To investigate whether cellular DNA synthesis in lymphocytes can be induced by carbachol, we studied the effect of carbachol in cultures of peripheral lymphocytes.
Three age groups of healthy female adults were examined: 40-49 (N=10), 51-59 (N=8), and 61-69 years old (N=8). Moreover, we studied lymphocytes from 14 female patients (47-69 years old) with probable Alzheimer's disease.
Lymphocytes were incubated for 72hrs at 37°C, with or without 5mM carbachol. The effects of carbachol on the initiation of DNA synthesis in lymphocytes were determined by 24hr-pulse-labeling with [³H]-thymidine ([³H]-dT). Stimulation indexes (S.I.) were defined as the ratios of DNA synthesis induced with or without carbachol.
In 37 out of 40 subjects, carbachol elicited an increase in [³H]-dT incorporation. Furthermore, carbachol induction of DNA synthesis was blocked by muscarinic antagonist, atropine. These data show that carbachol induces DNA synthesis in peripheral lymphocytes are well as the central nervous system, indicating that the proliferation is mediated by the muscarinic acetylcholine receptor. For healthy controls (age range 40-69 years old, N=26), a negative correlation (r=-0.505, p<0.01) was found between age and S. I. The regression equation was:
Y=-0.575X+142.1
where, X and Y designate the age of individuals and S. I., respectively. However, there were significant differences (p<0.05) with S. I. between age groups 40-49 and 61-69 years old. For patients with Alzheimer's disease, no correlation was obtained between age and S. I. Furthermore, significant differences (p<0.05) from S. I. were recognized in lymphocytes from Alzheimer's patients (55-69 years old, N=13), compared to age matched controls (57-69 years old, N=11).
These results indicate that the analysis of carbachol induction of [³H]-dT incorporation in lymphocytes may be useful in the study of changes associated with aging, and also in the evaluation of the clinical diagnosis of Alzheimer's disease.

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The aim of this study was to investigate the relationship between dietary ascorbic acid intake and serum lipid concentration in the aged. The amount of dairy food intake for three consecutive days were measured and the serum levels of total-cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDLC) were determined 279 subjects (135 males and 135 females), 65 years and over living in one community. The LDL-cholesterol (LDLC) was calculated by (TC-HDLC)-TG×0.2. Dietary ascorbic acid intake showed no significantly difference between males and females, but had a significantly positive correlation with HDLC, the intake of carbohydrates and protein and total fat. However it had a significantly negative correlation with LDLC and LDLC/HDLC. Multiple regression analysis showed that dietary ascorbic acid intake had a statistically significant relationship with HDLC, LDLC and LDLC/HDLC. Since HDLC, which is known to be an anti-atherogenic, was related to increase in the dietary ascorbic acid intake, and LDLC, which is known to be an atherogenic, was related to its decrease, it was suggested that dietary ascorbic acid intake might have an important effect on the genesis and prevention of atherogenic diseases.

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Changes in blood pressure (BP) and pulse rate were measured during visits to a doctor's office by means of an non-invasive ambulatory BP monitoring device in 47 elderly hypertensive patients (mean age 73.0 years). Systolic BP increased from 140.5/85.4mmHg to 157.9/85.7mmHg immediately after entering the doctor's office and tended to return to the previous level at 5 minutes after entering although diastolic BP did not change during the visit. Pulse rate also increased slightly, but significantly on entering the office. The difference in BP between 25 minute before and just after entering an office was +17.4mmHg in systolic. -0.1mmHg in diastolic. If an increment in systolic BP more than 10mmHg was defined as positive for white coat effect, they were observed in 59.6%. The frequency of white coat hypertension was 46.7% in the age of sixties, 65.2% in seventies and 66.7% in eighties but there was no significant difference among 3 groups. There was a tendency for white coat hypertensions to be more frequent in men compared than in women (p=0.07).

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The authors investigated the cause of cerebral infarctions in elderly patients with anemia. Among 411 patients with acute cerebral infarctions, eight patients showed anemia (Hb<10g/dl) at the time of stroke. Only 2 patients had strokes during hospitalization were aware of their anemias before stroke. They were classified into two groups. One was the sudden onset group (4 patients) of whom 3 had malignant tumors, and 2 showed disseminated intravascular coagulations (DIC). There were no patients with atrial fibrillation or cardiac disease. All patients showed cortical infarction, and two died soon after stroke. Autopsy revealed verruca formation of the mitral valve in one patient and thrombus in the right ventricle in another. We thought that nonbacterial thrombotic endocarditis (NBTE) was the major cause of cerebral infarctions in this group. The other group consisted of 4 cases of thrombotic stroke. Their neurological symptoms appeared to be progressive. They also showed cortical infarctions except for one case of pontine infarction. Severe stenosis of the cerebral arteries was revealed by angiography in two patients and by autopsy in one. We concluded that cerebral infarctions in elderly patients with anemia can be important signs of underlying malignant tumors in sudden onset strokes or cases of severe cerebral artery stenosis with thrombotic strokes.

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A survey to investigate the psychiatric and physical characteristics of centenarians was conducted from 1987 to 1989 in the Tokyo metropolitan area with a team of psychiatrists and psychologists using a semi-structured interview form. In that 3-three period, out of 509 centenarians living in Tokyo, 294 persons and their caregivers (57.8%) including the 65 institutionalized centenarians were examined. Two hundred and fifteen centenarians were not able to be interviewed due to various reasons. Out of 294 centenarians, 76 persons (25.9%) were interviewed by telephone. Also out of these, 176 (59.8%) were living with their son's or daughter's family. Ten male centenarians (12.8%) were living with their wives, while no female was living with a spouse. Five men and four women were living alone. There was a marked difference of education in years between both sexes. Mean years of education were 10.2 in the male and 5.5 in the female. According to the Clinical Dementia Rating, 31.6% out of 218 centenarians interviewed were not demented and those with dementia were even distribution of mild, moderate and severe dementia. There were marked differences according to sex, similar to that found in ADL. Of 63 males, 46.0% were not demented, whereas 25.8% of 155 females were not demented. Only 3.2% of males were severely demented, but in females 27.1% showed severe dementia. HDS scores decreased in relation to the advance in severity of dementia. Approximately 27% of the cases had no previous physical histories; 21.8% for the male and 29.2% for the female. Hypertension, cerebrovascular diseases and cardiac diseases were found in 51.1, 6.8 and 7.1%, respectively, without any marked difference according to sex. The most common previous illness was ophthalmologic diseases, found in 15.3%. In the present physical illness, 42.2% of all subjects were free from physical illnesses; 43.6% of males and 41.7% of females. As in the previous histories, ophthalmologic diseases were found most commonly in 17.0%, and hypertension, cerebrovascular diseases and cardiac diseases were recognized in 8.8, 3.7 and 7.8%, respectively. Cerebrovascular diseases and hypertension were most common in females (4.6% vs 1.3%, 10.2% vs 5.1%). Nine of the females with a cerebrovascular disease were demented. Of 218 centenarians 44% were almost bedridden, while 27.1% were active at home or outside the home. The rate of almost bedridden females was nearly twice that of males (52.9% vs 22.2%), and eight males (10.3%) were able to go out without any difficulty, whereas there was only one female (0.5%) who showed such activity. In conclusion, it was revealed that the prevalence rate of centenarians with dementia was 62.9% and some centenarians living in Tokyo in 1987-89 were able to keep their psychosomatic activity until the extremely old age. Though various hypotheses concerning determinants of longevity have been proposed, none have been confirmed. This is mainly due to the difficulty in conducting londitudinal studies to confirm factors relating to longevity, and also due to the difficulty in collecting a sufficient number of centenarians with reliably confirmed age. In this context, results from the present study could be a standard for future studies.

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The number of elderly patients with insulin-dependent diabetes mellitus (IDDM) is increasing because of the prolongation of life due to the improvement of diabetic control. For better management of elderly patients with IDDM, we investigated the clinical and genetic characteristic of older patients with IDDM in comparison with younger patients. The subjects studied consisted of 19 patients with IDDM treated at the Department of Geriatric Medicine, Osaka University Hospital. Among the 19 subjects, 7 patients (37%) were more than 50 years old, including 3 patients (16%) more than 65 years old. The clinical and genetic characteristics of these 7 patients (older patients group) were compared with those of 12 patients (younger patient group) whose age was less than 50 years old. The age at onset of IDDM was significantly higher in older patient group (46±13 years old; mean±SD) than in younger patient group (34±6 years old). There was no significant difference in the duration of IDDM between older and younger patients (13±6 and 12±8 years, respectively). There were no significant differences in daily insulin dose, glycemic control (fasting plasma glucose and HbA1c levels) and glycemic stability as measured by the standard deviation of 10 measured fasting plasma glucose levels between the two groups. The frequency of diabetic retinopathy and neuropathy in the older patients was slightly, but not significantly, higher than that in younger patients. The frequency of diabetic nephropathy was similar in both groups. Residual B-cell functions assessed by serum C-peptide response to intravenous glucagon and by urinary C-peptide excretion showed no difference between the two groups. The frequency of HLA-haplotypes was similar between the two groups, and all patients had DR4-DQA1^*0301-DQB1^*0401 or DR9-DQA1^*0301-DQB1^*0303 haplotype. We conclude that older patients with IDDM do not have a longer duration of the disease, but have a later onset of the disease than younger patients with IDDM, and that other clinical and genetic characteristics were not different between the groups.

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We studied neutrophil functions (phagocytosis, intracellular killing and chemotaxis with or without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and T cell functions (lymphocyte proliferation and production of GM-CSF in response to phytohemagglutin (PHA)) to clarify host defense mechanisms in the elderly. There was no significant difference in phagocytic activity of neutrophils between the elderly and control young adults. rhGM-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both groups. Killing activity of neutrophils evaluated by the new Nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p<0.001), however, pretreatment of neutrophils with rhGM-CSF resulted in an increase of killing activity in the elderly, raising their response to a level comparable to that of young adults pretreated with rhGM-CSF. There was no significant difference between the elderly and young adults in chemotaxis of neutrophils. rhGM-CSF alone did not prime chemotaxis, but primed chemotaxis in response to chemoattractant (N-formyl-methionyl-leucyl-phenylalanin) in both individuals. Lymphocyte proliferation and production of GM-CSF in response to PHA in the elderly were significantly lower than those in the young adults (p<0.001, p<0.05, respectively). These results indicated that impaired T cell functions may contribute, at least in part, to susceptibility to bacterial infection in the elderly.

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The relationship between fecal kinetics and body temperature was examined in elderly people. The subjects consisted of 34 hospitalized patients over 65 years of age (11 males aged 66-82 years, with a mean age of 70.3 years; and 23 females aged 65-84 years, with a mean age of 72.1 years). Then mean age of all subjects was 71.5 years. The subjects were divided into two groups: the non-constipation (NCP) group (patients who had been evacuating at least once daily) and the constipation (CP) group (patients who had not evacuated for 3 days or more). In the CP group, we analyzed the lowest and highest body temperature during two consecutive days (the day of evacuation and the previous day) and the lowest body temperature during another two days (the day of evacuation and the following day). In the NCP group, 3 consecutive days were selected at random for analyzing the lowest body temperature on the first day, the highest body temperature on the second day and the lowest body temperature on the third day. In the CP group, the body temperature before evacuation was 37.3°C or more in 6 of the 28 patients (21.4%). In the NCP group, the highest body temperature before evacuation averaged 36.39°C and the lowest body temperature after evacuation averaged 36.0°C, with a temperature difference of 0.39°C between the pre-and post-evacuation periods. In the CP group, the highest body temperature before evacuation was 37.03°C and the lowest body temperature after evacuation was 36.1°C, with a temperature difference of 0.93°C between the pre-and post-evacuation periods. Thus, the magnitude of temperature change between the pre-and post-evacuation periods was 0.54°C greater in the CP group than in the NCP group (p<0.001, F test). In the NCP group, the temperature change between the pre-and post-evacuation periods was 0.39°C for both males and females. In the CP group, the magnitude of temperature change was greater for both females (0.85°C) and males (1.02°C) (p<0.05). The change in temperature was smaller in patients under laxative therapy. In the NCP group, the change in temperature did not differ between patients with cerebral infarction, apoplexy or senile dementia and patients with other diseases. In the CP group the change in temperature was greater in patients with central nervous system disease (p<0.05). The temperature change did not differ between diabetic patients and diabetes-free patients. In the NCP group, the change in temperature increased with age. In the CP group, the change in temperature didn't increase with age, but was great at any age. From the pre-evacuation period to the post-evacuation period, leukocyte count decreased, erythrocyte sedimentation rate increased, C-reactive protein remained unchanged, body temperature decreased, and endotoxin level decreased or remained unchanged. These results indicate that elderly people without constipation have increased body temperature as feces increase in the intestine, and that elderly patients with constipation show a mean increase of 0.93°C in body temperature between the pre- and post-evacuation periods, irrespective of their ages.

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Previous reports suggest that nocturnal disorders of sleep and breathing have increased prevalence among the elderly, and episodic nocturnal oxygen desaturation (NOD) has an increased incidence in patients with chronic respiratory disease. Current Japanese criteria for home low flow oxygen therapy (LFOT), recommend LFOT for patients with daytime PaO₂<55torr or with daytime PaO₂≤60torr who have significant NOD. Strict adherence to these LFOT criteria requires full overnight monitoring of arterial oxygen saturation (SaO₂) in all patients with daytime PaO₂≤60torr. Since widespread nocturnal oximetry involves significant expenditure of time and resources, it is important among patients with chronic respiratory diseases to predict those who will have significant NOD. The aim of the present study was to formulate criteria for identification of patients who are most likely to demonstrate significant NOD based upon daytime respiratory function data. Subjects included 34 elderly patients with daytime PaO₂≥55torr, who had stable severe chronic respiratory disease (15 chronic emphysema, 6 chronic bronchitis, 12 post-tuberculosis, and 1 kyphoscoliosis). Study data included medical history, assessment of dyspnea by Hugh Jones classification, and measurement of daytime, awake arterial blood gases and spirometry. Each subject underwent full overnight oximetry monitoring. The percentage of total sleep time recorded with SaO₂≤85% was noted (DST85), and NOD was defined as DST₈₅≥1%. Of the 34 patients, 11 were identified as NOD, and 23 as non-NOD patients. Duration and severity of dyspnea were not different between NOD and non-NOD patients. No non-NOD patient presented a history of acute exacerbation; 7 patients with NOD had a clear history of acute exacerbation. Mean daytime PaO₂ of NOD patients was significantly (p<0.01) lower than that of non-NOD patients; 6 of 26 patients with a daytime PaO₂>60torr showed NOD. Mean daytime PaCO₂ and base excess of NOD patients were significantly higher than values for non-NOD patients (both p<0.01). Spirometry recorded for both NOD and non-NOD patients groups was not different. When the occurrence of a prior acute exacerbation or of daytime PaCO₂>45torr were employed as predictive criteria, prediction of NOD patients was possible with a sensitivity of 81.8% and a specificity of 78.3%. We concluded that patients with a history of acute exacerbation or daytime PaCO₂>45torr have an increased probability of NOD, so that full nocturnal oximetry is indicated in these patients.

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Two cases of adult onset of Still's disease is in a 83-year-old and a 61-year-old women. Both cases complained of high fever, arthralgia, sore throat and maculae. Examinations on admission revealed leukocytosis and negative antinuclear antibody. Administration of prednisolone resulted in improvement of the clinical symptoms and laboratory data. In general, the onset of this disease is usually in early adulthood, but in these two cases the onset was at an advanced age. These results suggest that Still's disease of adult onset should be included in the differential diagnosis of fever of unknown origin, if the patient is elderly. In the treatment of the disease, proper attention to side effects of prednisolone and complications can be important.

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The patient was a 74-year-old woman who had been obese since age 18. Her obesity was refractory to dietary manipulation. She had been suffering from increasing dyspnea for several months and eventually could not even move. She was admitted to a hospital and diagnosed as having heart failure. Although her cardiac function recovered with medical treatment, her symptoms did not improve. The patient was then sent to our hospital. On admission, her height and weight were 149cm and 81.9kg, respectively, yielding a body mass index (BMI) of 36.6kg/m². Arterial blood gas analysis in room air revealed hypoxemia and an apnea index of 27per hour. She was given a daily 500-1000kcal diet. After four months of treatment, her weight decreased to 65kg with a BMI of 29.3kg/m². Weight reduction together with the usage of progesterone-derivatives resulted in marked improvement of sleep apnea. The apnea index decreased to 3/h and arterial blood gas values normalized. This patient seemed to have suffered from both obesity hypoventilation syndrome and sleep apnea syndrome. Improvement of respiratory function was achieved through relief of airway obstruction and weight reduction, with activation of the respiratory center due to progesterone treatment.

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The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5cm in diameter) with an irregular margin in right S¹, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B¹ ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma.

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