Individualizing the doses of cancer chemotherapy agents and progress in supportive therapy have improved the prognosis for elderly patients with non-Hodgkin's lymphoma. Prolonged hospitalization elderly patients has adverse effects, which include dementia, difficulty in walking, and depression. We treated 10 elderly patients (≥85 years) with non-Hodgkin's lymphoma as outpatients with oral etoposide, 25mg or 50mg daily for as long as possible, or until the white blood cell count decreased to ≥2, 000/μl or the platelet count decreased to ≥5×104/μl. Complete remission was achieved in 4 patients and partial remission in 4; the median duration of survival was 19 months. Adverse effects included leukopenia in 1 patient (≥1, 000cells/μl), thrombocytopenia in 1 patient (≥5×104cells/μl), and anorexia in 1 patient. These results indicate that prolonged oral administration of low-dose etoposide is effective and safe for the treatment of non-Hodgkin's lymphoma in elderly patients. This outpatient chemotherapy caused no serious adverse reactions.
To examine the relationship between apolipoprotein E (apoE) phenotype and life span, we measured the frequenty of the apoE phenotype and allele in 54 Japanese centenarians who lived in the Tokyo metropolitan area in 1994, 1995, and 1996. The control group consisted of 973 subjects, 883 healthy volunteers who were described previously and 90 healthy people who came to the Keio health consulting center. The apoE phenotypes in the centenarians was 2 E2/E2 (3.7%), 5 E2/E3 (9.3%), 38 E3/E3 (70.4%), and 9 3E/E4 (16.7%). No other phenotype was observed. In the control group, the phenotypes were 2 E2/E2 (0.2%), 57 E2/E3 (5.9%), 712 E3/E3 (73.2%), and 179 E3/E4 (18.4%). The frequency of E2 was higher in the centenarians. The frequencies of the apoE allele in the centenarians and the control subjects were ε2 8.3% vs. 3.5%, ε3 83.3% vs. 85.4%, and ε4 8.3% vs. 10.9%. The frequency of the apoE allele differed significantly between centenarians and control subjects (χ2=6.84, p=0.033). Levels of serum cholesterol and apolipoprotein B were significantly lower in the E2/E2+E2/E3 centenarians. Studies of the frequency of the apoE allel in Japanese, French, and Finnish subjects showed that ε2 is more frequent and ε4 is less frequent in centenarians. These data show the apoE phenotype may affect life span: ε2 is positively and ε4 is negatively associated with longevity.
We retrospectively analyzed the effect of β-blocking agents on the incidence of cardiac events in elderly patients who had had myocardial infarction. A total of 1169 patients who had had a myocardial infarction (age, 60.2±11.4 years) were followed for a mean of 18.0±19.7 months and the incidence of cardiac events (fatal or nonfatal myocardial infarction, sudden cardiac death, and death due to congestive heart failure) was computed. There were 21 cardiac events in 653 patients who received β-blocking agents (3.2%) and 39 events in 516 patients who did not receive β-blocking agents (7.6%, p<0.01). Among patients less than 50 years old, the incidences of cardiac events were 4.1% in those who received β-blocking agents and 7.6% in those who did not; among those 50 to 59 years old the incidences were 3.0% and 7.5%, respectively; among those 60 to 69 years old they were 4.3% and 6.0%, respectively; and among those 70 years old or older they were 0.8% and 11.4%, respectively (p<0.01). We found that β-blocking agents prevented cardiac events both in elderly and in younger patients after myocardial infarction.
Studies in the United States and Europe revealed that a comprehensive geriatric assessment is useful in the management and treatment of elderly disabled patients. In Japan, there are few reports of the development of such assessment. We examined the reliability of a scale designed to assess the performance of activities of daily living (ADL), a revised version of Hasegawa's Dementia Scale) HDSR, and a depression scale (GDS-15), using results from 140 patients over 65 years old who were admitted to our hospital from the end of January to early February 1994. The reliabilities of the ADL and HDSR scales were acceptable, but the κ value of the GDS-15 was very low. The ADL score was low in patients with cerebrovascular diseases, dementia, and bone and joint problems, but the HDSR score was not low in the latter group. These results suggest that each disease has a characteristic pattern of impairments and disabilities. Although psychological assessment is essential and requires validation, a prospective study of outcomes in the evaluated elderly patients might also be fruitful.
Patient's reports of angina pectoris depend on cognition and communication, and onthe patient's physical and mental activity. In elderly people, these functions are often impaired, and we therfore looked for evidence of myocardial ischemia in 770 consecutive autopsies. We defined the coronary stenosis index (CSI) as the sum of the stenosis scores of three coronary arteries: 0%=1, 25%=2, 50%=3, 75=4, 90%=4.5 95 or 100%=5. A total score of more than 13.0 and a score of 5.0 in one vessel was assumed to have been associated with myocardial ischemia. Patients assumed to have had myocardial ischemia were classified according to the presence or absence of angina pectoris: 24 had angina pectoris and 92 were asymptomatic. As controls, 86 patients in whom the CSI was lower than 10.0 were studied. Death due to myocardial infarction was most frequent in patients with angina (67%). Acute myocardial infarction was more common in asymptomatic patients than in controls (27% vs. 1%). Small myocardial infarctions and inferior myocardial infarctions were more frequent in asymptomatic patiens than in those with angina. Cerebrovascular disease, problems doing activities of daily living, and communication disturbance were more common in asymptomatic patients than in those with angina. Electrocardiographic evidence of an old myocardial infarction was found in 40.9%, 16.6%, and 2.3% of patients with angina, asymptomatic patiens, and controls, respectively (p<0.05). Morphologic details of the myocardial infarction, coexistence of cerebrovascular disease, inability to perform activities of daily living, and impaired communication are associated with asymptomatic myocardial ischemia. Patients with asymptomatic myocardial ischemia should be identified and treated because of their relatively poor prognosis. Ischemic events might be detected by careful observation and prevented by appropriate treatment.
Until 1993, initial postgraduate medical training in Japan was conducted only at university hospitals or other teaching hospitals. In 1994, the number of types of training sites was expanded to include health centers, nursing homes, and extended care facilities, which gave trainees chances to understand primary medical care in various settings, providing in-home as well as other non-hospital medical services. Since the new program seemed to increase training opportunities in geriatric medicine, questionnaires regarding the new program were sent by mail to all teaching hospitals in Japan (261); 213 responded. The results showed that 29 hospitals already had a program of care for the aged. The teaching sections were mainly internal medicine, psychiatry and rehabilitation medicine. Fifty hospital had plans to include care for the aged in their program in the near future. The number of programs that includes training in care for the aged is gradually increasing. It is hoped that during their initial postgraduate training many young doctors will come to recognize the importance of geriatric medicine.
In patients who require total parenteral or enteral nutrition the intestinal lining may atrophy and the ability to absorb nutrients may be lost. To prevent atrophy of the small intestine, we administered a suspension of Clostridium butyricum to elderly patients receiving tube feeding, and then measured the activation of serum diamine oxidase and the number, form, water content, and bacteria content of stools, indicators of intestinal structure. We found a signficant increase in diamine oxidase activity and an improvement in stool condition: the number of stools per day decreased, form improved, and water content and the number of aerobic bacteria decreased significantly. These results indicate that in patients receiving long-term tube feeding, administration of Clostridium butyricum can restore condition to a near-normal state.
We studied concentrations of serum ferritin, glycosylated ferritin, and non-glycosylated ferritin in elderly patients with diabetes. The subjects were 111 people who were at least 60 years old: 54 healthy controls, 14 diabetic patients without retinopathy, and 43 diabetic patients with retinopathy. The mean levels of ferritin, glycosylated ferritin, and non-glycosylated ferritin in serum were significantly higher in the patients with retinopathy than in healthy controls. The mean percent glycosylated ferritin did not differ between patients with retinopathy and healthy controls. The mean levels of serum ferritin, glycosylated ferritin, and non-glycosylated ferritin, and the percent glycosylated ferritin did not differ significantly between patients without retinopathy and health controls. None of these values differed between subjects with macroangiopahty and those without macroangiopathy, in both groups of patients. In patients with diabetes, none of the values measured was significantly related to fasting plasma glucose, HbA1C, or the duration of diabetes. These results suggest that diabetic microangiopathy is associated with abnormally high levels of ferritin in serum.
The oldest man in Japan reached the age of 112 years in Octorber 1996. As an Okinawan centenarians, he had been followed closely for the previous 12 years. One sister, 8 years younger, was alive at the start of the study; all other family members were killed in the Okinawan War, 1945. The man did agricultural work until age 85, after which he continued to be physically active and to pay close attention to his health. Results of medical examinations, including blood tests, remained within the normal limits, with a few exceptions. Some abnormalities were found on the electrocardiogram; the red blood cell count and the hemoglobin and hematocrit values decreased relatively slowly. His intake of nutrients was relatively well-balanced, and at the age of 100 his intake energy was 1361 kilocalories per day, which is close to the value recommended for centenarians. His personality was categorized as “Type A”, but the pattern was typical of that seen in other Okinawan centenarians. He was able to perform almost activities of daily living until the age of 108. At that time he was admitted to the hospital and his ability to perform those activities decreased sharply. His scores on the revised version of the Hasegawa dementia scale was within the normal range when he was 106 years old, but 3 years later it was in the “dementia” range. The rapidity of the decreases in his mental status and in his ability to perform activities of daily living that occurred when he was admitted to the hospital indicate that, if circumstances permit, elderly men may benefit from living at home with their families. Close attention to diet and exercise from youth through senescence may also contribute to health and longevity.
To establish the guideline for nutrition in the very old, we analyzed biochemical and hematological data from 45 Japanese centenarians living in Tokyo metropolitan area during 1994 and 1995. Levels of cholesterol, HDL-cholesterol, apolipoprotein A1 and B, albumin, prealbumin in serum were lower than in a control group or lower than the reference range, which indicates that these centenarians were undernourished. RBC counts, hemoglobin, and hematocirt were also low in the centenarians. The concentration of albumin correlated positively with those of HDL-cholesterol and apolipoprotein A1, and negatively with concentration of Lp(a). The value for transferrin correlated positively with energy intake and with the concentration of apolipoprotein A1. The concentration of prealbumin correlated positively with the concentration of hemoglobin, hematocrit and the total cholesterol concentration. According to their nutritional status, the centenarians were divided into 2 groups: wellnourished and undernourished. Those who were wellnourished had higher levels of cholesterol, HDL, Hb, and apolipoprotein A1, their levels of ADL and cognitive function were also high. The findings of blood-chemical data in the centenarians may be partly due to undernutrition. Centenarians who were wellnourished were considered to be aging successfully. These results and others previously published indicate that the concentrations of albumin, prealbumin, transferrin and either CRP or IL-6 are useful for nutritional assesment in the very old.
A 65-year-old man was admitted to our department due to severe dysphagia, dysarthria, and aspiration pneumonia. Dysphagia and dysarthria were caused by lateral medullary infarction (Wallenberg' s syndrome). After the patient recovered from pneumonia, the abnormality of swallowing was assessed by a swallowing provocation test and videofluorography. Two months after the start of swallowing training, a swallowing provocation test showed that the swallowing reflex had improved and videofluorography showed that the magnitude of aspiration to the trachea had decreased. The patient began taking food by mouth. These tests are useful for quantitative assessment of dysphagia and for deciding when to start oral intake in elderly patients.