Injection of polydimethylsiloxane at the bladder neck achieved continence in 34% of neurogenic bladder cases. Results were better in girls with a stable bladder. Results deteriorated in the first 12 months of followup. No more than 3 injections are advised if a satisfactory result is not achieved.
Experiments were performed in which the effects of two β-blockers, tertatolol [dl-(hydroxy-2’-t-butyl-amino-3’-propyloxy)-8-thiochroman hydrochloride] and propranolol, on mean arterial pressure (MAP), heart rate (HR), and renal function were studied in the conscious sodium-replete dog. In all experiments renal function was evaluated from the effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) assessed respectively by measurement of p-aminohippurate and creatinine clearances. These parameters were measured during two 30-min control periods, after which two further measurements were performed over a similar time period, after intravenous administration of either propranolol (0.5 mg·kg-1; n = 8) or tertatolol (0.05 mg·kg-1; n = 8), these two doses being of equivalent β-adrenoceptor antagonist activity. Administration of propranolol and tertatolol did not change MAP but induced a significant and comparable decrease in HR. After propranolol a significant decrease in ERPF was observed, without any change in GFR or sodium excretion. In contrast, administration of tertatolol resulted in no modification of ERPF, a slight but significant increase in GFR, and a significant increase in sodium and potassium excretion. These results suggest that tertatolol and propranolol though acting similarly on systemic parameters have different effects on renal hemodynamics in the conscious dog.
The determination of the optimum dosage for antihypertensive therapy, i.e. the unit dose and the administration frequency, remains one of the least discussed subjects. For β-blockers as well as for other drugs, this determination is mainly based on the dose-effectiveness curve, the top of which corresponds to the right dose. Thus, a wide range of doses should be tested, and this as early as possible during drug development. The first step is to assess the optimum β-blocking dose in healthy volunteers during phase I studies. These dose-response studies are usually performed according to a cross-over design. Among the many techniques proposed for assessing the effects of β-blockers in man, isoprenaline and dynamic exercise tests are the most commonly used. The second step is to make use of the previous results to find the right dose for hypertensive patients in phase II studies. However, many individual factors which can influence the blood pressure response should be kept in mind, especially the initial blood pressure level. The choice of the design is generally based on the need to have repeated administration in order to obtain optimum control of the hypertension. Therefore, the cross-over design, although theoretically the best one, is rarely used on account of its practical and ethical problems. In contrast, the parallel design, with random assignment of treatments, is suitable to most experimental situations. Very different in nature, the stepped dose design stems from an ethical and practical approach of dose finding and thus is also widely used. Finally, correct measurement techniques of blood pressure are required. In this respect, accuracy of evaluation is markedly improved by automated noninvasive methods which allow a 24-hour recording of blood pressure and minimize the placebo effect by suppressing the subjective aspects of measurement. From this methodology applied to tertatolol, a new β-blocking drug, 5 mg was found to be the optimum dose in antihypertensive treatment. This dose caused an effective reduction in blood pressure both at rest and on exercise, a 24-hour antihypertensive activity and a high incidence of hypertension control both in short-term and long-term therapy. Thus, 5 mg tertatolol administered once daily may be recommended in the treatment of mild to moderate hypertension.
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