[in Japanese]

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An important background characteristic of anemia in the elderly is decrease in hematopoiesis due to aging.
Factors influencing hematopoiesis in the elderly include changes in the distribution of hematopoietic tissue, changes in hematopoietic stem cell density and changes in the hematopoietic inductive microenvironment. In the present study, in order to assess changes in the bone marrow with aging, the fat tissue area, nucleated cell-count and cellularity in the bone marrow, in addition to changes in the diameter of the vascular lumen which result primarily from sclerotic changes in the dorsomedial artery of the bone marrow were determined in different age groups. The results revealed that all of the aforementioned factors changed significantly with aging. We also describe on the results of assays of inflammatory cytokines (IL-1, IL-6, TNF-alpha), lactoferrin and transferrin receptors in cases of anemia of chronic disorders (ACD) which own secondary to chronic inflammatory diseases and is known to frequently afflict the elderly.

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Atherosclerotic plaque with central depression (depressed lesions) have been proposed as one morphological feature of atherosclerotic regression in the elderly. We have also revealed that depressed lesions have been found not only in the aorta of elderly human but also in rabbit aorta. In this study a relationship between apoptosis and atherosclerotic regression was immunohistochemically studied to clarify the possibility of the pathogenesis of depressed lesion in rabbit aorta. Twenty male New Zealand White rabbit (NZW) were fed with a 1.0% cholesterol diet during a 12-week atherogenic induction period. Then they were fed only with a basic diet for 36-week (n=6) and 48-week (n=6, experimental group) regression periods. A control group was fed with 1.0% cholesterol diet for 12-week (n=2) and 60-week (n=6). They were killed and aortas were fixed with formalin. Sections obtained from aortas were processed for histological and immunohistochemical studies including the TUNEL method, staining with Ki-67 and others. Several depressed lesions were found in the aortas of NZW animal, but none were noted in control aortas. Results of surface involvement in the experimental groups were significantly lower than in the control, and the aortas of the experimental group had atherosclerotic regression. Apoptosis was found in the depressed lesions, which had more apoptotic cells than non-regressed atherosclerotic plaques. Furthermore, the apoptotic cells were significantly greater in the center of depressed lesions than in marginal areas. Ki-67 staining was positive in the atherosclerotic plaque, but negative in the depressed lesions. It appears that the NZW aortic atherosclerotic plaques may transform to depressed lesions with apoptosis. Atherosclerotic regression has been associated with apoptosis.

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α-Tocopherol (α-Toc), a lipophilic phenolic antioxidant that is localized mainly in the biomembrane, protects cells against oxidation-associated cytotoxicity by prevention of membrane lipid peroxidation, maintenance of the redox balance intracellular thiols and stabilization of the membrane structure. We investigated the age-related changes in redox dynamics of α-Toc in plasma and erythrocyte membrane of an elderly (66 weeks old) and young group (10 weeks old). Total, α-, β+γ-, δ-Toc and α-tocopherolquinone (α-TocQ) in plasma and erythrocyte membrane were determined by high-performance liquid chromatography (HPLC) with a series of multiple coulometric working electrodes (CWE). Rat venous blood sample was divided into plasma and erythrocyte layers by centrifugation, and then erythrocyte membrane sample was prepared according to the method of Dodge et al. under a stream of nitrogen. In plasma, total and α-Toc concentrations were increased, and β+γ-, δ-Toc and α-TocQ concentrations were decreased age-dependently. In the erythrocyte membrane, total, α-TocQ concentrations and three fractions of tocopherols decreased age-dependently. Also, a decrease in the α-TocQ/α-Toc ratio in erythrocyte membrane was observed in the elderly group. These findings suggest that the α-Toc uptake in erythrocyte membrane and utilization rate of α-Toc in erythrocyte membrane decline age-dependently. This decline may promote membrane lipid peroxidation. α-Toc redox dynamics in erythrocyte membrane were useful to investigate the pathophysiology of aging mechanisms related to oxidative stress.

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Although calcium-channel blockers and angiotensin-I-converting enzyme inhibitors are often used for treatment of hypertension in the elderly in Japan compared to those in the United States and in European countries, there have been few investigations on the prognosis of the elderly receiving these antihypertensive treatments. The Research Group for “Guidelines on the Treatment of Hypertension in the Elderly” collaborated with the Comprehensive Research Projects on Aging and Health group of the Ministry of Health and Welfare of Japan in performing a 3-year survey on the outcome of 700 hypertensive elderly outpatients (≥60 years) receiving treatment of antihypertensive drugs. Antihypertensive drugs including dihydropyridine-type calcium cannel blockers, beta blockers, angiotensin-I-converting enzyme inhibitors, diltiazem, diuretics and old-type antihypertensives (hydralazine, budralazine, and centrally acting drugs such as clonidine, methyldopa and guanabenz) were administered to 71.3%, 30.4%, 26.2%, 14.0%, 8.6%, and 6.4% of the 642 elderly patients surveyed for three years, at the time of registration, respectively. Morbidity and mortality rates of total cerebro-cardiovascular diseases, stroke, and heart diseases, were 27.6 and 7.81/1, 000 patient-years, 15.1 and 3.6/1, 000 patient-years, 10.4 and 4.2/1, 000 patient-years, respectively. These results were similar or even better than those of megatrials of antihypertensive treatments for elderly patients in Europe and United States. After adjustment for potential confounding factors, multiple logistic analysis revealed that a past history of ischemic heart disease, use of the old-type antihypertensive drugs, male gender, and diastolic high blood pressure were independent risk factors for the morbidity of cerebro-cardiovascular diseases taking the group of non-cerebro-cardiovascular disease as the reference group. We also identified 22 cases of newly occurred malignancies including 7 fatal cases. However, none of the antihypertensives was significantly related to the occurrence of malignancies. These results lead support to the tendencies in the use of antihypertensive drugs in Japan.

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Little information is available concerning the latent effects of silent cerebral infarction (SCI) on dysarthria (DA), dysphagia (DP), or both. A detailed analysis of MR images of multiple cerebral infarction was carried out to determine whether SCI is associated with the development of DA or DP. In this study MR images of the supra- and sub-tentorial regions were obtained from 14 patients presenting with persistent DA and DP (DA+DP group) and 9 patients presenting with DA alone (DA group) after the first episode of cerebral infarction. The DA+DP inducing lesion was identified from the change in signal intensity and the side with symptoms in 6 patients. Involvement of 3 lesions of the bilateral cortical branches, striatum, and pons on the line connecting the contra-lateral SCI with the lesion were noted in 4 patients (67%, vs. 40% for the DA group). Latent association of SCI with the development of supra-nuclear DA and DP was noted in 1 patient each from the DA+DP and DA groups. The results of this study support the concept that SCI patients include those in which SCI is involved in the development of supra-nuclear DA or DP, and suggest that SCI should be treated.

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We followed 126 patients with senile dementia of Alzheimer type (SDAT), and 129 over age 65 with vascular dementia (VD) who were diagnosed at the Center for Elderly Dementia in our institution between February 1990 and February 1993. At 5-year follow-up, 62 patients with SDAT and 71 patients with VD had died. These patients were assessed prospectively to investigate the neuropsychiatric and somatic factors related to the prognosis of SDAT and VD.
There were no significant differences in the average age at onset and time of diagnosis of dementia between the SDAT and VD groups. Mean age at death, mean duration of dementia and 75% survival duration from dementia onset were shorter in patients with VD than in those with SDAT. Pneumonia was the most common cause of death in patients with either SDAT or VD, followed by geromarasmus in the SDAT group, and cerebrovascular and cardiovascular diseases in the VD group. In patients with SDAT, a poor prognosis was correlated with severe dementia, impaired intellectual function and degree of cortical atrophy. In patients with VD, physical complications, impaired motor function and hypoproteinemia enhanced the probability of death.
This study confirmed that a progressive neurodegenerative course and physical conditions such as motor dysfunction or malnutrition are closely associated with the prognosis of patients with SDAT and VD, respectively.

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Three bed-ridden patients who had had only one kind of enteral nutrition without sufficient copper element during a few years showed very low levels of serum copper. Two of them also had leukopenia. The abnormal findings disappeared after the feeding nutrients rich in copper element. The leukopenia may have been due to copper deficiency rather than zinc deficiency. We confirmed that long-term parenteral nutrition must contain trace elements, for example copper.

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A 70-year-old woman was referred to our hospital for treatment of cholelithiasis. A giant liver cyst (6cm in diameter) had been diagnosed three years earlier. On admission, she had low grade fever and hepatomegaly. High values were observed for WBC (9900/μl), CRP (8.9mg/dl), GPT (45IU/l), ALP (1399IU/l), γ-GTP (333IU/l) and LAP (249IU/l). The diagnosis of infected liver cyst (8cm in diameter) was made based on contrast-enhanced CT scan. Endoscopic retrograde cholangiopancreaticography showed no communication between the cyst and the intrahepatic bile duct. She was successfully managed with antibiotics and discharged without percutaneous aspiration the cyst. On abdominal CT scan 4 months after the discharge, the liver cyst had decreased dramatically in size (1cm in diameter). The patient remains healthy without symptoms.

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A 72-year-old man was admitted for examination of dyspnea and pitting edema of the lower legs in July, 1996. His hemoglobin level was 6.9g/dl, and myelodysplastic syndrome (MDS) was revealed by bone marrow aspiration, and frequent transfusions were needed. His renal function rapidly deteriorated in the middle of August (BUN 45mg/dl, Cr 4.8mg/dl) and IgA nephropathy (IgAN) with marked interstitial nephritis was disclosed by renal biopsy. In November, joint manifestations of warmth and pain, which suggested arthritis, appeared at the bilateral wrist and ankle joints. Soon after receiving prednisolone (20mg/day), the arthritis was relieved. Renal function also improved (BUN 41mg/dl, Cr 2.1mg/dl) and frequent transfusions were no longer necessary.
This is a case with various clinical manifestations of MDS, IgAN, and arthritis, and appears to be the first MDS case complicated with IgAN. A number of case reports have identified immune abnormalitis in patients with MDS. Immune and bone marrow abnormalities have been reported to be involved in the pathogenesis of IgAN. Thus, MDS could be complicated by IgAN. Their pathogenetic association is discussed in this paper.

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