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In order to determine whether the digital plethysmogram (PTG) can be used as an index of ageing or not, the PTG was recorded in 89 males and 110 females in a pilot study. Of the parameters which were calculated from the PTG, up-stroke time corrected by pulse rate (SX time) showed the strongest correlation with age. The PTG was recorded in 1066 males and 761 females. There was a significant correlation between age and SX time in both sexes. The change of SX time with age in the younger age group was more rapid than in the old age group. From these results, SXp time of the PTG can be used as an index of ageing, especially in the young to middle-aged group. [ABSTRACT FROM PUBLISHER]

The effects of aging on the relationships between changes in body weight, serum lipid levels (total cholesterol, HDL-cholesterol, triglyceride, beta-lipoprotein), and blood pressure (systolic pressure, diastolic pressure) were studied. The subjects were 17,689 Japanese (aged 19 to 88 years) who had received annual examinations at health centers for two consecutive years. After the date were adjusted for sex, body mass index, and serum lipid levels at baseline, changes in serum lipid levels and blood pressure per kilogram change in body weight were estimated for 3 age groups (under 45, 45 to 64, and 65 or older). Positive relationship between changes in body weight and blood pressure were noted for all 3 age groups. Although total cholesterol, triglyceride, and beta-lipoprotein levels all decreased with weight loss in the under-65 groups, total cholesterol in the 65-and-over group did not change significantly. The increases in total cholesterol, triglyceride, and beta-lipoprotein levels were associated with weight gain in the under-65 groups, but not in the 65-and-over group. HDL-cholesterol levels in all age groups decreased significantly with weight gain. These results suggest that aging affects the relationship between changes in body weight and serum lipid levels but not that between changes in body weight and blood pressure.

Reduced red cell deformability and increased platelet aggregability are assumed to contribute to various ischemic diseases, and it has been postulated that these abnormalities may be improved by drug treatment. In this study, the effect of nisoldipine (Bay K 5552, CAS 63675-72-9) on red cell deformability and platelet aggregation in patients with chronic ischemic cerebrovascular disease and hypertension was examined. Administration of nisoldipine for 4 weeks caused a significant improvement of red cell deformability and platelet aggregability without causing any adverse effects.

We present findings in the ninth known Japanese family with lecithin:cholesterol acyltransferase (LCAT) deficiency. A 54-year-old man (proband) and his 58-year-old brother presented with corneal opacity. Both subjects showed a marked decrease in serum high density lipoprotein (HDL)-cholesterol and in the cholesteryl ester ratio. Although apo A-I and A-II were low, apo E tended to be high. Serum LCAT activity and mass were not detectable. Urinary examination showed microhematuria or proteinuria. Renal function was normal and no anemia was demonstrated, but blood smears showed poikilocytosis with target cells. The serum LCAT activity of the proband's three sons, obligate heterozygotes of LCAT deficiency, was about one-half the normal level, and HDL-cholesterol and apo A-I levels were low normal.

The clinical, psychological, and neurologic characteristics of 37 Japanese patients with early-onset Alzheimer's disease (eAD; onset before age 65 years) were compared with those of 23 patients with late-onset Alzheimer's disease (lAD; onset at age 65 years or later). This study evaluated brain atrophy using computed tomographic (CT) scans, and the behavioral and psychological differences in the two groups using the Gottfries-Bråne-Steen scale, Japanese revision (GBSS-JR). Follow-up CT scans were obtained and compared in 20 patients with eAD, 24 patients with lAD, and 23 elderly nondemented control subjects. The size of lateral cerebral ventricular dilation, measured every 6 months following admission, was significantly larger in the eAD patients than in the control subjects. The characteristics of the 37 patients with eAD were compared with those of the 23 patients with lAD by evaluating the scores on all 38 items in the five categories of the GBSS-JR. To compare the test results by duration of disease, patients were divided into subgroups according to average duration of disease: eAD1 (nine patients), 2.2 years; eAD2 (16 patients), 5.0 years; eAD3 (12 patients), 9.0 years; lAD1 (seven patients), 1.6 years; lAD2 (10 patients), 3.1 years; and lAD3 (six patients), 5.3 years. The GBSS-JR scores were compared in duration-matched pairs, that is, eAD1 versus lAD1 and eAD2 versus lAD3. The eAD1 patients showed significantly worse scores in four categories and 13 items compared with the lAD1 patients. Fewer differences in scores were found between eAD2 patients and the lAD3 patients than between the eAD1 patients and the lAD1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Age is one of the most important factor of changes in energy metabolism. The basal metabolic rate decreases almost linearly with age. Skeletal musculature is a fundamental organ that consumes the largest part of energy in the normal human body. The total volume of skeletal muscle can be estimated by 24-hours creatinine excretion. The volume of skeletal musculature decreases and the percentage of fat tissue increases with age. It is shown that the decrease in muscle mass relative to total body may be wholly responsible for the age-related decreases in basal metabolic rate. Energy consumption by physical activity also decreases with atrophic changes of skeletal muscle. Thus, energy requirement in the elderly decreases. With decrease of energy intake, intake of essential nutrients also decreases. If energy intake, on the other hand, exceeds individual energy needs, fat accumulates in the body. Body fat tends to accumulate in the abdomen in the elderly. Fat tissue in the abdominal cavity is connected directly with the liver through portal vein. Accumulation of abdominal fat causes disturbance in glucose and lipid metabolism. It is shown that glucose tolerance decreases with age. Although age contributes independently to the deterioration in glucose tolerance, the decrease in glucose tolerance may be partly prevented through changes of life-style variables, energy metabolism is essential for the physiological functions. It may also be possible to delay the aging process of various physiological functions by change of dietary habits, stopping smoking, and physical activity.

We investigated the mechanisms by which corticosteroids affect atherosclerosis. Male New Zealand White rabbits were injected with 0.125 mg dexamethasone (n = 10) or vehicle (control group, n = 10). Both groups were fed a 1% cholesterol diet for 8 weeks. Although the dexamethasone-treated animals exhibited a greater degree of hyperlipidemia, they exhibited significantly less atherosclerotic plaque of the aortic surface than control animals (7.8% versus 47.2%). Immunofluorescence study of the aortic plaque specimens showed that dexamethasone administration reduced both macrophages and T lymphocytes. In vitro, dexamethasone suppressed the proliferation and differentiation of U937 cells and inhibited uptake and degradation of beta-very low density lipoproteins by mouse peritoneal macrophages. These findings suggest that dexamethasone suppresses the development of atherosclerosis in the aorta of rabbits by inhibiting recruitment and proliferation of macrophages and the formation of foam cells in plaques.

In 1949, Rinehart and Greenberg reported that marked arteriosclerosis occurs in vitamin-B6-deficient monkeys. The present study investigates the relationship between vitamin B6 and arteriosclerosis and summarizes the results. I found that thrombogenesis, disorder of collagen metabolism and production of free radicals may be the processes that cause arteriosclerosis in human and experimental animals with vitamin B6 deficiency.

A 65-year-old woman was admitted to our hospital on May 28, 1990, because of recurrent high fever, over 39 degrees C, headache and general fatigue. In June 1988, she suffered the first episode of high fever, headache and general fatigue. Since then, those symptoms attacked her recurrently at intervals of 7 to 10 days. She was admitted to a hospital for two months in 1988. However, the etiology was unclear and treatment, including antibiotics, was not effective. After admission to our hospital, the symptoms of high fever, headache and general fatigue developed suddenly, lasted for 2 to 4 days, then disappeared spontaneously. These symptoms recurred periodically at intervals of 7 to 10 days. Findings of lumbar puncture during the period with severe symptoms revealed a leukocytic pleocytosis (polymorphonuclear neutrophil count: 1,324/3 mm3, mononuclear cell count: 48/3 mm3, without Mollaret cells) increased protein (0.81 g/l) and decreased glucose (0.28 g/l). Cerebrospinal fluid (CSF) examination during the period without symptoms showed a dramatic decrease of pleocytosis (polymorphonuclear neutrophil count: 5/3 mm3, mononuclear cell count: 17/3 mm3, without Mollaret cells) with improved protein (0/64 g/l) and glucose (0.40 g/l). Various examinations revealed no evidence of infection, malignancy, collagen disease, endocrine disease or any disorders in the nervous system. Moreover, bacterial cultures of blood and CSF were negative and a brain CT scan showed no abnormal findings. We diagnosed this case as Mollaret's meningitis and gave 25 mg indomethacin after every meal (75 mg/day). Her symptoms were improved abruptly and the duration of symptoms shortened and symptom-free intervals became longer.(ABSTRACT TRUNCATED AT 250 WORDS)

Some elderly patients with chronic illness such as stroke, or Parkinsonism cannot take food orally because of dysphagia. In such cases, tube feeding can be used as a supplement to oral intake when malnutrition is present. This route allows for easier nursing care and decreases the frequency of aspiration pneumonia. Complications of tube feeding include nutrient deficiency states, pulmonary aspiration, gastrointestinal and metabolic disorders. We report two cases with complications of acute gastric ulcer which was thought to be induced with long-term tube feeding. Case 1 was a 61-year-old male patient with Parkinson's disease for ten years. L-DOPA had been administered with good control of his condition. However, his ability to swallow has deteriorated gradually. As he often suffered from aspiration pneumonia, nasogastric tube feeding was performed. After three years of tube feeding, he suddenly vomited much bloody material. He died from massive bleeding with acute gastric dilatation. Autopsy showed giant acute gastric ulcer covered with coagulated blood. UL3, 50 mm in maximum diameter, was observed in the middle portion of the greater curvature, where the top of tube probably came in contact with the gastric wall. Case 2 was an 83-year-old female patient with stroke and chronic heart failure. She had been hospitalized for about one year because of the intermittent deterioration of her cardiac condition. Furthermore, her inability to swallow increased during her hospitalization. She also suffered from aspiration pneumonia. Nasogastric tube feeding was performed to prevent aspiration pneumonia and malnutrition. She died of acute heart failure after twelve months. Autopsy revealed heart dilatation, old myocardial infarction and stroke. In addition, two acute gastric ulcers (UL3.10 and 30 mm in diameter) were recognized; one was in the upper portion of the greater curvature, the other in the lower portion of the greater curvature. The location of these gastric ulcers was unusual. Moreover, they coincided with location of top of the nasogastric tube. From these two cases, we conclude that in long-term tube feeding the tip of the tube often comes in contact with the gastric wall, and gastric ulcer could be produced by repeated mechanical stimulus of the wall. Reports of acute gastric ulcer induced by tube feeding have not been published previously. Therefore, we should pay much attention to this complication in the care of the elderly people with long-term tube feeding.

Three cases of Chilaiditi's syndrome are reported. Case 1: A 56-year-old woman was admitted with dysphagia. She had been suffering from progressive systemic sclerosis for 16 years. Three years before the admission, dysphagia developed and dilatation and hypomotility of the esophagus were observed. Chest and abdominal x-ray films on admission showed severe dilatation of the intestine, pneumatosis cystoides intestinalis, abdominal free air, and Chilaiditi's syndrome. Chilaiditi's syndrome and other signs disappeared after conservative treatment. She died four months later due to cor pulmonale. Case 2: An 87-year-old man was admitted with constipation and left lower abdominal pain. Physical examination showed ascites. Chest and abdominal x-ray examination showed Chilaiditi's syndrome. Cytological examination of ascites revealed adenocarcinoma cells. Diagnosis of peritonitis carcinomatosa due to cancer of pancreatic tail was made. Chilaiditi's syndrome disappeared after removal of ascites. Case 3: A 71-year-old bedridden man who had urinary incontinence developed meterorism. Repeated chest x-ray examinations constantly showed Chilaiditi's syndrome. He died of pneumonia two years later. The pathogenesis of Chilaiditi's syndrome was discussed and the literature was reviewed.

We studied the effects of a synthetic adrenocortical steroid, dexamethasone, on the development of experimental atherosclerosis in cholesterol-fed rabbits. Daily intramuscular injection of dexamethasone (0.125 mg/day) remarkably inhibited the aortic atherosclerosis induced by feeding a 1% cholesterol-rich diet for 8 weeks, although it aggravated diet-induced hyperlipidemia. Histologically, less foam cell accumulation was observed in the atherosclerotic lesions of the dexamethasone-treated rabbits as compared with the control animals. When rabbits were fed a normal chow diet for 10 weeks after receiving the 1% cholesterol-rich diet for 8 weeks, no regression of atherosclerotic lesions was observed with the daily injection of dexamethasone (0.125 mg/day); however, the drug again tended to inhibit further progression of atherosclerosis. The anti-atherogenic mechanism of dexamethasone may involve an inhibition of recruitment of blood monocytes and the insudation of atherogenic lipoproteins, mainly beta-very low density lipoprotein (beta-VLDL) in the present experiments, into the aortic intima, or it may involve a change in the size and structure of the lipoproteins, resulting in their decreased passage through the aortic endothelium into the intima.

The clinical significance of measuring glycated fibrinogen (G Fbg) in plasma was studied using a simple, rapid method for determining plasma G Fbg developed by the authors. This method is based on modified fibrin clot formation for purification of plasma Fbg, and G Fbg was estimated by improved colorimetric fructosamine assay. The values of plasma G Fbg were expressed as glycated polylysine equivalents (mumol/l). In this clinical study, 106 examinees who underwent a screening test for diabetes mellitus (DM) because of glycosuria or hyperglycemia were investigated. According to the WHO diagnostic criteria, they were divided into 3 groups: non DM group (n = 35), impaired glucose tolerance (IGT) group (n = 31) and DM (non-treated) group (n = 40). In addition, healthy controls (n = 40) and treated diabetic patients (DM treated) were involved. Plasma G Fbg/Fbg, fasting plasma glucose (FPG), fructosamine and glycated hemoglobin (HbA1c) were also analyzed in subjects of the 5 groups. Non-treated DM patients showed high levels of plasma G Fbg, which were significantly higher than those of any other groups. G Fbg levels in IGT group were significantly higher than those in healthy controls or the non-DM group. Together with a significant positive correlation between G Fbg and FPG, these results indicate that the levels of plasma G Fbg depend on plasma glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to characterize the nocturnal fall of blood pressure (NFBP) of elderly hypertensive patients (EH), with or without cerebrovascular disease or diabetes mellitus, as measured by automated blood pressure (BP) monitoring. Systolic and diastolic BP and heart rate was measured every 15 minutes in 133 hospitalized patients with nearly similar schedules and diets. The patients were divided into five groups: I, normotensive elderly patients over age 65: II, EH without cardiovascular diseases, controlled without medication: III, EH with cerebral infarction, chronic stage: IV, EH with noninsulin-dependent diabetes mellitus: and V, hypertensives under age 65, without cardiovascular diseases. A significant NFBP was observed in the patients of groups I and V, a significant but smaller NFBP in the hypertensives of groups II and IV, and no NFBP in the patients of group III. Administration of the antihypertensive drugs, enalapril and nifedipine, tended to augment the NFBP. These preliminary observations showed that NFBP did occur in elderly hypertensives but the fall was smaller than that observed in younger hypertensives or elderly normotensives. Although the ambulatory BP measurements were useful in the overall clinical evaluation of elderly patients, NFBP in elderly patients was affected by hypertensive drugs and therefore NFBP should be interpreted with caution.

The oxidative modification of low-density lipoprotein (LDL) is suggested to play an important role in the pathogenesis of atherosclerosis. The present study examined the role of the formation of LDL-copper (Cu) complex in the peroxidation of LDL. The amount of copper bound to LDL increased during incubation performed with increasing concentrations of CuSO4. More than 80% of the copper bound to the LDL particle was observed in the protein phase of LDL, suggesting that most of the copper ions formed complexes with the ligand-binding sites of apoprotein. The addition of histidine (1 mM), known to form a high affinity complex with copper, and EDTA (1 mM), a metal chelator, during the incubation of LDL with CuSO4 prevented the formation of both thiobarbituric acid-reactive substances (TBARS) and LDL-Cu complexes. EDTA inhibited the copper-catalyzed ascorbate oxidation whereas histidine had no effect, suggesting that the copper within the complex with histidine is available to catalyze the reaction, in contrast to EDTA. These observations indicate that the preventive effect of histidine on the copper-catalyzed peroxidation of LDL is not simply mediated by chelating free copper ions in aqueous phase. Evidence that copper bound to LDL particle still has a redox potential was provided by the observed increase in TBARS content during incubation of LDL-Cu complexes in the absence of free copper ions. The addition of either histidine or EDTA to LDL-Cu complexes inhibited the formation of TBARS by removing copper ions from the LDL forming the corresponding complexes. However, there still remained small amounts of copper in the LDL particles following the treatment of LDL-Cu complexes with histidine or EDTA. The copper ions remaining in the LDL particle lacked the ability to catalyze LDL peroxidation, suggesting that there may be two types of copper binding sites in LDL: tight-binding sites, from which the copper ions are not removed by chelation, and weak-binding sites, from which copper ions are easily removed by chelators. The formation of TBARS in the LDL preparation during incubation with CuSO4 was comparable to the incubation with FeSO4. In contrast, the formation of TBARS in the LDL-lipid micelles by CuSO4 was nearly eliminated even in the presence of ascorbate to promote metal-catalyzed lipid peroxidation, although a marked increase in TBARS content was observed in the LDL-lipid micelles with FeSO4, and with FeCl3 in the presence of ascorbate.(ABSTRACT TRUNCATED AT 400 WORDS)

The purpose of this study was to investigate the difference between species (mouse and rabbit) and the effect of hypercholesterolemia on the ability of their peritoneal macrophages to release unesterified cholesterol to an exogenous acceptor. The macrophages from mouse, normocholesterolemic rabbits and hypercholesterolemic rabbits (Mm, Mnr, Mhr) were loaded with cholesterol esters by incubation with oxidatively modified low density lipoprotein or plasma lipoprotein (beta-migrating very low density lipoproteins). When human HDL was used as cholesterol acceptor for 24 h of incubation, the Mm Cells, the Mnr cells and Mhr cells retained about 40%, 70%, and more than 90% of their cholesterol esters. The difference between species of lipoproteins were not effective for the ability to release cholesterol esters. ACAT (acylcoenzyme A: cholesterol acyltransferase) inhibitor 58-035 increased these capacities. These data suggest that the limited capacity of macrophages from hypercholesterolemic rabbits to release cholesterol may be related to the progression and resistance to regression of atherosclerosis, and that ACAT activity might influence this capacity.

Gastric xanthomas are single or multiple yellowish-white small nodules or plaques in the gastric mucosa. Microscopically they consist of macrophage-derived foam cells full of lipids. However, because of their benign nature, there are few reports of gastric xanthomas in the literature and their clinical significance still remains unknown. In this study, we studied 131 elderly cases (42 males and 89 females) with the average age of 75.6 +/- 12.3 (S.D.) years old who were examined gastroendoscopically. The endoscopic finding of gastric xanthomas was observed in 17 males (40.5%) and in 23 females (25.8%). Gastric xanthomas tended to increase with age, and the frequency was highest in the seventies (40.0%). Of the xanthoma cases, 42.5% had a solitary xanthoma, and 17.5% had more than 5 xanthomas. More than 70% of xanthomas were observed in antral and pyloric regions. There was no difference in serum lipids between the cases with and without xanthomas. Gastric mucosa biopsied from around xanthomas showed moderate to severe atrophic change of gastric glands in most cases (89%). Hyperplasia of gastric-pit epithelia and intestinal metaplasia were also often observed. However, there was no correlation between gastric xanthomas and small round cell infiltration in the gastric mucosa. It was concluded that gastric xanthomas in the elderly arise from the mucosa with atrophic change in most cases, which may have a disturbance of local lipid metabolism, and that the presence of gastric xanthomas may be a marker of the pathological aging change of gastric mucosa.

The authors investigated the involvement of red blood cell aggregation in thrombosis by comparing erythrocyte aggregation in patients with myocardial infarction (28 patients) or cerebrovascular accidents (68 patients) with that in a normal control group (38 subjects). The erythrocyte aggregation was assessed by light transmission aggregometer, and aggregation was induced by hexadimethrine-bromide. Increased erythrocyte aggregation was detected in all patients with thrombotic disorders. In addition, patients with diabetes mellitus showed a marked increase in erythrocyte aggregation as compared with those without diabetes. The effect of ticlopidine on erythrocyte aggregation was also studied. It was demonstrated that ticlopidine inhibited aggregation in vitro. An inhibitory effect was shown to be dose dependent, with 10 microM ticlopidine inhibiting aggregation completely. After four weeks' oral administration of 200 mg ticlopidine, there was significant decrease of abnormally increased erythrocyte aggregation in patients with thrombosis.

We examined the effect of phosphate buffer on the iron- and copper-catalyzed peroxidation of low-density lipoprotein (LDL). The incubation of LDL with CuSO4 in 0.15 M NaCl led to the peroxidation of LDL as evidenced by the detection of thiobarbituric acid-reactive substances (TBARS) and lipid hydroperoxides (LPO). The peroxidation of LDL was also observed with FeSO4 and FeCl3 in 0.15 M NaCl, although there was a lag phase with FeCl3. In 10 mM phosphate buffer, the peroxidation of LDL was observed with CuSO4 to an extent similar to that in 0.15 M NaCl. However, the peroxidation induced by incubation with FeSO4 and FeCl3 was significantly inhibited in phosphate buffer. Iron and copper each formed a complex with lipoprotein during incubation with LDL in 0.15 M NaCl. Although no effect on the formation of copper-LDL complex was observed in phosphate buffer, the formation of iron-LDL complex was reduced in the buffer. These observations suggest there are marked differences in the peroxidation of LDL and in the formation of complexes with LDL between iron and copper in phosphate buffer.

Mirror-writing is script that runs in the direction opposite to normal, with the individual letters also reversed. Although mirror-writing is well recognized as occurring in the presence of central nervous system damage, and is especially seen in association with hemiplegia, its mechanism has not yet been elucidated. The purpose of the present study is to document a high incidence of mirror-writing among patients aged 65 years or more, and to investigate the relationship of mirror-writing with brain damage and the degree of cognitive dysfunction. The subjects analyzed in this study were 112 patients (44 males and 68 females) and their average age was 73.8 years. Hasegawa's Dementia Scale (HDS) was used to evaluate their cognitive function. We could find no cases of mirror-writing with the right hand. A high incidence of mirror-writing was found in patients who could use their left hand. Mirror-writing was seen in 67% of patients with cerebral lesions on CT scan. However, we could not observe any relationship between the incidence of mirror-writing and damage to a given circumscribed area of the brain. More than 90% of demented patients, whose HDS scores were less than 20, showed mirror-writing with their left hand. The mean score on the HDS for those with a high incidence of mirror-writing was significantly lower than the score for those without mirror-writing. These results indicate that a high incidence of mirror-writing among aged patients is related to cerebral damage and cognitive dysfunction.

The authors compared the characteristics of the early-onset subtype of Alzheimer's dementia (AD) with those of the late-onset subtype (SDAT) to determine whether Alzheimer's dementia (AD/SDAT) can be divided into two different diagnostic categories. In this study, AD refers to Alzheimer's in which the onset of disease occurred before 65 years of age; and SDAT refers to cases in which onset of illness occurred at age 65 or more. The studied parameters were distribution of age at disease onset, progression of speed of ventricular dilation, speed of deterioration of Hasegawa's rating scale for dementia (HRSD) score, and lesional pattern on the Japanese revised version of the GBS scale (GBSS-JR). The distribution of age at onset in 258 patients with AD/SDAT showed one peak. These patients included both outpatients and inpatients. A 30-month follow-up study to determine the degree of ventricular dilation was performed in 20 AD and 24 SDAT patients. For CT measurement, the width of the third and lateral ventricle (cella media index) was measured every 6 months after admission. Average ventricle width at admission was matched between the two groups. Twelve and 24 months after admission, the mean cella media index of patients with AD was significantly wider than that of patients with SDAT. In addition a deterioration speed of HRSD scores of 16 AD and 14 SDAT patients was compared every month for 5 months after admission. The average duration of illness and HRSD score at admission were matched in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitronectin, a multifunctional glycoprotein present in the plasma and interstitial tissues, has recently been found to be localized in atherosclerotic lesions. In this study we examined the effects of vitronectin on the migration of cultured bovine aortic smooth muscle cells using a modified Boyden chamber assay. The cells migrated to fluid-phase vitronectin in a concentration-dependent fashion. The cells also migrated to membrane filter surfaces precoated with vitronectin for a few minutes in the absence of additional vitronectin in the fluid phase, suggesting that this substance binds easily to the filters and stimulates cell migration by haptotaxis under the conditions described. These observations suggest that vitronectin deposited in the intima may be involved in the pathogenesis of atherosclerosis by recruiting smooth muscle cells from the media into the intima.