Biophysical and biochemical characteristics of the aged were studied in a general population sample of 1, 621 or 2, 190 Hisayama residents aged 40 or over, which were screened at 1961 or 1978, respectively. The cause-specific mortality was compared between the earlier (1961-69) and the later cohort (1974-82) of the study during the initial 8 year of surveillance. This could allow us to estimate the changing pattern of the diseases in the aged over a 13-year period. In addition, 769 consecutive autopsy-cases of the Hisayama residents were examined to elucidate clinical and pathologic features of the diseases in the senescence. Body-mass index for both sexes decreased with advancing age-decade, and this trend was more proiment for males. Reduction in weight of brain, liver or kidneys of the autopsied cases aged 30 or over, was in progress with a decade of increasing age. Changes in blood chemical constituents by age-decade varied according to sex, namely, each constituent had its own pattern of ageing by sex. Systolic blood pressure developed a tendency to increase with progressing age, but a standard deviation of averaged systolic pressure became larger in the aged group. This variation was due to the difference in age-related changing pattern of systolic pressure each by each. An impact of hypertension as a risk factor for cardiovascular disease was less significant in the senescence, but systolic hypertension was not necessarily innocent for the development of cardiovascular disease in the elderly subjects. The frequency of deaths from cerebral stroke, heart diseases, or malignant neoplasms increased stepwise with advancing age-decade in both sexes. Recently, a total mortality in the residents of 7th, 8th and 9th decades, however, declined in the community of Hisayama. This was in part due to the reduction of the incidence of cerebral stroke in the aged population. Clinical pictures of cerebral storke, myocardial infarction, or malignant neoplasma were sometimes latent and unusual in the patients above the age of 70 years when compared with those below 70. The incidence of recurrent episodes of cerebral stroke was not so much in the old patients, but multiple ischemic lesions on the brain severely affected a daily activity of the patients. The frequency of double cancers increased with advancing agedecade and 10.2% of the autopsy-cases with malignant neoplasms aged 80 years or over. Vascular or senile dementia was found in 3.8% of the total consecutive autopsies, respectively, and senility was noted only in 1.2%. Pneumonia in the senescence was significant as an underlying cause of death and is likely to have a great influence on life expectancy of the aged.
The effect of aging on the pharmacokinetics and pharmacodynamics of tolbutamide was investigated in 25 type II diabetics. There were no significant differences in plasma concentration profiles and pharmacokinetic parameters of tolbutamide between normals and diabetics. Plasma concentrations of tolbutamide from 0 to four hours after oral administration of 500mg tolbutamide tended to be higher in aged diabetics (≥65 years) than younger (<55 years), but the differences were not significant. There were no significant differences in the pharmacokinetic parameters between aged and younger diabetics. There were no significant correlation between the pharmacokinetic parameters of tolbutamide and age, body surface area, ICG (15′), PSP (15′) or creatinine clearance. The differences between plasma glucose levels during oral glucose tolerance test (OGTT) with and without tolbutamide were significantly smaller at 150 and 180 minutes in aged diabetics than in younger. Plasma glucose and insulin responses to tolbutamide were negatively correlated with age (r=-0.45, p<0.05 and r=-0.41, p<0.05, respectively). In conclusion, no effect of aging on the pharmacokinetics of tolbutamide was observed, but the effect of the oral hypoglycemic agent on glucose and insulin response to an oral glucose load was decreased in aged diabetics.
It is well known that dietary treatment is very important for diabetes mellitus, obesity and cardiovascular disease, while sometimes it is difficult practically. Therefore, α-amylase inhibitors (strach blockers) may be administered to apply cliniically as a technique for restriction of diet. A large number of α-amylase inhibitor derived from kidney bean, wheat or fungus has recently received considerable attention by reason as mentioned above. X-2 substance which a strain of Streptomyces fradiae produce was purified by us using column chromatography on Sephadex G-50, DEAE-cellulose and TEAE-cellulose. The purified substance was an acid peptide, water soluble and stable at pH 2-12. The molecular weight of it was 6430. It was observed that X-2 substance has a specifically inhibitory effect on α-amylase and an effect on sucrase in vitro (Jap. J. Geriatrics, 1982, 19: 285-292) and significant effects in blood glucose and insulin responses after oral administration of starch in rats. Moreover, it was found as the direct evidence that X-2 substance has the effect making rats decrease those body weight. It is to say, when rats were given X-2 substance with ordinary chow for 4 weeks, the decrease in body weight was remarkable to compare with control group fed only ordinary chow. And effective dose of X-2 substance on this experiment was 10, 000U/kg or more. Effective inhibition of starch digestion in vivo would diminish glucose formation and absorption in the small intestine and increase the amount of undigested starch in bowel. Finally, it was supposed from above results that X-2 substance may be effective on weight-control in man and has a possibility to clinical usage.
A study of hypothermia in Tokyo Metropolitan Geriatric Hospital during a 6 year period revealed that axillary temperature of 79 patients (0.51% of total admitted patients and 3.8% of total died cases) have been 35.0°C or less for at least 3 days. Distinct seasonal variation was found in the occurrence of hypothermia, most frequent in winter. Mean age of the hypothermic patients, 80.2 years old, was higher than that of all admitted, 73.3 years old, or died cases, 76.8 years old. Disturbed consciousness (80%), generalized edema (44%), hypotension (27%) and bradycardia (14%) were associated with hypothermia. High frequency of abnormal laboratory findings was recognized in the hypothermic patients, low hemoglobin levels (less than 9g/dl): 46%, low hematocrit levels (less than 30%): 60%, leukocytosis (more than 10000/mm3): 41%, thrombocytopenia (less than 100000/mm3): 61%, prolonged prothrombin time (more than 14 seconds): 79%, low fibrinogen levels (less than 200mg/dl): 68%, high fibrin/fibrinogen degradation products levels (more than 10μg/ml): 53%, hypoproteinemia (less than 5g/dl): 47%, high GOT levels (more than 20 IU): 65%, high GPT levels (more than 20 IU): 36%, high LDH levels (more than 110 IU): 48%, hypocholesterolemia (less than 100mg/dl): 39%, hypochloremia (less than 98mEq/l): 45%, hypocalcemia (less than 7.5mg/dl). 47%, high blood urea nitrogen levels (more than 30mg/dl): 69%, high serum creatinine levels (more than 1.5mg/dl): 41%, low serum triiodothyronine levels (less than 80ng/dl): 92%, acidemia (pH<7.35), and atrial fibrillation: 32%. In one patient, J wave was recorded on electrocardiogram. Predominant clinical settings of hypothermia were cerebrovascular accidents (43%), pneumonia (34%), hypoproteinemia (33%), malignancy (28%) and disseminated intravascular coagulation (22%). The average survival period of the hypothermic patients was 20 days and about a half of cases died within 10 days after the onset of hypothermia. The average survival period of the patients who did not recover from hypothermia was shorter than that of the patients who recovered. Serum total protein and total cholesterol levels in the former were significantly lower than those in the latter (p<0.01 and p<0.02, respectively). It was concluded that hypothermia was not infrequent in various morbid states commonly seen in the elderly and that the prognosis of hypothermia in the elderly was poor.
We made a comparison between the 445 cases of advanced gastric carcinoma and early gastric carcinoma observed at our clinic, and the 176 cases of gastric carcinoma observed by Oshima-one of the authors-at Berlin Free University, and studied the gastric carcinoma in the aged over 60 in Japan and Germany. Within the cases of advanced gastric carcinoma, the proportion of the aged was 55.3% at our clinic and 78.5% in West Berlin, and early carcinoma in the aged was 34.6% at our clinic and 60.7% in Germany. The frequency of gastric carcinoma in the aged in Germany is obviously higher than that in Japan. At our clinic we had more male cases of gastric carcinoma in the aged. In the German cases, however, the proportion of male from 60s to 70 and older becomes lower, and in the cases over 70 the ratio of male and female finally becomes 1.0:1. These phenomena are probably dependent on the number of the aged and on the population structure. From the view of macroscopic form of advanced carcinoma in the aged, especially over 70, the sum of Borrmann types 1 and 2 increased, and Borrmann types 3 and 4 tended to decease at our clinic. But in the cases of West Berlin such tendencies were not found, and Borrmann types 3 and 4 in the aged did not decrease as much. Such tendencies are similar to the frequencies in histological forms. At our clinic the sum of papillary and tubular adenocarcinoma gradually increase from the 60s to the 70s and older, however, this cannot be observed in Germany. In the German cases the lesion of carcinoma are often larger than it of our clinic. Endoscopic atrophic gastritis was found obviously more in the gastric carcinoma cases of our clinic than the cases in Germany. It is thought that the characteristics of gastric carcinoma in the aged of Japan are more dependent on differentiated carcinima, and in the German cases undifferentiated carcinoma.
The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects from 25 to 85 years old were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. A hundred and twentyfive subjects who had no abnormalities in neurological examinations nor in CT scan, were divided into two groups smokers (48) and non-smokers (77). Those who had a smoking index (Number of cigarettes/day)×(years of smoking history)>200 were designated as smokers. The mean smoking index of smokers was 697. sixty-five of the 77 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 16. Increased reduction of CBF with advancing age was clearly observed. In the male, CBF was significantly lower in smokers than in non-smakers (mean CBF 15% lower in smokers, p<0.001). Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduced CBF. Age dependent decrease of CBF was deteriorated by chronic smoking. Then, chronic smoking was suggested to be a risk factor for brain aging. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels.
The incidence of the brain tumor observed in the aged was 116 cases (7.7%) among 1500 autopsies in the Tokyo Metropolitan Geriatric Hospital and metastatic one was composed of 62.1% of tumor cases. The hemorrhagic brain tumor consists of primary tumor in 34.1% and metastatic one in 22.2%. In the latter lung cancer was most frequent (62.5%), followed by 12.5% of gastric cancer. Considering that the lung cancer was the most frequent metastatic tumor (61.1%), the corrected incidence of the hemorrhagic metastasis was 22.7% of lung cancer and 33.3% of gastric cancer. The localization of the metastasis was in the cerebral cortex (80%), deep cerebrum (40%), cerebellum (33%) and brain stem (13%). Some were complicated by ventricular rupture and carcinomatous meningitis. The size of the bleeding was various and the cases with the hematoma measuring over 5cm in diameter showed consciousness disturbance. Multiple hemorrhages were observed in 12 cases among 15 hemorrhagic metastatic cases. The clinical symptomes of the hemorrhagic metastatic tumor was shown in 15 cases and convulsion was the most frequent one, then demintia, vertigo, hemiplegia, coma, etc. In the cases, in which such symptoms appeared before the detection of the tumor, the differential diganosis from cerebrovascular disease was often difficult. Such cases were 5 and other 11 cases showed neurological symptoms after detection of tumor. The former consisted of 4 cases of lung cancer and a case of gastric cancer. Their neurological symptoms were hemiplegia, convulsion, deafness, frontal sign, consciousness disturbance, gait disturbance, ataxia, tremor, vertigo, dysarthria, etc. However, the massive bleeding was not observed in these cases but in the cases in which the tumor had been already found. Complication of DIC was observed in 30% of hemorrhagic cases and that of hypertension in 50%. The incidence was not different from that of non-bleeding cases. The mechanism of bleeding of the metastatic brain tumor has been considered variously, e. g. rupture of neoplastic aneurysm, bleeding from intraneoplastic or perineoplastic proliferated capillaries, bleeding due to congestion of vein by compression, hemorrhagic infarction due to tumor embolism, or fibrinolysis in the peritumoral brain parenchym. Histological examination of bleeding focus of lung cancer metastasis by serial section did not reveal neoplastic aneurysm, but disrrupted capillaries due to tumor infiltration.
The investigation was performed to clarify the present status of the accidental hypothermia in Japan. “Questionnaires on the death from cold and the hypothermia” were sent in 4 selected area, i. e. Hokkaido, Tokyo, Kanagawa and Yamanashi. Of the 2366 questionnaires sent out, 597 response including 30 casereport were returned. I) oncerning accidental hypothermia the obtained results were: 1) The accidental hypothermia was occurred due to a diseaster (10 cases), drinking (13 cases) or from various diseases (7 cases), and involved a greater number of male than female. 2) When core temperature was above 20°C at the time of discovery, the patients could be successfully treated. When core temperature was below 30°C, the patients could die due to hypothermia. 3) Rewarming, artificial ventilation, transfusion, administration of cardiotonic and other drugs were found to be effective treatments. II) Concerning senile hypothermia (accidental hypothermia in the aged), the following results were obtained. Eight of the 30 cases were aged above 60 years. 1) The senile hypothermia occurred as a result of disaster (2 cases), drinking (2 cases) and from various diseases (4 cases). No healthy aged individual encountered accidental hypothermia under conditions that were not dangerous for the healthy adults. 2) The social conditions of the patients were reported in 5 cases. The aged live with their family, and their economical status was considered average. The three patients needed the medical care, and only one patient exhibited urinary incontinence and dementia. The phenomenon of senile hypothermia occurring in the aged, who live alone under poor economical condition as seen in Europe and USA, was not found in the present survey.