Diabetic autopsy cases were collected from the Annual Report of Pathological Autopsy Cases published by Japanese Society of Pathology for the year 1971-1975. Total number of collected cases were 2921 and 2515 cases were classified as primary diabetics. The causes of death and pathoanatomical findings in various organs were analysed in these primary diabetic cases, and following results were obtained. 1) The main causes of death were cardiovascular disease (40.2%), infections (19.6%), malignant neoplasms (19.4%), diabetic coma (2.4%) and hypoglycemia (0.8%). 2) In cardiovascular diseases, the leading cause was diabetic nephropathy (15.0%), followed by cerebral (12.5%) and coronary artery disease (9.2%). 3) Tuberculosis and pneumonia, which had been frequent among infectious diseases before 1970, decreased to 2.3% and 0.6%, respectively. Infection in urinary tract (4.1%) was the most frequent in infectious diseases, and its frequency was higher in female than in male. 4) In malignant neoplasms, cancer of the stomach (4.0%), lung (3.8%) and liver or biliary tract (3.5%) were frequent. 5) The frequency of arteriosclerotic cardiovascular diseases and malignant neoplasms as causes of death increased with age. Infectious diseases increased with age until 5th decade and remained similar levels during 6th to 8th decade, but it increased again after 9th decade. Diabetic coma was the most common cause of death before 3rd decade and decreased with age. Diabetic nephropathy appeared as a cause of death in 3rd decade and became the leading cause of death in 4th decade, then decreased with age. 6) In pathoanatomical findings the frequencies of glomerulosclerosis, myocardial infarction, cerebral infarction and hemorrhage were 34.1%. 15.1%, 14.8% and 6.9%, respectively. Myocardial and cerebral infarction were found at 4th decade and increased with age, while no change with age was observed in cerebral hemorrhage. Diabetic glomerulosclerosis was found in the cases of 2nd decade. In 4th decade glomerulosclerosis was revealed in 49.4% of the cases. Although the frequency of glomerulosclerosis decreased with age after 5th decade, it was higher than those of other vascular lesions. These results showed that the characteristics in the causes of death of diabetics in Japan are a low incidence of coronary artery disease and a high incidence of diabetic nephropathy. These are the same as those pointed out in our previous report on the cases before 1970. But the dietary fat intake in Japanese is increasing recently. Moreover, the elongation of life span results in increase in number of elder diabetics, and consequently increase in the frequency of the death due to arteriosclerotic cardiovascular diseases. On the other hand, the incidence of death due to diabetic nephropathy in younger patients will decrease reflecting the progress of the therapy and medical care. It is expected that the incidence of arteriosclerotic coronary disease will increase and that of diabetic nephropathy will decrease.
Electron-micromeasuring studies have been made on the hepatic cell mitochondria of the long lived parabiotic unions between old and young rats. The mitochondria of the younger partners were significantly larger in size and those of the older partners were significantly larger in number and smaller in size compared with those of young and old control rats respectively. The mitochondrial cristae seemed to become more compactly arranged in the younger partners and more sparsely in the older ones. Some discussions have been made on the influence of the parabiosis with different aged rats upon age change of the mitochaondria and of their function.
Previously, we have reported that the bone mineral content in Japanese decreased with aging and that the loss of bone mineral content in the aged female with fractures was significantly greater than that in the aged matched females without fracture. Therefore, the purpose of the present study is to clarify the role of endogenous estradiol (E2) and 25-hydroxycholecalciferol (25-OHD3) on the loss of bone mineral (RMC) in the aged females. In fifty three female subjects over 60 years, radial mineral contents were measured using photon absorption method developed by Norland-Cameron. Serum E2 and 25-OHD3 levels were measured by the specific radioimmunoassay and competitive protein binding assay, respectively. Serum 25-OHD3 levels showed significant positive correlation with serum calcium levels. However, there was no significant correlation between the age of the subjects and serum E2 and serum 25-OHD3 levels, respectively. Radial mineral contents were significantly correlated with age (r=-0.408, P<0.01), serum Ca (r=0.345, P<0.02), serum E2 levels (r=0.396, P<0.01) and serum 25-OHD3 (r=0.510, P<0.01), respectively. In the aged females with fractures, RMC, serum Ca levels and serum 25-OHD3 levels were significantly smaller than those in the age matched females without fracture. On the other hands, serum E2 levels in the aged female with fractures did not differ from those in the age matched females without fracture. In conclusion, in the aged females it was clearly demonstrated that the low serum 25-OHD3 level was intimately correlated with the pathological osteoporosis characterized by the fractures.
Weight-height index must be independent of height, but correlate with weight. Four indices were studied in this respect on 6, 272 men and 7, 230 women who were apparently healthy employees of Tokyo Metropolitan Government. These indices were simple weight-height ratio (W/H), body mass index or Quetelet's index (W/H2, BMI), ponderal index (H/3√W) and Broca-Katsura's index [W/(H-100)×0.9, BK], where W is weight in kg and H is height in cm. The result showed that BMI was preferable over the other irdices, because it was most independent of height and highly correlated with weight in each decade of both sexes. In the third decade there was no change of BMI with a change of height and this was quite different from the others. In males a increase of BMI was observed in the period of age from the third to the fourth decade, after which it plateaued until 69 years of age. In females, however, there was a gradual rise of BMI from the third until the seventh decade. Frequency of high blood pressure was significantly higher in the group with high BMI (26 or over) than the group with low or normal BMI. In male there was no significant relationship of BMI to the smoking habit or the amount of cigarette consumption.
Pulmonary diffusing capacity (DLCOSS) and fractional CO uptake (COF) measured with endtidal air sampler in steady state were studied in normal elderly persons over 60 years old including 19 males and 11 females (mean; 67.7 and 71.6, respectively) and in normal young volunteers (mean age; 22.3 y.o.). By assuming endtidal CO fraction for the mean alveolar in this method, the respiratory dead space (VD) for carbon monoxide was easily calculated with Bohr's equation and was related to the tidal volume (VT) as follows: VD=0.289VT+0.012 (liter: 1 SE; 0.027, r; 0.860) in elderly persons, and VD=0.303VT+0.015 (liter: 1SE; 0.022, r; 0.903) in young volunteers. Thus obtained VD is considered as a kind of physiological dead space. Mathematical analysis of the parameters (VD/VT, DLCOSS and COF) in this method leads us to comparehend graphycally that DLCOSS (BP-47)/VE and COF are in hyperbolic relation, one of whose asymptotes is 1-VD/VT.
To elucidate a pathogenetic mechanism of stress erythrocytosis in the aged, hematological study was performed in 13 patients above 60 years old, diagnosed as a stress erythrocytosis. The results obtained were as follows: 1) All of these patients were male. Venous hematocrit (Ht) value of these patients was always higher than 48% prior to admission. However, the circulating red cell volume measured using 51Cr tagging method was within the normal limit in all cases, while the plasma volume measured with T-1824 or 125I-RISA decreased comparing with the control value measured in healthy aged men in 11 out of 12 cases. A ratio of whole body Ht to venous Ht was markedly reduced in all cases. 2) Change of venous Ht value after admission was followed up in 10 cases. Either a prompt or a gradual decrease in Ht value was observed one or two days after admission, and a high Ht value diappeared during three to five weeks after admission in all cases. Furthermore, change of plasma volume was investigated in three out of these cases at the times of both high and normal Ht values, respectively. It increased at various drgrees in all cases as a high Ht value normalized. Relationship of high Ht value to blood pressure was studied in a course of the time after admission in ten cases. No significant relationship between Ht values and systolic or diastolic blood pressure was observed in these cases. 3) Viscosity of whole blood was markedly elevated at the shear rate of 0.00062 or 0.073sec-1 in ten out of 12 cases and of 4.6 sec-1 in all cases. From these findings it is indicated that there are both a contraction of plasma compartment and an intravascular shift of the plasma and red cells in stress erythrocytosis. Since stress erythrocytosis brings out an elevation of blood viscosity, it is an important risk-factor for an occurrence of thromboembolic disease in the aged. Therapeutic procedure should be taken against a stress erythrocytosis in the aged.
Patients with cerebrovascular disease (CVD) commonly have symptoms of circulatory disorders, i.e., diziness, light headedness, idiopathic peripheral edema. and so on. These symptoms may hinder rehabilitation and interfere with the improvement of their clinical symptoms. Accordingly, it seemed important to assess the circulatory effects of postural change in order to improve medical care for patients with CVD. The present study was designed to evaluate an orthostatic dysregulation of patients with chronic internal carotid arterial occlusion (ICAO). Effects of rapid 45° head-up tilt on systemic circulation were examined in 12 patients with ICAO (mean age of 73yrs) and 20 healthy subjects (mean age of 74yrs). Arterial blood pressure, heart rate and cardiac output were measured by sphygnometer, electrocardiogram, and a dye-dilution method using ear-piece photocell, respectively. These measurements were performed at least twice at supine rest, and then at 0min, 5min, and 10min after tilt. These hemodynamic responses in ICAO were compared with those in the normal subjects. At supine rest, systolic (SBp), diastolic (DBp) and mean blood pressure (MBp) in ICAO were 145±21, 85±11 and 105±12mmHg, respectively, and these were higher than the result for normal subjects (130±18, 72±9 and 90±10mmHg) (p<0.05). However, there was no difference between ICAO and normal subjects in the other parameters: heart rate (HR), pulse pressure (pp), cardiac index (CI), stroke index (SI) and total peripheral vascular resistance index (TPRI) in ICAO and normal subjects were 74±12 Vs 68±9 beats/min, 61±20 Vs 58±13mmHg, 2.33±V0.68 s 2.23±0.35L/min/M2, 32.0±10.0 Vs 33.4±6.4ml/beat/M2 and 3860±1162 Vs 3354±640 dynes. sec.cm-5/M2, respectively. Hemodynamic changes induced by the tilt were represented as a percentile ratio of the value after tilt to that at supine rest, and those changes were compared between the two groups. Falls after tilt of SBp (-11.9±10.3%), DBp (-2.9±7.1%), MBp (-7.2±8.0%) and pp (-26.0±10.3%) in ICAO were greater than those in normal subjects (+1.0±5.5%, +3.7±6.9%, +3.3±6.7% and -4.6±10.8%) (p<0.05). Increase after tilt of HR in ICAO (+12.7±11.0%) was greater than that in normal subjects (+2.6±5.8%) (p<0.01). Falls of CI (-16.8±13.3%) and SI (-25.8±12.1%) in ICAO were greater than those in normal subjects (-3.3±12.6% and -6.4±10.2%) (p<0.01). However, changes of TPRI in ICAO (+13.6±18.6%) were not more significant than those in normal subjects (+7.3±15.5). These difference of hemodynamic responses between the two groups became progressively greater as elapesed time after tilt increased. The patients with ICAO were classified into two groups according to their activity of daily life (ADL) and clinical features. The two groups were poor ADL (ADL score≤5) and good ADL (ADL score>5). When the hemodynamic responsiveness to tilt in the two groups was compared, falls of SBp, DBp and MBp were significantly greater in the poor ADL group than in the good ADL group (p<0.05). These results indicate that patients with ICAO have orthostatic dysregulation; moreover, the poor ADL group had more distinct orthostatic dysregulation than the good ADL group. Response of HR and TPRI to tilt suggests that the increased blood pressure falls after tilt in patients with ICAO may be related to loss of elasticity of blood-vessels in systemic circulation. However, there remains the possibility that central nervous control may partially affect these orthostatic dysregulations. These abnormalities may contribute in part to the pathophysiological characteristics of patients with ICAO; furthermore, they may affect the prognosis or clinical features.
Locus caeruleus is a brainstem nucleus which consists of melanin-containing nerve cells and recently it is reported that the number of nerve cells decreased markedly in the elderly persons (Brody, 1976). In this report, we investigated the locus caeruleus of the aged human brains, with or without degenerative diseases, on the following changes: nerve cell number, neurofibrillary change, Lewy body, and further, on the relationship with hypertension and cerebral bleeding. The results were as follows: 1) Number of nerve cells: The number of nerve cells was counted on the cross section of the middle part of locus caeruleus in the upper pons. The mean value of the numbers from 60 cases of the aged persons over 60 years without degenerative diseases was fewer than that of 12 younger cases, and a statistically significant decrease was observed in the over 90 year- old persons. 2) Neurofibrillary tangles and Lewy bodies: Neurofibrillary change was observed in 10-20% of 60-90 year- old persons and 100% in over 100 year-old ones. Lewy bodies were observed in 33% of the over 90 year- old persons. In the cases showing Lewy bodies, the number of nerve cells was prominently decreased. 3) Degenerative diseases: Marked decrease of nerve cells of locus caeruleus was observed in the cases of Parkinson's disease, multiple system atrophy and senile dementia. On the other hand, 2 cases of progressive supranuclear palsy showed no decrease of the number. 4) Hypertension and cerebral bleeding: No correlation of nerve cell number and hypertension or cerebral bleeding was found. However, Lewy bodies were observed frequently in the cases without hypertension or cerebral bleeding. These findings suggest that the neurons of locus caeruleus are strongly affected in old age and various senile degenerative diseases. As the result of it, various autonomic dysfunction, including sleep disturbance, can appear in the aged persons.
Antithrombin III (AT III) concentrations in healthy Japanese and with thromboembolic disorders were measured by use of single radial immunodiffusion. 300 healthy controls were examined: 25 males and 25 females in each decade from 10 to 70. The concentration of AT III in healthy males slowly decreases with age. The decrease after the age of forty is even greater. No significant decrease occurs in females. Therefore, in the determination of AT III levels in thromboembolic disorders, it is necessary that the results be compared with age-matched controls. AT III was determined in patients with various thromboembolic disorders, DIC, myocardial infarction and cerebral infarction, and in patients with liver cirrhosis. 24 patients suffering from each disease were selected, matched by sex and age. The lowest levels of AT III were found with DIC, followed by myocardial infarction and cirrhosis of the liver. With cerebral infarction no significant changes were found. The results in all cases were the same when a biologic assay was used. In diabetics, no difference in AT III was found between diabetics without vascular complication and healthy controls. In diabetics with retinopathy there was a significant decrease. The concentrations were even lower in those with retinopathy and proliferative changes. Moreover, in diabetics with vascular complications the degree of decrease in AT III was also related to the duration of the disease. The lowest AT III levels were found in those patients with vascular complications of over 10 years duration in whom platelet hperaggregability with ADP could also be demonstrated. It is suggested that decreased concentrations of AT III together with platelet hyperaggregability may take a role in pathogenesis of vascular changes in diabetics.
A quantitative study for fibrinogen, fibrin (Fg) in intima-media samples were carried out on 47 human aortas aged 0-81yr (average 41.4) using single radial immunodiffusion method modified in our laboratory. 22 cases died of the various diseases and 25 cases died of accidents, in which 19 cases kept fluidity of their blood. Different small parts of intima-media were sampled after washing with 0.9% saline and classified macroscopically into 5 groups according to atherosclerotic severity (SC O-IV). Soluble Fg antigen (Sol. Fg. A) was extracted from tissue samples by homogenation. Using supernate, unclottable and supernatant Fg antigens (U. Fg. A and Sup. Fg. A) were prepared by incubation with thrombin and thrombin-plasmin respectively. Sediments were incubated with plasmin to measure the insoluble Fg antigen (I. Fg. A). These antigens were subjected to immunoplate. Clottable Fg (C. Fg) and total Fg (T. F) were calculated from antigen values as follows; C.Fg=Sol.Fg-U.Fg, T.F=Sup.Fg+I.Fg. Results obtained were represented as mg/wet tissue g of equimolar fibrinogen. C.Fg, I.Fg and U.Fg were found in all samples of normal intima-media, and mean values were 0.149±0.076, 0.408±0.223 and 0.138±0.155 respectively. C.Fg and I.Fg significantly increased with advancing atherosclerotic changes, while a highly significant increase was observed in I.Fg. C.Fg increased with aging, and there was a significant correlation between I.Fg and aging. On the other hand, there was no significant correlation between U.Fg and severity, and besides aging showed no influence on U.Fg levels. In comparison between fluid and non-fluid blood cases, C.Fg and U.Fg were almost in the same in both groups, while in non-fluid groups significant increase of I.Fg was observed, postulating that one part of fibrin originates from deposited fibrin on luminal surface or mural thrombi. No significant differences were found in Fg levels of samples from subjects in 3-12hr and 12-24hr postmortem. In addition, each Fg levels were in the same in both sex groups. Aging, nature of intravascular blood, sex and postmortem time showed no influence on the relationship between Fg and seventies. From these findings, it is supposed that fibrinogen entering through arterial wall under the physiological condition would remain there in form of intact for a while and that increase of fibrinogen caused by increased endothelial permeability and by structural changes of arterial wall associated with aging process, which would cause the disturbance of passage, might play an important role in deposition of fibrin.
Effects of Isoproterenol (ISP) infusion (0.02μg/kg/min, for 5min.) on the systolic regurgitation murmur, a regurgitant flow and a cardiac index were studied in the non-rhematic mitral regurgitation (MR) in the aged. The group I, whose systolic murmur decreased after ISP, were 16 cases and the group II, whose systolic murmur did not decrease, were 7 cases. We found no differences in the intensity of systolic murmur and cardio-thoracic ratio. Seven cases in the group I had old myocardial infarction but none of the group II had. Electrocardiogram after ISP showed ischemic ST changes in 69.2% of the group I and 50% of the group II. Mitral regurgitant flow estimated by dye dilution method was 48.9% (mean) in the group I and 76.4% in the group II. Cardiac index increased from 2.48l/min/m2 to 3.96l/min/m2 in the group I but did not increase so much in the group II (from 2.38 to 3.37). Decrease of mitral regurgitant flow after ISP was lager in the group I than that in the group II. The difference between stroke volume from echocardiogram and that from dye dilution, which represents mitral regurgitant flow, was smaller (28.4ml) in the group I than that (44.1ml) in the group II. It is suspected that in some cases of mitral regurgitation in the aged mitral regurgitant flow decrease after ISP because of improved left ventricular free wall motion after ISP.
Routine sections of the pancreas (an average of 2 slides per case) from 423 autopsy cases from new born infant to 92 years old female were reviewed at every ten years old. And following results were obtained. 1) Arteriosclerosis was the only evident senile change due to aging. Slight mutural relationship with aging were also recongnised in fatty cell infiltration and metaplasia of duct epithelium. 2) Possibility of secondary histological changes derived from fundamental disease of each case were speculated in inter- and intralobular fibrosis and histological changes of exocrine gland. 3) 39 cases of chronic pancreatitis were detected in 423 autopsy cases and about 50% of them were above 60 years old. On the other hand, only one case with clinical diagnosis of chronic pancreatitis was recognised. 4) 3) indictes that many subclinical chronic pancreatitis are existing especially in adults above 60 years old. 5) The incidence of cause of chronic pancreatits were alcohol, operation of abdomen, peptic ulcer and gall stone. Moreover, 38.4% of chronic pancreatitis with unknown cause were recognised.