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Biomedical subjects

H Fukuzaki

Publications and source records attributed to H Fukuzaki.

At least 37 records · Page 2Linked to original sources

Doppler assessment of right ventricular filling dynamics during volume loading in ischemic heart disease.

To assess the effects of volume loading on right ventricular (RV) filling dynamics, the RV inflow pattern was recorded using pulsed Doppler echocardiography (PDE) during dextran infusion in 7 normal subjects (Group I) and 24 patients with ischemic heart disease. The patients with ischemic heart disease were divided into three groups according to the left ventricular (LV) and RV ejection fractions (EF). Group II consisted of 11 patients whose LVEF and RVEF exceeded 50%. Group III consisted of 7 patients whose LVEF was lower than 50% and RVEF was higher than 50%. Group IV was comprised of 6 patients whose LVEF and RVEF were lower than 50%. Peak flow velocity of the RV rapid filling wave in early diastole [R(T)] and that of the atrial contraction wave [A(T)] were measured, and the ratio of A(T) to R(T) [A(T)/R(T)] in each cardiac cycle was calculated. In some of the subjects, simultaneous right-sided cardiac catheterization was performed with a Swan-Ganz thermodilution catheter. The LV and RV function during volume loading were calculated according to the following formulae: delta Stroke volume index (SVI)/delta pulmonary artery wedge pressure (PAWP) and delta SVI/delta right atrial pressure (RAP), respectively. After dextran infusion, R(T) increased significantly in Groups I, II, and III, but not in Group IV. The A(T) and A(T)/R(T) ratio remained unchanged in all groups. The percent change of the R(T) correlated well with delta SVI/delta RAP (r = 0.56, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A new biodegradable copolymer of glycolic acid and lactones with relatively low molecular weight prepared by direct copolycondensation in the absence of catalysts.

Relatively low-molecular-weight copolyesters of glycolic acid (GA) with lactones such as gamma-butyrolactone (BL), delta-valerolactone (VL), and epsilon-caprolactone (CL) were synthesized by copolycondensation without catalysts. The resulting copolyesters are intended as carriers for drug delivery systems. Copolyesters with approximately 85 mol% GA (number-average molecular weight (Mn): 2900 +/- 100) are crystalline and solid and show a parabolic-type in vivo degradation pattern. The in vivo degradation of amorphous-pasty poly (GA/CL) (approximately 50/50 mol%) changed from parabolic-type to linear-type to S-type pattern as their molecular weight increased. A luteinizing hormone-releasing hormone agonist, [D-Leu6, des-Gly10]-LHRH ethylamide monoacetate (LHRH agonist), was incorporated into small cylinders with these copolyesters. An initial burst of LHRH agonist was observed for cylinders prepared with parabolic-type degrading copolyesters, in contrast to a marked delay in LHRH agonist release for cylinders prepared with S-type degrading copolyesters. The resulting daily dose of drug was maintained an approximately constant, though decreasing stepwise with time. For example, the daily amount of LHRH agonist released in vivo from a cylinder prepared with poly(GA/CL) (50/50 mol%; Mn = 4500) was 61 +/- 39 micrograms/day throughout an experimental period of 10 weeks with a corresponding pharmacological effect on the rat prostate.

Animals↗

Two cases of gastric antral vascular ectasia--response to medical treatment.

Two patients with severe iron deficiency anemia and gastric antral vascular ectasia (GAVE) are reported. The anemia caused by the chronic blood loss from the abnormally dilated mucosal and submucosal capillary veins in the gastric antrum was unresponsive to oral iron supplementation. However, one of the patients was successfully treated with intramuscular injection of (Asu1,7) eel calcitonin. The other one was treated by oral prednisolone with resulting improvement iron deficiency anemia. The possible mechanisms of successful calcitonin and prednisolone treatments on chronic blood loss from GAVE is discussed.

Aged↗

In vivo characteristics of high molecular weight copoly(L-lactide/glycolide) with S-type degradation pattern for application in drug delivery systems.

Amorphous copoly(L-lactide)/glycolide, 70/30 mol%) with weight average molecular weights of 16,900-41,300 were synthesized by ring-opening polymerization in the presence of catalysts using a molecular weight moderator lauryl alcohol. The in vivo degradation profiles of the copolyesters, which were evaluated by implanting them subcutaneously in the back of rats, showed a typical S-type degradation pattern. A luteinizing hormone-releasing hormone agonist (LH-RH agonist), des-Gly10-[Leu6]-LH-RH ethylamide monoacetate, was incorporated into the small cylinders of copoly (L-lactide/glycolide) with a weight average molecular weight of 24,000. The cumulative amount of drug released in vivo from the cylinders showed an S-type profile in analogy with the in vivo degradation pattern. This was demonstrated from data such as serum drug level and pharmacological influence on rat prostates.

Animals↗

The effect of Ca and Mg supplementation and the role of the opioidergic system on the development of DOCA-salt hypertension.

The effect of calcium and magnesium supplementation and the role of opioidergic system was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were divided into four groups receiving standard laboratory rat diet (control group; n = 9); a calcium-rich diet with 2% CaCl2 added (Ca-group; n = 12); a magnesium-rich diet with 0.5% MgO added (Mg-group; n = 11); and a calcium and magnesium-rich diet with 2% CaCl2 and 0.5% MgO added (Ca/Mg-group; n = 11); each diet contained 7% NaCl. After four weeks on these diets, the rats were decapitated and blood was obtained for the measurement of plasma electrolytes, intraerythrocyte sodium, potassium and magnesium content (RBC-Na, -K, in mEq/L cells and RBC-Mg, in mg/dL cells) and plasma beta-endorphin concentration (beta-END, in pg/mL). In the control group, systolic blood pressure and RBC-Na were obviously higher than in the other groups. Plasma beta-endorphin concentration was 45.1 +/- 13.4 in the control group, 70.7 +/- 17.4 in the Ca-group (P less than .05 v control group), 58.0 +/- 20.1 in the Mg-group and 83.8 +/- 24.8 in the Ca/Mg-group (P less than .01 v control group). The blood pressure correlated significantly with both RBC-Na (r = 0.416, P less than .01) and beta-END (r = 0.436, P less than .005). A negative correlation was also observed between RBC-Na and beta-END (r = 0.437, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Suppressive effect of sulfate on the development of hypertension in DOCA-salt hypertensive rats.

The purpose of this study was to examine the effect of the sulfate ion on blood pressure in DOCA-salt hypertension, which involves increased sympathetic nervous activity. Male Wistar rats were divided into four groups, and received one of the following drinking solutions: distilled water [control], 171 mmol/L sodium chloride [NaCl group], 171 mmol/L sodium chloride plus 12 mmol/L magnesium sulfate [S(+) group], or 171 mmol/L sodium chloride plus 12 mmol/L magnesium chloride [S(-) group]. In the S(+) group, the elevation of systolic blood pressure (SBP; mm Hg) was significantly attenuated (168 +/- 17 v 213 +/- 26, P less than .005) and intraerythrocyte calcium concentration (R-Ca; mumol/L cells) was significantly lower (11.5 +/- 3.0 v 17.4 +/- 6.5, P less than .05) than in the S(-) group. The cardiac norepinephrine content (H-NE; ng/100 g tissue) of the S(+) group was significantly lower than that of the S(-) group. SBP was correlated negatively with H-NE (r = -0.70, P less than .001) and positively with R-Ca (r = 0.45, P less than .005). R-Ca was negatively correlated with H-NE (r = -0.36, P less than .05). These results suggest that the replacement of chloride with sulfate ion suppresses the development of hypertension in DOCA-salt rats at least in part by its inhibitory effect on sympathetic nervous activity through the decreased intracellular calcium concentration.

Administration, Oral↗

Arterial oxygen saturation, blood pressure, and pulse rate during upper gastrointestinal endoscopy--influence of sedation and age.

We studied the effect of sedation by I.V. meperidine on blood pressure, pulse rate, and arterial oxygen saturation during upper gastrointestinal endoscopy. Meperidine increased the tolerance of the patients and attenuated the endoscopy-induced rise in blood pressure and pulse rate. Arterial oxygen saturation was transiently depressed in the first few minutes of the endoscopic procedure even without sedation, and meperidine administration did not aggravate this oxygen desaturation. Therefore, meperidine may be a favorable sedative for upper gastrointestinal endoscopy because its treatment increases the tolerance of patients and decreases cardiac oxygen demand without decreasing arterial oxygen saturation.

Age Factors↗

Calcium supplementation in salt-dependent hypertension.

To clarify the mechanism of the antihypertensive effect of oral Ca loading, we studied the effect of Ca supplementation on salt-induced blood pressure elevations in patients with essential hypertension and DOCA-salt hypertensive rats. When the diet was changed from low to high salt (300 mEq/day), the percent increase in mean blood pressure was smaller (p less than 0.01) in the Ca-supplemented (2,160 mg/day) patients than in the Ca-restricted (250 mg/day) ones. Oral Ca loading resulted in a smaller weight gain, a greater urinary sodium excretion, and an increase in red cell Mg. In the experimental study, high Ca (4% CaCl2) intake attenuated the blood pressure elevation in DOCA-salt-treated rats, accompanied with an increase in urinary sodium excretion, with the resultant attenuation in intra- and extracellular sodium retention. The decrease in catecholamine contents of hearts was improved, and a higher survival rate was observed in Ca-supplemented DOCA-salt rats. The results suggest that Ca supplementation may prevent a rise in BP in salt-dependent hypertension by inducing natriuresis with the resultant attenuation in sodium retention. The altered intracellular Mg level in hypertensive patients and the normalization of enhanced sympathetic nervous activity in DOCA-salt rats may, in part, be involved in its mechanism.

Adult↗

Single-beat estimation of the slope of the end-systolic pressure-volume relation in the human left ventricle.

This study assessed a new method of estimating the slope (Ees) of the end-systolic pressure-volume relation (ESPVR) from a single beat of the human heart. Left ventricular pressure was recorded with a high-fidelity micromanometer in patients with heart disease during left ventriculography. Peak isovolumic pressure at the end-disastolic volume was estimated by a curve-fitting technique from an isovolumic left ventricular pressure curve. The ESPVR line was drawn from the estimated peak isovolumic pressure-volume point tangential to the left upper corner of the pressure-volume loop. The slope of this estimated ESPVR line from single-beat analysis was compared with the slope of the ESPVR line obtained from three pressure-volume loops in 16 patients given angiotensin II or nitroglycerin infusion. The estimated Ees was 5.0 +/- 2.2 mm Hg/ml/m2, and the conventional Ees was 4.9 +/- 2.7 mm Hg/ml/m2. The estimated Ees showed a positive correlation with the conventional Ees (r = 0.91, p less than 0.001, SEE = 1.2 mm Hg/ml/m2). In the other 13 patients, after dobutamine infusion (5 micrograms/kg/min i.v.) the estimated Ees increased significantly from 5.6 +/- 1.4 to 7.4 +/- 2.0 mm Hg/ml/m2 (p less than 0.01). Thus, the estimated Ees approximated the conventional Ees and was sensitive to a positive inotropic intervention. We conclude that this single-beat analysis method facilitates assessment of the beat-by-beat ESPVR of the human heart.

Angiotensin II↗

Evaluation of new pasty-type implantable devices consisting of poly(epsilon-caprolactone/delta-valerolactone) and Estracyt or estramustine.

Biodegradable pasty-type copolyesters with a relatively low molecular weight of 4500 were synthesized by direct copolycondensation of epsilon-caprolactone (CL) and delta-valerolactone (VL) in the absence of catalysts to evaluate in vivo capabilities of the polymer for implantable controlled release devices in drug delivery systems. The devices in cylindrical shape were prepared by the melt-pressing technique using pasty-type copoly(CL/VL) with 53 mol% CL unit, in which Estracyt and estramustine were used as a water soluble and insoluble drug, respectively. The degradation and drug release in vivo of the devices were examined by subcutaneous implantation in the backs of male rats. The degradation of the device was remarkably accelerated by the presence of hydrophilic Estracyt, and was slightly suppressed by hydrohobic estramustine. The estramustine release profile roughly corresponded to the polymer degradation one. It was found that the degradation of the polymer in the device was affected by hydrophilicity of the drug. A reasonable release of estramustine from the device was kept for a period of more than 20 weeks. Furthermore, the release of the drugs in vivo was able to lead to an atrophy of accessory sex organs such as ventral prostates (VP) and right-side seminal vesicle (SV), resulting in pharmacological influence.

Animals↗

Small GTP-binding proteins in bovine aortic smooth muscle.

In bovine aortic smooth muscle, GTP-binding activity was equally distributed in the membrane and cytosol fractions. The most abundant GTP-binding proteins (G proteins) in each fraction were purified to near homogeneity and characterized. The most abundant G protein in the membrane fraction had a Mr value of about 22,000 (m22K G) as estimated on sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE). m22K G and the human platelet smg p21, a ras p21 like G protein having the same effector domain as ras p21s, were eluted at the same retention time on C4 reversed-phase high performance liquid chromatography (HPLC). Moreover, m22K G was specifically recognized by an anti-smg p21 polyclonal antibody. m22K G was phosphorylated by cyclic AMP-dependent protein kinase with a stoichiometry of one phosphate/molecule of protein. The most abundant G protein in the cytosol fraction had a Mr value of about 21,000 (c21K G) as estimated on SDS-PAGE. c21K G was ADP-ribosylated by botulinum ADP-ribosyltransferase and about 0.4 mol of ADP-ribose was maximally incorporated into 1 mol of c21K G. c21K G and the bovine brain rhoA p21, another ras p21 like G protein, were eluted at the same retention time on C4 reversed-phase HPLC and migrated at the same position on two-dimensional gel electrophoresis. These results indicate that the major G proteins in the membrane and cytosol fractions of bovine aortic smooth muscle are smg p21 and rhoA p21, respectively. Possible roles of these G proteins in vascular smooth muscle are discussed.

Animals↗

Heart rate responses to autonomic drugs in sick sinus syndrome--correlation with syncope and electrophysiologic data.

To assess the influence of autonomic regulation on automaticity in patients with intrinsic sinus node dysfunction, heart rate responses to autonomic drugs were evaluated in 28 patients with sick sinus syndrome and in 8 normal subjects. Heart rates before and after intravenous administration of isoproterenol (Isp), propranolol, atropine, and methoxamine were measured. To compare the results with electrophysiologic data, heart rate and automaticity recovery time (ART) before and after pharmacologic autonomic blockade (AB) were evaluated. Seventeen patients without syncope showed a similar heart rate response after administration of Isp to that of normal subjects, but 11 patients with syncope showed a significantly lower response than patients without syncope. Responses to atropine and methoxamine were lower and response to propranolol was larger in patients as compared to normal subjects. However, no significant difference was observed between patients with and without syncope. Twelve patients showed severely prolonged max ART exceeding 5000 msec after AB. Seven of them showed preserved response to Isp and max ART before AB was significantly shorter than that after AB. The other 5 patients with lower response to Isp showed no significant change in max ART before and after AB. In conclusion, sympathetic regulation in patients with preserved response to Isp might compensate for the impaired intrinsic automaticity in preventing syncope even in patients with severely impaired intrinsic sinus node function.

Adult↗

Effects of long-term beta-blockade (metoprolol) therapy in patients with dilated cardiomyopathy.

Twenty-two patients with dilated cardiomyopathy (DCM) were treated with metoprolol and their clinical courses were compared with those of 26 patients untreated with beta-blocking agents (non beta group). Of the 22 patients treated with metoprolol, 19 (beta group) were treated for a long period, 3 patients left the study within its first 6 months. Using the NYHA classification, 4 patients of the beta group were evaluated as having clinically improved, while none was aggravated, excluding 2 cases of death which occurred during the follow up period. In the non-beta group, clinical improvement was found for 2 patients and aggravation in functional class for 10. The left ventricular diameter was significantly decreased and parameters of systolic function and exercise tolerance were significantly improved in patients of the beta group, while no such improvements occurred in patients of the non-beta group. Twenty-four-hour ECG monitoring demonstrated a significant reduction in incidences of ventricular extrasystole in the beta group but not in those of the non-beta group. Improvement of arrhythmias, evaluated using Lown's grading system, was also identified more frequently in the beta group than in the non-beta group. During the follow-up period, 2 patients of the beta group and 10 patients of the non-beta group died. The survival curve for patients of the beta group prepared using the Caplan Meier Method was better than that for patients of the non-beta group. Metoprolol was therefore found to be useful for treatment of DCM.

Arrhythmias, Cardiac↗

The significance of resting thallium-201 delayed SPECT for assessing viability of infarcted regions--comparison with exercise thallium-201 SPECT.

To clarify the clinical significance of resting thallium-201 (Tl) delayed SPECT for assessing the viability of infarcted regions, we studied resting Tl initial and delayed Tl SPECT one week after exercise (Ex) Tl SPECT in 38 patients (40 regions) with old myocardial infarction (OMI) and 35 patients (37 regions) with effort angina pectoris (EAP). Analysis of resting Tl and Ex Tl SPECT divided the patients with OMI into 3 groups. Twenty-three patients whose perfusion defect (PD) on resting delayed image was same as that of Ex delayed image were divided into 12 patients with Ex Tl redistribution (RD) (G1) and 11 patients without Ex Tl RD (G3). Fifteen patients showed a decrease of PD on resting delayed image compared with Ex delayed image (G2). Thirty-five patients with EAP were divided into 18 patients who had no PD on Ex delayed image (G1) and 17 patients whose PD did not disappear on Ex delayed image but disappeared on resting delayed image (G2). The increase of pulmonary artery wedge pressure on Ex was higher in G2 than in G1 of both OMI and EAP (OMI; G1 15 +/- 16 mmHg vs G2 27 +/- 7 mmHg; p less than 0.01, EAP; G1 12 +/- 7 mmHg vs G2 22 +/- 6 mmHg; p less than 0.05). The percent Tl uptake of the PD on Ex Tl initial images was lower in G2 than in G1 of both OMI and EAP (OMI: G1 63 +/- 7% vs G2 55 +/- 9%; p less than 0.05, EAP: G1 72 +/- 7% vs G2 65 +/- 9%; p less than 0.05). That of the PD on resting Tl delayed images was higher in G1 and G2 than in G3 of OMI (G1 78 +/- 7%, G2 74 +/- 8%, G3 41 +/- 10%; G1 vs G3, G2 vs G3 p less than 0.001). The prevalence of akinetic or dyskinetic wall motion on left ventriculography was higher in G2 than G1, and in G3 than G2 (G1 24.3%, G2 52.2%, G3 85.7%; p less than 0.001). Thus, in patients with OMI the decrease of Tl PD on resting Tl delayed images compared with Ex delayed images may indicate severe ischemia induced by stress as well as in patients with EAP, and furthermore the presence of viable muscle. On the other hand, the infarcted region without decrease of Tl PD on resting delayed images may lack viable muscle.

Aged↗

The role of myocarditis and myocardial fibrosis in dilated cardiomyopathy. Analysis of 28 necropsy cases.

The hearts of 28 necropsy cases with DCM and 10 control cases were analysed to elucidate the role of myocarditis and fibrosis in dilated cardiomyopathy (DCM). The extent of fibrosis and myocyte diameter were measured in the transverse sections of the left ventricle. The degree and pattern of fibrosis varied widely from case to case. The DCM cases were then classified into 3 groups: 1) Group Ia, 8 cases with mild diffuse fibrosis; 2) Group Ib, 9 cases with severe diffuse fibrosis and 3) Group II, 11 cases with segmental fibrosis. Myocardial fibrosis and hypertrophy were significantly more prominent in Groups Ib and II than in the control group (p less than 0.01), but no differences were observed between Group Ia and the control group. Thus, it is reasonable to attribute the chronic CHF and LV dilatation in Groups Ib and II to the extensive myocardial fibrosis. In contrast, it is not reasonable to attribute the chronic CHF and LV dilatation in Group Ia to myocardial fibrosis. Focal lymphoid cell infiltration was graded to assess inflammatory changes. Group II showed more prominent inflammatory changes than the other 2 groups (p less than 0.05). Thus, it is possible that myocarditis is an etiologic factor for DCM with a segmental pattern of fibrosis.

Adolescent↗

The molecular heterogeneity of the smg-21/Krev-1/rap1 proteins, a GTP-binding protein having the same effector domain as ras p21s, in bovine aortic smooth muscle membranes.

smg p21 is a member of the ras p21/ras p21-like small GTP-binding protein (G protein) superfamily, having the same putative effector domain as ras p21s. In the preceding report, we showed that smg p21 was a major G protein in bovine aortic smooth muscle membranes. Recently, two different smg p21 cDNA clones, designated smg-21A and -B, were isolated from a bovine brain cDNA library. In the present studies, we resolved the bovine aortic smg p21 fraction into two distinct G protein fractions on hydroxyapatite column chromatography and purified them separately to near homogeneity (22K G1 and -2). Both 22K G1 and -2 were specifically recognized by an anti-smg p21 polyclonal antibody. 22K G1 and -2 were identified as smg p21B and -A, respectively, by peptide map and amino acid sequence analyses. Purified smg p21A and -B showed GDP/GTP-binding and GTPase activities similar to each other. The GTPase activities of smg p21A and -B were equally stimulated by smg p21 GTPase activating protein 1 and -2. Moreover, both smg p21A and -B were phosphorylated by cyclic AMP-dependent protein kinase with a stoichiometry of one phosphate/molecule of protein. These results indicate that smg p21A and -B coexist in bovine aortic smooth muscle membranes and suggest that smg p21A and -B may serve as intermediates for cyclic AMP actions.

Amino Acid Sequence↗

[Transmitral flow velocity patterns as influenced by preload, afterload and heart rate alterations: pulsed Doppler echocardiographic study].

The influences of preload, afterload and heart rate alterations on the pattern of left ventricular filling were investigated using pulsed Doppler echocardiography (PDE) in humans. Transmitral flow at the level of the valvular tip was recorded during dextran infusion, lower body negative pressure, angiotensin II infusion, and atrial and atrioventricular sequential pacings. Peak velocity of rapid filling (R), peak velocity of atrial contraction (A), the ratio of peak velocities (A/R), flow velocity integrals of the rapid filling phase (IR) and atrial contraction (IA) were obtained. PDE and the measurement of hemodynamics during lower body negative pressure (0, -10 mmHg, -20 mmHg) and dextran infusion (100 ml, 200 ml) were studied in 22 patients with ischemic heart disease. R decreased significantly after lower body negative pressure, and increased significantly during dextran infusion. Before and during angiotensin II infusion, PDE and the measurement of hemodynamics were studied in 14 patients with ischemic heart disease. The patients were categorized into 2 subgroups according to left ventricular function. During afterload stress, the A/R and IA increased in patients with normal left ventricular function; whereas, the A/R decreased in patients with poor left ventricular function. PDE was recorded during right atrial and atrioventricular sequential pacings at the heart rates of 60 to 100 beats/min in 29 patients with ischemic heart disease. When the heart rates increased, R decreased during atrial and atrioventricular sequential pacings. The A increased after the occurrence of the summation between the rapid and atrial filling waves. The A/R gradually increased with incremental heart rate. These results indicate that changes in the preload alter the peak velocity of left ventricular filling pattern of transmitral flow. The effects of the increasing afterload depend on the basal left ventricular function, with an increase in the peak velocity of atrial contraction being observed in the presence of normal left ventricular function. Both the peak velocity of rapid filling and atrial contraction were related to the heart rate and atrioventricular conduction delay. In assessing left ventricular filling dynamics using PDE, the influence of the preload, afterload and heart rate must be considered.

Angiotensin II↗

Primary chylopericardium with pulmonary shadow and large granular lymphocytosis: a case report.

A 79-year-old man with primary chylopericardium associated with large granular lymphocytosis was followed for more than 26 years. Except for development of dyspnea on exertion during the past four years and more recently cough with sputum production, he has remained largely asymptomatic over this interval. Based on detailed examinations of cellular and humoral immunity, we speculate that increased natural killer cell activity and an increased number of large granular lymphocytes circulating in his peripheral blood represent a reactive response to production of various cytokines secondary to persistent loss (? chyloptysis) and sequestration of central lymph.

Aged↗