Effects of age on autonomic circulatory functions, plasma norepinephrine, plasma renin activity and lymphocyte β receptor were investigated in normotensive and hypertensive subjects. Autonomic functions were tested by Valsalva maneuver, 70° head up tilting, cold pressor and atropine injection (0.02mg/kg iv). Baroreceptor reflex sensitivity index (BRSI) measured with a linear relationship between systolic blood pressure and RR interval in the Valsalva maneuver was significantly decreased with aging. Hypertensives had significantly lower values of BRSI than age-matched normotensives. The magnitude of the change in heart rate in Valsalva maneuver (Tachycardia ratio) was also depressed in hypertensives. The increase in heart rate was also inhibited in normotensive and hypertensive elderly subjects on atropine, cold pressor and tilting tests. The ratio of the increase in heart rate to increase in plasma norepinephrine on tilting was reduced with aging the both groups. In normotensives, aging caused an increase in plasma norepinephrine at rest and a decrease in response of plasma renin activity on tilting. Neither affinity nor capacity of binding sites in lymphocytes for radio-labeled pindolol was affected by age and hypertension. These results suggest that parasympathetic and sympathetic regluation of heart rate are altered with aging and that hypertension has additive effects on these changes. These dysfunctions may be caused at least in part, by the reduced baroreflex sensitivity as well as the decreased sympathetic responsiveness of hearts, apparently due to a postreceptor defect.
Platelet aggregation, circulating Platelet aggregates, β-thromboglobulin (β-TG) of plasma and platelet, plasma lipid, apoprotein, antithrombin III and euglobulin lysis time (ELT) were estimated in 29 diabetic patients (DM group) and 37 nondiabetic patients (AS group) with arteriosclerosis compared to 18 normal subjects (NC group). Platelet aggregation induced by ADP, collagen, adrenaline and arachidonic acid was studied by the turbidometric method and circulating platelet aggregates was studied by the method of Wu and Hoak. β-TG, apoprotein and antithrombin III were measured by radioimmunoassay, immunodiffusion and amidolytic heparin cofactor method, respectively. The most enhanced platelet aggregation was found in AS group. The level of circulating platelet aggregates in AS and DM group was higher than that in NC group. The level of β-TG of plasma and platelet in DM group was the highest among the 3 groups. The apoprotein A-I and A-II in DM group were the lowest. ELT in DM group was significantly lengthened, but there was no significant difference among the 3 groups. Theses results indicate that diabetic macroangiopathy is associated with the elevated levels of β-TG and circulating platelet aggregates and the reduced levels of apoprotein A-I and A-II and fibrinolysis and that the abnormal platelet function, blood lipid and fibrinolysis may contribute to the progression of diabetic macroangiopathy.
Ninety-four patients with congenital heart disease, aged 40 and over, visited our department between Jan., 1973 and Dec., 1983. The ages of the patients ranged from 40 to 79 years. The frequent lesions were atrial septal defect (66 cases), ventricular septal defect (9 cases), patent ductus arteriosus (7 cases), endocardial cushion defect (4 cases), Ebstein's anomaly (3 cases), tetralogy of Fallot (3 cases), ruptured aneurysm of sinus of Valsalva (1 case) and cor triatriatum (1 case). Only 14 of 94 patients were diagnosed as having congenital heart disease previously, while the presence of cardiac disease was first pointed out by us in 10 patients. The number of patients with marked limitation of physical activity, classfied as NYHA calss III or IV, increased with the advancing age: 31.3% in fifth decade, 45.5% in sixth decade and 100% in patients over the age of 60 years, respectively. The courses of 64 cases followed for more than 2 years were generally good under appropriate medical or surgical care. Fifteen patients who underwent radical operation were all doing well. Only 3 died, while 7 patients worsened. Five of the latter 7 cases were not treated at any medical institution after their first visit to our hospital.
There were 57 cases of hemorrhagic gastro-duodenal ulcers, on whom endoscopic local injections of absolute ethanol was performed because of active bleeding or fresh blood clots in emergent endoscopic examinations for 3 and a half years from June 1979 to January 1983. Of them, 25 cases over 60 years old were evaluated. There were 20 cases of gastric ulcer (80%) and 5 cases of duodenal ulcer (20%), including 2 cases of post bulbar ulcer. Of gastric ulcers, 10 were in the C region, 8 in the M region and 2 in the A region. They located comparatively in the upper portion of the stomach, and 40% of them were multiple ulcers. Bleeding conditions were as follows: Projective hemorrhage 4, venous hemorrhage 4 and fresh blood clots 17. Exposed vessels were observed in 13 cases. Fifteen cases (60%) developed shock because of massive bleeding. As basic diseases, 11 were malignant neoplasma and its postooerative cases, 2 postoperative cholelithiasis, 3 severe diabetes mellitus, 2 congestive heart failure and 5 miscellaneousness. Many were considered to have high risk for emergent operation for hemorhage. Endoscopic hemostasis by local injection of absolute ethanol was successful in all 25 cases. Except for 3 cases died of basic diseases and one case of the embolism of superior mesenteric artery for which elective operation was performed after hemostasis, 21 cases colud be medically cured. Massive bleeding or re-bleeding often occurs and conservative treatment sometimes fails in elderly gastric ulcer patients. Additionally, the prognosis of surgical treatment was not so good because of severe complications. Endoscopic hemostasis by local injection of absolute ethanol has reliable efficacy and has succeeded in hemostasis in these cases, for whom the emergent operation is absolutely indicated, and has made it possible to cure by elcctive operation or conservative treatment. It is quite significant that this method is effective curable conservatively for elderly gastroduodenal ulcer patients, who have required nothing but surgical operations and had high mortality.
The purpose of this study is to determine if cytogenetic changes are present in Alzheimer disease. The chromosomes of four groups of people were studied: 1) cases of Alzheimer disease (13 cases, age range 38-62 years), 2) control individuals (12, 36-63 years), and 3) cases of senile dementia of Alzheimer type (6, 77-88 years), 4) senile control individuals (4, 80-91 years). Fifty cells per individual were examined using conventional Giemsa staining to allow chromosome identification. A statistically significant increase in aneuploidy was found in 117 of 650 cells in Alzheimer group (18.0%, p<0.01) when compared with the frequency of aneuploidy in control group (3.5%). However, the frequency of aneuploidy in group of senile dementia of Alzheimer type (12.6%) did not differ significantly from senile control group (10.5%, p=0.1). In addition, almost all of individuals in Alzheimer group exhibited a significant increase in aneuploidy over senile dementia group, raising the possibility that Alzheimer disease differs from senile dementia, since patients affected with Alzheimer disease are younger than individuals suffering from senile dementia, on the average. Furthermore, the missing and extra chromosomes in the two groups were consistenly the C-X group chromosomes. For further clarifying the origin of the aneuploidy, lymphocytes from an Alzheimer-patient were cultivated in Eagle's MEM medium containing serum from control individual. It was found that the aneuploidy was derived from the lymphocytes, not from the serum or other factors.
In senile dementia of Alzheimer's type (SDAT), cerebral cortex is widely involved and recently the cholinergic pathway from the basal forebrain to the cerebral cortex is reported to be selectively disturbed. However, the distribution of the Alzheimer's neurofibrillary tangles, one of the characteristic pathological changes of SDAT, is not restricted in the cerebral cortex but also in the hypothalamus, midbrain and brainstem, as well as nucleus basalis of Meynert. Locus ceruleus is a brainstem nucleus and mainly adrenergic in its function, that is an important center of the catecholamine neurons. Ten cases of SDAT, 6 cases of multi-infarct dementia (MID) and 12 cases of age-matched controls were examined. The number of nerve cells of locus ceruleus on the cross section of the middle part of the upper pons was counted. The number of nerve cells of locus ceruleus was compared with the incidence of the neurofibrillary tangles and the changes of the nucleus basalis of Meynert and cerebral cortex. The results revealed that (1) the number of cells in the locus ceruleus decreased with age and severely in 4 cases (40%) of SDAT. In MID the decrease of nerve cells was almost the same to the controls. (2) The grade of the change of locus ceruleus of SDAT was related to the quantity of the neurofibrillay tangles and the serverity of lesion of the nucleus basalis of Meynert, not of the cerebral cortex. In SDAT, subcortical lesions of locus ceruleus, as well as nucleus basalis of Meynert, may contribute to the clinical picture in some ways.
We had reported that the brain atrophy progressed significantly with advancing age using the two dimensional CT measurement by digitizer which was connected with personal computer (Fig. 1). Using this method, we studied the age-related infra-tentrial brain atrophy in 67 normal subjects (14-90 years), and compared that with agerelated supra-tentrial brain atrophy. There was a significant correlation between age and all indices [cranio-ventricular index (CVI), ventricular area index (VAT) and brain atrophy index (BAI)] in supratentrial brain. These indices did not correlated to the age in infra-tentrial brain (brainstem and cerebellum). Significant change of the brain atrophy occured above 60 years old was observed by BAI and VAI in supra-tentrial brain (Fig. 2). There was a significant correlation between supra-tentrial brain atrophy index (BAI) and that of infratentrial brain (Table 1). These results indicate that age-related brain atrophy might progress more slowly in brainstem and cerebellum than in cerebrum.