Influence of Naftopidil on Plasma Monoamine Levels and Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia.

OBJECTIVES: To clarify the influence of naftopidil, an α1D/A -adrenergic receptor antagonist, on the autonomic nervous system, we examined the relation between lower urinary tract symptoms (LUTS) and the plasma monoamine levels before and after naftopidil treatment in benign prostatic hyperplasia (BPH) patients. METHODS: A total of 43 patients with BPH were studied. The frequency of urination, international prostate symptom score (IPSS), quality of life (QOL) index, overactive bladder symptom score (OABSS), and plasma monoamine levels (adrenaline, noradrenaline, dopamine, and serotonin) were evaluated before and after naftopidil treatment. RESULTS: Naftopidil significantly improved urinary frequency in daytime and nighttime, IPSS, QOL index and OABSS in all patients, and decreased the plasma adrenaline level at 8 weeks. When the patients were divided into two groups based on the median adrenaline level (40.5 pg/mL) before treatment, urinary frequency in daytime and/or nighttime, incomplete emptying and poor flow in the IPSS, and the QOL index were significantly improved in the high adrenaline (HA) group, but not in the low adrenaline (LA) group. The pretreatment plasma serotonin level was significantly lower in the HA group than in the LA group, but it increased gradually after the start of treatment until there was no difference between the groups. CONCLUSIONS: The modulation of plasma adrenaline and serotonin levels by naftopidil in patients with increased sympathetic activity contributed to improvement of LUTS associated with BPH, in addition to its antagonistic effects of α1D/A -adrenergic receptor on the detrusor and prostatic urethral smooth muscle, the urothelium, and the central nervous system.

[Effect of distigmine at 5 mg daily in patients with detrusor underactivity].

PURPOSE: Since distigmine can cause the serious side effect of cholinergic crisis, its dosage regimen has been reduced to 5 mg/day for patients with difficulty in urination due to detrusor underactivity. Therefore, the efficacy and safety of add-on therapy with distigmine at 5 mg daily were examined in patients with persistent urination problems due to detrusor underactivity despite administration of alpha1-blockers. PATIENTS AND METHODS: The subjects were 39 patients with underactive bladder (18 men and 21 women with an average age of 75 years) who showed no improvement of difficulty in urination or had a residual urine volume > or = 50 ml despite the administration of alpha1-blockers for more than 4 weeks. They received treatment with distigmine (5 mg daily after breakfast) in addition to their alpha1-blockers for 8 weeks. The international prostate symptom score (IPSS), quality-of-life (QOL) score, residual urine volume, blood pressure, and biochemistry tests were investigated before and after addition of distigmine. RESULTS: After four and eight weeks of distigmine administration, all items of the IPSS and QOL score, as well as the residual urine volume, showed a significant decrease. In contrast, the pressure and pulse rate were unchanged. Serum creatinine showed a slight but significant decreased. As adverse events, frequent defecation, fecal incontinence, diarrhea, frequent urination and poor physical condition were recognized in 4 patients, but there was no serious event. CONCLUSION: For difficulty in urination due to detrusor underactivity, the combination of an alpha1-blocker with distigmine at 5 mg daily showed early efficacy and good safety.

Evidence for an association between increased oxidative stress and derangement of FOXO1 signaling in tumorigenesis of a cellular angiofibroma with monoallelic 13q14: a case report.

Cellular angiofibroma (CAF) is a rare soft tissue tumor characterized by random arrangement of spindle tumor cells in the stroma with short collagen bundles and thick- and hyalinized small vessels. CAFs share histological characteristics with spindle cell lipomas and mammary type myofibroblastomas. Because these tumors harbor monoallelic 13q14, common genetic and molecular mechanism for tumorigenesis is presumed. In this study, we reported a case of CAF in a 69-year-old man with monoallelic 13q14. Immunohistochemical analysis revealed that FOXO1, which is located in chromosome 13q14, was not expressed in the tumor. We also detected oxidative stress markers and found p38 MAPK activation, which is often induced by cellular stressors such as reactive oxygen species (ROS). Because FOXO1 induces the expression of genes encoding enzymes that generate antioxidants, oxidative stress induced by loss of FOXO1 expression may be common among CAFs, spindle cell lipomas, and mammary type myofibroblastomas.

Effect of Imidafenacin before Sleeping on Nocturia.

OBJECTIVES: Clinical efficacy, influence on quality of life (QOL), and safety of imidafenacin before sleeping were assessed in patients with overactive bladder (OAB) who suffered from nocturia. METHODS: A total of 60 OAB patients with a mean age of 74 years (45 men and 15 women) who mainly complained of nocturia were enrolled. Imidafenacin (0.1 mg) was administered once daily before sleeping for four weeks. Then the patients were divided into two groups, "a stable-dose group" with sufficient efficacy who remained on 0.1 mg of imidafenacin daily, and "a dose-escalation group" with insufficient efficacy in whom the daily dose of imidafenacin was increased to 0.2 mg before sleeping. Lower urinary tract symptoms and postvoid residual volume (PVR) were examined before treatment and after 4 and 8 weeks of imidafenacin therapy. RESULTS: In the stable-dose group, nighttime frequency decreased significantly from 3.4 ± 1.1 to 2.3 ± 1.1 and 2.6 ± 2.0 times after four and eight weeks, respectively. In the dose-escalation group, nighttime frequency did not change significantly (from 3.8 ± 1.5 to 3.6 ± 1.8 times) at four weeks, but decreased significantly to 2.8 ± 1.4 times at eight weeks. Daytime frequency, OAB symptom score, and IPSS-QOL index score were significantly improved in both groups at four and/or eight weeks. There was no increase of PVR and no serious adverse events. CONCLUSION: Administration of imidafenacin at 0.1-0.2 mg once daily before sleeping was safe and effective for the treatment of OAB with the main symptom of nocturia.

[Risk factors for duration of urinary incontinence after radical prostatectomy].

PURPOSE: In this study, we examined risk factors for duration of incontinence after radical prostatectomy at our hospital. MATERIALS AND METHODS: From April 1988 to March 2000, 45 patients with prostate cancer underwent retropubic radical prostatectomy at our hospital. Thirty-eight of 45 patients could be followed up. The patients' age, height, weight, body mass index (BMI), preoperative prostatic specific antigen level, clinical stage, nerve-sparing surgery or none, operation time, bleeding volume, resected prostate weight, cancer positive or negative at surgical margins, postoperative stage, radiation therapy or none, anti-androgen therapy or none, duration of postoperative incontinence, and follow-up period were examined. RESULTS: All patients had postoperative stress incontinence, and no one had urge incontinence. Medians of duration of postoperative incontinence and follow-up period were 5.5 and 12 months, respectively. When the patients were divided into 2 groups by the value of each parameter, postoperative anti-androgen therapy (chi 2 test, p = 0.0429) and high BMI (> or = 25.0 kg/m2, p = 0.0206) were related to the long duration (> or = 5.5 months) of postoperative incontinence. CONCLUSION: These results suggest that common factors are involved in the etiology of prolonged incontinence after radical prostatectomy and genuine stress incontinence in women. Therefore, both body weight control and pelvic floor muscle exercise might be also important for the treatment of incontinence after radical prostatectomy.