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Biomedical subjects

N Sugihara

Publications and source records attributed to N Sugihara.

At least 37 records · Page 2Linked to original sources
PubMed1993

The influence of increased plasma protein binding on the disposition of quinidine in turpentine-treated rats.

The effect of the increased plasma protein binding of quinidine on its disposition was investigated in turpentine-treated rats, since turpentine treatment is known to increase the plasma concentration of alpha 1-acid glycoprotein which preferentially binds basic drugs. The plasma free fraction of quinidine 16 and 48 h after turpentine treatment was decreased by 30 and 76%, respectively, compared to the control value. The treatment did not cause liver injury nor alter the hepatic blood flow. The disappearance of quinidine in plasma after an intravenous injection (3.0, 7.0, 12.5 mg/kg) was analyzed by a two-compartment open model in both control and turpentine-treated rats. The blood total body clearance (CLb) of quinidine at 48 h after the treatment was decreased by 30 to 65% in a dose-dependent manner, compared to that in control rats. The distribution volume (Vdss) of quinidine (12.5 mg/kg) at 16 and 48 h after turpentine treatment was decreased by 30 and 79%, respectively. Hepatic extraction ratio (HER) of quinidine, which was determined at steady state blood concentrations from 0.5 to 2.3 micrograms/ml, was decreased from 0.8 to 0.35 with an increase in the quinidine concentration in control rats. The HER value 48 h after turpentine treatment was consistently reduced by 15 to 40% in a concentration-dependent manner compared to the corresponding control value. These findings indicate that the increased plasma binding of quinidine caused a reduction of HER of the drug, and the reduced HER resulted in the decrease in CLb in turpentine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The influence of severe bone loss on mitral annular calcification in postmenopausal osteoporosis of elderly Japanese women.

We assessed the influence of aging bone calcium metabolism on mitral annular calcification (MAC) and aortic valve calcification (AVC) in 239 septua- and octogenarians (62 men, 177 women; 80.2 +/- 4.4 years). Osteoporosis was diagnosed by vertebral bone fracture. Both MAC and AVC were derived by 2-dimensional echocardiography. Bone mineral content (BMC) of the lumbar vertebral body was obtained by single-energy quantitative computed tomography using a calibration phantom. Serum calcium, phosphorus, parathyroid hormone, calcitonin, and osteocalcin were examined. Patients were classified into 3 age-matched groups in each sex: Group-C included patients with MAC (-) and AVC (-) (n = 96); Group-A was those with AVC (+) and MAC (-) (n = 80); Group-M consisted of those with MAC (+) and AVC (-) or AVC (+) (n = 63). Osteoporosis-frequency and BMC in women were significantly higher (p < 0.01) and lower (p < 0.001) respectively than those in men. Among men, osteoporosis-frequency and BMC showed no difference between the 3 groups. Among women, osteoporosis-frequency (52%) and BMC (32 +/- 23 mg/cm3) in Group-M were higher (NS) and significantly less (p < 0.01) than those (37%, 49 +/- 36) in Group-C, respectively. In both sexes, serum examinations revealed no differences between the 3 groups. These results suggest that: 1) MAC in elderly women can be attributed to ectopic calcium deposits, related to the severe bone loss caused by postmenopausal osteoporosis; 2) there is no significant relationship between the incidence of MAC or AVC and the humoral factors of calcium metabolism; and 3) AVC may be mainly caused by pressure or stress loading.

Aged↗
PubMed1993

Preload dependency of left atrial pump function in hypertrophic cardiomyopathy.

In our previous study, we reported that the left atrial contribution to left ventricular filling was decreased to a greater extent in patients with hypertrophic cardiomyopathy than in those with myocardial infarction or normal subjects during lower body negative pressure (LBNP)-induced preload reduction. To clarify the factors responsible for this difference in response, we examined changes in left atrial hemodynamic and M-mode echocardiographic indices during LBNP in patients with hypertrophic cardiomyopathy and myocardial infarction. The same degree of decrease in left atrial preload and afterload was found in both groups. Moreover, we detected no change in the left atrial fractional shortening during left atrial systole (%LAFS) in patients with hypertrophic cardiomyopathy, in contrast to a significant increase found in patients with myocardial infarction. These results showed that the greater decrease in the left atrial contribution in hypertrophic cardiomyopathy during LBNP could not result from differences in changes in left atrial preload or afterload, suggesting that it may be closely related to limitations in the compensatory augmentation of left atrial contractility.

Atrial Function, Left↗
PubMed1993

Prevalence of root caries in a Japanese adult population aged 20-59 years.

The purpose of the present study was to investigate the prevalence of root caries in an adult population in Japan. A total of 770 company employees aged 20-59 were examined in 1990. The subjects were all dentate and had 27.2 present teeth on the average. The proportion of gingival recession in this population ranged from 20.1% for the 20-29 year old group to 75.2% for the 50-59 year old group, with an average of 44.0%. In the present study, 3.2% of the subjects showed one or more active root caries. The prevalence of active root caries ranged from 0.4% at age 20-29 to 7.1% at age 50-59. The proportion of persons with active root caries and/or root fillings ranged from 1.3% at age 20-29 to 36.3% at age 50-59. The percentage of subjects with active and/or inactive caries and/or root fillings varied from 3.1% at age 20-29 to 43.4% at age 50-59. The prevalence of active root caries in the subjects at risk (with gingival recession) was 7.4% on the average and ranged from 2.2% at age 20-29 to 9.4% at age 50-59. The percentage of persons with active root caries and/or root fillings in the subjects at risk ranged from 6.7% at age 20-29 to 48.2% at age 50-59. The mean number of teeth with active root lesions was 0.09 per person, and the mean number of teeth with root fillings was 1.25 at age 50-59.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cardiac characteristics and postoperative courses in Cushing's syndrome.

To assess the cardiac characteristics and postoperative courses in patients with Cushing's syndrome, electrocardiography and echocardiography were performed to study 12 consecutive, unselected patients, and results were compared with those of essential hypertension and primary aldosteronism. Eleven patients had hypertension and 7 had diabetes mellitus. Before adrenalectomy, common electrocardiographic abnormalities consisted of high-voltage QRS complexes (10 patients) and negative T waves (7 patients). Echocardiograms showed left ventricular hypertrophy in 9 patients, and all the patients had evidence of asymmetric septal hypertrophy. In patients with left ventricular hypertrophy, the thickness of the interventricular septum ranged from 16 to 32 mm, whereas the ratio of the thickness of interventricular septum to that of the posterior wall ranged from 1.33 to 2.67. The interventricular septum in Cushing's syndrome was extremely thicker and asymmetric septal hypertrophy occurred more often than essential hypertension and primary aldosteronism. Nine patients could be followed up after operation. In these patients abnormal electrocardiographic findings had normalized, the thickness of interventricular septum had decreased and asymmetric septal hypertrophy had disappeared except in 1 patient. The reason why left ventricular hypertrophy in Cushing's syndrome is severe is still unknown. Because left ventricular hypertrophy is more severe and the frequency of asymmetric septal hypertrophy much greater in Cushing's syndrome than in essential and other secondary hypertension, it is thought that not only increased aortic pressure but excessive plasma cortisol may be etiologic factors in the progression of left ventricular hypertrophy in Cushing's syndrome.

Adrenal Gland Neoplasms↗
PubMed1992

The thickness of the sound and periodontally diseased human cementum.

Cementum of teeth previously analysed for fluoride was re-examined in order to determine whether or not periodontal disease had affected the thickness of the tissue. In the periodontally diseased teeth the cementum was thinner than normal in the middle region of the root. The apical cementum, however, was significantly thicker in periodontally diseased than in the sound teeth of subjects over 60 yr old. This may account for the higher total fluoride levels previously reported in the apical cementum of these same teeth.

Adult↗
PubMed1992

Long-term course and cardiac sympathetic nerve activity in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To investigate the relation between regional myocardial sympathetic nerve activity and the electrocardiographic and cardiac functional changes in hypertrophic cardiomyopathy. DESIGN: A retrospective study to compare the findings of myocardial scintigraphy with iodine-123 metaiodobenzylguanidine (MIBG) and the serial electrocardiographic changes. SETTING: Myocardial scintigraphy was performed with iodine-123 MIBG and thallium-201 and single photon emission computed tomography (SPECT) in the division of nuclear medicine of Kanazawa University Hospital. Both SPECT studies were performed within a week. PATIENTS: 22 patients with hypertrophic cardiomyopathy classified according to their serial electrocardiographic changes--namely, 15 patients with an increase in or the appearance of a negative T wave (group A) and seven patients with a conduction disturbance or a decrease in or disappearance of the negative T wave (group B). The mean follow up period was 45 (range 12-143) months. RESULTS: Group B showed a high rate of decreased activity or defects in MIBG uptake compared with group A (p less than 0.005). The areas of decreased activity or defects corresponded with the hypertrophied portion of the left ventricular wall. Although the early myocardial uptake (MIBG: thallium ratio) was similar in both groups, the mean (SD) MIBG clearance rate was significantly higher (p less than 0.05) in group B (0.25 (0.17)) than in group A (0.10 (0.15)). CONCLUSION: Abnormalities of regional myocardial sympathetic nerve activity may be important in patients with hypertrophic cardiomyopathy and suspected progression of myocardial damage.

3-Iodobenzylguanidine↗
PubMed1992

Distribution of quinidine in rats with carbon tetrachloride-intoxicated hepatic disease.

The disposition of quinidine was investigated in rats with experimental hepatic disease caused by an intraperitoneal injection of CCl4. The plasma disappearance of quinidine after a 12.5 mg/kg i.v. bolus injection was analyzed by a two-compartment open model in both control and CCl4-intoxicated rats. In the CCl4-intoxicated rats, plasma total body clearance (CLtot), elimination rate constant of the central compartment (kel) and the volume of distribution (Vdss) of quinidine were decreased by 73, 51 and 36%, respectively, compared to those in the control rats. At a steady state of quinidine plasma concentration of 1 micrograms/ml, tissue-to-plasma partition coefficient (Kp,vivo) of the drug in the lung, spleen, heart, kidney and liver in the CCl4-intoxicated rats were decreased ranging from 32 to 42% compared to those in the control rats. The plasma free fraction of quinidine in the intoxicated rats was decreased by 34% of that in the control rats. Neither tissue binding of quinidien in vitro, nor plasma pH was altered in the intoxicated rats. Thus, the decrease in Vdss and Kp,vivo for quinidine in the intoxicated rats seems likely to be due to an increase in plasma protein binding of the drug. Metabolic activity in the liver, the hepatic extraction ratio for quinidine, and the hepatic blood flow in the CCl4-intoxicated rats were decreased by 84, 57 and 47%, respectively, compared to those in the control rats. The decrease in CLtot and kel in the intoxicated rats is considered to be attributed to both the reduction of liver functions and the increase in the plasma protein binding of the drug.

Animals↗
PubMed1992

Accumulation of propranolol in cultured rat fibroblasts.

In order to clarify the involvement of phosphatidylserine (PhS) in the cellular accumulation of propranolol, we have characterized the binding of 3H-propranolol to cultured rat fibroblasts and to liposomes containing PhS. The properties of propranolol binding to the cells and liposomes were analyzed by means of a Scatchard plot. The cells contained at least two classes of propranolol binding sites, one site of high affinity/low capacity and the second site of lower affinity/higher capacity, while the liposomes contained only one class of binding site. The values of the association constant (K) and number of binding sites (n), given on a PhS basis for the propranolol binding site in the liposomes, were both very close to those of corresponding binding parameters for the high affinity/low capacity binding site in the cells. Cell death, caused by various toxic reagents, resulted in a marked decrease in propranolol accumulation in the cells. Kinetic analysis of the drug binding to dead cells showed one binding site with binding parameters comparable to those of the low affinity/high capacity binding site in the intact cells. Polar cations, methylamine and NH4Cl, completely inhibited propranolol binding to the liposomes. On the other hand, these cations partially inhibited propranolol accumulation in intact cells and failed to inhibit the drug binding to dead cells. These results suggest that PhS in cytomembranes represents the high affinity/low capacity propranolol binding site in cultured rat fibroblasts.

Ammonium Chloride↗
PubMed1992

Plasma alpha 1-acid glycoprotein concentration in rats with chemical liver injury.

The influence of liver injury on the plasma concentrations of alpha 1-acid glycoprotein (AGP) and albumin was examined in several different models of chemically-induced liver injury. The plasma AGP concentration in carbon tetrachloride (CCl4), allyl alcohol, bromobenzene, acetaminophen or N-nitrosodimethylamine-induced liver injury was increased to 2-3.5 times the normal level at 24 h after the intoxication. The plasma AGP concentration was unchanged in ethionine-induced liver injury and was markedly decreased in galactosamine-induced injury. The plasma albumin concentration was significantly decreased by the damage due to galactosamine, allyl alcohol or N-nitrosodimethylamine-induced liver injury, while no influence was observed by other hepatotoxin-induced liver injury. The plasma protein binding of propranolol was also determined in relation to the plasma concentrations of AGP and albumin in all the experimental models. Propranolol binding, expressed as bound to free ratio, showed a good correlation with the AGP concentration (r = 0.940; p < 0.001), but not with the albumin concentration.

Animals↗
PubMed1992

Histopathological factors related to diastolic function in myocardial hypertrophy.

To clarify the histopathologic influence on diastolic function in the hypertrophied heart, we compared the echocardiographic and histopathologic findings in 9 controls, 10 patients with hypertrophic cardiomyopathy (HCM), and 8 hypertensive patients with asymmetric septal hypertrophy (HT-ASH). M-mode echocardiography was used to determine the left ventricular diastolic function. Mean diameter of myocytes, percentage of fibrosis and disarrangement were quantitatively calculated from right ventricular endomyocardial biopsy specimens. In both HT-ASH and HCM, the isovolumic relaxation time was significantly longer and the rapid filling volume tended to be smaller than in the controls. Histopathologically, the mean diameter of myocytes and percentage of myocardial interstitial fibrosis did not differ significantly between HT-ASH and HCM. However, quantitative disarrangement of myocytes in HCM was significantly greater than that in HT-ASH. Multiple regression analysis showed that the percentage of fibrosis was the most significant factor related to diastolic left ventricular dysfunction in HT-ASH, while disarrangement of myocytes was the most significant in HCM. We conclude that diastolic dysfunction in HT-ASH can be attributed to the percentage of fibrosis, and to disarrangement of myocytes in HCM.

Adult↗
PubMed1992

Disproportionate hypertrophy of the interventricular septum and its regression in Cushing's syndrome. Report of three cases.

Three patients of Cushing's syndrome with severe disproportionate hypertrophy of the interventricular septum are reported. All three underwent adrenalectomy and the diagnosis of Cushing's syndrome was confirmed by the presence of adrenal adenoma. All three showed hypertension before the adrenalectomy and two remained hypertensive following adrenalectomy. Before the operations the electrocardiograms revealed inverted T waves in broad leads, and mechanocardiogram systolic and diastolic dysfunction. After the adrenalectomies, abnormal findings on electrocardiograms were normalized and septal hypertrophy was completely regressed. It appears that not only high aortic pressure but also excessive plasma cortisol may be an etiologic factor of the left ventricular hypertrophy in Cushing's syndrome.

Adrenalectomy↗
PubMed1992

[The relation between bone calcium metabolism and senile aortic valve calcification].

The authors assessed the affect of bone calcium metabolism on aortic valve calcification (AVC) in 189 septua- and octogenarians (49 males and 140 females, 81.0 +/- 4.4 yrs). Both AVC and mitral annular calcification (MAC) were evaluated by two-dimensional echocardiography, and then the degree of AVC was classified into three categories; C-1: calcification seen in one cusp of the aortic valve, C-2: calcification in two cusps, and C-3: calcification in three cusps. Bone mineral content (BMC) of three lumbar vertebral bodies was obtained by quantitative computed tomography using a calibrated phantom. Serum calcium, phosphate, parathyroid hormone, calcitonin, and osteocalcin were also examined within a month. The patients were classified into age-matched five groups in both sexes; Group-C: MAC (-) and AVC (-) (n = 79); Group-A1: MAC (-) and AVC (+) with C-1 (n = 35); Group-A2: MAC (-) and AVC (+) with C-2 (n = 19); Group-A3: MAC (-) and AVC (+) with C-3 (n = 15); and Group-AM: MAC (+) and AVC (+) in any cusp (n = 42). In males, BMC decreased in the order of Groups-A3 (83 +/- 27 mg/cm3), -C (67 +/- 50), -AM (62 +/- 62), -A2 (61 +/- 38), and -A1 (59 +/- 58), but there was no significant difference between any of the five groups. In females, the BMC in Group-AM (29 +/- 24) was significantly less than that in Group-C (48 +/- 35) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Left atrial booster pump function in patients with hypertrophic cardiomyopathy and essential hypertension: evaluations based on left atrial pressure-volume relationship].

In patients with hypertrophic cardiomyopathy (HCM) and essential hypertension (HT), left ventricular dysfunction in early diastole which is associated with left atrial contraction plays an important role in left ventricular filling. To evaluate left atrial booster pump function, we analyzed left atrial preload (left atrial pressure at the end of diastasis; LAPd, left atrial volume index at the end of diastasis; LAVd), left atrial afterload (left ventricular end-diastolic pressure; LVEDP, left ventricular chamber stiffness constant; K), and left atrial ejection indices (left atrial ejection fraction during atrial contraction; LAEF, left atrial ejection volume index during atrial contraction; ACVI). The study subjects consisted of control subjects (n = 5), HT patients (n = 6), and HCM patients (n = 11). The left ventricular wall was significantly thicker in the HT and HCM groups. The left ventricular rapid filling volume index was less in the HT group, and significantly less in the HCM than in the control group. LAPd and LAVd were greater in the HT group than in the control group, and greater in the HCM group than in the HT group. LVEDP and K were greater in the HT group than in the control group, and significantly greater in the HCM group than in the other 2 groups. ACVI was greater in the HT group than in the control group, but in the HCM group, ACVI was significantly less than in the HT group and did not differ significantly from that in the control group. LAEF was significantly less in the HCM group than in the other 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Response of coronary arteries to intracoronary acetylcholine infusion in patients with familial hypercholesterolemia].

Loss of the vasodilator response to acetylcholine (Ach), an endothelium-dependent vasodilator, has been demonstrated in animal models of atherosclerosis and in atherosclerotic coronary arteries of humans studied in vitro. The response of normal coronary arteries on angiograms to the intracoronary injection of Ach in patients with familial hypercholesterolemia (FH) was studied. Ten patients with FH (mean age, 53.6 +/- 6.5 years) with a mean serum total cholesterol of 334.8 mg/dl and 12 controls (mean age, 55.8 +/- 14.5 years) with a total cholesterol level of 183.6 mg/dl, and with normal coronary arteries on angiograms were studied. Patients with clinical histories suggestive of coronary spastic angina were excluded from this study. A bolus of 20, 50 micrograms Ach and 2 mg isosorbide dinitrate (ISDN) were infused into the left coronary artery in each subject. Changes in coronary diameters were measured after each injection with a videodensitometric analysis system. In the control group, the diameter at the middle segments of the left anterior descending artery (LAD) and at the proximal and middle segments of the left circumflex artery (LCX) increased significantly in response to Ach; whereas, in the FH group the diameter at the proximal segments of the LAD decreased significantly. There were significant differences in the coronary diameter changes in response to 50 micrograms Ach at the proximal and middle segments of the LAD and the LCX between the 2 groups. In contrast, between these 2 groups, there were no significant differences in the vasodilator responses to ISDN, a direct vascular smooth muscle dilator. The vasodilator response of coronary artery to Ach was diminished in patients with FH.

Acetylcholine↗
PubMed1992

[The functional significance of coronary collateral circulation during sudden coronary occlusion].

The functional significance of the coronary collateral circulation remains controversial. It has been suggested that collateral circulation possibly helps prevent myocardial ischemia. Seventeen target lesions in 15 patients were studied to determine the relationship between the extent of the coronary collateral circulation and the degree of ventricular dysfunction during percutaneous transluminal coronary angioplasty (PTCA). During the first balloon inflation, diastolic indices such as left ventricular end-diastolic pressure, max negative dP/dt and the time constant of early relaxation were measured immediately before and at 60 sec following balloon inflation. During the second inflation, the contralateral and ipsilateral collateral circulations were evaluated. The latter was graded as follows: 0 = none; I = filling of side branches only; II = partial filling of the epicardial segment; and III = complete filling of the epicardial segment. Following balloon inflation, a significant increase was noted in the time constant of early relaxation in patients with grade 0 collateral circulation (40 +/- 7 to 47 +/- 7 msec: p < 0.01) and grade II collateral circulation (52 +/- 12 to 56 +/- 13 msec: p < 0.05). The percent increase in the time constant of early relaxation of patients with grade 0 and I collateral circulations exceeded that of patients with grade II (p < 0.05) or grade III collateral circulation (p < 0.05). Left ventricular end-diastolic pressure was elevated in all groups during PTCA. There was no significant difference in the percent increase of left ventricular end-diastolic pressure (LVEDP) between the 4 groups. However, LVEDP before PTCA was higher in patients with grade III collateral circulation than in patients in the other groups. Max negative dP/dt did not change significantly in any group. In conclusion, collateral circulation helps prevent myocardial ischemia during acute coronary occlusion, which is most precisely shown by the time constant of early relaxation. The degree of this protective function of collateral circulation seems to vary.

Aged↗
PubMed1992

[Distribution of myocardial damage in patients with hypertrophic cardiomyopathy: evaluation by exercise thallium-201 scintigraphy].

The characteristic of myocardial damage in hypertrophic cardiomyopathy (HCM) was evaluated as to whether the damage is limited to the hypertrophied wall or extends throughout the entire wall. The myocardial damage was detected by exercise thallium-201 (Tl-201) scintigraphy and was evaluated using circumferential profile analysis, calculation of initial uptake and washout rate. Eleven patients with asymmetrical hypertrophy (ASH), whose septal and posterior wall thickness ratio exceeded 1.3 on left ventriculography and biventriculography, and 13 age-matched control subjects without heart disease were studied. The mean values of initial uptake in both groups did not differ significantly, but the washout rate for the entire heart was significantly decreased only in the HCM group (p < 0.05). All of the regional washout rates (antero-septal, apical and postero-lateral) were significantly decreased in the HCM group (p < 0.05), without any difference between the hypertrophied wall and the non-thickened free wall being noted. These results demonstrated that the analysis of myocardial damage by exercise Tl-201 scintigraphy using calculation of the washout rate is a very sensitive means of detecting myocardial damage in HCM, and that such myocardial damage is not restricted to the hypertrophied wall, but rather extends to the entire wall, including the free wall which is not thickened.

Aged↗