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T Oka

Publications and source records attributed to T Oka.

At least 1,009 records · Page 56Linked to original sources
PubMed1988

[Operations during a 5-year period (1982-1986) at our department].

The statistics of urological operations performed at our department between Jan., 1, 1982 and Dec., 31, 1986 were reviewed. During the 5 year period, 2331 patients were admitted to our hospital and 2192 urological operations were performed on 1834 patients. These statistics were compared with earlier statistics for two periods (1972-1976 and 1977-1981) and the recent trend of urological operations was investigated. With regard to operated organ, operations on the kidney were the most frequent followed by those on the urinary bladder. Operations on the ureter decreased during the recent 5 year period and they were the fourth most frequent following those on the scrotum, scrotal contents and penis. Operations on the adrenal gland, retroperitoneal space and parathyroid gland have gradually increased. As in the former report, transurethral resection of bladder tumor (TUR-Bt) was the most frequent and nephrectomy, TUR of prostate (TUR-P) and renal allotransplantation have followed. TUR-Bt and TUR-P have increased more and more and due to the introduction of percutaneous nephrolithotripsy and transureteral lithotripsy, open surgery for urolithiasis has greatly decreased. Endourological operations will still be on the increase.

Female↗
PubMed1988

[Dissolution therapy of struvite calculi with solution G].

In 6 patients (9 kidneys) irrigation with Solution G in the renal pelvis was performed for the dissolution of their infectious stones. Staghorn calculi larger than 30 mm in diameter were observed in all patients. In two kidneys all stones were dissolved and the rest were dissolved into small fragments that constituted no problem in those kidneys. Irrigation was done with no major side effects or complications. The dissolution of infectious stones with Solution G is another possible treatment that could be first chosen among percutaneous nephrolithotripsy, extracorporeal shock wave lithotripsy and other treatments.

Adolescent↗
PubMed1988

[Serum estrone sulfate levels in patients with breast cancer].

Estrone and estradiol-17 beta concentration in breast cancer tissue are reported to be an order of magnitude higher than those of circulating plasma in breast cancer patients. This high level of estrogen is provided by local production from estrone sulfate (E1-S) through the sulfatase pathway. Then serum E1-S level was determined using direct radioimmunoassay method in order to monitor the estrogen kinetics of post-operative breast cancer patients. Peri-operative sequential E1-S determination was carried out in 10 patients. Among them, extremely higher level, as compared with normal menstruating level of 625-2670pg/ml, was observed just after an administration of tamoxifen (three weeks after operation) in two of 5 pre-menopausal patients. In order to evaluate the effect of tamoxifen on serum level of E1-S in post-operative pre-menopausal patients, serum E1-S level in 42 post-operative outpatients was examined. Although there was no difference in the average level of E1-S in post-menopausal patients treated with or without tamoxifen, average E1-S level in pre-menopausal patients treated with tamoxifen as adjuvant therapy was significantly higher than that in patients without tamoxifen. These results suggests that the administration of tamoxifen to premenopausal patients should be reconsidered from a view point of the estrogen kinetics.

Adult↗
PubMed1988

[Clinical and pharmacokinetic evaluation of imipenem/cilastatin sodium in neonates and young infants].

Twenty three neonates and young infants were treated with imipenem/cilastatin sodium (IPM/CS) and its clinical efficacy and side effects were evaluated. Ages of the patients ranged from 0 to 83 days, and their body weights ranged from 750 to 4,760 g. Doses of IPM/CS ranged from 17.4 to 21.5 mg/kg as IPM every 6 to 12 hours for 3 to 12 days. Sixteen patients with infections including sepsis, meningitis and pneumonia, appeared to have responded to the IPM/CS treatment. Among them, clinical results were excellent in 2, good in 12 and fair in 2 patients. The drug was well tolerated, but 1 patient had diarrhea, 1 had redness of body during infusion, 1 had elevated GOT and GPT, and 2 patients showed only elevated values of GOT only among the 23 patients. The pharmacokinetics of IPM/CS were studied in 7 patients. Their ages ranged from 0 to 9 days, and body weights ranged from 2.5 to 4.0 kg. Serum concentrations of IPM were between 18.0 and 96.9 micrograms/ml and those of CS ranged 31.7 and 144.5 micrograms/ml in 6 patients at the end of intravenous drip infusion 20 mg/20 mg/kg during 30 or 60 minutes. Elimination half-lives of IPM ranged from 1.2 to 2.0 hours, and those of CS ranged from 1.4 to 2.7 hours. Serum concentrations of IPM was 14.7 micrograms/ml and that of CS was 32.4 micrograms/ml in 1 patient at the end of 30 minute-drip infusion 10 mg/10 mg/kg. The elimination half-lives of IPM was 1.5 hours, and that of CS was 2.9 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMed1988

Slow dissociation of the new slow-onset and long-acting calcium antagonist benidipine hydrochloride from 3H-nitrendipine binding sites.

The dissociation rates of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) and some calcium antagonists from 3H-nitrendipine binding sites were studied by a centrifugation technique and a filter-absorbed tissue method. KW-3049 dissociated from 3H-nitrendipine binding sites more slowly than other calcium antagonist, namely nifedipine, nitrendipine, nilvadipine, nicardipine and nisoldipine. The slow dissociation of KW-3049 from 3H-nitrendipine binding sites was supported by the equilibrium binding studies. When KW-3049 was preincubated with rat cardiac membrane, its inhibitory potency was enhanced 2.6-fold, whereas nifedipine did not alter its potency. In ex vivo binding, following administration of KW-3049 to rat, 3H-nitrendipine binding site was occupied in a dose-dependent manner and this occupation returned to a control level after 24 h. These results of receptor binding studies are in agreement with the pharmacological characteristics of KW-3049.

Animals↗
PubMed1988

Antihypertensive effects of intravenous administration of benidipine hydrochloride and some other calcium antagonists in conscious, spontaneously hypertensive rats.

The antihypertensive effect of intravenously administered (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was examined in conscious, spontaneously hypertensive rats (SHR) and comparatively evaluated with those of nifedipine, nicardipine, nitrendipine, nisoldipine, verapamil and diltiazem. When nifedipine (10 and 100 micrograms/kg), nicardipine (10 and 100 micrograms/kg), nitrendipine (10 and 100 micrograms/kg), verapamil (100 and 1000 micrograms/kg) and diltiazem (100 and 1000 micrograms/kg) were intravenously administered to SHR, at their lower doses, only transient decreases of blood pressure were observed and, even at their higher doses, decreased blood pressures returned to the initial levels after 80 to 120 min. Nisoldipine at 10 micrograms/kg (i.v.) decreased the blood pressure (by 23 mmHg), lasting for 100 to 120 min, and the antihypertensive effect of 100 micrograms/kg (i.v.) of it (by 63 mmHg) lasted for longer than 240 min though a tendency of blood pressure to recover was observed. The peak effects of these 6 calcium antagonists were observed 1 min after the drug injection. When KW-3049 (1, 3, 10 and 30 micrograms/kg i.v.) was administered, a dose-dependent decrease of blood pressure (by 23 to 67 mmHg) was observed. The effect of KW-3049 was longer than those of the above 6 calcium antagonists, including nisoldipine. The maximal effects were attained 10 to 30 min after the drug injection and the decreased blood pressure did not return to an initial level even 180 min (at 1 and 3 micrograms/kg) and 240 min (at 10 and 30 micrograms/kg) after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in conscious, renal-hypertensive dogs.

The antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4- (m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was evaluated in conscious, renal-hypertensive dogs. When KW-3049 (0.1, 0.3 and 1 mg/kg) was orally administered, antihypertensive action and increased heart rate with peak time after 60 to 120 min of administration were observed, and the duration of actions at the dose of 0.3 mg/kg (p.o.) or more lasted for more than 7 h. When nifedipine (0.3 and 1 mg/kg) and nicardipine (1 and 3 mg/kg) were orally given, the duration of antihypertensive action was shorter. Nitrendipine (1 and 3 mg/kg p.o.) showed antihypertensive action and increased heart rate with peak time after 45 to 60 min of administration, and the duration of action at 3 mg/kg (p.o.) lasted for 7 h or longer. The antihypertensive activity of KW-3049 at the action peak was 6.1, 12.1 and 8.9 fold as compared with those of nifedipine, nicardipine and nitrendipine, respectively. Also, when KW-3049 at 0.3 mg/kg (p.o.) was administered after 1 h of propranolol (20 mg/kg p.o.) administration, the increase of the heart rate was markedly inhibited while its antihypertensive action remained unchanged. From these results, it was demonstrated that KW-3049 shows potent and long-lasting antihypertensive action with gradual appearance of action, and was suggested that it may be an useful antihypertensive agent.

Animals↗
PubMed1988

Effects of benidipine hydrochloride on atrioventricular conduction time and postural reflex in gallamine-immobilized cats.

Using gallamine-immobilized cats, the effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was compared with those of other drugs in terms of the propensity for atrioventricular conduction disturbances and orthostatic hypotension. The administration of KW-3049 at doses of 1 to 300 micrograms/kg i.v. dose-dependently lowered the blood pressure and also reduced the heart rate. In terms of the maximum blood pressure lowering activity, KW-3049 was similar in degree to nifedipine and approximately 30 times as potent as diltiazem, verapamil and phenoxybenzamine. KW-3049 as well as nifedipine, at doses with which the mean blood pressure can be reduced by 50 mmHg, hardly affected the PR-interval of ECG, whereas diltiazem and verapamil at their hypotensive doses markedly prolonged the PR interval. These four calcium antagonists at their high doses elicited 2nd or 3rd degree atrioventricular blocks in some cases. On the other hand, phenoxybenzamine did not affect the atrioventricular conduction at its hypotensive doses. Inhibitory action on the pressor responses to head-up tilting in cats was observed neither in KW-3049, nifedipine, verapamil nor diltiazem. On the contrary, phenoxybenzamine strongly inhibited the orthostatic pressor reflexes. From these results, it was suggested that in terms of the prolongation action of atrioventricular conduction KW-3049 is less potent than diltiazem and verapamil but similar in degree to nifedipine, and that KW-3049 is not likely to cause orthostatic hypotension.

Animals↗
PubMed1988

Antianginal effects of the new calcium antagonist benidipine hydrochloride in anesthetized rats and spontaneously hypertensive rats. Electrocardiographic study.

Antianginal effects of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) in various experimental angina-pectoris models (anesthetized rats, spontaneously hypertensive rats (SHR] were compared with those of nifedipine, propranolol and hydralazine. Furthermore, the effects of these drugs on the pressure-rate product were evaluated. 1. Vasopressin test (SHR): The administration of KW-3049 at 10 micrograms/kg (i.v.) developed an inhibitory effect comparable to that of nifedipine at 200 micrograms/kg (i.v.) against the ischemic ECG changes caused by the intravenous administration of vasopressin at 1 U/kg. The effects of KW-3049 at 3 and 10 mg/kg (p.o.) lasted for 8 h or more. 2. Coronary occlusion test (rat): The rise of T-wave of epicardial ECG following ligation of coronary artery was inhibited by the administration of KW-3049 at doses of 30 and 100 micrograms/kg i.v. Nifedipine at dose of 200 micrograms/kg i.v. was slightly effective. 3. Isoproterenol (isoprenaline) test (rat): The fall of ST in ECG by the continuous infusion of isoprenaline (10 micrograms/kg/min) was almost completely prevented by propranolol (500 micrograms/kg i.v.). Also, KW-3049 (200 micrograms/kg i.v.) and nifedipine (200 micrograms/kg i.v.) significantly inhibited the decline of ST, in which the former was more effective than the latter. 4. Anoxia test (SHR): The fall of ST and rise of T-wave of ECG, induced by stopping artificial respiration of gallamine-immobilized SHR, were suppressed by the administration of KW-3049 at doses of 10 and 30 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1988

Vasodilating effects of the new calcium antagonist benidipine hydrochloride in anesthetized dogs and cats.

Vasodilating effects of a new 1,4-dihydropyridine derivative, (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were investigated in anesthetized dogs and cats. Intravenous administrations of KW-3049 at doses of 0.3 to 10 micrograms/kg exhibited a greater vasodilation in vertebral and coronary arteries than in common carotid and femoral arteries. The maximal effects of KW-3049 were equal to or more potent than those of nifedipine and nicardipine. Vertebral and coronary vasodilation following intravenous administration of 10 micrograms/kg of KW-3049 continued for 240 min or more, whereas those following nifedipine or nicardipine (10 micrograms/kg i.v.) disappeared within 30 min. A gradual and long-lasting increase of the vertebral and coronary blood flows following the intraduodenal administration of KW-3049 (0.1 mg/kg) was observed as compared with those of nifedipine (0.3 mg/kg i.d.) and nicardipine (0.3 mg/kg i.d.). When KW-3049 at a dose of 0.1 micrograms/kg was intraarterially administered to vertebral or coronary arteries, the blood flow increased without affecting systemic blood pressure and its effects lasted longer than those of nifedipine and nicardipine (0.1 micrograms/kg i.a.). In particular, the duration time in increase of coronary blood flow by KW-3049 was extremely longer, i.e. 11-fold and 6-fold those by nifedipine and nicardipine, respectively. Coronary vasodilating effect of KW-3049 was influenced neither by propranolol, atropine, diphenhydramine nor by aminophylline. Moreover, KW-3049 did not affect the vasodilator effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of the new calcium antagonist benidipine hydrochloride on cardiohemodynamics in anesthetized dogs.

The effects of (+/-)-(R*)-2,6-dimethyl-4-(m-nitro-phenyl)-1,4-dihydropyridine -3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinylester, methylester hydrochloride (benidipine hydrochloride, KW-3049) on the cardiohemodynamics were investigated in open-chest, anesthetized dogs, in comparison with those of nifedipine. When KW-3049 at a dose of 3 micrograms/kg was intravenously administered, hypotensive action (delta dBP = -20 mmHg) with a peak attained 3 to 5 min after the administration was observed and its action lasted for 2 h or more. Simultaneously, a slight decrease of heart rate and continuous increases of LV max dp/dt and cardiac output were recognized. At the administration with 10 micrograms/kg i.v., hypotensive action (delta dBP = -35 mmHg) with a peak 3 min after the administration appeared and continued for 3 h or more. At this time, continuous decrease of heart rate by about 18% and continuous increase of cardiac output were observed. The LV max dp/dt transiently decreased and then turned to increase, and the cardiac work was continuously decreased. When nifedipine at doses of 10 or 50 micrograms/kg was intravenously administered, hypotensive action (delta dBP = -31 and -52 mmHg) with a peak attained 1 min after the administration was observed and its action rapidly began to recover. At the administration with 50 micrograms/kg i.v., the heart rate was slightly decreased (10%). The LV max dp/dt was transiently reduced by 18% at 10 micrograms/kg i.v. and by 45% at 50 micrograms/kg i.v., respectively, and the augmented cardiac output lasted for 30 to 60 min. At the administration of 50 micrograms/kg i.v., cardiac work was continuously decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Beneficial effects of the new calcium antagonist benidipine hydrochloride on myocardial dysfunction following coronary occlusion and reperfusion in anesthetized dogs.

The protective effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1, 4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) on ischemic myocardium was examined comparing with that of nifedipine in anesthetized dogs subjected to a brief (10 min) coronary artery occlusion and reperfusion (2h). Occlusion of left anterior descending coronary artery elicited elevation of ST-segment and T-wave of epicardial ECG in the ischemic area. Regional myocardial contractile force in this area was depressed throughout the reperfusion period as well as during coronary occlusion period. LV max dp/dt, stroke volume and cardiac output tended to be reduced. In the dogs pretreated with 10 micrograms/kg of KW-3049 (i.v.) and 50 micrograms/kg of nifedipine (i.v.), both of which lowered the blood pressure to the same extent, elevation of ST-segment and T-wave was inhibited, and the prevention of irreversible depression of regional myocardial contraction observed at reperfusion periods was slightly more prominent in KW-3049 administration group. Stroke volume and cardiac output in both KW-3049 and nifedipine administration groups were maintained at higher levels than those in control group throughout coronary occlusion and the following reperfusion periods. LV max dp/dt of KW-3049 administration group was kept higher than that of the control group, while the value of the nifedipine administration group changed as that of the control group. These results demonstrate that KW-3049 as well as nifedipine exert protective effects on ischemic myocardium induced by coronary occlusion and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Pharmacological actions of benidipine hydrochloride in several isolated smooth muscles and myocardium.

Using various isolated smooth muscles and myocardium, the calcium antagonistic effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049), and its specificity were examined. Furthermore, the in vitro duration of action and the antispasmodic actions in coronary arteries were investigated in comparison with those of nifedipine, verapamil and diltiazem. 1. Ca antagonisms of KW-3049 When the Ca antagonistic effect of KW-3049 was investigated, for which the contractile responses to KCl in isolated mesenteric arteries in rabbits were taken as an indicator, the activity of KW-3049 was of about the same degree as nifedipine and approx. 30 times greater than those of verapamil and diltiazem. On the other hand, the negative inotropic action in isolated atria in rabbits was weaker than that of nifedipine. 2. Influences on responses to various agonists From the investigations using various isolated organs, it was evident that KW-3049 had neither agonistic nor antagonistic actions or very weak actions on the following receptors: alpha 1, alpha 2, beta 1, beta 2, H1, H2, muscarinic acetylcholine, 5HT2, angiotensin II, and prostaglandin F2 alpha. 3. Duration of in vitro actions Inhibitory actions of KW-3049 on 55 mmol/l-induced contractions in isolated mesenteric arteries in rabbits persisted even 180 min after the removal of drug solution and the repeated wash-out of tissues. On the other hand, those of nifedipine, verapamil and diltiazem disappeared within 60 to 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Gas chromatographic method for the quantification of the new calcium antagonist benidipine hydrochloride in plasma using electron capture detection.

A gas chromatographic assay procedure was developed for measuring subnanogram order concentrations of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) in plasma. KW-3049 yielded the oxidation product partially during gas chromatography. To avoid decomposition, KW-3049 was oxidized in advance by nitrogen dioxide, extracted by diethylether under alkaline condition, chromatographed on the OV-1 column and measured using electron capture detector.

Animals↗
PubMed1988

Sensitive radioreceptor assay of the calcium antagonist benidipine hydrochloride in plasma and urine.

Plasma and urinary concentrations of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were measured by the radioreceptor assay using 3H-nitrendipine and rat cardiac membrane receptor. After methanol deproteinization and ethyl ether extraction under alkaline conditions as pretreatment, the detection limit for KW-3049 in plasma was 0.2 ng/ml using 0.5 ml of sample. For the urine, 0.05 ml of urine sample was directly added to the assay system, and detection limit of drug was 1 ng/ml. The cross-reactivity of the presumable metabolites was 1% or less of the unchanged drug. This radioreceptor technique was applied to pharmacokinetic studies and useful for monitoring the drug after therapeutic dosing.

Animals↗