Recently, along with an increase in aged patients, the frequency of drug administration has increased. It is said that drug hazards of treatment result in side effects; however, I would like to study the problematical points of why there are many side effects among the aged. First, studies in the determination of drug doses, discovery of pharmacological effects. and establishing drug standards were made using young, healthy animals and humans. Furthermore, this dose is applied to aged people as is. Secondly, dosage is calculated by drug concentration in the blood. However, in calculating this, the distribution volume is calculated from percentage of weight of the lean body mass without taking into consideration the constituent fat in the composition of the body; in the case of the aged with obesity, and those using liposoluble drugs, it does not mean that drug concentration in the blood will reflect the effective amount. Therefore, as the third point, it is considered that side effects will not occur if the drug dose is given within the permissible limits for the organ function. If the changes due to aging which have to do with absorption metabolism and excretion of the drug dose are measured and compared with that of young and prime ages, and the common factor of each organ function is calculated, that will be the safety minimum. As a result of my studies on the change of organ function in aging, it became clear that aged liver function is 1/2 to 1/2.4, kidney excretion function is 1/2 to 1/3, digestive function drops, and immune function is 1/2. Therefore, from the standpoint of organ function, it is appropriate to start with 1/2 to 1/3 dose, gradually increasing this to seek the optimum amount. The fourth problem is that side effects occur due to combined dosage, even though each dose is not excessive in itself. This is due to drug interaction. Therefore, since side effects occur due to delay in absorption, abnormality of pH of the stomach, stagnation of contents of the stomach, conflict of protein in the process of distribution, substitution phenomena, enzyme induction, changes in the effects of drugs due to inhibition, abnormality in the order of the function of excretion, and inhibitors of metabolism, the combined use of drugs which cause interaction should be avoided. The fifth point is that to gain the benefits of drugs, the right dose must be taken; however, the aged lack in correctly taking drugs because of misunderstanding, and have troubles with eyesight and hearing ability due to senility. Therefore, the lack of education of the elderly in taking drugs can be raised as an additional problem. Solving these points will greatly reduce side effects in drug treatment of the aged.
A quantitative analysis of serum high density lipoprotein (HDL) was carried out using rocket immunoelectrophoresis with a commercially prepared anti-HDL-serum as a clinically convenient method. The values obtained from healthy subjects were compared with those from patients with myocardial infarctions. In the Ouchterlony method using the anti-HDL- serum, precipitation lines were detected only against whole serum and HDL (1.21<d<1.063), and these lines were fused. No precipitation lines were detected against VLDL (d<1.006) and LDL (1.063>d>1.006). Under immunoelectrophoresis, two precipitation lines were found between antiserum and human whole serum. One strong arch of precipitations had an electrophoretic mobility corresponding to that of serum-α-globulin, the other was faintly detected in a more cathodal site. The strong arch was shown by the lipid stain Sudan Balack B. With rocket immunoelectrophoresis, only one precipitation line developed in each serum sample agarose gel plate containing anti-HDL-serum, and each of these lines was stained by Sudan Black B. Accordingly, antiserum can be used for the clear determination of serum HDL levels and especially, the apoHDL concentration. Serum HDL levels were determined quantitatively in patients with old myocardial infarctions and healthy subjects. The mean value of serum HDL was significantly lower in the former group than in the latter group. It is interesting to investigate not only the serum HDL-cholesterol levels but also the serum apoHDL values. Especially important is the interrelation between these values in patients with ischemic heart disease. The rocket immunoelectrophoresis is simple and useful method for this purpose.
The purpose of this study is to evaluate clinical significance of electrocardiographic findings in the elderly patients under prolonged bed fast. ECG findings were analyzed and compared with underlying diseases, clinical laboratory data, and pathological findings of the heart in the 124 elderly patients under bed fast over 3 months (Group A), in the 273 subjectively healthy men living in an old-age home (Group B), and in the 112 autopsy cases of the elderly patients died after prolonged bed fast (Group C). 1) Group A was revealed to show ECG abnormalities in 96.8% of the patients, of which the incidence was higher than 76.2% in Group B. 2) The significant ECG abnormalities observed in Group A were low voltage of QRS complex, ischemic ST, T change, left ventricular hypertrophy, and nonspecific ST, T change. Among them, the finding of low voltage was the most significant and specific in Group A and was accompanied with ST, T abnormalities in high incidence (76%). 3) Making a comparison of the patients with low voltage (Group LV) to those without low voltage (Group NLV), none of the findings of age, blood pressure, heart rate, serum protein level, hemoglobin level, and serum electrolyte levels could be specific. 4) The incidence of low voltage increased as the period of bed fast became longer and as the time of the ECG recording became near to the time of death. 5) Congestive heart failure was the most common cause of death in the patients with low voltage in Group C. Pathological findings of the heart of them frequently revealed brown atrophy of the heart muscle, cardiac hypertrophy, myocardial infarction, diffuse fibrosis, and fatty degeneration of cardiac muscle. These findings indicate that the ECG findings of low voltage is specific in the elderly patients under long bed fast and it may also reflect cardiac impairment of these patients so that it can be a guide of prognosis of these patients.
Quantitative analysis of the autofluorescent lipofuscin pigment granules in the human hepatic cells of 87 native male Japanese (21-116 years of age) and 97 U. S. male Caucasian s (22-89 years of age) were made statistically. Number of hepatic cells with pigment granules and amount of the pigment per hepatic cell are both larger in the central zone than in the peripheral, and they are also generally larger in U. S. Caucasians than in the native Japanese. The amount of pigment per hepatic cell of the native Japanese increased with age significantly after 70 years of age; in case of the U. S. Caucasians the pigment increased in amount significantly in seventh decade but did not increase thereafter. Mean value of size of the pigment granules increased with age, especially markedly after 60 years of age in the native Japanese, but in the U. S. Caucasians, it decreased slightly after 60 years of age. The increase in amount of lipofuscin pigment and decrease in number of hepatic cells were generally noticed with advancement of age, however, no statiscical significant correlation was noted between them. Although large amount of the lipofuscin pigment was accumulated very frequently in the aged individuals, the pigment deposition was not considered to be an essential change of senility, but seemed to be due to some of metabolic changes, which occur more frequently in the aged.
The purp se of this study is to establish the most effective method of stimulation for plasma renin secretion in the aged subjects, even if who have significantly impaired physical activities. For the stimulation, methods of sitting, walking, and intravenous administration of Furosemide (0.5mg/Kg) were employed. Each or combination of two of them were used for testing responsiveness of renin secretion in 21 normotensive and 105 hypertensive patients over 60 years old. The noticiable variation of plasma renin activity (PRA) was not observed during the period from 5am to 10am. Evaluation of relationship between the duration of these stimuli and PRA responsiveness revealed that the duration of 60min for sitting, walking, Furosemide + sitting, and Furosemide + walking and the time of 30min after IV injection of Furosemide were most adequet. Among these five methods, method of Furosemide, that of Furosemide+60min sitting, and that of Furosemide +60min walking showed significant increase of PRA. However, there was no difference among the increments of PRA by these three methods. These findings indicate that the method of Furosemide (0.5mg/Kg, I. V.) +60min sitting was effective and the most suitable for the stimulation of renin secretion in the aged. This stimulation method is safety and applicable for the elderly patients under prolonged bed fast.
The peripheral blood figures and incidence of anemia were investigated and types of anemia in hospital patients were studied in the aged. The results obtained were as follows: 1) Hemoglobin concentration, red blood cell counts and thrombocyte counts were shown to decrease in the aged. Of the erythrocytic indices, MCHC decreased, but MCV increased in the aged. As the criterion foranemia in the aged, hemoglobin concentration of less than 11.2 or RBC less than 3.5 million appeared to be adequate. The incidence of anemia in healthy subjects who lived at home was 11% in male and 13% in female. On the other hand, in hospital patients, that was 33% in male and 53% in female, respectively. 2) High incidence of anemia in the aged hospitalized were observed not only in patients with hematological diseases, liver diseases, gastrointestinal bleedings, malignancies and infections, but also in patients with cerebrovascular diseases, cardiovascular diseases and fractures which made them tend to the bedridden. 3) Seventy two females and 29 males with mild, moderate or severe anemia were classified into irondeficiency, folate-deficiency, B12-deficiency and miscellaneous anemia. Iron-deficiency anemia was found in 36 patients (36%). All of 12 patients whose percentage iron-binding saturation was less than 16% were treated with iron, and the remaining 24 patients recieved treatment against the underlied disease. Sixteen patients showed an adequate response and 20 patients achieved a normal level. Folate-deficiency anemia found 17 patients (17%) and 11 patients of them were associated with iron-deficiency. All of the cases received folate therapy and only 5 patients showed an adequate response, 3 patients achieved a normal level and 5 patients died. There were some folate-deficiency anemia which had a few megaloblast in bone marrow showed hypersegmented neutrophils. No B12-deficiency anemia was found in our series studied. This finding was thought to be due to medicate vitamines in most of hospital patients. Miscellaneous anemia was found in 48 patients (48%). Some cases were with subnormal levels of serum B12 and folate, and with hypersegmented neutrophils, and with macrocytic anemia. This finding suggested that some patients with miscellaneous anemia would become B12-deficiency or folate-deficiency anemia in future. These findings suggest the aged have a tendency to become anemic in various disease and the effect of anemia is more serious in elderly patients than younger ones, and so, anemia in the elderly should always be checked. The supply of B12 and folate would be necessary for the bedridden patients who are not able to have diet sufficiently.
Lumbago or low back pain is one of the most common complaints in geriatric clinics. Among 2, 284 patients above the age of 49 who visited the Department of Geriatrics, University of Tokyo Hospital during the period from 1975 to 1977, 598 patients (26.2%) (male 22.6%, female 29.3%) had lumbago, and it was the chief complaint in 55 (6.9%) (male 5.2%, female 8.3%). The causes of lumbago were investigated in 202 patients, of whom lumbar spondylosis deformans were most common in male (39%), followed by spinal osteoporosis (14%), spondylolisthesis (11%). protruded intervertebral disk (10%) and parkinsonism (9%), whereas the common causes in female were spinal osteoporosis (40%), spondylosis deformans (22%), spondylolisthesis (13%) and lumbago of obscure nature (13%). The spondylotic and osteoporotic changes of the lumbar spine seen in the plain roentogenograms were compared between two patient groups with and without lumbago, matched in age and sex. When the patient distribution according to the degree (0-III) of the alterations (spur formation, narrowing of the intervertebral space, or osteoporosis) was compared between these groups, there was a statistically significant difference concerning osteoporosis alone, suggesting more important role of osteoporosis in the pathogenesis of lumbago in the elderly. Canal to body ratio (Jones & Thomson) and the anteroposterior diameter of the bony spinal canal and of the lateral recess were measured in the plain films on five lumbar vertebrae of each patient. Either of two anteroposterior diameters of the lumbar canal, one expressed by the mean of five diameters determined at the middle level of individual lumbar vertebrae and another by the minimum value throughout the lumbar spine, was significantly smaller in the patients with lumbago (mean 19.1±1.7mm, minimum 17.8±1.9mm) than that in the patients without lumbago(mean 19.7±1.4mm, minimum 18.6±1.3mm). The minimum anteroposterior diameter of the lumbar canal not exceeding 15mm was observed exclusively among the patients with lumbago, as well as the minimum of five canal to body ratios and the minimum of five anteroposterior diameters of the lateral recesses in each patient not exceeding 1:5 and 5mm, respectively. No significant difference of these values was noted be tween two patient groups with and without sciatic pain associated with lumbago. Of 17 patients who had cauda equina claudication, three were examined through myelography, with an identification of lumbar canal stenosis in all. Seven of these 17 patients showed the minimum canal to body ratio not exceeding 1:5, and either of the mean and the minimum of five canal to body ratios was significantly smaller in the patients with cauda equina claudication (mean 1:4.4±0.6, minimum 1:4.9±0.7) than that both in the patients with lumbago, but without cauda equina claudication (mean 1:3.9±0.6, minimum 1:4.3±0.6) and in the patients without lumbago (mean 1: 3.7±0.6, minimum 1: 4.0±0.5), thus confirming the usefulness of canal to body ratio in the detection of probable lumbar canal stenosis.
Blood glucose content after one hour oral 50gr glucose tolerance was measured in 2, 543 residents aged 35 and over of Toda City (population 75, 000), an urban area of Japan, between March and December, 1976. Several other cardiovascular examinations were also carried out simultaneously. Further oral 50gr glucose tolerance test with serum immunoreactive insuline measurement was undertaken in the 413 subjects whose blood glucose value was 160mg/dl and over, or who showed positive urine glucose at the one hour glucose tolerance. Results obtained in the present study were as follows: 1) Mean values of blood glucose at the one hour glucose tolerance were elevated according to age increase in both sexes. Females showed higher blood glucose levels than males from age 50 and over. 2) Both males and females revealed significant positive partial correlation of blood glucose levels with age, systolic blood pressure and serum triglyceride. Neither diastolic blood pressure nor uric acid value was related to blood glucose levels. Relative body weight (Quetelet index) and total serum cholesterol were found to be significantly associated with blood glucose levels only in females. 3) Variation in blood glucose levels did not effect the frequency of calcifications in the aortic knob on 100mm chest X-ray film, Q and T changes in electrocardiogram, and notable vascular changes with bleeding in fundus oculi. 4) The frequency of chemical diabetes mellitus (according to the criteria of Japanese Expert Committee) among the 2, 543 subjects was 4.3per cent in males and 5.4per cent in females. Immunoreactive insuiine/Blood sugar (30 minutes) was 0.95±0.98 in normal glucose tolerance pattern, 0.53±0.53 in border line pattern and 0.25±0.26 in diabetes mellitus pattern. 5) The mean value of blood glucose showing positive urine glucose was higher in females (201±67mg/dl) than in males (158±57mg/dl). This indicates that females have a higher renal threshold for glucose, a fact which should be borne in mind when using urine samples for the detection of diabetes mellitus.