left ventricular dilatation; 1) 40 patients with hypertrophic obstructive cardiomyopathy (HOCM) who had resting intraventricular pressure gradients of 20 mmHg or more, 2) 80 patients with non-obstructive HCM, each of whom had ASH of the entire ventricular septum (typical ASH), and 3) 25 non-obstructive patients whose hypertrophy was localized to the apical region of the ventricular septum (apical ASH). Patients having apical hypertrophy with a spade-like configuration on the left ventriculogram were excluded from the study. Compared with HOCM and typical ASH groups, the patients with dilated HCM had family histories of significantly more frequent HCM and less frequent hypertension. The patients with dilated HCM also had significantly less fractional shortening (FS), decreased interventricular septal thickness, greater left ventricular end-diastolic pressure (LVEDP), and left ventricular dilatation. During the follow-up period (average: 3.5 years), seven patients (35%) with dilated HCM died; five from congestive heart failure (CHF), one suddenly, and one three days following mitral valve replacement. The other five patients had CHF at the time of their follow-up examination. The patients with apical ASH had clinical features similar to those of dilated HCM; a higher familial frequency, less marked septal hypertrophy, and higher LVEDP. They tended to develop left ventricular dilatation, associated with reduced fractional shortening, although left ventricular diameter at end-diastole did not exceed 50 mm. These findings suggested that dilated HCM is not a rare condition. It is observed in 12% of consecutive patients with HCM.(ABSTRACT TRUNCATED AT 400 WORDS)
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The present study investigates the clinical significance of several possible causative or conditioning factors which have been proposed to be involved in the pathogenesis of dilated cardiomyopathy (DCM). By reviewing the medical records of 68 patients with DCM, we found a definite, and suggestive family history in 16%, and 28%, respectively, and antecedent flu-like symptoms in 43%. A history of hypertension was observed in 35%, habitual alcoholism in 49% and diabetic pattern on glucose tolerance test in 37%. We then classified the study patients into three groups; familial, myocarditic and acquired groups. The familial group showed advanced myocardial damage with the poorest prognosis. Abnormal T-cell subsets in this group suggested that genetically determined abnormal immune response is involved in the development of DCM. In the myocarditic group, endomyocardial biopsy demonstrated mononuclear cell infiltration in 53% and the myocardial damage and prognosis were of intermediate severity. The acquired group showed significantly more frequent histories of hypertension, habitual alcoholism or diabetes than their age- and sex-matched controls, suggesting that they developed the disease in association with these factors. The severity of hemodynamic impairment and myocardial damage was the least extensive and prognosis was relatively favorable in this group. These different clinical features in the three groups may provide evidence that these factors actually contribute to the development of myocardial damage in DCM and that the condition is a clinical syndrome associated with heterogeneous etiologies or conditioning factors. Determination and management of these factors would be of practical value in treating patients with DCM that has no established therapy against underlying etiologies.
To investigate mechanisms for a reduced coronary vasodilatory capacity in patients with hypertrophic cardiomyopathy (HCM), maximum coronary blood flow and minimum coronary vascular resistance were measured by administering dipyridamole (0.56 mg/kg) to 19 patients with non-obstructive HCM and to 7 control subjects. The maximum coronary blood flow was significantly lower (131 +/- 46 vs 192 +/- 41 ml/100 g . min, p less than 0.01, mean +/- SD) and the minimum coronary vascular resistance was significantly higher (0.64 +/- 0.23 vs 0.44 +/- 0.13 mmHg/ml/100 g . min, p less than 0.05) in HCM patients. There were no significant correlations between maximum coronary blood flow or minimum coronary vascular resistance and the baseline left ventricular end-diastolic pressure or the severity of systolic narrowing of the left anterior descending artery of the septal perforator. In contrast, the minimum coronary vascular resistance was correlated significantly with the left ventricular muscle mass (r = 0.55, p less than 0.05), but its correlation to small coronary vessel disease could not be studied. In addition, HCM patients with a reduced exercise tolerance (less than 7 metabolic units) demonstrated a significantly lower maximum coronary blood flow and higher minimum coronary vascular resistance than control subjects. These findings suggest that: (1) there is a group of HCM patients who have a reduced coronary vasodilatory capacity, (2) abnormal coronary vasculature is a possible underlining mechanism of HCM, either due to inadequate growth unassociated with left ventricular hypertrophy or as small coronary vessel disease, and (3) a reduced coronary vasodilatory capacity.
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Expression of interleukin 2 (IL-2) receptor on peripheral blood lymphocytes after stimulation with concanavalin A (Con A) or anti-T3 monoclonal antibody was analyzed in patients with dilated cardiomyopathy (DCM) in order to clarify the abnormalities of lymphocyte activation mechanism in DCM. The expression of IL-2 receptor after the stimulation with either Con A or anti-T3 monoclonal antibody was found to be reduced in the patients with DCM when the results were compared with those of controls. A significant correlation was noticed between the expression of IL-2 receptor after Con A stimulation and T4+/T8+ cell ratio, and between the expression of IL-2 receptor after anti-T3 monoclonal antibody stimulation and the left ventricular end-diastolic pressure (LVEDP). The results suggest that there are abnormalities of lymphocyte activation in DCM and that the alteration may be associated with the cause or clinical conditions of DCM.
Three cases of hypertrophic cardiomyopathy (HCM) which presented with different modes of appearance of left ventricular hypertrophy are reported. Case 1: A 24-year-old man had three relatives with HCM. At 13 years of age, he showed no electrocardiographic or echocardiographic abnormalities characteristic of HCM. During the ensuing 11 years, he developed asymmetric septal hypertrophy (ASH) and systolic anterior motion of the mitral valve (SAM), with right bundle branch block and T-wave inversion. Cardiac catheterization confirmed the diagnosis of hypertrophic obstructive cardiomyopathy by demonstrating an intraventricular pressure gradient of 25 mmHg. These observations indicate that this case developed abnormal hypertrophy during adolescence on the basis of genetic predisposition of an autosomal dominant trait. Case 2: A 51-year-old woman had three proven and three possibly affected relatives. At 35 years of age, she had a normal electrocardiogram, although the echocardiogram was not available. Now, 16 years later, she had developed ASH with abnormal Q-waves and was diagnosed as having non-obstructive HCM. These suggest that ASH can be manifested as late as during middle-age, even in those with genetic predisposition. Case 3: A 47-year-old woman was diagnosed as having hypertension and her blood pressure was 190/100 mmHg at 40 years of age, though she had no abnormal electrocardiographic findings and heart murmurs. Now, at 47 years of age, she had developed T-wave inversion, ASH, SAM, and an intraventricular pressure gradient of 50 mmHg. Thus, her ASH appeared during middle-age, and was probably provoked by hypertension, though a complete family survey could not be conducted. These three patients' findings indicate that there may be various modes of appearance of left ventricular hypertrophy in HCM. In the majority of patients with genetic predisposition, abnormal hypertrophy may develop during adolescence as in Case 1. In others, it may develop in middle-age, as it did in Case 2. The disease spectrum of HCM may additionally include those who develop abnormal hypertrophy during middle-age, following provocation by hypertension, as in Case 3.
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Videodensitometric analysis of digital subtraction coronary arteriography, a new approach for calculating contrast disappearance half-life (T1/2), was assessed in determining regional myocardial blood flow quantitatively. Forty-one patients with coronary artery disease and 12 with angiographically normal coronary arteries underwent digital subtraction coronary arteriography by manual injection of contrast medium into the left main coronary artery. The T1/2 was calculated from a time-density curve generated in the four sectors of the myocardium perfused by the left anterior descending coronary artery. The mean T1/2 value of the four sectors correlated inversely with the great cardiac vein flow measured by the thermodilution method (r = -0.89), and appeared to be a reliable index of myocardial blood flow. The relation of mean T1/2 with percent stenosis of the left anterior descending coronary artery was curvilinear (r = 0.88) and an abnormally high T1/2 occurred in patients with coronary stenosis greater than 75%. In patients with comparable stenosis of the left anterior descending artery, the apical T1/2 was significantly increased in those with impaired apical wall motion, while it was significantly decreased in those with coronary collateral vessels. These findings suggest that regional myocardial blood flow begins to decrease in vessels with greater than 75% stenosis, and that myocardial contraction and collateral flow are additional factors that modify regional myocardial blood flow. Thus, the contrast disappearance half-life (T1/2) derived by computerized washout analysis of digital subtraction coronary arteriograms proved useful as an index for quantitative evaluation of regional myocardial blood flow.
To elucidate a mechanism and clinical implications of chest pain and ST segment depression during exercise in patients with hypertrophic cardiomyopathy (HCM), we investigated myocardial lactate metabolism during atrial pacing in 18 patients with HCM and 7 control subjects with normal coronary arteriograms. At an average peak pacing rate of 146 beats/min, 11 patients with HCM showed the lactate extraction ratio decreasing to less than 5%, and 6 of them produced lactate, suggesting the development of myocardial ischemia. These 11 patients with abnormal lactate metabolism demonstrated ST segment depression (82%) and chest pain (73%) during pacing and also presented abnormal results (55%) on an exercise stress test. These abnormal findings were not observed in the other 7 patients who had ratios of 5% or more at peak pacing. These observations suggest that ST segment depression and chest pain are manifestations of myocardial ischemia even in patients with HCM who have normal coronary arteriograms, and that patients with pacing induced abnormal lactate metabolism are at an increased risk of developing myocardial ischemia during exercise.
The effects of oral diltiazem, 180 mg/day, were compared with those of oral verapamil, 240 mg/day, in 32 patients with hypertrophic cardiomyopathy (HCM), using a double-blind crossover study design. In the first treatment period, diltiazem and verapamil improved subjective complaints in 83% and 71% of those who were symptomatic in the baseline period. Maximal oxygen consumption on exercise stress test increased with verapamil by 2.9 +/- 4.2 ml/Kg/min (p less than 0.05), and tended to increase with diltiazem. Verapamil also reduced the amplitude of negative T wave. In the statistical analysis based on the crossover design, diltiazem and verapamil did not differ in global improvement, overall safety and global utility ratings. In addition, both drugs showed comparable effects on electrocardiographic and echocardiographic variables and exercise tolerance except for minor differences in diastolic blood pressure, T wave amplitude and peak exercise heart rate. On the other hand, verapamil tended to induce more serious side effects, forcing the discontinuation of medication in 3 patients. Therefore, the present study indicates that diltiazem is essentially equally as effective as verapamil and is preferable in the treatment of patients with HCM since it may exhibit fewer serious side effects.
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A long-term cohort study of 639 males in a farming area and 677 males in a fishing area in Kyushu, Japan, has been conducted to evaluate risk factors for ischemic heart disease. The present investigation utilized this long-term cohort study to assess the role of drinking and cigarette smoking habits in the causation of liver cancer. The O/E ratio (ratio of the observed to expected number of deaths) of liver cancer was 7.5 (P less than 0.001) among shochu drinkers in the fishing area. Further, a clear dose-response relationship of O/E ratio was noted: 5.7 (P less than 0.001), 7.5 (P less than 0.001) and 20.0 (P less than 0.001) for drinkers of less than 1, 1-2, and 2 or more units of shochu (a distilled alcoholic beverage made in Japan; about 25% alcohol). Although no excess risk was found among shochu drinkers in the farming area, observed and expected numbers were too small to make valid judgements. Among sake drinkers, the observed and expected numbers were very similar in both areas. Cigarette smokers in the fishing area appeared to have a high risk for liver cancer, the O/E ratio being 4.8 (P less than 0.001). However, there was no clear dose-response relationship and O/E ratios among cigarette smokers according to their drinking habits indicated no excess risk among nondrinkers. A multiple logistic regression analysis showed an insignificant effect of cigarette smoking on the development of liver cancer after adjustment for shochu drinking. These findings suggest a significant involvement of shochu drinking in the etiology of liver cancer, at least in this fishing area.