Effect of advancing age on the pituitary function has been uncertained. In the present paper, in order to evaluate the role of aging in pituitary responses following thyrotropin-releasing hormone (TRH) injection, 11 carefully selected healthy subjects (5 males and 6 females) over eighty years, in comparison with 40 young healthy controls (20 males and 20 females), ranged from 21 to 35 years, were examined. Thyroxine (T4) and triiodothyronine (T3) concentration in the serum and T3-uptake (Thyrotest-3) value were determined and the serum thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) responses to TRH were evalulated. There were no differences in the serum T4 concentration, the value of Thyrotest-3, free thyroxine index (FTI) and the serum basal PRL and GH concentration between elderly subjects and young controls, on the other hand, the serum T3 and basal TSH concentration were slightly lower, but not statisticaly significant, in elderly subjects than in young controls. When compared with the young controls, the serum TSH response to TRH was definitely reduced or even abscent in 5 elderly subjects and the serum TSH decrease after the maximum value following TRH injection was delayed in 4 elderly subjects. In 2 of 5 elderly subjects in whom TSH response to TRH was reduced or even abscent, the serum PRL response to TRH was definitely reduced as compared with the young controls. In only one of 11 elderly subjects TRH raised significantly the serum GH level (the peak level, 8.0ng/ml). These findings may suggest a decreased sensitivity of the pituitary TRH receptor to TRH with aging and the possibility of changes with aging in hypothalamic catecholamine contents.
Human very low density lipoprotein (VLDL) apoprotein peptides have been quantified by analytical isoelectric focusing. Material and Method The subjects are 20 healthy human, 7 patients with type IV hyperlipidemia, 3 patients of xanthelasma palpebrae without hyperlipidemia and 3 of familial chylomicronemias. For isoelectric focusing, polyacrylamide gel (7.3%, 8×0.7cm) containing 8M Urea and 1.63% Ampholine pH 3.5-7, was used. Results A good lineality of densitometric response was obtained between concentrations of 50 and 150μg of VLDL total protein per gel. As for reproducibility, coefficient of variation was less than 7.4%. Apo E variant, E-IV, was observed in 2 of 3 familial chylomicronemias and one of 7 type IV hyperlipidemias. No apo E-IV was observed in 20 healthy subjects. In healthy subjects, apo E-II/E-III ratio was 0.48 (Mean). The mean values of type IV hyperlipidemia and familial chylomicronemia are 0.46 and 0.56, respectively. While, the ratio was higher, 0.61, in the patients of xanthelasma palpebrae without hyperlipidemia than in the others. Relative decrease of VLDL apo E-III in those patients of xanthelasma may be associated with the heterozygous form of type III hyperlipidemia as reported by Douste-Blazy et al. VLDL apo E-IV may have a role of inhibition of lipoprotein lipase-activity in the patients with hypertriglyceridemia like as familial chylomicronemia.
Serum thyroxine (T4), triiodothyronine (T3), reverse T3 (r-T3), thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG) were measured by radioimmunoassay methods in 68 normal human subjects (male 34, female 34) ranging from 17 to 90 years of age, with special emphasis on sex difference in their serum levels. Serum T4 level tended to decrease with advancing age in males, while no significant change was observed in female. Serum T3 level was significantly decreased with an increase of age in both sexes of apparently normal subjects. There was a significant positive correlation between serum T3 and T4 levels in both sexes. Serum r-T3 levels remained unchanged with increasing age in both sexes and there was no significant correlation between serum r-T3 and T3 levels. Serum TSH levels significantly increased with advancing age in females, although all values were within normal limits. Serum TSH levels in males, however, remained unchanged with aging. Serum TBG levels were not influenced by aging in males, but tended to decrease in females with an increase of age. T4/TBG ratio in male was not influenced by aging, but the level in female were significantly increased with an increase of age. Free thyroxine index (FTI) was significantly decreased in males with advancing age, but the level in females was not influenced by increasing age. These findings suggest that metabolism of thyroid hormones may be decreased in elderly subjects, partially due to a decrease in the conversion of T4 to T3 in peripheral tissue of elderly subjects.
We studied relationships between results from mass health examination of the apparently healthy elderly at the old people's homes and their survivorship after 5.5 years. Subjects were inmates of the Tokyo Metropolitan Geriatric Homes comprising 713 men and 1064 women, who underwent health examinations in 1972. Participation rate was 98.5%. Average age at examination was 73.7 in men, and 76.4 in women. We used age-standerdized relative mortality ratio (SMR) and a multiple regression analysis. 1. Mortality rates increased with age both in men and women. During 5.5 years, 274 men (38%) and 300 women (28%) died. Mortality rates for men exceeded those of women at all age groups. 2. Actively participat ng men and women in jobs such as cleaning of the garden, arranging meals and working for extra income, had better prognosis. Some signs such as low serum A/G ratio, ECG abnormalities and albuminuria indicated poorer prognosis in women; in men, the same tendency was observed, too. SMR appeared to be higher, when blood pressure was higher and skinfold thickness lower. Serum cholesterol did not show any correlation with survivorship in this population. 3. In a multiple regression analysis, age and participation to jobs in men and women, and A/G ratio, skinfold thickness and ECG abnormalities in women, revealed significant association to the prognosis.
Effects of long-term (48 weeks) treatment with colestipol hydrochloride, a bile acid sequestrant, in 33 subjects with heterozygous familial hypercholesterolemia are reported in this paper. Treatment with 10 or 15 grams a day produced significant (p<0.001) reductions in the serum cholesterol levels (mean reduction of 20%) from 351±63mg/dl (mean±SD) to 272±54mg/dl after 4 weeks of treatment, and the mean cholesterol values were 268-283mg/dl (-17%- -22%) during the 4th week through the 48th week. Eleven subjects with pretreatment cholesterol levels over 400mg/dl showed a significantly higher reduction (27.2±12.3%) than the other patients (15.8±13.1%) after 48 weeks. There was no changes in serum triglyceride levels throughout the observation period. The phospholipid and β-lipoprotein levels fell significantly from 302±47mg/dl and 678±141mg/dl to 266±38mg/dl and 541±111mg/dl after 48 weeks, respectively. The high density lipoprotein-cholesterol (HDL-C) levels increased significantly from 36.2±9.4mg/dl to 43.0±8.7mg/dl after 48 weeks. The decrease of phospholipid and β-lipoprotein, and the increase of HDL-C were significant at each observation time. Ultracentrifugal analysis of fifteen patients revealed a significant reduction of low density lipoprotein (LDL)-cholesterol from 274±68mg/dl to 183±50mg/dl (-31.5%). LDL-triglyceride and LDL-phospholipid also decreased significantly, from 52mg/dl to 41mg/dl and 155mg/dl to 115mg/dl, respectively. A slight and insignificant increase of very low density lipoprotein (VLDL)-triglyceride levels (from 51mg/dl to 66mg/dl) was observed, but indivisual changes were variable. In contrast to the increase of HDL-C measured by precipitation method, the cholesterol concentration in d>1.063g/ml fraction showed no significant changes. Long-term treatment with colestipol showed no effects on Achilles tendon thickness, but a skin xanthoma disappeared in a patient. A patient with angina pectoris requiring medication reported subjective improvement. No serious side effects were attributed to the drug treatment. Four patients claimed constipation. One patient complained of abdominal fullness after five days of therapy. The levels of GOT, GPT and alkaline phosphatase elevated in five patients, but returned to normal or slightly elevated levels in four of the five patients. In conclusion, colestipol hydrochloride significantly reduced serum and LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia. The absence of severe side effects in long-term therapy indicates the efficacy of this resin in the treatment of this hereditary metabolic disease which represents an important risk factor in atherosclerosis.
The purpose of the present study is to clarify the clinical significance of brain atrophy by computed tomography in age-related dementia. Eighty elderly patients with clinical diagnosis of presenile or senile dementia whose mental states were assessed clinically and by several psychometric test were studied by computed tomography. Patients with suspected cerebrovascular disorders and normal pressure hydrocephalus were excluded. Three tomographic sections through anterior and posterior horns and cella media of lateral ventricles and cortex with intracranial space of 60-80cm2 were evaluated. CSF spaces (%) were measured as a index of brain atrophy. The measurement of CSF spaces (%) was carried out by the computarized planimetric method to avoid visual definition of ventricular borders. In this study, CSF spaces comprised ventricular and subarachnoid spaces. Hasegawa's dementia scale, Bender-Gestalt test and Kohs' block design test were employed for the cognitive assessment of the subjects. In two sections through lateral ventricles, significant correlation were obtained between CSF spaces (%) and scores of Hasegawa's dementia scale and Kohs' block design test. Scores of Bender-Gestalt test did not correlate with CSF spaces (%) in these two sections. In the section through cortex, no correlation were found between CSF spaces (%) and scores of any psychometric test. Also, no positive correlations were obtained between age and CSF spaces (%) in the three sections. The present results suggest that brain atrophy could be one of the significant predictors to screen patients with dementia and to identify patients with so called reversible dementias. Also, it is suggested that ventricular enlargement is more etiological to the intellectual impairment than cortical atrophy. Taking into consideration that the correlation coefficients are fairly low in the present study, it seems quite essential to evaluate etiological factors other than morphological changes such as brain atrophy shown in CT. Finally, the present study will need to be confirmed by both follow-up studies and more extensive inquiries in larger groups of patients.
A patient associated with megaloblastic anemia due to folate deficiency caused by the tube feeding is described. An 86-year-old woman was admitted to Tokyo Metropolitan Geriatric Hospital because of consciousness disturbance, right hemiparesis and motor aphasia. She was diagnosed as cerebral vascular disease and was treated conservatively. On admission the hemoglobin level was 12.4g/dl and morphological findings of red cells were within normal limits. Nasogastric tube feeding was begun, which contained 1545 Cal daily (protein 69.6g, sugar 44.2g, fat 182g, folic acid 60μg). Seven months later, the hemoglobin level fell to 6.9g/dl with macrocytosis. A bone marrow aspirate revealed megaloblastic changes and giant metamyelocytes. The serum folic acid activity was 0.90ng/ml, the vitamine B12 level 440pg/ml, and the serum iron level was 118μg/dl. Although some drugs such as INH, anticonvulsant and glutethimide, are known to give rise to megalblastic anemia, she was not given any of these, except antihypertensive drugs. Thus, the insufficient daily intake of the folate was considered to be the cause of the megaloblastic anemia. She was treated with folic acid 30mg/day through nasogastric tube following the elevation of the hemoglobin level to 8.3g/dl in two manths. Including this case, six patients feeded with the diet of the same composition through nasogastric tube were examined hematologically. After the duration of the tube feeding of 17.3±8.0 months, their serum folic acid activity had become under normal value (0.93±0.14ng/ml). They responded to the treatment with 30mg of folic acid daily, and their hemoglobin level and folic acid activity increased significantly.
High Density Lipoprotein (HDL) Cholesterol in fasting blood samples was measured in 1615 men and 2844 women aged 25 and over of Toda City (population 78, 115), an urban area of Japan, between March 1979 and Feburuary 1981. Total serum cholesterol, serum triglyceride, and fasting blood glucose were measured simultaneously. The number of cigarette smoked daily and the amount of alcohol consumed weekly were also calculated by interview. MgCl2 and dextran sulfate were used to precipitate LDL and VLDL. Cholesterol of the supernate was measured by an enzymic method. The results obtained were as follows: 1) The value of HDL cholesterol obtained by our method was lower than that measured by Heparin Mn+2, Liebermann Burchard. 2) Distribution curves of HDL cholesterol revealed a slight right-skew for both sexes. The mode was 40-40mg/dl in men, 50-59mg/dl in women. 3) The value of HDL cholesterol did not vary according to age increase. Women showed significantly higher value than men, 48.2±14.2mg/dl, 52.1±13.0mg/dl, respectively. 4) Total cholesterol and amount of alcohol consumed were positively correlated to HDL cholesterol when partial correlation analysis was used. Questelet's index, triglyceride, and the number of cigarettes smoked were inversely correlated to HDL cholesterol. Age was not correlated to HDL colesterol in either sex. Fasting blood glucose was positively correlated only to men.
Aspirin has been widely used as a potent antithrombotic drug in clinical practice. However, the optimal dosage for the prevention of thrombo-embolic events is still controversial because high-dose aspirin inhibits PGI2 production in vessel walls as well as TXB2 production in platelets. This study was designed to investigate the optimal clinical aspirin dosage from the view point of its effects on ADP-induced platelet aggregation. The materials were composed of 13 normal subjects (control group) and 71 patients with cardiovascular diseases. Various daily doses of aspirin (80, 160, 330, 660 and 990mg) were given to patients (aspirin group) for more than 4 weeks, and percent ADP aggregation was studied. There was no significant difference in percent aggregation between any two of the aspirin-treated groups, all of which showed a tendency to have lowered percent aggregation as compared with the control group. A single dose of 160mg of aspirin inhibited ADP platelet aggregation within one hour after oral ingestion. The inhibitory effect of aspirin on collagen- and epinephrine-induced aggregation persisted for 4 days when 330mg of aspirin was given and for 5.5 days when 660mg was adminstered. No significant correlation was observed between plasma concentration of aspirin and its effects on platelet aggregation. The present study showed that a daily dose of as small as 80mg of aspirin was sufficient to inhibit platelet aggregation. However, further clinical trials should be made to ascertain that this low daily dosage of aspirin will effectively prevent future thrombo-embolic events.
The changes of vital functions in 101 patients (43 males, 58 females, more than 65 years of age) during upper G.I. endoscopy were reported. The respiratory rate, systolic & diastolic blood pressure and heart rate were increased significantly during endoscopy, and diastolic blood pressure had a tendency to increase higher not only during but also after endoscopy. Electrocardiographically, the appearance and/or aggravation of ischemic changes and arrhythmias were recognized in some patients, but these changes were found chiefly in the aged with underlying cardiovascular diseases. The changes of electrical axis due to air inflation of stomach were not remarkable. Serum cortisol concentrations were increased significantly after the endoscopy. This fact suggests endoscopic examination will give the patients considerable emotional stress. To perform safely the endoscopic examination for the aged, endoscopists must pay attention to general conditions and complications, especially cardiovascular diseases, of patients.
It is generally accepted that responses of peripheral lymphocytes from the aged to phytohaemagglutinin (PHA) and concanavalin A (Con-A), which are well known stimulators of T cells, are lower than those from the young. However, the functional capacity of Bcells from the aged has not'as yet been fully i vestigated. In this report, peripheral lymphocytes 'from the aged over 70 years of age and the young from 22 to 36 years were examined for their responsiveness to PHA and Con-A'in vitro, and the imparied T cell function of the aged was reconfirmed. Furthermore, B cell responses to pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I strain bacteria (SpA) were also compared in vitro between the two age-groups. Peripheral lymphocytes were cultured for a period of 24hrs to 8 days in the presence of PHA, Con-A or PWM to measure 3H-uridine and 3H-thymidine uptake by the cells. Peripheral lymphocytes from the aged responded significantly less to PHA and Con-A than those from the young. No significant difference was detected in responses to PWM between the two age-groups. Peripheral lymphocytes were separated into ′T cell-enriched and B cell-enriched populations by rosetring with neuraminidasetreated sheep red blood cells. Mitomycin C (MMC)-treated T cells+B cells were cultured in the presence of PWM for 4 days to measure 3H-thymidine uptake by B cells. 3H-thymidine uptake by MMC-treated T′ cells from the young+B cells from the aged was significantly lower than that by MMC-treated T cells from the young+B cells'from the same group. 3H-thymidine uptake by MMC-treated T cells from the aged+B cells from the aged was also significantly lower than that by MMC-treated T cells from the aged+B cells from the young. Effect of SpA, which is a known polyclonal activator of human B cells, was similarly studied, revealing that 3H-thymidine uptake by the lymphocytes from the aged was significantly lower than that from the young. These results indicate that the decreased immune function in the aged reflects the impaired functions of not only T cells but also B cells and/or monocytes.