Eleven aged patients over 65 years of age with advanced lung cancer (mean age=70.8±1.4, non-small cell:small cell=9:2, stage III:IV=5:6) were treated with combination chemotherapy consisting of cisplatin (50 or 80mg/m²) and vincaloid (vindesine 3mg/m² or etoposide 80mg/m²). To evaluate this cisplatin combination therapy, the aged group was compared with a young group consisting of eleven patients (mean age=53.3±1.7, non-small cell:small cell=9:2, stage III:IV=5:6) matched for cell type, stage and dose regimen. The mean dose of cisplatin was 58.2mg/m² in the aged and 63.6mg/m² in the younger group. A notable reduction in tumor size was observed in 9.1% of the aged and 27.3% of the young, while one-year survival rate was 63.6% in the aged and 72.7% in the young. The common side effects were nausea and vomiting, while diarrhea was seen in 18.2% of the aged. Neutropenia, anemia and thrombocytopenia were found in both groups and the time course of myelosuppression in the aged (18.2±0.8 days) was significantly shorter than that in the younger patients (22.0±1.4 days, p<0.05). With regard to nephrotoxicity, creatinine clearance rate in the aged decreased remarkably from 56.9 to 38.9ml/min, while there was no significant change in BUN, serum creatinine and urine NAG between the aged and the young. Disorders of electrolytes such as hypokalemia and hyponatremia were seen in 45.5% of the aged. We conclude that advanced lung cancer in the aged was effectively treated with cisplatin combination therapy with tolerable nephrotoxicity and myelosuppression.

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The bone mineral status of the cancellous bone in the lumbar vertebrae was evaluated by analysing density histograms and measuring the mean density by computed tomography. The results obtained were as follows: (a) the distribution pattern of bone density in lumbar vertebrae revealed a normal distribution. (b) high correlation coefficents between peak density (r=-0.79) or mean density (r=-0.77) and age was obtained in males, whereas peak densities in females were maintained well at ages younger than 50 years and peak densities abruptly decreased after 50 years of age. Osteoporotic vertebrae, in which multiple osteosclerotic changes were observed, had several peak densities and did not show normal density distribution pattern. These results indicated that our methods combining analysis of density histograms and measurement of mean density are useful to evaluate the bone mineral status.

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To investigate the relationship between middle cerebral artery (MCA) trunk lesions and the etiology of Binswanger type (B type) infarction, which was demonstrated as a diffuse subcortical low density area/high intensity area by CT/MRI, patients with both MCA lesions and B type infarction were studied clinically. Eighteen patients with B type infarction were diagnosed among 224 patients with MCA occlusion/stenosis on angiography accounting for 8%. The incidence was as high as 25% in M2 stenosis. The mean age of B type infarction patients was 64 years and 16 of them were men. Chronologically stepwize/slowly-progressive deterioration of clinical manifestations were observed in 14. All patients had hemiplegia, though half of them were mild or moderate in severity. Furthermore, aphasia, Gerstmann syndrome and dementia were present in 10, 1 and 2 patients, respectively. Twelve had a history of hypertension, while 11 showed transient decreases with marked changes (more than 31mmHg in mean arterial blood pressure) in arterial blood pressure during their clinical course. Out of 9 patients in whom cerebral blood flow (CBF) was measured by ¹³³Xe injection method/inhalation method, 7 demonstrated mild to moderate decreases in mean CBF (more than 30ml/100g/min) with no relation to the severity of MCA lesions. These findings suggested that hemodynamic mechanisms associated with hypoperfusion due to marked fluctuations in blood pressure are accelerating factors of B type infarction and MCA lesions, even though ischemia in the subcortical area due to leptomeningeal anastomosis may be mild or moderate.

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Velocity, step length and walking rate during fastest walking were measured together with maximum torque (MVC) in the left knee extension for 81 healthy males with aged from 22 to 79 years. Velocity and step length showed an accelerated decline from the sixties, while walking rate decreased with age linearly. Multiple regression analysis with age, height, weight and MVC as independent variables and velocity, step length and walking rate as dependent variables indicated that (1) walking velocity was significantly related to age, MCV and weight, (2) step length to MVC and weight, and (3) walking rate to age.

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The circadian rhythm of the heart rate was assessed using 24 hour electrocardiographic recordings in 18 hospitalized elderly patients with wasting diseases receiving total parenteral nutrition. The nutrient solutions were administered at doses ranging from 360 to 1640kcal/day. To determine if the heart rate fluctuates rhythmically with a circadian period, the mean hourly heart rate on 24hour electrocardiographic recordings was used to fit cosine curves by the statistical technique of least squares, and three parameters of the rhythmdesignated the mesor, amplitude, and acrophase-were estimated. The cosine curves fitted with a P value of 0.01 or less in all patients before and after insertion of central venous catheters. The mesor represented the rhythmadjusted mean of the heart rate. The mesor increased significantly with increase in the energy infusion rate (p<0.01). The amplitude values were derived from one half of the total diurnal variation of heart rate and the acrophase indicated the time when heart rates were at their peak above the mean. Neither amplitude nor acrophase changed significantly with increase in the energy infusion rate. Furthermore, neigher norepinephrine nor epinephrine plasma levels changed with nutrient administration. There were no significant changes in thyroid hormone concentrations. There was a significant positive correlation between mesor changes and rectal temperature with increase in the energy infusion rate (r=0.76, p<0.01). In severely malnourished subjects, changes in the level of feeding can profoundly affect cardiac functions and thermogenic response.

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Clinical and neuropathological studies of a case of pallido-nigro-luysian atrophy with thalamic degeneration and ossification of the posterior longitudinal ligament (OPLL) is reported. The patient was a 72-year-old man, suffering from gait disturbance caused by OPLL for about 3 years. The clinical features were characterized by gradual development of disorientation in place, time and person, memory disturbance, vertical gaze palsy and rigidity of extremities. Dysarthria, dysphagia, bradykinesia, masked face and neck dystonia appeared at the advanced stage of his illness. There was no tremor or other involuntary movements. A clinical diagnosis of parkinsonism was suspected. The main neuropathological findings were neuronal loss and gliosis in globus pallidus, substantia nigra, subthalamic nucleus and thalamus. In addition, neuronal loss of the anterior horn of the cervical spinal cord due to compression by OPLL (C4-C7) was recognized. The neuropathological findings of the present case were consistent with systemic degenerative disorder of the nervous system affecting the pallido-nigro-luysian tract. This rare disorder should be considered in the differential diagnosis of parkinsonism in old people.

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The authors have investigated the incidence of chronic subdural hematoma and hygroma (CSH) in two hospitals for elderly patients with dementia syndrome over a period of three years and nine months. All observed patients had been in the hospital for 2 weeks or more and had had brain computed tomography (CT) on admission. The total of 613 patients included 212 males and 401 females. Based on the CT findings observed in patients on admission, the authors found 47 patients with CSH. This was equivalent to 7.7% of all patients observed. After admission, almost all patients had brain CT twice per year, with a mean of 2.2 CT examinations during the observation period. Sixteen patients who had no CSH on admission developed CSH. Thus a total of 63 (10.3%) demented patients demonstrated CSH during the observation period. It was assumed that the high incidence of CSH in this study may be due to the practice of performing routine CT examinations in hospitalized patients and the fact that demented patients are prone to fall and hit their heads. From the investigation of past history, tastes, and patterns of daily behavior, we found the risk factors for CSH development to be male sex, alcohol abuse and wandering as a symptom of dementia. We performed CT examinations on all patients who showed subjective or objective neurosymptoms related to the central nervous system, but we could find only 2 patients with high-density lesions in the subdural space that indicated acute bleeding. This was only 3.1% (2/65) of all patients who developed subdural effusion. Thus, this fact supports the hypothesis that a leak of cerebrospinal fluid might have developed before bleeding in the subdural space in these elderly cases.

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The sequential changes in blood pressure and electrocardiographic findings of populations living in three districts of Okayama prefecture, with differing environments and life styles, were analyzed during the seventeen year period from 1966 to 1982. Futhermore, factors influencing the causes of mortality among these populations were evaluated in 790 males and 1, 118 females (total 1, 908), aged from 35 to 65 years at the beginning of the survey (1966). During the survey period 94 subjects moved out of the district and 210 subjects died, so that in 1982, 975 subjects (61.1%) could be examined. Cerebrovascular disease, cancer, and cardiac disease were the major causes of death in all these districts. A higher mortality from cerebrovascular disease was recorded in the mountainous district, with harsh weather and living conditions, in contrast to the other two lowland district. There was no significant difference in mortality due to cardiac disease among the three districts. In the mountainous district, the incidence of hypertension, especially systolic hypertension, was higher than in the other two districts throughout the whole of this survey. However, after 1980, the difference in the incidence of hypertension among the districts diminished sequentially. The incidence of hypertension was higher in the elderly than in younger subjects. However, even this age difference in incidence was seen to diminish sequentially, (especially for diastolic hypertension). The ratio of the number of people who were actually treated to the population who needed hypertensive therapy increased gradually, and in 1978 there was no significant difference concerning this ratio among the three districts. Finally over 80% of the subjects who qualified for antihypertensive therapy were treated continuously. The appearance ratio of abnormal ECG findings, (Minnesota Code, Code 3, Code 3+4, 5 and especially Code 4 and 5), increased in proportion to the increase of blood pressure in the hypertensive group. The sequential appearance ratios for the borderline hypertension and stage I hypertension groups showed an inverse relationship to that of the normal group. However the appearance ratios of stage II & III hypertension groups increased sequentially with no relation to that of the normal group. Subjects whose ECG showed ST-T changes without subjective symptoms apparently increased sequentially in all districts. The incidence ratios of angina pectoris and myocardial infarction showed no significant sequential changes. These results suggested that high blood pressure (both systolic and diastolic) was controlled fairly well in all age groups by therapy. However, the fact that the sequential appearance ratios of LVH and ST-T changes increased in spite of good control of blood pressure, showed that complete protection from the progression of myocardial hypertrophy and ischemic changes might not be achieved by the control of blood pressure alone. Probably other factors such as population aging and the type of drug therapy might have influenced the myocardial pathophysiological findings in these hypertensive patients.

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It has been previously reported that responses of T-lymphocytes to stimulation by phytohemagglutinin declined as age advanced. However, it has not been demonstrated whether receptor binding capacity decreased with age. The potent muscarinic cholinergic antagonist, 3-quinuclidinyl benzilate (QNB) was used to detect the characterization of muscarinic acetylcholine receptors (mAChR) on human lymphocytes. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for the [³H]-QNB. Three age groups of healthy female adults were examined: 42-49 (N=7), 50-59 (N=7) and 60-69 years old (N=8). Moreover, we studied mAChR on lymphocytes from 11 patients (54-65 years old, female) with probable Alzheimer's Disease. Specific binding is saturable, proportional to cell concentration, and can be displaced by atropine. For control subjects (age range 42-69 years old, N=22), a positive correlation (r=0.634, α<0.01) was found between Kd and age. Also positive correlation between Bmax and age was shown to be strong (r=0.434, α<0.05).
The regression equations are:
Y=3.25X-109.5(Kd)
Y=24.7X-201.8(Bmax)
where, X and Y designate the age of individuals and Kd (or Bmax), respectively.
Hence, for patients with Alzheimer's Diseases, the correlation betwee Kd and age, and between Bmax and age, were weak (r=-0.352, 0.011, not significant, respectively). No significant change in Kd or Bmax was obtained on lymphocytes from patients, compared to agematched controls. Furthermore, significant changes of Kd (α<0.01) were found on lymphocytes from healthy control between age groups 42-49 and 50-59 years old, and also age groups 42-49 and 60-69 years old.

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The effects of acute administration of human parathyroid hormone (1-34) [PTH(1-34)] on the blood pressure of 15 young (mean age±SD, 20.9±1.7 years; 7 males and 8 females) and 11 elderly (78.1±5.9 years; 4 males and 7 females) normal subjects were compared. The elderly subjects have a slightly, but significantly higher mean basal systolic blood pressure (132.4±17.7mmHg) than the young subjects (118.7±11.4mmHg), but the basal diastolic and mean blood pressures of the two groups were similar. Intravenous bolus infusion of PTH(1-34) at a dose of 100U induced transient, but marked hypotension in all subjects. The mean maximal decrease in systolic blood pressure (-ΔSBP) was significantly more (p<0.01) in the elderly subjects (42.5±13.9mmHg) than in the young subjects (8.0±8.9mmHg), but the maximal decrease in diastolic blood pressure (-ΔDBP) was similar in the elderly (25.6±13.9mmHg) and young (27.3±10.9mmHg) subjects. The maximal decrease in the mean blood pressure (-ΔMBP) was also significantly higher (p<0.01) in the elderly subjects (31.9±8.7mmHg) than in young ones (20.6±7.6mmHg). The corrected serum level of calcium (scCa) was significantly (p<0.01) lower in the elderly subjects (9.6±0.2mg/dl) than in the young ones (10.0±0.3mg/dl), and the serum level of C-terminal parathyroid hormone (C-PTH) was significantly higher in the elderly subjects (270±80pg/ml) than in the young ones (150±80pg/ml). Individual values for the scCa level in all subjects showed a significant inverse correlation (r=-0.52, p<0.01) with their -ΔSBP values, and their C-PTH levels showed significant positive correlations with their values for -ΔSBP (r=0.61, p<0.01) and -ΔMBP (r=0.42, p<0.05). These observations suggest that in elderly subjects, acutely administered PTH(1- 34) causes not only vasodilation but also suppression of cardiac function and that abnormal calcium metabolism may contribute to this effect on the heart.

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Thyroid function was investigated in 222 elderly euthyroid subjects (79.6±7.6 years, males 68, females 154). Serum free T₃, free T₄, and TSH levels were measured by radioimmunoassay. To assess the factors influencing serum free T₃ and free T₄, we applied multiple regression analysis. 1) Serum free T₃ concentrations were directly proportional to both serum albumin levels and hemoglobin levels. Serum free T₃ levels were lower in bedridden male subjects and in female subjects with dementia. 2) Serum free T₄ concentrations were negatively correlated to serum TSH levels in male. Serum free T₄ levels were higher in bedridden female subjects, and increased in proportion to serum albumin concentrations in females. 3) Age had no apparent effect on either serum free T₃ or free T₄ concentrations.

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