The hemodynamic effects of a new betablocking agent, acebutolol, dl-1- (2 acetyl-4-butyramidophenoxy) -2-hydroxy-3-isopropylaminopropane hydrochloride were studied in 10 dogs anesthetized with pentobarbital sodium and 33% nitrous oxide in oxygen.
1 mg/kg of acebutolol was given intravenously every 5-7 minutes up to total dose of 5 mg/kg. The administration of increasing doses of acebutolol produced a progressive decrease in heart rate (3 mg/kg, P<0.01), mean arterial pressure (2 mg/kg, P<0.01), left ventricular pressure (3 mg/kg, P<0.01), first derivative of left ventricular pressure (4 mg/kg, P<0.05), peak aortic flow velocity (3 mg/kg, P<0.05), acceleration of aortic flow (4 mg/kg, P<0.05), cardiac output (2 mg/kg, P<0.05), and cardiac work (2 mg/kg, P<0.05), while left ventricular end-diastolic pressure was increased progressively (2 mg/kg, P<0.05). Total peripheral resis tance was not altered significantly. So called Vmax (V' max) as an index of myocardial contractility obtained by extrapolation of the pressure-velocity descending limb to zero load was progressively decreased (3 mg/kg, P<0.05). Based on the fact that heart rate, ventricular wall tension (or ventricular pressure), and myocardial contractility correlates closely with myocardial oxygen consumption, it was postulated from above findings that acebutolol would decrease myocardial oxygen consumption. Acebutolol in a dose which did not significantly depress myocardial contractility (V' max, dp/dt) in normal heart showed an antiarrhythmic effect on epinephrine induced ventricular arrhythmia during halothane anesthesia.
In conclusion acebutolol could be considered as a clinically useful drug to relieve anginal attack and to control cardiac tachyarrhythmia and hypertension. However, it should be emphasized that acebutolol has a possibility to cause heart failure, if it was used in unreasonable high dose.

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The pharmacokinetic evaluation of tranexamic acid following intravenous (i. v.) and intramuscular (i. m.) administrations to three volunteers, and oral administration (p. o.) to ten volunteers was made. The results obtained from various admini stration routes are discussed.
The maximum plasma levels of tranexamic acid were 21.2 μg/ml at 0.5 hour after i. m. administration (500 mg dose), and 6.0 μg/ml at 2 hours after oral admini stration (500 mg dose), and the plasma level at 15 minutes after i. v. administration (1000 mg dose) was 60 μg/ml. The biological half-lives for i. v., i, m. and p. o. were 1.9, 2.0 and 3.3 hours, respectively. Urinary excretion of tranexamic acid during 24 hours after administration was 80% of the dose for i. v., 76% for i. m. and 40-70% for p. o. This suggests that tranexamic acid is absorbed slowly from the intestine and is mainly eliminated from the kidney.

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The effect of instant coffee, its caffeine-free product (Nescafé) and caffeine on operant behaviors were investigated in rats well trained on fixed ratio (FR30) or fixed interval (FI·1) schedule of food reinforcement. The effect on conditioned suppression, which was produced by electric shock associated with the reinforcement and component alternation under the same schedule, was also observed. Both FR and FI responses significantly increased after oral administrations of 0.125-0.5g/kg of instant coffee, when compared with those after the same dosings of caffeine-free product. These changes, however, did not reveal the linear dose-effect corelation. Almost the same pattern of the changes was obtained when 2.5-20 mg/kg of caffeine were given orally.
On the other hand, markedly attenuated effect on the conditioned suppression was observed in fairly good parallel with the dosages of instant coffee and caffeine with the exception of caffeine-free product, especially in FR schedule.
From these results, it is assumed that in some conditions coffee or caffeine may show not only a stimulative effect on operant respondings but also an anti-anxiety effect.

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The purpose of the present study was to elucidate an anxiolytic drug effects on reminiscence by mirror drawing test and a sequential optimum selection plan with Play-the-Winner sampling and the stopping rules in a finite population in this experiment.
The subjects were thirty healthy volunteers of junior college women. They were tried on mirror drawing test, two three-minute work periods being separated by a forty-minute rest pause. After the first work period, one group was given a tablet of ID-540 0.5 mg and the other group, a placebo by double blind method. The tests were repeated 15 times for the respective pairs drawn from both groups.
As the results, reminiscence was not found out the drug-group but for the placebo-group, so that the effect of dissociation of learnig was found in anxiolytic drug.
In the veiw of such a decision procedure, an extensive Play-the-Winner Sam pling Rule, with a successive success stopping rule, was proposed to select the stronger of two treatments on the drug effects in the ethical sence, which gave us the minimum expected loss in a finite population.

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The precise accumulation method, a new method of analysis of variance, may be more appropriate for the analysis of survival-time data than hitherto used other methods in respect of following points;
1) Factors that may affect survival are compared properly over the entire period rather than at the isolated time points only. Mean lengths of survival and rates of survival at respective time points are estimated simultaneously.
2) Interactions between factors and time are calculated as well as main effects of factors, hence it enables one to test the difference between patterns of survival curves.
3) Uneveness of the sizes among patient groups is treated by harmonic mean method. Missing data arising from loss of follow up etc. are handled by successive approximation method.
As an example of application of this method, the statistical analysis of survival-time data of prostatic cancer patients in Sapporo Medical College for evaluation of estrogen therapy was presented.

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