With advancing age there is a gradual decrease in the ability to sustain physical exercise, and the exercise limitation is mainly caused by the the diminished cardiovascular reserve. This present study was performed to classify the changes of cardiocirculatory response to exercise with aging noninvasively. Hemodynamic measurements using systolic time intervals and Minnesota impedance cardiograph were made on 65 normotensive men during graded exercise on a sitting bicycle ergometer. Continuous pulmonary functions were recorded simultaneosuly. The age range of the group was from 20 to 79 years. After resting recumbent recordings were obtained, the subjects exercised twice with a resting period of 10 minutes in between; first at a low level of 50 watts for 5 minutes, and then at a level from 75 to 125 watts adapted to the subjects' tolerance. The results were as follows; at rest the group over 60 years had lower cardiac output, higher total peripheral resistance and more prolonged QS 2I and PEP than younger subjects. LVETI did not significantly shortened. Resting oxygen uptake diminished with aging, but exercised oxygen uptake was nothing further to be significant among them. Maximal heart rate in exercise was higher at a low level, while lower at a high level in older subjects. Systolic and diastolic blood pressure during exercise showed a greater change in older subjects. Immediately after exercise the percent increment of cardiac output and stroke volume and the percent derement of total peripheral resistance were significantly greater in older subjects. Furthermore shortening PEP and lengthening LVETc were prominent. Especially in the group over 60 years, QS 2c was little shortened becasue of more prolonged VLETc The relationship between oxygen uptake and pulmonary ventilation (ventilation volume, oxygen removal, respiratory exchaneg ratio) at variable loads was not influenced by aging. However oxygen debt increased and the recovery of the cardiocirculatory values delayed in older subjects. In conclusion, therefore, the faulty cardiovascular adaptation which occurs with aging is prominently revealed in exercise. On the other hand pulmonary disability does not appear to take part in the exercise hemodynamics in this study. For the older subjects the cardiac response to exercise appears to be adapted with greater increase of stroke volume which is more important in the subjects with diminished cardiac reserve. Moreover the following factors may also play a role; lower sympathetic discharge, inefficiency in the distribution of blood, restrictive vascular beds, local metabolic disability, and so on.
Essential hypertension is an unknown disorder affecting the normal regulation of blood pressure at rest and under the stress of exercise. In this study the hemodynamic response to graded exercise using a sitting bicycle ergometer was evaluated in 59 men with essential hypertension and 37 normotensives by systolic time intervals and Minnesota impedance cardiograph. The hypertensive patients were divided into three groups; group I comprised 18 subjects with labile hypertension; group II, 20 uncomplicated fixed hypertensive subjects with diastolic blood pressure over 90mmHg; group III, 21 hypertensive sujects with left ventricular hypertrophy. The age of hypertensive group covered from 23 to 58 years old. All the hemodynamic changes of those were compared to the age-matched normotensives. After resting recordings at recumbency, the subects exercised twice with a resting period of 10 minutes in between; first at 50 watts for 5 minutes and at 100 or 125 watts. Continuous respiroventilatory recordings were performed simultaneously. At rest group I was characterized by a significant increase of oxygen uptake and heart rate, shortened QS2I and LVETI and normal PEP, while group II and III showed prolonged PEP and shortened LVETI. In addition decreased PTT was shown in group II and III. Maximal heart rate of group I in exercise was higher than the others. Group III showed the lowest maximal heart rate in exercise, while the systolic blood pressure showed a greater increase. Immediately after mild exercise the percent increment of cardiac output and stroke volume and the decrement of total peripheral resistance were significantly smaller in group I and greater in group II than control, but the circulatory response to higher load of exercise did not differ between group I and control. However the recovery of the cardiovascular values were rapid in group I. LVETI after exercise showed a decrease in group I, but remained unchanged or increased in group II. On the other hand in group III, the increase of cardiac output and stroke volume were less than in group II, although the decrease of total peripehral resistance was not significant. Moreover the prolongation of QS2I and PEP immediately after exercise were most prominent in group III. These findings indicate that in response to exercise: (1) in group I, enhanced myocardial contractility and increased afteroad with exercise are found to be mediated by increased sympathetic stimulation, (2) in group II, augmented myocardial contractility in exercise, probably adapted to increased preload, higher blood pressure elevation and so on, is suggested to be more dominant, (3) group III indicates the presence of depressed myocardial contractility and restrictive vascular changes.
In order to clarify the senile changes of the stomach, histological and micromeasuring studies have been made on the stomach tissues without any pathological changes, obtained by surgery in case of early gastric cancer or gastric and duodenal ulcers. 1. Lamina propria mucosae of the stomach decreased gradually in thickness with age, and the decrease is due mainly to a decrease in thickness of the glandular portion. 2. Chief cells, parietal cells and mucous neck cells in the gastric glands decreased in number gradually with age. These changes were noticed more markedly in the chief cells, less markedly in the parietal cells and slightly in the mucous neck cells. The decrease in number of cells is considered to be proportional to grade of differentiation of the cells. 3. Size of the surface epithelial cells, chief cells, parietal cells and their nuclei is the largest in the fifth decade. In the aged, a slight decrease in volume is noticed in chief cells, but less marked in other glandular cells. A significant increase was observed in volume of surface epithelial nuclei. 4. The smooth muscle layer increased in thickness with age until sixth decade. The increase was supposed to be due to increase in number of smooth muscle cells. However, after seventh decade, there were observed decrease in number and increase in volume of the muscle cells. 5. Some characteristics in the aging process observed in the stomach have been discussed comparing with age changes of other organs and tissues.
Authors reported already the effects of noradrenaline and lecithin on contraction of smooth muscle in rabbit aortae on this Journal in 1977. On this paper, authors observed the effects of prostaglandin E1, E2 and other derivatives (GNo-1142, 747-1) on contraction of smooth muscle in rabbit aortae by noradrenaline, serotonine and histamine, and also the effects of these drugs on platelet aggregation in human Plasma. We observed that the smooth muscle in rabbit aortae was contracted by prostaglandin and other derviatives. In the contraction activity on smooth muscle in aortae, prostaglandin E2 was strongest, the E1 was hardly effective, and other derivatives were not so stronger than E2 but more effective than E1. These drugs inhibited the contraction of smooth muscle in rabbit aortae by noradrenaline, histamin and serotonine. These inhibitory effects were noncompetititional. In these inhibitory activities, the E2 was strongest, the E1 was hardly effective, and other derivatives were not so stronger than E2 but more effective than E1. The E2 itself aggregated the platelet in human plasma, but E1 inhibited the platelet aggregation by noradrenaline. Other derivatives inhibited very strongly the platelet aggregation by ADP and noradrenaline. We supposed from above results that there will be different mechanisms between the effect of prostaglandins on the contraction in smooth musdle and platelet aggregation.
The return of the elevated blood pressure after discontinuing antihypertensive drugs was investigated in 65 hypertensive aged patients. The blood pressure was elevated at a certain level one month after the withdrawal of drugs, and remained around the same level for six months. The lower the blood pressure during the antihypertensive treatment, the lower the blood pressure level reached after the withdrawal of drugs. The elevation of systolic blood pressure over 160mmHg after the withdrawal of drugs was observed in 65% and in 87.5% patients who showed the systolic pressures of 149 or less and 150 to 159mmHg during the treatment respectively. The elevation of systolic pressures in patients with systolic pressure of 160 to 169, and 170 to 179, were by 56.3% and 67.1% respectively, and systolic blood pressure remained the same level in patients with blood pressure over 180mmHg. As a whole, 26.5% remained at 159mmHg or less after withdrawal of drugs. The elevation of diastolic blood pressure over 90mmHg after the withdrawal of drugs was observed in 13.6% and 53.6% of patients who showed the diastolic pressures of 79 or less and 80 to 89mmHg during the treatment respectively. Patients with diatolic pressure of 90 to 99 showed the elevation of diastolic pressure by 41.7%. and no elevation of diastolic pressure was observed in patients with diastolic pressure over 100mmHg. Thus, 64.0% remained at 89mmHg or less after withdrawal of drugs, indicating one of the characteristics of aged hypertension. Drugs used during the treatment were mainly thiazide diuretics, and no difference in elevation of blood pressure after withdrawal was observed between one drug treatment and two or more drugs treatment.
In parkinsonism, L-DOPA treatment has been reported to be effective in reducing signs & symptoms. Vitamin B6 (VB6), however, has been reported to reduce the effect of L-DOPA, if VB6 is given orally or parenterally. On the contrary, the peripheral L-DOPA decarboxylase inhibitors (PDI) were reported to block L-DOPA decarboxylase (AAD) activity in the peripheral organs even when VB6 was added to them. Clinically, some literatures described that the combined treatement (L-DOPA+PDI) showed much improvement by VB6 administration, the others indicated that the additional VB6 to the combined therapy showed the clinial deterioration. In order to clarify the effect of VB6 loading on the combined treatment, authors carried out the following in vitro and in vivo animal experiment. a) In vitro experiment In rat liver homogenate, the effect of VB6 concentration on AAD was examined. As a result, there was some adverse relation between B6 concentration and AAD. Namely, the more VB6 concentration increased, the more the inhibition ratio of AAD was observed. b) In vivo experiment Two PDIs (MK-486 and RO4-4602) were examined in Wistar rats: One was fed with VB6 containing diet (VB6 (+)), the other was fed with VB6 deficient diet (VB6 (-)). Furthermore, VB6 (+) was divided into two groups; a) MK-486 (or R04-4602) 50mg/kg orally. b) a)+pal-p 10mg/Kg (i. p.) and VB6 (-) group was MK-486 (or R04-4602) 50mg/Kg orally. After 15 weeks' feeding, rats were sacrificed by decapitation. Measurement of AAD was carried out in liver, kidney, brain & small intestine. In addition to AAD, GOT & GPT in liver and kidney were also examined. As a result, PDIs blocked the AAD activity in kidney, brain & small intestine, especially in small intestine, but not in liver. In pal-p loading groups, there was the marked reduction of AAD, compared with no VB6 loading. Almost similar results were obtained in VB6 (-). AAD in liver, however, showed the decrease in the VB6 (-), which was different from VB6 (+). GOT & GPT in liver and kindey showed no remarkable changes. From the above in vitro and in vivo experiment, authors supposed that VB6 can combine with L-DOPA (condensation) in the blood and/or organs by the increasing concentration of VB6, and that the increasing concentration of L-DOPA induced by blocking effect of PDI would be reduced by the increasing VB6 in the blood and/or organs. Namely, the condensation between VB6 and L-DOPA resulted in the decrease of substrate to AAD. Authors would recommend the careful administration of VB6 even in the combined therapy of parkinsonism.
The long term results of treatement in 1339 patients with chronic arterial occlusive disease at the 1st Dept. of Surg., Univ. of Tokyo for 1955-1975, have been analysed. In this series, 449 patients with arteriosclerosis obliterans (A. S. O.), and 890 patients with thromboangiitis (T. A. O.) were included. Recently the number of patients with A. S. O. has increased remarkably. In this paper, the characteristics of A. S. O. with special reference to its prognosis is reported comparing with T. A. O.. 1) A. S. O. involved the males predominantly (ratio 6:1), and about 80 percent of cases was over 51 years of age. 2) Commonly, the ischemic skin changes of the lower extremity such as coldness and the intermittent claudication were regared as initial symptoms of this disease. 3) In 286 cases, hypertension was found by 66%, hypercholesterolemia by 38%, diabetes mellitus by 17%, and visceral vascular involvement by 30%. These highly associated abnormalities seemed to be rsik factors for the progression of atherosclerotic changes. 4) About 32 percent of cases with aorto-iliac occlusion were suitable for or required surgical treatment. However, patients with diffuse obstruction, severe associated disease, advanced age were not candidates for reconstructive operation, and treated with lumbar sympathectomy or conservative therapy. Reconstructive operation was entirely succesful in 70 percent of cases, whereas lumbar sympathectomy or conservative therapy was beneficial for ischemic skin changes with poor improvement for intermittent claudication. 5) In 417 cases, diabetes mellitus was observed in 71 (17.0%), cerebral vascular disease in 37 (8.8%), myocardial infarction in 24 (5.8%), angina pectoris in 18 (4.3), renal failure in 14 (3.6%), and malignant tumor in 18 (4.3), respectively. Visceral vascular involvement were associated with rather high frequency. 6) Over-all mortality rate for 10 years after the onset of symptoms were accounted for 40.2% and the cause of death were mainly attributed to cerebral, coronary and renal insufficiency. Because the long term result of treatment in A. S. O. was closely related to advanced age, generalized atherosclerosis, and some risk factors stated above, the treatment should be based not only on the limb salvage, but also on the accurate estimation of general condition, Further, surgical intervention will be neccesary to suppress the progress of the atherosclerotic occlusion in the selected cases.
This study was carried out to know what part might platelet aggregation take in clinical course of diabetes mellitus. 296 subjects were chosen in our diabetic clinic, and examined simultaneously platelet aggregation induced by two concentrations' adenosine diphosphate solution (high concentration: 2μmol, low: 0.4μmol) with two channel aggregometer. Aggregation curves were divided into four patterns according to the presence or absence of second wave in aggregation process. 1) Platelet aggregation was influenced by the age of diabetics. As advanced in age, its was found that the percentage of hyper-aggregation pattern was increasing clearly in proportion to the decrease of normal aggregation pattern. It could not be evaluate without the age of diabetes whenever hyper-aggreagtion was recorded. 2) Relationship between platelet aggregability and duration of diabetes was studied. In proliferative retinopathy of above Scott III, diabetes with more than 10 years duration had higher percentage of platelet hyper-aggregation pattern than below 5 years duration. 3) Patients with retinopathy of the degree of Scott I-II were shown in no significant difference compared with age-sex matching diabetic control. But retinopathy with the degree of Scott III, IV and V showed in significant increasing hyper-aggregation patpattern. Thus, platelet hyperfunction was thought to be a risk factor to proliferative retinopathy. 4) Platelet aggregation was under the influence of the kinds of antidiabetic therapy. Hyper-aggregation patterns appeared to be remain in 52.4% in diet therapy group and 43% in insulin therapy group. But the figure of hyper-aggregation in oral antidiabetic therapy group had reached up to 66.6% which was apparently highert han the others. 5) Aspirin as correcting agent to platelet hyper-aggregation was given to diabeets upon ordinarily diabetic therapy. The effect of aspirin on platelet aggregation showed the difference according to the kinds of antidiabetic therapy. The improvement of hyperfunction was in significant with both of diet and insulin therapy groups. But significant improvement was not obtained in diabetes with oral antidiabetic therapy.
A 57-year-old woman died of an acute gastrectasia 5 years after the onset of the progressive mental deterioration. Besides fragmented mental functions, the patient had showed a characteristic psychosyndrome with akinesia, aresponsiveness and refusal to talk from relatively early stage of the disease. Some release phenomena and flexion contracture of the exrtemities were observed at the endstage, but the neurological symptoms were not manifest. The neuropathological examination revealed a large number of senile plaques and Alzheimer's neurofibrillary changes in the cerebral cortex and widespread atrophic-degenerative processes of the cerebral cortex and white matter, which were very much stressed in the frontal and temporal lobes. Namely, this case showed morphological characteristics of both Alzheimer's and Pick's disease. The clinico pathological relationship was discussed in reference to the frontal lobe syndrome as well sa to akinetic mutism or “apallisches Syndrom”. In this respect, it is to be remarked that the severe cerebral lesions were localized mainly in the frontal lobe and other association areas and the primary sensory-motor areas and their surroundings were relatively well preserved, and that the brain damages were of the nature of mild and slow-progressive one in this example.
For the measurement of serum lipid peroxid three methods using tiobarbituric acid have been demonstrated and established. These are Yagi's Naito's and Takeuchi's ones. We modified Takeuchi's method slightly, and examined its problems with the aim of clinical applications. Moreover, we determined the reference values of serum lipid peroxid in healthy volunteers with ages between 20 and 100 years old. When the Takeuchi's method was applied, the better reproducibility was obtained with empolyment of a fluorescence spectrophotometer (Hitachi, Modal MPF-2A) than in case of using a spectrophotometer (Hitachi, Model 181) indicated originally. Therefore, a fluoresecence spectrophotometer was used through all the experiements. The influences on the measurement, of diet, storge of samples, required volume of specimens and boiling time were evaluated. The precision, recovery rate and correlation with the original method were studied. The following experimental results were considered to be important. 1) The diet did not affect the levels of serum lipid peroxid. 2) In the refrigerator samples could be stored for seven days without any effect on the values of concentration. 3) The voluem of specimen, 0.1ml, was enough for an analysis. 4) The boiling time should be strictly controlled. The recovery rate was more than 90%. The precision was determined by analyses of the sample selected ten times. The coefficient of variation was 3.20%. There existed the positive correlation with the original method and the coefficient was 0.71. These show accuracy of the modified method. The reference valves (means±SD) of serum lipid peroxid in healthy volunteers are: 2.437±0.836nmol/ml for the age group of twenties; 2.834±0.969 for the thirties; 3.053±0.824 for the forties; 3.046±0.511 for the fifties; 2.969±0.607 for the sixties; 2.393±0.661 for the seventies; 2.109±0.565 for the eighties; 1.922±0.428 for the nineties; 1.651±0.461 for the centenarians. These figures told us that until time of 60 years old aging was accompanied with the increase of concentration of serum lipid peroxid. This formed a contrast with the fact that after the sixties increment of age coexisted with the decrease of level of serum lipid peroxid. Because the statistically significant differences among the adolescence, the middle-aged and the old-aged are recognized with regared to concentration values of serum lipid peroxid, it must be very careful to interpret data of serum lipid peroxid obtained from persons of various age groups.
We have obtained the following conclusions through neuropathological examinations of the vessels in the monkey (Maraca fuscata) brain. 1) A senile change of congophilic angiopathy is seen in brain of aged monkeys, coinciding with that of human. 2) Arterioles were found to have a close relationship to senile plaques. 3) Congophilic angiopathy in monkey appears only after the age of 20 years. 4) Pathological changes resembling hypertensive angionecrosis were also observed in the vessels of the striatum and the thalamus, but the changes were milder than in humans. 5) No atherosclerotic change was seen in basal arteries. 6) Venous vessels of the brain surface showed the same degeneration as in the“Kapillarfibrose”of man.
In our recent study 20 normal adults aged 21-79 were each given 0.5g/kg of arginine hydrochloried by intravenous drip infusion over 30 minutes; blood samples were collected before, and 15, 30, 45, 60 90 and 120 minutes after, the beginning of the infusion, to measure the serum insulin and blood sugar; and the following were found: 1) In the age group fo 20-39, ΔIRI gave a curve with the peak of 29.4±3.7μu/ml appearing 15 minutes after the beginning of the infusion, which was high, compared with the peaks in the other groups, and ΔBS, a diphasic curve, with the peak of 13.0±3.6mg/dl in 30 minutes and the bottom of -9.4±4.5mg/dl in 60 minutes. 2) In the age group of 40-59 ΔIRI gave a curve with the peak of 19.2±5.7μu/ml appearing in 30 minutes, and ΔBS, a slightly less conspicuous diphasic curve with the peak fo 14.0±5.0mg/dl appearing in 30 minutes and the bottom of -3.0±5.8mg/dl in 60 minutes. 3) In the age group of 60-79 ΔIRI gave a curve with the low peak of 6.7±2.7μu/ml appearing in 30 minutes, and ΔBS, a monophasic curve with the peak of 8.7±3.5mg/dl in 30 minutes. 4) In order to observe the relationship between ageing and the arginine-induced secretion of insulin, age was plotted on the abscissa, and ΔIRI on the ordinate: a significant inverse correlation was found between these parameters, with correlation coefficient, r=-0.70 (P<0.01). 5) With age plotted on the abscissa and ΔBS on the ordinate, no correlation was found between these parameters, with the correlation coefficient, r=-0.16, nor was there any correlation between ΔIRI and ΔBS, with the correlation coefficient, r=0.37. 6) The arginine-induced insulin secretion was more decreased, the higher was age. This phenomenon appeared derived from the decreased insulin release from the pancreas with ageing.