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Hideji Tanaka

Publications and source records attributed to Hideji Tanaka.

18 recordsLinked to original sources
PubMed2006

Population pharmacokinetics of darbepoetin alfa in haemodialysis and peritoneal dialysis patients after intravenous administration.

AIMS: To characterize the pharmacokinetics of darbepoetin alfa and covariate relationships in haemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Data were collected from 131 (63 HD and 68 PD) patients who received darbepoetin alfa intravenously. A total of 917 serum concentrations were available. The data were analysed by nonlinear mixed effect modelling using NONMEM with a model including endogenous erythropoietin production. In addition, the final model was evaluated using bootstrap resampling. RESULTS: The selected basic model was a two-compartment model with a combination of additive and the constant coefficient of variation error models. The significant covariates were weight (WT) for clearance (CL) and the volume of central compartment (V(1)), and the dialysis technique (DIA) for V(1). The typical values of CL and V(1) were 0.0807 l h(-1) and 2.51 l, respectively. V(1) in PD patients was 17% higher than in HD patients. With the introduction of WT in CL and WT and DIA in V(1), interindividual variability decreased from 27.1% to 20.6% in CL and from 29.1% to 21.8% in V(1). The mean parameter estimates from the bootstrap datasets were similar to those from the original dataset. Evaluation by bootstrapping showed that the final model was stable. CONCLUSIONS: The results of the present analysis suggest no dosage regimen change is warranted for darbepoetin alfa in HD and PD patients over the range of distribution of covariates included in this study.

Adult↗
PubMed2006

Swim speeds and stroke patterns in wing-propelled divers: a comparison among alcids and a penguin.

In diving birds, the volume and resulting buoyancy of air spaces changes with dive depth, and hydrodynamic drag varies with swim speed. These factors are important in the dive patterns and locomotion of alcids that use their wings both for aerial flight and underwater swimming and of penguins that use their wings only for swimming. Using small data-loggers on free-ranging birds diving to 20-30 m depth, we measured depth at 1 Hz and surge and heave accelerations at 32-64 Hz of four species of alcids (0.6-1.0 kg mass) and the smallest penguin species (1.2 kg). Low- and high-frequency components of the fluctuation of acceleration yielded estimates of body angles and stroke frequencies, respectively. Swim speed was estimated from body angle and rate of depth change. Brünnich's (Uria lomvia) and common (Uria aalge) guillemots descended almost vertically, whereas descent of razorbills (Alca torda), rhinoceros auklets (Cerorhinca monocerata) and little penguins (Eudyptula minor) was more oblique. For all species, swim speed during descent was within a relatively narrow range. Above depths of 20-30 m, where they were all positively buoyant, all species ascended without wing stroking. During descent, little penguins made forward accelerations on both the upstroke and downstroke regardless of dive depth. By contrast, descending alcids produced forward accelerations on both upstroke and downstroke at depths of <10 m but mainly on the downstroke at greater depths; this change seemed to correspond to the decrease of buoyancy with increasing depth. The magnitude of surge (forward) acceleration during downstrokes was smaller, and that during upstrokes greater, in little penguins than in alcids. This pattern presumably reflected the proportionally greater mass of upstroke muscles in penguins compared with alcids and may allow little penguins to swim at less variable instantaneous speeds.

Animals↗
PubMed2005

Determination of lipophilicity by reversed-phase high-performance liquid chromatography. Influence of 1-octanol in the mobile phase.

Lipophilicity was evaluated using a novel RP-HPLC stationary phase (Discovery-RP-Amide-C16) with and without 1-octanol added to the mobile phase. A set of 46 drugs and flavonoids characterized by a broad structural diversity and a wide log Poct range (-0.69 to 5.70) was selected for this study. This set consists of neutral solutes and solutes with acidic or ampholytic functionalities which were maintained neutral at pH 2.5 or 4. In our conditions, the addition of 1-octanol in the mobile phase proved a key factor to derive a lipophilicity index log k(w) highly correlated with log Poct for all investigated solutes. 1-Octanol improved the correlation between log Poct and log k(w) mainly by influencing the retention behavior of the solutes with log Poct values below +3. This study brings additional evidence that under proper experimental conditions of stationary and mobile phases, RP-HPLC is a very useful method to obtain log Poct values.

1-Octanol↗
PubMed2005

Left ventricular geometry and myocardial contractility in patients with essential hypertension evaluated by myocardial velocity profile.

BACKGROUND: Left ventricular (LV) systolic function in the hypertensive heart has been evaluated considering geometric differences. The maximal systolic myocardial velocity gradient (Gmax) obtained from myocardial velocity profile can evaluate regional myocardial contractility. The purpose of this study was to assess LV myocardial contractility in the hypertensive heart using Gmax regarding geometric differences. METHODS: The study included 93 patients with essential hypertension. Gmax was correlated with relative wall thickness and LV mass index. LV myocardial contractility was assessed by classifying patients into normal geometry, concentric remodeling (CR), eccentric hypertrophy, and concentric hypertrophy (CH). RESULTS: Gmax has shown significant negative relationship with LV end-diastolic dimension. LV end-diastolic dimension in CH and eccentric hypertrophy groups was significantly greater than that in normal geometry and CR groups (CH vs CR, 4.9 vs 4.2 cm, P < .001). LV mass index was significantly greater in CH and eccentric hypertrophy groups than in the other groups (CH vs CR, 196 vs 122 g/m2, P < .001). Although there was no difference in relative wall thickness between CH and CR groups, Gmax was significantly smaller in CH than in CR group (1.8 vs 2.8 s(-1), P < .05). CONCLUSIONS: In patients with essential hypertension, LV myocardial contractility worsened corresponding to increase in LV dimension with similar wall thickness. Gmax obtained from myocardial velocity profile detected depressed myocardial contractility in patients with increased LV dimension.

Female↗
PubMed2005

Application of a stepwise flow ratiometry without phase separation to the determination of the chloroform/water distribution coefficients of volatile diazines.

The chloroform/water distribution coefficients (K(D)) of sixteen diazine compounds were determined by a stepwise flow ratiometry. An aqueous solution of analyte was delivered and merged with chloroform. The flow rate ratio of both the phases was varied stepwise under a constant total (chloroform+aqueous) flow rate. The analyte was extracted to chloroform while both the phases, which were segmented by each other, were passing through an extraction coil. The segmented stream was then led to a UV/Vis detector directly without phase-separation. The absorbance of the chloroform and aqueous phases (A(o) and A(a), respectively) was each measured at the maximum absorption wavelength of the analyte. The plots of A(-1) against R(f), (AR(f))(-1) against R(f)(-1), and AR(f) against A gave straight lines, where A was A(o), A(a) or the sum of them (A(S)). The K(D) of the analyte was calculated from the slopes and intercepts of the plots. The log K(D) values obtained for the analytes (-0.5-1.4) were agreed well with the values measured by a shake-flask method. The present method is simple, rapid (5 min/determination) and applicable to the volatile compounds with reasonable precision (standard deviation of log K(D)<0.07).

Chemical Phenomena↗
PubMed2005

High-throughput photometric titrimetry based on a feedback-based and subsequent fixed triangular wave-controlled flow ratiometry.

The principle of flow ratiometry for high-throughput titration, which we recently proposed for potentiometric titration, was extended to photometric titration. The flow rate (FB) of a base solution containing an acid-base indicator was linearly varied in response to a control voltage (Vc) generated from a computer. With the total (acid + base) flow rate (FT) being kept constant, the base solution was merged with an acid solution, which was aspirated to the confluence point at a flow rate of FT - FB. Downstream, the relative transmittance of the mixed solution was measured at the maximum absorption wavelength of the base form of the indicator. Initially, a feedback-based control was applied, where the scan direction of Vc was reversed from upward to downward, and vice versa, whenever the transition of the indicator at the equivalence point (EP) was sensed. Next, the scan range of V. was further limited to the range just around EP by using fixed triangular waves. These processes avoided scanning in a range of no interest. Thus, an unprecedentedly high throughput rate (maximally 34 titrations per minute, corresponding to 1.76 s per titration) was realized with reasonable precision (RSD < 0.5%).

Algorithms↗
PubMed2004

Diagnosis of cardiac amyloidosis based on the myocardial velocity profile in the hypertrophied left ventricular wall.

The myocardial velocity profile (MVP), derived from color-coded tissue Doppler imaging (TDI), can identify transmural heterogeneity based on the physiology and pathology of the myocardium. This study sought to clarify whether the MVP can differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy. We recorded the MVP and determined its myocardial velocity gradient (MVG) in the ventricular septum and left ventricular posterior wall using color-coded TDI in 10 patients with cardiac amyloidosis, in 25 patients with hypertensive hypertrophied left ventricular wall, in 25 patients with asymmetric septal hypertrophy of hypertrophic cardiomyopathy, and in 20 clinically normal controls. End-diastolic ventricular septal thickness was similar among the cardiac amyloidosis, hypertension, and hypertrophic cardiomyopathy groups. Percent systolic thickening of the ventricular septum and left ventricular posterior wall calculated from M-mode left ventricular echocardiograms was lower in the cardiac amyloidosis group than in the hypertension, hypertrophic cardiomyopathy, or control group. Peak MVGs during systole and early diastole were lowest in the cardiac amyloidosis group, followed, in order, by the control, hypertension, and hypertrophic cardiomyopathy groups. The systolic and early diastolic MVPs in the ventricular septum and left ventricular posterior wall showed a characteristic serrated pattern in all patients with cardiac amyloidosis, but not in any other patient groups. In conclusion, MVPs in the ventricular septum and left ventricular posterior wall show a distinctive serrated pattern that may be related to amyloid deposition in the myocardium. Myocardial tissue characterization using color-coded TDI provides diagnostic information in patients with cardiac amyloidosis.

Adult↗
PubMed2004

Potential application of tissue Doppler imaging to assess regional left ventricular diastolic function in patients with hypertrophic cardiomyopathy: comparison with 123I-beta-methyl iodophenyl pentadecanoic acid myocardial scintigraphy.

BACKGROUND: Tissue Doppler imaging (TDI) has been utilized to evaluate left ventricular myocardial dysfunction in patients with hypertrophic cardiomyopathy (HCM); however, no clear explanation for the abnormality of TDI variables has been forthcoming. HYPOTHESIS: Peak negative myocardial velocity gradient (MVG) derived from TDI may correlate with a disorder of fatty acid metabolism in patients with HCM. METHODS: Tissue Doppler imaging and 123I-beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP) myocardial scintigraphy were performed in 15 patients with asymmetric septal hypertrophy (mean age 47 +/- 18 years) and in 12 healthy controls (mean age 43 +/- 10 years). RESULTS: In early 123I-BMIPP images, accumulation defects were observed in the ventricular septum in 12 patients and in the posterior wall in 8 patients with HCM. Peak negative MVG in the ventricular septum (1.1 +/- 0.5 vs. 2.8 +/- 0.5, p < 0.0001) and posterior wall (5.2 +/- 1.4 vs. 6.7 +/- 0.8, p < 0.01 ) was significantly lower in the HCM group than in the controls; also, these parameters were significantly lower in patients with than in those without a defect in the region in question. The peak negative MVG in the ventricular septum and posterior wall correlated inversely with the washout rate in all subjects. CONCLUSIONS: Peak negative MVG according to TDI is related to disorder of fatty acid metabolism in the regional left ventricular myocardium of patients with HCM.

Cardiomyopathy, Hypertrophic↗
PubMed2004

Analyses of the partition coefficient, log P, using ab initio MO parameter and accessible surface area of solute molecules.

To analyze the log P(sol/w) values (sol: n-octanol or chloroform, w: water) in the framework of the molecular orbital (MO) procedure, we selected solute descriptors such as the solvation energy difference between aqueous and organic solvent phases and the "surface" area of solute molecules to which water molecules are accessible. The solvation energy of solute molecules in their minimum free-energy conformation was calculated using the ab initio self-consistent reaction field-MO method with the conductor-like screening model. The experimentally measured log P(sol/w) value of various solutes except for those of amphiprotics was shown to be analyzable reasonably well by the MO model with additional descriptors for the hydrogen-bonding patterns in the solute-solvent interactions.

1-Octanol↗
PubMed2004

Losartan improves regional left ventricular systolic and diastolic function in patients with hypertension: accurate evaluation using a newly developed color-coded tissue doppler imaging technique.

BACKGROUND: Angiotensin II receptor antagonists have recently been accepted as antihypertensive therapy. Tissue Doppler imaging (TDI) has been developed as a noninvasive tool to assess quantitatively regional myocardial motion abnormalities. This study was designed to determine whether our newly developed technique of color-coded TDI may be a useful means of quantifying the improvement in regional left ventricular (LV) myocardial contractility and relaxation after treatment with losartan in patients with hypertension. METHODS AND RESULTS: Losartan (50 to 100 mg) was administered for 6 months to 37 previously untreated patients with essential hypertension. Averaged myocardial velocity profiles (MVPs) for color-coded TDI were recorded in the ventricular septum and LV posterior wall before and after treatment. Peak myocardial velocities and peak myocardial velocity gradients (MVGs) in the LV walls were determined during systole and early diastole. The plasma concentration of transforming growth factor (TGF)-beta1 also was measured in all patients. Blood pressure and plasma TGF-beta1 level decreased after initiation of losartan therapy. The LV mass index and LV meridional end-systolic wall stress also decreased after treatment with losartan. LV geometry changed from a pattern consistent with concentric hypertrophy to normal geometry in 10 patients and to a pattern consistent with concentric remodeling in 5 patients, and from concentric remodeling to normal geometry in 5 patients after treatment with losartan. The ratio of early to late diastolic filling for the transmitral flow velocity increased after losartan treatment. The peak systolic and early diastolic myocardial velocities and MVGs in the ventricular septum and LV posterior wall increased after treatment with losartan, although the values 6 months after treatment with losartan were still lower than those in normal individuals. There were good correlations between changes in plasma TGF-beta1 level and changes in systolic and early diastolic MVGs 6 months after losartan. However, there were no significant correlations between changes in the systolic blood pressure and LV end-systolic wall stress and changes in the TDI parameters. CONCLUSION: Losartan improves regional LV function in patients with hypertension. Our newly developed averaged MVP and MVG measurements may be useful for accurately evaluating regional LV myocardial contractility and relaxation in these patients.

Aged↗
PubMed2004

A comparison of the bioequivalence of two formulations of epoetin alfa after subcutaneous injection.

BACKGROUND: The previous formulation of epoetin alfa in Japan was a citrate-buffered protein solution containing gelatin hydrolysate as the protein protective agent. To eliminate pain at injection sites, and the risks of anaphylactic shock and unknown infections by gelatin we have developed a new formulation of phosphate-buffered epoetin alfa, which does not contain gelatin hydrolysate. AIM: To compare the bioequivalence of two formulations of epoetin alfa administered by the subcutaneous route. METHODS: Four separate studies were performed to assess the bioequivalence of two epoetin alfa formulations using different strength and doses, i.e. 750 IU per 0.5 ml x 0.5 ml (= 750 IU per subject), 750 IU per 0.5 ml x 4 ml (= 6000 IU per subject), 6000 IU per 0.5 ml x 0.5 ml (= 6000 IU per subject) and 24,000 IU per 0.5 ml x 0.125 ml (= 6000 IU per subject). Each study was a single-centre, open-label, randomized, two-treatment, two-period, crossover study for which healthy volunteers were enrolled. Bioequivalence was assessed using the confidence interval (CI) of the ratios for the log-transformed, baseline-corrected Cmax and AUC(0,t). Baseline-corrected AUC(0,t) was calculated using the following equation: AUC(0,t) = AUC(0,t), uncorrected -- predose level x observation period. RESULTS: The ratios (gelatin-free/gelatin-containing) for the log-transformed Cmax and AUC(0,t) after 6000 IU per subject injection of three different concentrations of epoetin alfa were well within the usual range for bioequivalence (90% CI 0.8, 1.25). The 90% CI of the ratio for Cmax after 750 IU per subject injection was 0.906, 1.24, which was within the bioequivalence range. However, the ratio for AUC(0,t) was not determined in this lowest dose because of negative AUC(0,t) values obtained in 12/60 cases. The overall safety data were consistent with those expected for a healthy study population, and did not present any concerns suggestive of adverse effects due to either formulation. CONCLUSIONS: The point estimates and 90% CIs of the ratios of Cmax and AUC(0,t) for the gelatin-free/gelatin-containing formulations indicated that the two formulations are bioequivalent.

Adult↗
PubMed2004

Pharmacokinetics of pegylated recombinant human megakaryocyte growth and development factor in healthy volunteers and patients with hematological disorders.

OBJECTIVES: The purpose of this study is to examine the pharmacokinetics of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in healthy volunteers with normal hematopoiesis and patients with idiopathic thrombocytopenic purpura (ITP), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and aplastic anemia (AA). METHODS: PEG-rHuMGDF was intravenously administered to healthy volunteers and patients with ITP, AML, MDS, and AA. The serum concentration of PEG-rHuMGDF was measured and the pharmacokinetics was investigated using non-linear mixed-effects modeling technique. RESULTS: The systemic clearance (CL) and volume of distribution at steady-state (Vss) consistently decreased in the healthy subjects, when the dose increased. In AML patients, CL and Vss decreased when the dose increased, but the change of CL was not statistically significant. In contrast, no significant dose dependency of these parameter estimates was observed in MDS patients. In AA patients there was no significant change in Vss but the CL of the higher dose groups was slightly smaller than that of the lower dose groups. Relatively smaller CL and Vss in ITP patients than those of healthy volunteers at the same dose were observed. CONCLUSIONS: This saturable pathway of CL may involve the receptor-mediated endocytosis and degradation by megakaryocyte lineage cells and platelets. The saturable distribution space can be also explained by the receptors on hematopoietic cells. The non-saturable distribution space corresponds to the value of plasma and interstitial fluid volume.

Case-Control Studies↗
PubMed2004

Determination of acid/base dissociation constants based on a rapid detection of the half equivalence point by feedback-based flow ratiometry.

Acid dissociation constants (Ka) were determined through the rapid detection of the half equivalence point (EP1/2) based on a feedback-based flow ratiometry. A titrand, delivered at a constant flow rate, was merged with a titrant, whose flow rate was varied in response to a control voltage (Vc) from a controller. Downstream, the pH of the mixed solution was monitored. Initially, Vc was increased linearly. At the instance that the detector sensed EP1/2, the ramp direction of Vc changed downward. When EP1/2 was sensed again, Vc was increased again. This series of process was repeated automatically. The pH at EP1/2 was regarded as being pKa of the analyte after an activity correction. Satisfactory results were obtained for different acids in various matrices with good precision (RSD approximately 3%) at a throughput rate of 56 s/determination.

Journal Article↗
PubMed2003

Prognostic value of the atrial systolic mitral annular motion velocity in patients with left ventricular systolic dysfunction.

BACKGROUND: Transmitral flow velocity variables are powerful predictors of poor prognosis in patients with left ventricular (LV) systolic dysfunction. However, these variables may not accurately reflect the severity of pulmonary congestion. This study was designed to determine whether the peak atrial systolic mitral annular motion velocity (MA-Aw) measured by pulsed Doppler tissue imaging can predict cardiac death or hospitalization for worsening heart failure in patients with LV systolic dysfunction. METHODS: MA-Aw was recorded in 96 patients with LV systolic dysfunction who were followed up for 29 +/- 10 months. All patients underwent Doppler echocardiography on entry into the study, and cardiac catheterization was performed in 45 patients. Patients were divided into 3 groups on the basis of the ratio of early (E) to late (A) diastolic filling (E/A) of the transmitral flow velocity: group 1 (n=31; E/A < 1); group 2 (n=37; 1 < or = E/A < 2); and group 3 (n=28; E/A > or = 2). RESULTS: During follow-up, 36 patients (38%) died of cardiac causes and 34 (35%) were hospitalized for worsening heart failure. There were 2 cardiac deaths (6%) in group 1, 14 (39%) in group 2, and 20 (56%) in group 3. The MA-Aw correlated closely with the mean pulmonary capillary wedge pressure. Univariate Cox model analysis showed that MA-Aw < or = 5 cm/s was the most powerful predictor of cardiac death or hospitalization for worsening heart failure compared with clinical, hemodynamic, and the other echocardiographic variables. Furthermore, MA-Aw < or = 5 cm/s was clearly discernible as a good predictor of cardiac mortality on multivariate Cox model and as assessed by Kaplan-Meier method. CONCLUSION: The MA-Aw obtained by pulsed Doppler tissue imaging is a sensitive index of pulmonary congestion in patients with LV systolic dysfunction. It is a simple and noninvasive outcome measure and can be used to monitor treatment.

Blood Flow Velocity↗
PubMed2003

Novel approach to the quantitation of regional left ventricular systolic and diastolic function using tissue Doppler imaging to create a myocardial velocity profile and gradient.

The myocardial velocity profile (MVP) and gradient (MVG) between the endocardium and epicardium of the left ventricular (LV) wall measured by color-coded tissue Doppler imaging (TDI) are new indices for evaluating regional LV myocardial function. However, accurate recording and measurement of the MVP is difficult using conventional methodology because of the stochastic nature of the ultrasound signal; that is, the effect of speckled noise. The aim of this study was to validate the accuracy and establish the validity of a newly developed method for measuring the MVP and MVG using 10 clinically normal controls and 10 patients with a hypertensive hypertrophied LV posterior wall. A non-isotropic, averaging algorithm was developed that was capable of obtaining a stable MVP (averaged MVP). Averaged MVP was recorded using parasternal, LV short-axis, color-coded TDI, placing regions of interest along the LV posterior wall with the reference point for angle-correction being at the center of LV contraction. The velocity from epicardium to endocardium within the region of interest was automatically angle-corrected to calculate the velocity component radially relative to the LV cavity and was spatially averaged along the circumference within the region of interest. Inter- and intraobserber variabilities of measurements were lower in the averaged MVP and MVG than in the conventional MVP and MVG. The correlation coefficients of the linear regression lines of systolic and early diastolic MVPs in the LV posterior wall were higher in all controls and hypertensive patients with the averaged method than with the conventional TDI procedures. The mean peak systolic and early diastolic MVGs were lower in the hypertensive group than in the controls. In conclusion, the newly developed averaged MVP provides a stable and reproducible index for the quantitative assessment of regional LV myocardial function.

Adult↗
PubMed2002

Population pharmacokinetics of the novel anticancer agent KRN7000.

PURPOSE: KRN7000 is a novel anticancer agent, acting through stimulation of the immune system. The first clinical trial with this agent, which included pharmacokinetic studies, has recently been completed. The aim of the study presented here was to develop a population pharmacokinetic model for KRN7000. METHODS: Plasma concentration-time data were gathered from 24 patients enrolled in a phase I trial in which KRN7000 was administered as a weekly slow injection at doses ranging from 50 to 4800 microg/m(2). These data were used to build a pharmacokinetic model using the nonlinear mixed-effect modeling (NONMEM) program. The model was validated by performance of 200 bootstraps. RESULTS: A three-compartment model with interindividual variability on the central and two peripheral volumes of distribution (V1, V2 and V3) and on clearance (CL) adequately described the data. The final estimates were: V1 2.34 l, V2 2.61 l, V3 2.13 l, and CL 0.130 l/h. Of 24 covariates tested, including both demographic and pathophysiological factors, none showed a significant relationship with the pharmacokinetic parameters obtained. The bootstrap analysis provided parameter estimates within approximately 15% of the original estimates, indicating stability of the model. CONCLUSION: The pharmacokinetic behavior of KRN7000 in the clinical trial could be described by a three-compartment model. Hence, KRN7000 demonstrates linear pharmacokinetics over the investigated dose range. The pharmacokinetics of KRN7000 are not influenced by patient demographic or pathophysiological characteristics.

Adult↗
PubMed2002

Prediction of the 1-octanol/H2O partition coefficient, log P, by ab initio MO calculations: hydrogen-bonding effect of organic solutes on log P.

To predict the 1-octanol/H2O partition coefficient, log P, based on molecular structures, we calculated the solvent accessible surface area and the solvation energy difference of 166 organic molecules between 1-octanol and water environments with the ab initio molecular orbital self-consistent reaction field method, and then analyzed the relationships among the measured log P values with these two structural quantities by multiple linear-regression analyses. Physicochemically meaningful correlations were obtained, suggesting that non-hydrogen bonding and hydrogen-acceptor molecules behave similarly to each other in partitioning, but that hydrogen-donor molecules behave differently from the former molecules. The results provide a new computational approach for predicting log P.

Journal Article↗