[in Japanese]

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Age-related alterations of the lymphocyte subsets as determined by the flow cytometry analyses and by the abilities to produce or accept interleukins were described. Experiments with the aged→young and young→aged radiation bone marrow chimeras suggested the central importance of the thymic environment rather than the stem cell itself in the age-related functions of the thymusderived lymohocytes.

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In order to discuss whether somatosensory evoked response (SER) and contingent negative variation (CNV) are suitable indicators of the aging process, SER to mechanical stimulation and CNV, as well as electroencephalography (EEG) and inteligence scales, were performed on the healthy aged adults. Subjects are the 41 aged adults of 61-80 years (12 males and 29 females) who participate in lesson programs of Osaka Prefectural Center for the aged. For the recording of SERs, tapping stimuli are applied on the right palm by a pulse generator. The paradigm for eliciting the CNV consists of a warning signal (S₁) followed by an imperative signal (S₂) to which the subjects make a motor response (MR). The CNV appears as a surface-negative shift of potential when 15 responses are summated. The results are summarised as follows. 1. The mean score of Hasegawa's dementia rating scale (HDRS) exercised for the 41 aged adults was 30.9 ranging from 23 to 32.5. The mean IQ of Kohs's blocking design test (KBDT) was 87.3 ranging from 45 to 124. 2. Abnormal EEG was observed in 7 subjects (17.1%) of the 41 aged adults, while normal EEG was observed in 26 subjects (63.4%). Normal SERs were observed in 28 subjects of the 41 aged adults, and peak latencies of SER were abnormally prolonged in 11 subjects of them. On the other hand, peaks of SERs were absent in only 2 of them. The atypical type of CNV was observed in 7 subjects of the 41 aged adults, and then PINV (post imperative negative variation), which is defined as the delayed base line return of CNV after S₂, was also observed in 7 subjects of them. 3. From the results of clinical neuropsychiatric examination, intelligence scales and electroencephalographic findings, we selected the 29 normal aged out of the 41 aged adults, and then discussed the results of SER and CNV in the 29 normals. The mean latencies of P₂, N₂ and P₃ peaks in SERs were not influenced by the aging process. But the mean latency of N₃ peak in SER was 69.0msec in 60's, 70.9msec in 70's, and this mean value was much higher than that (62.5msec) in the 48 normal adults (mean age 31.5 year; ranging from 19 to 50). In conclusion, it is considered that the latency of N₃ peak in SER is a suitable indicator of the aging process. There was little difference in the morphology and the amplitude of CNV between the normal adults and the normal aged. PINV, which was often observed in the demented aged, did not appear in the normal aged nearly. It is considered that the appearance of PINV is probably a suitable indicator of the dementing process.

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Progressive subcortical vascular encephalopathy of Binswanger type (PSVE) was observed in 73 cases (4.9%) of the 1500 elderly autopsied cases. Patients were divided into the following three groups according to cerebral white-matter degeneration (WMD). I) Anterior type (25 cases) WMD of fronto-parietal lobes was more remarkable than that of temporo-posterior lobes. II) Posterior type (6 cases) WMD of temporo-posterior lobes was more remarkable than that of fronto-parietal lobes. III) Diffuse type (42 cases) WMD was observed in all lobes. A clinicopathological study was performed on three groups.
Results. 1) In all groups, WMD was related to arteriosclerosis in white matter. 2) Anterior type and diffuse type consisted of most part of elderly PSVE. Posterior type which Binswanger had originally reported was rare. 3) Neuropsychic symptoms were dementia, urinary incontinence, pseudobulbar palsy, psychosis parkinsonism, mutism, etc. No specific symptoms to each group were observed. Hypertension and cardiac disease were frequent complications. 4) Senile changes as much as senile dementia of Alzheimer type were observed in 10% of anterior type and diffuse type. Concerning etiological factors of PSVE, it was considered that arteriosclerosis in white matter was the most important and various complications might accelelate WMD. PSVE was observed in 3.8% of the elderly persons autopsied in 1974-1977 and in 4.9% of the cases in 1978-1983.

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In 1965, food frequency interview inquriing about usual intake, in terms of the frequency of consumption of various food items, was carried out in Hisayama, Fukuoka Prefecture, a rural area located in the south-western part of Japan. Data concerning frequency of taking rice, meat, fish, milk, green vegitable, “tukemono” (pickled vegetables), “misoshiru” (miso soup), cigarette smoking and alcohol drinking were obtained from 1, 724 (94 per cent) residents, aged 40 to 69 years. Long-term follow-up was completed for 1, 609 (726 men and 883 women) at the time of health examination performed almost every couple of years in the community and it was confirmed that 309 (181 men and 128 women) out of 1, 609 subjects died during the subsequent 15 year follow-up period. Survival rate for the women was nearly 10 per cent higher than that for the men after the follow-up period (chisquare=30.12, P=0.0001). To evaluate effects of frequency of foods, alcohol and tabacco on total mortality, analyses using Cox's proportional hazard model were executed with a computer software PHGLM in SAS. After controlling for age at the baseline in 1965 and sex, univariate analysis showed that meat, “tukemono” and cigarette smoking were significant (p<0.05) for mortality. When all of the food items were taken into the Cox's model, multivariate analysis showed that for the whole subjects, advancing age, male sex, cigarette smoking and “tukemono” were significant (p<0.05) for mortality, and that advancing age, cigarette smoking, low intake of “tukemono” and meat for the men and advancing age alone for the women. Blood pressure, body height, weight, serum protein and serum total cholesterol were determined for 1, 378 subjects at the time of examination in the summer of 1965, independent of the food frequency interview. After controlling for age and sex, univariate analysis showed that systolic and diastolic blood pressure were selected as significant (p<0.01) for mortality. When all of these data from 1, 378 subjects were added into the multivariate model, advancing age, elevated systolic blood pressure, cigarette smoking and male sex were selected as significant (p<0.05). More detailed information about incidence of cerebrovascular diseases (CVD) or malignant neoplasms was obtained from the subjects who were followed-up since 1961 as cohort of Hisayama Study, an ongoing longitudinal epidemiological study. As a result, it was confirmed that 111 out of 1, 111 subjects who belonged to the Hisayama cohort had newly developed CVD and other 59 died from malignant neoplasms verified by autopsy. Analyses based on these cases showed that elevated systolic blood pressure, male sex and advancing age were selected as significant (p<0.05) for development of CVD and cigarette smoking for mortality from malignant neoplasms. As the questionnaire did not record precisely what the respondent had eaten but revealed their usual pattern of consumption, it was strongly suggested that alcohol drinking precipitates development of CVD through the previously established effects of elevated blood pressure and that there is a highly close relationship between cigarette smoking and mortality from malignant neoplasms.

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Hemodynamic effects of the active sitting and standing from the supine position were investigated in the middle age group (8 males and l female, 51±2 years old) and the old age group (13 males and 17 females, 80±7 years old). Blood pressure was determined by a recording of intra-arterial pressure, and cardiac output was determined by dye-dilution ear-piece method. Total peripheral resistance was calculated from measured cardiac output and blood pressure (formula: blood pressure=cardiac output×total peripheral resistance). In the supine position, blood pressure was 112/57 and 150/65mmHg, heart rate 66 and 65 beats/min, cardiac index 4.3 and 3.4l/min/m², stroke index 63 and 57ml/beat/m² and total peripheral vascular resistance 1439 and 2324 dyn·sec·cm^-5·m² in the middle age group and the old age group, respectively. The active sitting from the supine position induced a fall of blood pressure 12/4 and 18/5mmHg, and the active standing caused a fall of 6/2 and 6/-3mmHg in the middle age group and the old age group, respectively. The standing induced a 32% and a 25% increase in heart rate, in the middle age group and the old age group, respectively. The keeping of standing position for 30sec induced a 14% and a 19% increase in heart rate form control values of the supine position, a 10% and 4% reduction of stroke volume, a 5% reduction and a 16% increased in cardiac output, and a 20% increase and no change in total peripheral vascular resistance, in the middle age group and the old age group, respectively. The increase of cardiac output was significantly correlated with the reduction of total peripheral vascular resistance. The standing position elevated total peipheral vascular resistance in the middle age group, but not in the old age group. The increase in concentration of plasma catecholamines by the standing was no difference between the middle age group and the old age group. Blood pressure change induced by the active standing was controled by the elevation of total peripheral vascular resistance in the middle age group, in contrast the change was controled by the increase in cardiac output in the old age group. Orthostatic hypotension was observed in the old age, which could not increase cardiac output during standing position.

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The relationship between the age and clinical efficacy of calcium entry blocker, nicardipine, was investigated in essential hypertension by using a double blind group comparison method. In Monotherapy study, 82 patients were divided into three groups; 16 younger patients of less than 49 years (mean age of 43.2 years), 31 of middle aged patients of fifties (mean age of 54.0 years), and 35 elderly patients of 60 years or more (mean age of 66.1 years). In combination therapy with diuretics, 63 patients were enrolled in the study, consisting of 38 younger patients of 59 years or less (mean age of 50.3 years), and 25 elderly patients of 60 years or more (mean age of 66.4 years). Nicardipine was used 20mg three times daily for 12 weeks in both studies. The positive antihypertensive effect was defined as blood pressure fall of 20/10mmHg in systolic/diastolic pressure or a decrease of 13mmHg or more in mean pressure. In nicardipine monotherapy, this effect was observed in 43.8% of younger patients, in 63.3% in middle aged patients, and in 66.7% in the elderly patients, showing no significant difference in each age group. In combination therapy with diuretics, the hypotensive effect was demonstrated in 71.1% in the younger patients and in 68.0% in the elderly patients. There was no significant difference between the two age groups. The average decrease in blood pressure was 19-24/10-13mmHg in the monotherapy, and 20-25/14-15mmHg in the combined therapy, and was not different in each age gorup. The fall in blood pressure was not correlated with the age, but with the pretreatment blood pressure. Heart rate changed little in both monotherapy and combined therapy. The incidence of side effect was 0% in the younger patients, in 25.8% in the middle aged patients and in 14.3% in the elderly patients in the monotherapy. The incidence of side effect was higher in the middle aged patients than the younger patients, the side effect was observed in 13.2% in the younger patients and in 12.0% in the elderly patients, showing no significant difference. The laboratory data revealed no metabolic effect to raise risk factor in each age group. The comprehensive efficacy was judged by the hypotensive effect, side effect and the clinical and laboratory findings, and the rate of usefulness (useful or above) was 56.3% in the younger patients, 58.1% in the middle age patients, and 65.7% in the elderly patients in the monotherapy, while the rate in combined therapy was 65.8% in the younger patients and 60.0% in the elderly patients. There was no significant difference in each age group in either therapy. The calcium entry blocker, nicardipine, is considered to be equally useful for the aged and younger patients in the treatment of essential hypertension.

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