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Biomedical subjects

T Ohkubo

Publications and source records attributed to T Ohkubo.

At least 145 records · Page 8Linked to original sources
PubMed1997

Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study.

To investigate the relation between nocturnal decline in blood pressure and mortality, we obtained ambulatory blood pressures in 1542 residents aged 40 years or over of a rural Japanese community. Subjects were followed-up for a mean of 5.1 years and were then subdivided into four groups according to the percent decline in nocturnal blood pressure: 1) extreme dippers: percent decline in nocturnal blood pressure > or = 20% of the daytime blood pressure; 2) dippers: decline of > or = 10% but < 20%; 3) nondippers: decline of > or = 0% but < 10%; and 4) inverted dippers: no decline. The relationship between the decline in nocturnal blood pressure and mortality was examined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, previous history of cardiovascular disease, and the use of antihypertensive medication. The mortality risk was highest in inverted dippers, followed by nondippers. There was no difference in mortality between extreme dippers and dippers. This relationship was observed for both treated and untreated subjects, was more pronounced for cardiovascular than for noncardiovascular mortality, and did not change after the data were adjusted for 24-h, daytime, and nighttime blood pressure levels.

Aged↗
PubMed1997

Factors that affect blood pressure variability. A community-based study in Ohasama, Japan.

Factors that affect blood pressure (BP) variability, ie, standard deviation (SD) and variation coefficient (VC: SD/average ambulatory BP) of ambulatory BP, were examined in a community-based sample in northeastern Japan. Screening and ambulatory BPs were measured in 823 subjects > or = 20 years of age, and the effects of age and BP on the SD and the VC were examined. In bivariate regression analysis, the SD of ambulatory BP was positively correlated with age and the ambulatory BP. The VC was also correlated with age. Both the SD and the VC were strongly correlated with the magnitude of the nocturnal decline in BP. Ambulatory BP was positively correlated with age and negatively correlated with heart rate and the SD of heart rate. Multivariate analysis demonstrated that the nocturnal decline in BP showed the strongest association with the SD and the VC of 24-h BP. However, age and BP were still independently and positively associated with the SD and the VC of ambulatory BP. Furthermore, pulse pressure and BMI were independently and positively associated with the SD and the VC of ambulatory BP. Since the SD and the VC of 24-h ambulatory BP were determined mainly by the nocturnal decline in BP, this variable appears to be an index of the circadian variation in BP and not an index of short-term BP variability. Pulse pressure, an index of arterial stiffness, was a relatively strong predictor of the SD and the VC of BP. In addition, the SD of heart rate, an index of baroreflex function, decreased with increasing age. Findings suggest that the increase in BP variability in hypertensive and elderly subjects may be explained, in part, by a disturbance of baroreflex function associated with an increase in arterial stiffness due to aging and hypertension.

Adult↗
PubMed1997

Solution structure of an extracellular domain containing the WSxWS motif of the granulocyte colony-stimulating factor receptor and its interaction with ligand.

We have determined the NMR structure of a ligand-binding domain of the granulocyte colony-stimulating factor (G-CSF) receptor, containing the highly conserved WSxWS motif. The domain consists of seven beta-strands with the fibronectin type III-like topology seen in several cytokine receptors. Comparisons between the spectra of the 15N-labelled domain with and without G-CSF indicate that the major ligand-recognition site is on the FG loop just upstream of the WSxWS sequence, and not on the BC loop which is mainly used in the growth hormone system. The WSxWS residues are suggested to contribute to ligand-recognition and to the protein architecture of the G-CSF receptor.

Amino Acid Sequence↗
PubMed1997

Relationship between single oral dose pharmacokinetics of alprazolam and triazolam.

The relationship between the single oral dose pharmacokinetics of alprazolam and triazolam was studied in 10 healthy male volunteers. Each subject took single oral doses of alprazolam 0.8 mg and triazolam 0.5 mg with at least a 2 week interval between each dose. Blood samplings were performed up to 48 h after alprazolam dosing and up to 12 h after triazolam dosing. Plasma concentrations of both drugs were measured by high-performance liquid chromatography. The means +/- standard deviation of the peak plasma concentration, the total area under the plasma concentration-time curve and the elimination half-life of alprazolam were 11.3 +/- 3.1 ng/ml, 232.4 +/- 59.2 ng/h/ml and 16.5 +/- 4.6 h, respectively, and those of triazolam were 3.2 +/- 1.0 ng/ml, 11.8 +/- 5.2 ng/h/ml and 2.5 +/- 1.1 h, respectively. There was no significant correlation between the two drugs in any pharmacokinetic parameters (r = 0.35, 0.25 and 0.50). The present study thus suggests that the single oral dose pharmacokinetics of alprazolam and triazolam do not correlate well in individuals.

Adult↗
PubMed1997

Carbamazepine toxicity induced by clarithromycin coadministration in psychiatric patients.

Seven psychiatric inpatients receiving carbamazepine 600 mg/day were coadministered clarithromycin 400 mg/day for 5 days to treat atypical pneumonia. Blood samples were taken after clarithromycin coadministration and at 1 and 4 weeks after its discontinuation. Plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide were measured using high-performance liquid chromatography. During clarithromycin coadministration, four out of the seven patients developed moderate-to-severe toxic symptoms of carbamazepine, such as drowsiness, dizziness, and ataxia, which resolved within 5 days after clarithromycin discontinuation. In these four patients, plasma carbamazepine concentrations after clarithromycin coadministration were approximately twice as high as those after its discontinuation. In the seven patients, the mean plasma concentration of carbamazepine, but not of carbamazepine-10,11-epoxide, after clarithromycin coadministration was significantly (p < 0.01) higher than those at 1 and 4 weeks after its discontinuation. The present report suggests that clarithromycin coadministration induces increased plasma carbamazepine concentrations, which may result in carbamazepine toxicity. Therefore, care should be given to prescribing clarithromycin for patients receiving carbamazepine.

Aged↗
PubMed1997

Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama.

OBJECTIVE: To compare the prediction of mortality by ambulatory blood pressure monitoring and screening blood pressure measurements in a general population. DESIGN: A prospective cohort study. PATIENTS AND METHODS: We obtained blood pressure data for 1542 subjects (565 men and 977 women) aged > or = 40 years who were followed up for up to 8.1 years (mean 5.1 years). Subjects were subdivided into five groups according to their ambulatory and screening blood pressure levels. The prognostic significance of blood pressure for mortality was examined by the Cox proportional hazards regression model. RESULTS: The association between blood pressure level and mortality was more distinctive for the ambulatory blood pressure than it was for the screening blood pressure. The risk of cardiovascular mortality increased significantly for the highest quintiles of 24 h ambulatory blood pressure, whereas there was no significant association between the screening blood pressure and the cardiovascular mortality. When both 24 h and screening blood pressure values were included in the Cox model, only the systolic ambulatory blood pressure was related significantly to the increased risk of cardiovascular mortality. CONCLUSIONS: The ambulatory blood pressure had a stronger predictive power for mortality than did the screening blood pressure. This appears to have been the first study of the prognostic significance of ambulatory blood pressure monitoring versus screening blood pressure measurements in a general population.

Adult↗
PubMed1997

Factors affecting the nocturnal decrease in blood pressure: a community-based study in Ohasama.

OBJECTIVE: To investigate factors affecting the nocturnal decrease in blood pressure. DESIGN: A cross-sectional study of 823 community-based untreated subjects aged > 20 years. Screening and ambulatory blood pressures were measured and the effects of age and the ambulatory blood pressure on the nocturnal decrease were examined. RESULTS: The magnitude of the decrease and the percentage decrease in the nocturnal blood pressure increased with increasing daytime ambulatory blood pressure and decreased with increasing night-time ambulatory blood pressure. Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels in hypertensives were still higher than those in normotensive subjects. The magnitude decreased with increasing age for men but not for women, whereas the percentage decrease decreased with increasing age both for men and for women. The SD of the 24 h blood pressure correlated strongly to the magnitude of the nocturnal decrease (systolic blood pressure r = 0.62, P < 0.0001; diastolic blood pressure r = 0.52, P < 0.0001), suggesting that the SD of the 24 h blood pressure is representative of the nocturnal decrease. A minimal nocturnal decrease was observed frequently in elderly normotensive men but infrequently in hypertensive individuals from the general population. A marked nocturnal decrease was observed frequently in hypertensive women aged > 70 years. CONCLUSION: Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels increased with increasing daytime ambulatory blood pressure. Therefore, the blood pressure in hypertensive subjects should essentially be lowered throughout the 24 h period. A marked nocturnal decrease in blood pressure in some elderly hypertensive women was observed without treatment. The nocturnal blood pressure levels of such subjects should be considered during treatment.

Adult↗
PubMed1997

Increases in plasma concentration of m-chlorophenylpiperazine, but not trazodone, with low-dose haloperidol.

Our previous study suggested that cytochrome P4502D6 (CYP2D6) is involved in the metabolism of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP). The purpose of this study was to examine the degrees of increase in plasma concentrations of trazodone and m-CPP induced by haloperidol, which is an inhibitor of CYP2D6. The subjects were nine depressed inpatients receiving trazodone at bedtime (150 mg in seven patients and 300 mg in two) for 2-19 weeks. Haloperidol at 4 mg/day was coadministered for 1 week, and blood samplings were taken before and after the coadministration. Contrary to our expectation, haloperidol did not significantly increase the mean plasma trazodone concentration (810 +/- 382 vs. 856 +/- 357 ng/ml). However, haloperidol significantly increased (p < 0.01) the mean plasma m-CPP concentration (78 +/- 31 vs. 92 +/- 34 ng/ml).

Adult↗
PubMed1997

Single-dose pharmacokinetics and pharmacodynamics of oral triazolam in relation to cytochrome P4502C19 (CYP2C19) activity.

Previous studies have suggested that triazolam is at least partly metabolized by cytochrome P4503A4 (CYP3A4). However, no study has examined the relationship between the metabolism of triazolam and CYP2C19, which is involved in the metabolism of diazepam. Therefore, the single-dose pharmacokinetics and pharmacodynamics of oral triazolam were studied in relation to the CYP2C19 status assessed by the S-mephenytoin 4-hydroxylation capacity in 12 healthy male volunteers, consisting of seven extensive metabolizers (EMs) and five poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Each subject was administered a single oral dose of 0.5 mg of triazolam, and blood was sampled up to 12 hours after the dosing. Psychomotor function was assessed by the Digit-Symbol Substitution test, Visual Analogue Scale, and Udvalg for Kliniske Undersøgelser (UKU) scale. Plasma triazolam concentrations were measured by high-performance liquid chromatography. There were no significant differences in plasma concentrations from 20 minutes to 6 hours after the dosing nor in pharmacokinetic parameters of triazolam between the EM and PM groups. No significant difference was found in psychomotor function between the EM and PM groups. These results suggest that CYP2C19 is not involved in the metabolism of triazolam and that CYP2C19 status is not a pharmacodynamic determinant of this triazolobenzodiazepine.

Adjuvants, Anesthesia↗
PubMed1997

The selective capsaicin antagonist capsazepine abolishes the antinociceptive action of eugenol and guaiacol.

The dental phenolic medicaments, eugenol and guaiacol, are partly similar in chemical structure to capsaicin, the pungent constituent of chili peppers, which selectively activates sensory neurons via a specific receptor. We have previously demonstrated that these phenolic compounds show capsaicin-like action. In the present study, an attempt was made to investigate the possibility that these compounds interact with the same cellular site as capsaicin, by using capsazepine, a selective and competitive anta-gonist of capsaicin. Intrathecal (i.t.) treatment with eugenol (12.5 to 50 micrograms), guaiacol (25 to 150 micrograms), or capsaicin (1 to 4 micrograms) for 24 h dose-dependently inhibited the formalin-induced nociceptive response. Capsazepine (5, 10 micrograms, i.t.) shifted these dose-response curves in parallel to the right. Similarly, capsazepine abolished antinociceptive effects of eugenol (50 micrograms), guaiacol (150 micrograms), or capsaicin (2 micrograms) in the acetic acid writhing test. These results suggest that eugenol and guaiacol may exert their antinociceptive effects via the capsaicin receptor located on sensory terminals in the spinal cord.

Analgesics, Non-Narcotic↗
PubMed1997

Eugenol activates Ca(2+)-permeable currents in rat dorsal root ganglion cells.

Although little is known about the mechanism of action of eugenol, some related compounds have been compared with capsaicin derivatives in terms of the relationship between their chemical structure and activity. To elucidate whether eugenol and capsaicin act via a common mechanism at the neuronal membrane, we investigated the effects of eugenol on rat DRG neurons using the whole-cell patch-clamp technique. Eugenol (0.125-1 mmol/L) produced an inward current in a concentration-dependent manner. The reversal potential for this inward current was around 0 mV in PSS. In Na(+)-deficient solutions, the amplitude of the inward current was slightly reduced at negative holding potentials, whereas in Ca(2+)-free solution, it was markedly reduced at all holding potentials tested. The reversal potential was not changed by superfusion with either solution. Niflumic acid (100 mumol/L) produced a significant inhibition of the current without a change in the reversal potential. These results suggest that eugenol activates a Ca(2+)-permeable channel as well as a Cl- channel. The latter channel may have been activated by the increase in intracellular Ca2+ concentration caused by the activation of the Ca(2+)-permeable channel. Capsazepine (10 mumol/L) partially inhibited the eugenol-induced current and completely inhibited the capsaicin-induced current. Eugenol (1 mmol/L) produced an inward current even after occurrence of desensitization of the capsaicin-induced current had occurred. Our results suggest that eugenol activates a Ca(2+)-permeable ion channel in rat DRG neurons through two different mechanisms: a capsaicin receptor-mediated pathway and a pathway independent of the capsaicin-receptor.

Animals↗
PubMed1997

Predictive value of home blood pressure measurement in relation to stroke morbidity: a population-based pilot study in Ohasama, Japan.

We investigated the utility of home blood pressure measurements for determining the risk of stroke. We also analyzed the relationship between home blood pressure and the incidence of stroke. Home blood pressure and screening blood pressure measurements were obtained from 1,789 residents (aged 40 yr or older) of a rural Japanese community. Blood pressure was measured at home with a semiautomatic device. A mean (+/-SD) of 23.0 +/- 7.5 measurements were made for each subject. Subjects without a history of stroke and who were not receiving medication for hypertension (n = 1,256) were prospectively followed up for 4.4 +/- 2.1 yr. Subjects were subdivided into quintiles according to their baseline blood pressure. The association between the baseline blood pressure and the incidence of the first-ever stroke was examined with the Cox proportional hazards regression model, adjusted for age and sex. The lowest risk of stroke morbidity occurred in the subjects in the third quintile for home systolic blood pressure (117-123 mmHg) and in those in the second quintile for home diastolic blood pressure (66-70 mmHg). The subjects in the fifth quintiles for home systolic (> or = 133 mmHg) and diastolic blood pressure (> or = 81 mmHg) had a significantly increased risk of stroke morbidity. The subjects in the first and the second quintiles for home systolic blood pressure and those in the first quintile for home diastolic blood pressure tended to have an increased risk as compared with subjects in the lowest risk groups, although this increase was not statistically significant, indicating two possibilities: a trend toward a J-shaped relationship or no-decrease in risk of the first-ever stroke in subjects with home blood pressure level less than 123/70 mmHg. This relationship was not observed for screening blood pressure. We conclude that home blood pressure measurements can provide additional prognostic information to that obtained from blood pressure measurement in a medical environment.

Adult↗
PubMed1997

Determinants of circadian blood pressure variation: a community-based study in Ohasama.

We investigated factors affecting the nocturnal decline in blood pressure (BP). A cross sectional study was done in 706 community-based untreated subjects > or = 20 years of age. Screening and ambulatory BPs were measured and the effects of age and the ambulatory BP on the nocturnal decline were examined. Bivariate analysis demonstrated that the magnitude of the decline and the percent decline in the nocturnal BP increased with increase in daytime ambulatory BP and decreased with increase in nighttime ambulatory BP. Although the magnitude of the nocturnal decline in BP increased with increasing daytime BP, the nocturnal BP in hypertensives was still higher than those in normotensives. The magnitude decreased with increasing age in men but not in women, while the percent decline decreased with increasing age in both men and women. Since bivariate analysis demonstrated that the daytime BP, nighttime BP, and standard deviation of the 24-hour BP strongly correlated with the magnitude of the nocturnal decline, these parameters were excluded as independent variables from the multivariate analysis. In the multivariate analysis the nighttime pulse pressure was negatively and daytime pulse pressure was positively associated with the magnitude of the decline and the percent decline in the nocturnal BP. A non-dipping circadian variation was frequently observed in elderly normotensive men but the rate of nondipper was rather low in hypertensive individuals in the general population. A marked dipping pattern was frequently observed in hypertensive women > or = 70 years of age. The nocturnal BP levels in subjects with daytime hypertension are higher than those in subjects with daytime normotension. Therefore, BP must ideally be lowered over 24-hour period in hypertensive subjects. The diminished magnitude of the decline and the decrease in the percent decline in the nocturnal BP in the elderly may be mediated by the disturbed baroreflex function due to the decrease in compliance of large elastic artery. However, in some elderly hypertensive women, excess nocturnal decline in BP is observed. In such subjects, we should take care of the nocturnal BP levels during treatment.

Adult↗
PubMed1997

Vegetative and psychological symptoms associated with depressed mood over the first two years after stroke.

INTRODUCTION: In patients with acute physical illness, symptoms used in the diagnosis of major depression such as sleep or appetite disturbance may be nonspecific for depression. This study was undertaken to examine the association of depressed mood with other depressive symptoms to determine which symptoms were most useful in the accurate diagnosis of major depression after stroke. METHODS: Using a structured mental status examination, 142 patients with acute stroke were followed at three, six, twelve, and twenty-four months. RESULTS: The median number of vegetative and psychological symptoms among patients with depressed mood was more than three times the respective rates among nondepressed patients at all time points over two years. Autonomic anxiety, morning depression, subjective anergia, worrying, brooding, loss of interest, hopelessness, and lack of self-confidence were significantly more frequent among depressed patients than nondepressed patients throughout the entire two-year period. Some symptoms such as anxious foreboding and loss of libido, as well as self-depreciation, feelings of guilt, and irritability were no longer significantly more common among depressed compared with nondepressed patients after six months. Standard DSM-IV diagnostic criteria and modified DSM-IV diagnostic criteria which included only specific symptoms of depression (i.e., symptoms which were significantly more frequent among depressed than nondepressed mood patients) yielded similar frequencies of major depression diagnosis. There were only a few patients (i.e., 2% to 3%) with depressive symptoms without a depressed mood (perhaps "masked" depression). CONCLUSIONS: Vegetative and psychological depressive symptoms are significantly more common in depressed patients over the first two years after stroke and DSM-IV criteria do not overdiagnose major depression even in this population with chronic physical illness. The symptoms which characterize major depression appear to change between the subacute and chronic post-stroke periods.

Adult↗
PubMed1997

The epidemiology of ambulatory blood pressure monitoring in Japan.

Ambulatory blood pressure monitoring is now being used widely in Japan. Several Japanese studies have value demonstrated that the ambulatory blood pressure is superior to the casual blood pressure in prediction of target organ damage. Ambulatory blood pressure monitoring has also been reported to be more cost effective than are casual blood pressure measurements. Nonetheless, no agreement has been reached regarding its use in clinical settings. This problem has arisen partly because no reference for ambulatory blood pressure value has been established. We reviewed several cross-sectional studies and one prospective study performed in Japan and propose tentatively a reference ambulatory blood pressure value for Japanese: 135/80 mmHg. Further prospective studies are needed in order to confirm this value in different community settings and with different prognostic parameters.

Journal Article↗
PubMed1997

Proposal of reference values for home blood pressure measurement: prognostic criteria based on a prospective observation of the general population in Ohasama, Japan.

The purpose of this study was to propose reference values, from a viewpoint of prognostic significance, for blood pressure (BP) measured at home with a semiautomated device (home BP measurement) to differentiate normotension and hypertension. We obtained home BP measurements for 1,913 population-based subjects aged 40 years and over in a rural Japanese community and followed up their survival for a mean duration of 5.0 years. There were 141 deaths during the follow-up period. The association between baseline BP values and the overall mortality was examined by Cox proportional hazards regression model, adjusted for age, gender, and the use of antihypertensive medication. The results indicated that the predictive power of home BP level for subsequent mortality was stronger than that of casual screening BP. There was a linear association between home systolic BP and mortality. The association between home diastolic BP and mortality was nonlinear and well approximated with the secondary degree equation of diastolic BP values. Based on this relation, we propose that the reference value for hypertension is 137/84 mm Hg, and normotension is below 137 mm Hg for home systolic BP and between 66 and 83 mm Hg for home diastolic BP. Home diastolic BP below 66 mm Hg should be considered as low diastolic blood pressure. In this population, home systolic BP of 137 mm Hg and home diastolic BP of 84 mm Hg corresponded to the 80th and 87th percentiles, respectively. Then, 29% of the subjects were classified as having hypertension, 52% as normotension, and 19% as low diastolic blood pressure. All previous studies proposing reference values for home BP measurement, derived from cross-sectional observations, were based on the statistical distribution of home BP values. The reference value must, however, be the one that best predicts the risk for morbidity and mortality from hypertension-related complications. This is the first report proposing reference values for home BP measurement based on prognostic criteria.

Adult↗
PubMed1997

[Two cases of adenosquamous cell carcinoma of advanced cervical cancer treated by carboplatin-based chemotherapy with peripheral blood stem cell autotransplant].

In two cases with adenosquamous cell carcinoma of advanced cervical cancer, carboplatin-based chemotherapy was given intraarterially from the internal iliac artery as neoadjuvant chemotherapy, and peripheral blood stem cells (PBSCs) were harvested. After the operation, conventional intravenous chemotherapy with PBSC autotransplant was performed. PBSCs were mobilized by neoadjuvant chemotherapy and G-CSF administration. By the apheresis procedures, 0.7-2.6 x 10(6)/kg CD34 positive cells were obtained. They had no severe side effects from intravenous chemotherapy with PBSCT, and they were free of disease 20 months. Neoadjuvant chemotherapy and G-CSF administration may be capable of mobilization of PBSCs, and chemotherapy with PBSCT may be useful in radioresistant advanced adenosquamous carcinoma of the cervical cancer.

Adult↗