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Adverse drug reactions (ADR) in elderly people, which have been shown to increase with age, are often attributed to functional decline and polypharmacy. A multi-institutional retrospective survey was undertaken to investigate the current status of ADR in geriatric wards of university hospitals. The inpatient database from 2000 to 2002 in 5 university hospitals was studied, and a total of 1,289 patients were analyzed. The incidence of ADR, as determined by attending physicians, was 9.2% on the whole but varied from 6.3% to 15.8% among the institutions. The factors significantly related to ADR were number of diagnoses, number of geriatric syndromes, number of prescribed drugs, increase of more than two drugs during admission, longer hospital stay, emergency admission, depression and apathy. These results are mostly consistent with previous reports and will provide important information on pharmacotherapy in elderly people.

Flow-mediated dilation (FMD) of the brachial artery, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) have been shown to be good surrogate markers of clinical atherosclerosis. We determined the interrelation between these measurements, and examined whether their combination would be of clinical significance. One hundred and thirty-five consecutive subjects (79 women/56 men) were enrolled, including 110 patients with risk factors for atherosclerosis, and 33 patients with atherosclerotic disease such as coronary heart disease, stroke or arteriosclerosis obliterans. IMT and plaque formation of the carotid artery and FMD of the brachial artery were assessed using ultrasonography. Brachial-ankle PWV (baPWV) was measured using an automated device (form ABI/PWV, Colin). Age, FMD, IMT and PWV were significantly correlated with each other. Multivariate analysis revealed an independent correlation between the parameters except for FMD, and all four parameters were independently correlated with each other in subjects <70 years. Next, we classified the subjects by tertile according to the values of FMD, IMT and PWV. Each of the worst tertiles was associated with a higher prevalence of atherosclerotic disease and carotid plaques compared to the other tertiles. Moreover, subjects with the worst tertiles of all three measurements had a markedly higher prevalence of atherosclerotic disease and carotid plaques. These results suggest that FMD, IMT and PWV are related to each other, but the combination of these measurements will be of stronger clinical relevance.

Increased short-term blood pressure variability is known to be associated with hypertensive target organ damage. Sinoaortic denervation (SAD) induces a marked increase in blood pressure lability without affecting the average blood pressure level. The aim of this study was to investigate the effects of blood pressure lability on endothelial vasomotor function and neointimal formation after balloon injury in SAD rats. Direct longterm measurement of mean arterial pressure showed no significant difference in the average of mean arterial pressure between the SAD group and sham-operated control group. In contrast, the standard deviation of mean arterial pressure, as an index of blood pressure lability, was 3-fold greater in SAD rats. To study endothelial function, isometric tension of aortic rings was measured 4 weeks after SAD or sham operation. Endothelium-dependent vasorelaxation induced by acetylcholine was significantly reduced in the SAD group (20% reduction at maximum relaxation). Endothelium-independent vasorelaxation induced by sodium nitroprusside was similar in each group. Acetylcholine-induced NO release from aortic rings was significantly reduced in the SAD group. Next, we examined neointimal formation in carotid arteries in SAD and sham-operated rats at 2 weeks after balloon injury. The neointimal-to-medial area ratio in the SAD group was 50% higher than that in the sham-operated group. The percentage of proliferating cell nuclear antigen-positive cells in the intima was significantly higher in the SAD group. These findings suggest that increased blood pressure lability, independently of average blood pressure level, impairs endothelial function by inhibiting NO production, enhances neointimal formation after balloon injury, and may thereby contribute to atherogenesis.

Objectives and Background: Nocturnal apnea and hypoxia are implicated in the pathogenesis of pulmonary and systemic hypertension in obstructive sleep apnea syndrome (OSAS). We have hypothesized that vasodilating factors including nitric oxide (NO) are affected by nocturnal apnea and hypoxia in patients with OSAS., Method: We examined the serum level of NO production in 24 patients with OSAS (mean age 54.2+/-7.9 years) and 24 age-matched control subjects (53.4+/-8.1 years) and tested the effects of oxygen administration on the production of NO in the patients., Results: The serum level of nitrite/nitrates (NO(x)), which are stable metabolites of NO, was lower in patients with OSAS than in control subjects. Administration of 1-2 l/min of oxygen during night increased the patients' NO(x) level from 35.6+/-7.3 to 57.8+/-11.6 microM. Compressed air administration did not affect the NO(x) level in the patients., Conclusion: These results indicate that systemic NO production is impaired in OSAS patients, possibly due to nocturnal hypoxia.

Objective: Repeated nocturnal hypoxia is implicated in the pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS). We hypothesized that circulating vascular endothelial growth factor (VEGF) levels are affected by nocturnal hypoxemia in patients with OSAS., Methods: We examined the serum VEGF levels in patients with OSAS and in control subjects. We also tested the effects of oxygen or air administration on the subjects' VEGF levels., Patients and Materials: Twenty-four OSAS patients (mean age 54.2 +/- 3.6 years) and 24 age-matched control subjects (53.2 +/- 3.6 years). Their serum samples were tested., Results: Serum VEGF levels at 8:00 AM were significantly higher in OSAS patients than in controls (p<0.01). VEGF levels decreased from 515 +/- 31 (pg/ml) to 178 +/- 16 (pg/m) (p<0.01) in OSAS patients whose nocturnal hypoxemia was found to be improved by administration of 2 l/min of oxygen during the night. However, the administration of compressed air affected neither the VEGF level nor nocturnal oxygen desaturation in OSAS patients., Conclusion: These results indicate that circulating VEGF levels are elevated in OSAS patients, primarily due to nocturnal hypoxemia.

To evaluate verbal communication ability in the elderly, we developed a new portable "mini-communication test (MCT)" with 13 sub-scales, which was constructively validated based on 45 items from other reported scales. Clinical reliability and validity were tested in 354 inpatients in a long-term care hospital (81.9 +/- 8.3 years old) and 124 inpatients (80.39 +/- 8.1 years old) and 34 outpatients (76.5 +/- 7.0 years old) in Kyorin University Hospital. All patients were evaluated in approximately 7 minutes each. The test-retest correlation coefficient was 0.99. Inter-rater coefficient of variation was 0.107. The Cronbach alpha value of the test was 0.93. MCT positively correlated with the Barthel Index (r = 0.65, p < 0.01). Hasegawa Dementia Scale Revised version (r = 0.93, p < 0.001) and Vitality Index (r = 0.66, p < 0.01). MCT could be a new tool to assess communication ability in elderly patients with or without dementia.

Objective: Short-term estrogen therapy improves endothelial function in postmenopausal women. However, there are few reports on its long-term effects on endothelial function and carotid intima-media thickness. Further, we determined whether a reduced dosage of estrogen may maintain its beneficial effects., Design: Eighteen postmenopausal women (53.7+/-1.1 years) who had been diagnosed as having osteoporosis were enrolled. Among them, 11 women were prescribed oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg per day, and 7 women were prescribed an oral calcium supplement as the control group. Each patient decided whether she would take hormone replacement therapy or a calcium supplement. We performed ultrasound measurement of endothelial function of the brachial artery and carotid intima-media thickness. Examinations were scheduled to be performed pre-therapy and after 3, 6, 12, 18, 24, and 36 months of therapy., Results: After three years of therapy, 6 women in the hormone replacement therapy group agreed to take half the dose of oral conjugated estrogen. Improvement of flow-mediated dilatation was observed at 3 months and the improvement was preserved up to 36 months. A similar improvement was also observed while women were on hormone replacement therapy even at the reduced dosage. Intima-media thickness of the common carotid artery in the control group increased after 12 months, which was not observed in the hormone replacement therapy group., Conclusions: Our results indicate that even at half the dose of estrogen, hormone replacement therapy may improve endothelial function and prevent the progression of carotid intima-media thickening in postmenopausal women.