Kazuki Kawabe

Use of an α1-Blocker, YM617, in the Treatment of Benign Prostatic Hypertrophy

AbstractA recently synthesized αl-blocker, (R)(-)-5-[2-[[2-(o-ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide hydrochloride (YM617), was evaluated in 270 patients with benign prostatic hypertrophy in a double-blind study. After 2 weeks on placebo the patients were assigned at random to 4 groups: group P—placebo, group L—0.1mg., group M—0.2mg. and group H—0.4mg. of YM617. Comparing the placebo to the treatment period, subjective symptoms, such as nocturia and urgency, were significantly decreased in group H (p <0.01). The sensation of incomplete voiding was significantly improved in groups M and H (p <0.01). However, the differences among the groups were statistically insignificant. Residual urine volume was significantly decreased in groups L, M and H after instillation of saline into the bladder (p <0.01) but not in group P. The maximum and average flow rates were significantly increased in groups L, M and H (p <0.01) but not in group P. Average flow rate showed significant differences bet...

Laparoscopic Adrenalectomy: Clinical Experience with 12 Cases

Laparoscopic adrenalectomy is a new procedure for the treatment of adrenal tumors. The clinical experience with this operation in 12 patients is reported. While adrenal tumors are relatively small and seem to be good candidates for laparoscopic surgery, this procedure is difficult because of the anatomical location. In our study laparoscopic adrenalectomy appeared to be successful, although massive bleeding occurred in 3 patients. These problems should be overcome as the technique is improved and new laparoscopic instruments are introduced.

NOCTURIA IN THE ADULT: CLASSIFICATION ON THE BASIS OF LARGEST VOIDED VOLUME AND NOCTURNAL URINE PRODUCTION

PURPOSE We propose a criterion to clarify the underlying etiologies of nocturia. MATERIALS AND METHODS Frequency-volume charts were recorded for 24 hours by 35 men and 32 women who were subjectively free of lower urinary tract symptoms and had no evidence of voiding disorders. At least 5 subjects were included in each of 5 age groups of 20 to 49, 50 to 59, 60 to 69, 70 to 79, 80 to 89 years for both genders. The charts were used to make a tentative criterion, which was validated in 39 elderly individuals with nocturnal frequency. RESULTS Correlation and regression analyses indicated that the quotients of nocturnal urine output divided by body weight (U(N)/BW) and largest voided volume divided by body weight (V(L)/BW) were useful classification factors. Cutoffs, which were set close to worst quartiles, were 10 ml./kg. for U(N)/BW and 4 ml./kg. for V(L)/BW, respectively. Correction by body weight made the same criterion applicable irrespective of weight. Symptomatic elderly patients were classified into 3 mutually exclusive groups of nocturnal polyuria (U(N)/BW greater than 10 ml./kg.), low bladder capacity (V(L)/BW less than 4 ml./kg.) and combined nocturia. Of 20 subjects who voided 2 times a night 11 (55%) were classified as having nocturnal polyuria and 15 of 19 who voided 3 or 4 times (79%) were classified as having low bladder capacity or combined nocturia. CONCLUSIONS The criterion provides a reasonable distinction of etiologies of nocturia, and may be usefulness in examination and treatment.

Binding characteristics of naftopidil and α1-adrenoceptor antagonists to prostatic α-adrenoceptors in benign prostatic hypertrophy

Abstract Binding properties of naftopidil and α 1 -adrenoceptor antagonists to α-adrenoceptors in prostates from benign prostatic hypertrophy (BPH) were characterized by radioreceptor assays usinh [ 3 H]prazosin and [ 3 ]- rauwolscine. Specific binding of [ 3 H]prazosin and [ 3 H] rauwolscine in human prostatic membranes was saturable and of high affinity, and it showed a pharmacological specificiwhich characterized α 1 and α 2 - adrenoceptors, respectively. Naftopidil and several α 1 antagonists competed for prostatic [ 3 H]prazosin binding in order: R-(-)-YM-12617 >prazosin>bonazosin>terazosin>naftopidil>urapidil, and the inhibitory effect (Ki = 11.6 nM) of naftopidil was 10 to 45 times less potent than quinazoline derivatives such as prazosin, bunazosin and terazosin. The potencies of these antagonists in competing for [ 3 H]prazosin binding sites in human prostates correlated well with their pharmacological potencies (pA 2 ). Scatchard analysis indicated that the decrease of prostatic [ 3 H]prazosin binding by naftopidil was due to a marked increase in the Kd value without a change in the Bmax value. The inhibition of prostatic [ 3 H]prazosin binding by naftopidil was reversible. Naftopidil also inhibited prostatic [ 3 H]rauwolscine binding (Ki = 70.0 nM). Thus, it is suggested that naftopidil antagonizes α 1 -adrenoceptors in human prostates in a competitive and reversible manner.

Gasless Laparoscopy-Assisted Nephrectomy without Tissue Morcellation for Renal Carcinoma

PURPOSE The efficacy of gasless laparoscopy-assisted nephrectomy for renal tumors is determined. MATERIALS AND METHODS Seven patients with renal tumors underwent gasless laparoscopy-assisted nephrectomy. The results were compared to those of patients undergoing open nephrectomy. RESULTS Although a long operating time was required, convalescence was significantly more rapid. En bloc removal of the kidney and complete pathological examination were possible in all patients. CONCLUSIONS This procedure may be useful for the treatment of noninvasive renal carcinoma, especially in patients with cardiovascular and/or ventilatory complications. However, long-term followup is necessary to confirm the efficacy in preventing recurrence.

Density and Localization of Alpha1-Adrenoceptors in Hypertrophied Prostate

Alpha-adrenoceptors have been considered to play an important role in the regulation of the voiding force. In order to determine the density and localization of the alpha-adrenoceptors in the prostate, binding assays for alpha-adrenoceptors were performed with [3H]prazosin and [3H] yohimbine in membrane preparations from enucleated hyperplastic prostate tissues. Furthermore, autoradiographic analysis of alpha-adrenoceptors in the sliced tissue specimens from benign prostatic hypertrophy was performed. Specific binding of both ligands were saturable and of high affinity in membrane preparations, and Scatchard analyses indicated Bmax = 104 fmole/mg. protein, Kd = 0.488 nM for [3H]prazosin, and Bmax = 41 fmole/mg, protein, Kd = 1.83 nM for [3H] yohimbine. Bmax and Kd for [3H]prazosin were greater in the adenoma than in the submucosal tissue of the prostatic urethra. No relationship was noted between the size of enucleated prostate and the density of alpha-adrenoceptors. Image analysis of autoradiograms using [3H]prazosin showed specific binding sites could not be clearly demonstrated, but only [125I]HEAT slightly exposed specific binding sites in the prostate.

[3H]Bunazosin, a Novel Selective Radioligand of Alpha1 Adrenoceptors in Human Prostates

The binding properties of a new radioligand, [3H]bunazosin, were studied in membranes of human prostates with benign prostatic hypertrophy (BPH). Specific binding of [3H]bunazosin was saturable, reversible, and of high affinity (Kd = 0.55 +/- 0.04 nM). The density of [3H]bunazosin binding sites (Bmax) was 676 +/- 33 fmol/mg. protein. [3H]Bunazosin rapidly associated with its binding sites in membranes of human prostates and reached steady state by 20 min. at 25C. The rate constants for association and dissociation of [3H]bunazosin binding were calculated to be 0.11 +/- 0.01/nM/min. and 0.05 +/- 0.02/min. (n = 4), respectively. Seven alpha 1 adrenoceptor antagonists competed with [3H]bunazosin for the binding sites in the rank order: R-(-)-YM-12617 greater than prazosin greater than SGB-1534 greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil. In parallel studies with [3H]bunazosin, the Kd and Bmax values for [3H]prazosin binding in human prostates were slightly lower. There was a similarity in the potency and rank order of seven alpha 1, adrenoceptor antagonists for the inhibition of [3H] bunazosin and [3H]prazosin binding in human prostates. The new [3H]bunazosin binding assay in human prostates is remarkable for its low degree of nonspecific binding as compared to [3H]prazosin, especially at high ligand concentrations. Thus, [3H]bunazosin may become a useful radioligand for the further analysis of the alph 1 adrenoceptor binding sites in human prostates.

Treatment of ureteral and renal stones by electrohydraulic lithotripsy

Manipulation of ureteral and renal calculi can be done under direct vision using a fiberscope with increased safety and efficacy. We treated 207 ureteral and renal stones in 198 patients using electrohydraulic lithotriptor combined with transurethral fiberscope from July 1985 till January 1991. Electrohydraulic lithotripsy (EHL) successfully fragmented 187 out of 207 stones (90.3%). A total of 119 patients (57.5%) became stone-free 3 months after operation, which increased to 170 cases (82.1%) at a mean follow-up of 20 months. There were 6 ureteral perforations (4 due to fiberscope and 2 due to EHL spark damage to the ureteral mucosa), which were treated immediately by open operation (2.9%). In 7 cases (3.4%), the stone could not be fragmented due to its hardness.We believe electrohydraulic lithotripsy treatment combined with transurethral fiberscopy is a safe, effective, noninvasine and economical method for the treatment of urinary tract stones.