We studied how the severity of hemiparesis was related to cardiovascular and metabolic responses to exercise. Eleven clinically stable patients who had had strokes were studied two to four weeks after they began walking as rehabilitation. After motor function of the lower limbs was assessed, the patients were divided into two groups according to Brunnstrom stage: one group comprised patients at stages III, IV, and V of lower limb function (n=5), and the other comprised patients at stage VI (n=6). A control group of 6 patients who had been hospitalized because of benign paroxysmal postural vertigo was also studied. Exercise consisted of 3-minute walks at speeds of 1.6, 3.2, and 4.8km/hr. Blood pressure, heart rate, and the concentrations of catecholamines and of lactic acid in blood were measured before and after each stage of exercise. The double product (systolic blood pressure × heart rate) was also calculated. Changes in these variables were compared among the three groups. Increases in walking speed were associated with increases in systolic blood pressure and heart rate in hemiparetic patients, but no such changes occurred in the control group. In the patients at Brunnstrom stages III, IV, and V, the double product and the lactic acid level increased, and after the patients walked at the highest speed these were significantly higher than in the other two groups. Serum catecholamine levels did not differ among the three groups during exercise. Low intensity exercise can increase cardiovascular responses, and anaerobic metabolism can become dominant in patients with poor motor function.
We compared trends in the prescription of antihypertensive drugs in elderly patients with those in middle-aged patients. We analyzed prescriptions given to 141 patients with hypertension who were 65 years old or older (mean age, 73 years) and to 511 patients with hypertension who were 64 years old or younger (mean age, 59 years). The numbers of drugs prescribed did not differ between the elderly and the non-elderly patients. In both groups, about 50% of patients were given prescriptions for one antihypertensive drug, about 40% were given prescriptions for two drugs, and about 10% were given prescriptions for three drugs. Calcium antagonists were the agents most commonly prescribed as monotherapy (51.4% and 56.4% in the non-elderly and elderly respectively; n.s.); followed by β-blockers (32.2% and 25.6%; n.s.). Diuretics were prescribed less often to non-elderly patients than to elderly patients (5.1% and 10.0%; p<0.01). When prescriptions for more than one antihypertensive agent were included in the analysis, calcium antagonists were still the most commonly prescribed agents (63.8% and 66.4%; n.s.), followed by β-blockers (53.3% and 66.4%; p<0.05). Diuretics were less commonly prescribed to non-elderly patients (13.5% and 21.3%; p<0.005), while ACE inhibitors (19.0% and 11.6%; p<0.005) and β-blockers (52.3% and 44.0; p<0.05) were more commonly prescribed to non-elderly patients. When we classified the data according to the time of the first visit, we found that patients whose first visit was earlier were more likely to have been given a prescription for a diuretics, whether they were elderly or non-elderly. Calcium antagonists were the most commonly prescribed agents in all time periods studied, followed by β-blockers. Comparison of our results with those of a similar study done at our clinic in 1990 showed that the use of calcium antagonist monotherapy doubled in both groups (non-elderly: 26.4% in 1990 to 51.4% in 1995, p<0.001; elderly: 29.5% in 1990 to 56.4% in 1995, p<0.001) and that the use of diuretics declined markedly (non-elderly; 20.3% to 5.1%, p<0.001; elderly: 30.2% to 10.0%, p<0.001). A similar trend was seen when prescriptions for more than one antihypertensive drug were included in the analysis.
Non-insulin-dependent diabetes mellitus, obesity, and essential hypertension are associated with hyperinsulinemia that results from insulin resistance and insulin has been reported to accerelate atherosclerosis. We studied the effects of insulin and insulin-like growth factor-1 (IGF-1) on the growth of porcine vasucular smooth muscle cells and on the synthesis of extracellular matrix. The cells were cultured 3-8 changes of Dulbecco's modified Eagle's medium (DMEM) with 10% FCS. Subconfulent cells were put in wells 1×104 or 1×105cells/well in DMEM with or without insulin or IGF-1. The number of cells was counted, and protein and DNA synthesis, expression of genes for collagen α1 (1), and collagen synthesis were measured. Insulin (0, 16, and 160nM) and IGF-1 (0, 1, 31, and 13.1nM) increased number of cells by 50% and 40%, in a dose-dependent manner. Protein and DNA synthesis were also increased by insulin (3.8 and 3.0 times) and by IGF-1 (3.9 and 1.8 time). Collaged protein synthesis was increased 2.3-fold by IGF-1 at 13.1nM, and insulin (16, 000nM) caused a 26.5-fold increase. Levels of collagen α1 (1) mRNA were also increased by both insulin and IGF-1. These results suggest that insulin and IGF-1 can cause vascular hyperplasia associated with increased collagen synthesis, which indicates that insulin, IGF-1, or both may have an important role in vascular growth.
Atherosclerotic plaque with central depression (depressed lesion) has been hypothesized to be a morphological feature of atherosclerosis regression. We tested this hypothesis in New Zealand white rabbits. After the animals were fed a diet containing 1% cholesterol for three months, they were changed to a normal diet for 6 to 9 months. Several aortas had centrally depressed lesions similar to those found in elderly people, and the animals had low serum cholesterol levels. Immunohistochemical study showed that the depressed lesions contained more smooth muscle cells and collagen type IV, and fewer macrophage-derived foam cells than did common atherosclerotic elevated lesions found in rabbits. We know of no other report of depressed lesions in rabbits with atherosclerosis. Thus we believe that the centrally depressed lesion is a histological characteristic of regression of atherosclerosis.
To establish the prevalence of carotid atherosclerosis and its relation to aging in Japanese population, 270 participants in voluntary health screening at our hospital were studied with 7.5MHz B-mode ultrasonography and accelerated plethysmography (APG), and their levels of serum lipids were measured. The subjects consisted of 84 people in the fifth decade of life, 89 in the sixth decade, 67 in the seventh decade, and 30 in the eighth decade. Carotid lesions were deemed to be present when occlusion, atheromatous plaque, or both were found. Atheromatous plaque was defined as a thickened intimamedia complex of 2.1mm or more. Plaques were divided into two types based on morphometric criteria, and into three types based on echogenic criteria. Thickness of the intimamedia complex (IMT) was measured at two randomly chosen points along the common carotid artery. APG was obtained by double-differentiation of finger-plethysmograph record, and the APG index was calculated as (-b+c+d)/a, where the letters are the distances from the baseline to the peaks of each wave (a, b, c, and d waves) on the APG waveform. Carotid lesions were seen in 5% of subjects in the fifth decade of life, 7% of subjects in the sixth decade, 24% of those in the seventh decade, and 27% of those in the eighth decade. All the lesions were plaques, and neither plaque type nor size differed between young-adult and elderly subjects. Multiple regression analysis revealed that the thickness of the intima-media complex correlated significantly with age, but not with carotid lesions, sex, body weight, serum lipid levels, hemoglobin A1 level, or uric acid level. The APG index also decreased significantly with age, but no correlation was seen with carotid lesions or with the thickness of the intimamedia complex. These findings indicate that people aged 60 or over could be at risk for plaque formation in the carotid arteries and their carotid arteries should be examined carefully even in the absence of risk factors for vascular disease. These findings also suggest that both increased thickness of the intima-media complex and a low APG index arise via pathophysiologic mechanisms different from those that lead to atheromatous plaque.
Long-term administration of active vitamin D3 can reduce the loss of bone mass and the incidence of fractures in Japanese whose intake of calcium (Ca) is low. In a crossover study, we examined the safety and efficacy of 1α(OH)D3 and combination therapy with a Ca preparation. We measured bone mass, the incidence of fractures and bone metabolism in 33 elderly patients with a high risk of fracture (mean age: 77.5±7.8 (SD) years). Subjects were randomly assigned to receive calcium lactate alone for 12 months after 12 months of combination therapy with 1α(OH)D3 (1μg/day) (A-C group, 17 patiens) or to take calcium lactate alone for 12 months and then undergo 12 months of combination therapy with 1α(OH)D3 (C-A group, 16 patients). These subjects were followed for 24 months. In the A-C group, the bone mineral density (BMD) of the lumbar spine (L2-4 BMD) measured 6 months after the start of 1α(OH)D3 administration was 3% higher than the baseline value. In the C-A group, L2-4 BMD measured 6 months after the start of calcium lactate administration had decreased by approximately 2%. The rate of decrease was the same 12 months after the start of administration. The differences in L2-4 BMD between the two groups 6 and 12 months after the start of administration were significant (p=0.023 and p=0.005, respectively). In the A-C group, the mean BMD of the distal one-third radius measured 6 months after the start of administration had increased by 5%, but the increase was 1% when measured 12 months after the start of administration. In the C-A group, there were no such changes. The incidence of vertebral fracture during combination therapy with 1α(OH) D3 and Ca preparations in the A-C group was significantly lower than that in the C-A group (chi sequare test, p<0.05). The serum Ca level in the C-A group gradually increased, as measured 6 and 12 months after the start of combination therapy with 1α(OH) D3 and Ca preparations, although these changes were within the reference range. There was no hypercalciuria. Serum intact parathyroid hormone levels had decreased from 26.5±11.3pg/ml and 30.7±10.3pg/ml to 19.8±9.7pg/ml and 25.5± 9.6pg/ml in the A-C group and the C-A group, respectively, by 6 months after the start of administration. The rate of decrease was significantly higher in the A-C group (p=0.004). These findings suggest that long-term administration of 1α(OH)D3 is safe even when combined with administration of Ca preparations, and that this agent inhibits parathyroid function, and thus prevents loss of bone mass and reduces the incidence of vertebral fracture.
A randomized prospective study was done to evaluate the two treatments for pressure sores infected with methicilin-resistant Staphylococcis aureus in elderly patients: Gentian violet plus dibutyryl cAMP (GVcAMP, n=8) and povidone-iodine plus sugar (IS, n11). Age, underlying diseases, and nutritional status did not differ between the two groups. Specimens were obtained biweekly from the pressure sores and were cultured. The percentage of culture dishes with no methicillin-resistant S. aureus was 93% for the patients given GVcAMP, but only 74% for those given IS (p<0.01). By the 14th week after the start of treatment, the mean area of the pressure sores in the GVcAMP group had decreased to 45% of the area at the start of treatment. In the IS group, the decrease was smaller to 56% of the area before treatment. No local or systemic adverse effects occurred in either group. GVcAMP is useful to treat pressure sores infected with methicillin-resistant S. aureus.
We examined changes in outcomes among elderly patients with stroke who were admitted to the rehabilitation unit of our hospital from April, 1985 to March, 1995. During that period, 933 patients (489 men and 444 women, average age 71.3 years) were admitted and received physical therapy. During those 10 years, the average age of the patients increased, functional status with regard to sitting up and walking worsened, and the incidence of urinary incontinence at the time of discharge increased. In contrast, the percentage of patients discharged to home (50-60%), the degree of impairment of lower extremities, and the onset-to-admission interval (3 to 4 months) did not change.
We compared bedridden elderly poeple living at home to others who were hospitalinpatients. Questionnaires regarding medical status and care were returned by 85 of 116 people caring for a bedridden elderly person at home in Obu city, Aichi prefecture and by 62 of 64 nurses and family members caring for bedridden inpatients at Chubu National hospital. All subjects were at least 65 years old. The median age in both groups was 81 years, neither age distribution nor female sex predominance differed between both groups. The perecentage of subjects with only one underlying disease was 62.5% among those living at home and 64.4% among inpatients. In both groups the most common disease was cerebrovascular disease (42.5% among those at home and 39.0% among inpatients), followed by dementia (31.3%), infirmity of old age (17.5%) and bone fracture (13.8%) among those at home, and by bone fracture (27.1%), dementia (20.3%) and infirmity of old age (16.9%) among inpatients. The median durations of bedriden status were 2 years and 3 months among those at home and 3 months among inpatients. The proportion of subjects bedridden for less than 6 months was greater among inpatients (p<0.0001). The percentage who needed medical treatment was 60.0% among those at home and 67.7% among inpatients. The most common conditions for which drugs were taken were hypertention, dementia, chronic cerebrovascular dysfunction, and osteoporosis. Among inpatients, 54.8% were ambulatory before admission, 24.2% were almost completely bedridden, and 17.7% were completely bedridden. The most common cause rending the patients bedridden was infection (usually pneumonia). The degree of disability did not differ between groups. Decubitus ulcers were present in 25.9% of those at home and 17.7% of inpatients.
A 73-year-old woman with a long-standing history of right-sided chronic empyema complained of lumbago. An artificial pneumothorax had been induced to treat pulmonary tuberculosis about 40 years previously. The year after she began to complain of lunbago, a tumor mass over the right anterior chest wall had grown rapidly. Pathologic examination revealed that it was a malignant lymphoma (Non-Hodgkin's lymphoma, diffuse large cell, B cell type). Chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone, and then radiation therapy were given. The patient responded very well. The tumor mass on the surface of the chest wall disappeared completely. She was alive and well and there was no evidence of recurrence at the seven-month follow-up examination. Analysis with the polymerase chain reaction showed that the tumor contained DNA of the Epstein-Barr virus. The chronic empyema and local infection with the Epstein-Barr virus might have been a factor in the development of the malignant lymphoma.