The efficacy and safety of duloxetine in a multidrug regimen for chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE To evaluate the efficacy and safety of duloxetine hydrochloride in the treatment of patients affected by chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS Thirty-eight CP/CPPS patients completed the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Index of Erectile Function-Erectile Function-5 (IIEF-5) questionnaires, uroflowmetry, and evaluation of psychologic status using Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Scale (HAM-D). Patients were randomly assigned to 2 treatments groups. Treatment in group 1 consisted of a simultaneous oral administration of tamsulosin (0.4 mg/d, 60 mg/d), saw palmetto (320 mg/d), and duloxetine (60 mg/d). Treatment in group 2 consisted of tamsulosin (0.4 mg/d) and saw palmetto (320 mg/d). NIH-CPSI and IIEF-5 questionnaires, uroflowmetry, and evaluation of the psychological status were repeated at 16 weeks of follow-up. RESULTS At 16 weeks, a significant improvement in NIH-CPSI pain subscore, NIH-CPSI quality of life subscore, and NIH-CPSI total score were observed in group 1 patients compared with those in group 2 (P <.01, respectively), together with a significant improvement in HAM-A and HAM-D scores (P <.01, respectively). Patients in group 2 showed a significant improvement in NIH-CPSI total score, in the urinary symptoms subscore, and in the HAM-A total score. No significant differences were observed in IIEF-5 scores in the 2 groups. Maximum flow rate significantly increased in both groups. In group 1, 20% of patients stopped the study due to adverse effects. CONCLUSION The use of duloxetine in a multimodal treatment with an alpha-blocker medication and a saw palmetto extract allowed better results in controlling clinical symptoms, psychologic status and quality of life patients affected by CP/CPPS

Pelvic floor muscle behavior during Valsalva leak point pressure measurement in males and females affected by stress urinary incontinence.

PURPOSE: We evaluated pelvic floor muscle (PFM) behavior during Valsalva leak point pressure (VLPP) measurement in males and females affected by stress urinary incontinence and investigated whether VLPP results are influenced by PFM contraction. MATERIALS AND METHODS: A total of 25 females and 14 males underwent surface electromyographic (EMG) recording of PFM activity while performing VLPP. We investigated 2 conditions, VLPP during spontaneous strain (test A), and with simultaneous relaxation of the pelvic floor (test B). We analyzed average EMG activity (microV) at rest and during VLPP in tests A and B, the increasing EMG activity during tests A and B (the difference between average EMG activity during tests A and B and at rest), and the mean duration (seconds) of EMG activity during tests A and B. RESULTS: We detected a significant increase in EMG activity during tests A and B as compared to activity at rest (p <0.0001). Increasing EMG activity during test B was significantly reduced in females (p <0.05) but not in males. During test A patients reporting urinary incontinence showed a significantly lower EMG activity than that of continent patients (p <0.05). A significant reduction in maximum abdominal pressure was detected in test B compared to test A, but there was no difference in VLPP values between tests A and B. CONCLUSIONS: PFM activity significantly increases during VLPP measurement. Eliminating muscular contraction of the pelvic floor does not significantly alter VLPP results

Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: A pilot study

Objective: We evaluated the efficacy and tolerability of botulinum A toxin (BTX-A) intravesical injections in patients affected by painful bladder syndrome with increased urinary frequency, refractory to conventional treatment modalities. Methods: Twelve women and two men were prospectively included in the study. Under short general anaesthesia patients were given injections of 200 U of commercially available BTX-A diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the trigone and bladder floor under cystoscopic control. Voiding chart, the Visual Analog Scale (VAS) for pain, and urodynamics were performed before treatment and 1 and 3 mo afterward. Results: Overall, 12 patients (85.7%) reported subjective improvement at 1 and 3 mo follow-up. The mean VAS score was significantly reduced at 1 and 3 mo after treatment (p < 0.05 for both); at the same time points daytime and nighttime urinary frequency significantly decreased (p < 0.01 and p < 0.05, respectively), and bladder cystometric capacity significantly increased (p < 0.01). Two patients reported incomplete bladder emptying. We did not detect any systemic side effects during or after treatment. Conclusions: The results of this pilot study indicate that BTX-A intravesical injections are effective in the short-term management of painful bladder syndrome. By modulating afferent C-fiber activity within the bladder walls, BTX-A significantly improves urodynamic parameters and reduces bladder pain and urinary frequency

Intravesical oxybutynin: mode of action assessed by passive diffusion and electromotive administration with pharmacokinetics of oxybutynin and N-desethyl oxybutynin.

PURPOSE: A proportion of patients with detrusor hyperreflexia who are unresponsive to oral oxybutynin often benefit from intravesical oxybutynin instillation. To our knowledge the precise mode of action of this method is obscure. MATERIALS AND METHODS: In 12 patients with detrusor hyperreflexia who were previously unresponsive to oral and intravesical passive diffusion of 5 mg. oxybutynin we administered 5 mg. oxybutynin orally as well as increased doses of 15 mg. oxybutynin intravesically with passive diffusion and with 15 mA. associated electric current. Each administration mode per patient was associated with an 8-hour urodynamic monitoring session during which oxybutynin and N-desethyl oxybutynin plasma levels, and intravesical oxybutynin uptake were measured. RESULTS: A dose of 5 mg. oxybutynin orally induced no urodynamic improvement with an area under the plasma concentration time curve of combined N-desethyl oxybutynin plus oxybutynin of 16,297 ng./8 hours and an area under the curve ratio of N-desethyl oxybutynin-to-oxybutynin of 11:1. Passive diffusion oxybutynin resulted in 12 mg. oxybutynin intravesical uptake and significant improvement in 3 of 8 urodynamic measurements, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was only 2,123 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was 1.1:1.0. Electromotive administration of oxybutynin resulted in almost complete intravesical uptake of the 15 mg. dose, significant improvement in all 8 urodynamic measurements and an increased oxybutynin level versus oral and passive diffusion, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was 4,574 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was inverted at 1.0:1.4. The oral dose of 5 mg. oxybutynin caused anticholinergic side effects in 8 of the 12 patients. Neither intravesical passive diffusion nor electromotive administration caused side effects with an uptake of 12 and 15 mg., respectively. CONCLUSIONS: A large proportion of intravesical oxybutynin is sequestered, probably in the urothelium. Intravesical oxybutynin administration confers therapeutic benefits via localized direct action within the bladder wall. Comment in Intravesical treatment of bladder dysfunction. [J Urol. 2001

Assessment of Botulinum a Toxin High Affinity SV2 Receptors on Normal Human Urothelial Cells.

The clinical use of Botulinum A toxin (BoNT/A) is based on its ability to block the vesicular release of Acetilcholine (Ach) and other neurotransmitters at the level of the neuronal plasmatic membrane. This process requires the internalization of the neurotoxin within the target cell, what it happens by means of the binding with high affinity receptors. These receptors are the synaptic vesicle proteins type 2 (SV2). To date three different types of SV2 receptors have been identified in synaptic structures and endocrine tissues

Botulinum-A toxin injections into the detrusor muscle decrease nerve growth factor bladder tissue levels in patients with neurogenic detrusor overactivity

Purpose: We investigated the effects of BTX-A on visceral afferent nerve transmission by measuring bladder tissue NGF levels in patients with neurogenic detrusor overactivity before and after intravesical treatment with BTX-A. We also compared the bladder tissue NGF content with clinical and urodynamic data. Materials and Methods: A total of 23 patients underwent clinical evaluation and urodynamics with detection of the UDC threshold, maximum pressure and maximum cystometric capacity before, and at the 1 and 3-month followups. Endoscopic bladder Wall biopsies were also obtained at the same time points. NGF levels were measured in tissue homogenate by enzyme-linked immunosorbent assay (Promega, Madison, Wisconsin). Results: At 1 and 3 months mean catheterization and incontinent episodes were significantly decreased (p < 0.05 and < 0.001, respectively). On urodynamics we detected a significant increase in the UDC threshold and maximum cystometric capacity, and a significant decrease in UDC maximum pressure at the 1 and 3-month followups compared to baseline (each p < 0.001). At the same time points we detected a significant decrease in NGF bladder tissue content (each p < 0.02). Conclusions: BTX-A intravesical treatment induces a state of NGF deprivation in bladder tissue that persists at least up to 4 months. As caused by BTX-A, the decrease in acetylcholine release at the presynaptic level may induce a decrease in detrusor contractility and in NGF production by the detrusor muscle. Alternatively BTX-A can decrease the bladder level of neurotransmitters that normally modulate NGF production and release

Preoperative Valsava leak point pressure may not predict outcome of mid-urethral slings: analysis from a randomized controlled trial of retropubic versus transobturator mid-urethral slings

OBJECTIVE: To test the hypothesis that preoperative Valsalva leak point pressure (VLPP) predicts long-term outcome of mid-urethra slings for female stress urinary incontinence (SUI). MATERIALS AND METHODS: One hundred and forty-five patients with SUI were prospectively randomized to two mid-urethra sling treatments: Tension free vaginal tape (TVT) or transobturator tape (TOT). They were followed-up at 3, 6, 12 months post-operatively and then annually for the primary outcome variable, i.e. dry or wet and secondary outcome variables such as scores on the urogenital distress inventory (UDI-6) and the impact of incontinence on quality of life (IIQ-7) questionnaire as well as patient satisfaction as scored on a visual analogue scale (VAS). Preoperative VLPP was correlated with primary and secondary outcome variables. RESULTS: Mean follow-ups were 32 + 12 months (range 12-55) for TVT and 31 + 15 months (range 12-61) for TOT. When patients were analyzed according to VLPP stratification, 95 (65.5%) patients showed a VLPP > 60 cm H2O and 50 (34.5%) patients had a VLPP 60 cm H2O and 72% for those with VLPP 60 cm H2O (82 % vs. 68.9% p of 60 cm H2O), preoperative VLPP was not linked to outcome after TVT or TOT procedures

Distress and quality of life characteristics associated with seeking surgical treatment for stress urinary incontinence

<p>Abstract</p> <p>Background</p> <p>Current research focuses on three variables in evaluating the impact of stress urinary incontinence (SUI) on daily living: severity of incontinence, distress or bother resulting from incontinence, and effect on health related quality of life (HRQoL). Understanding the impact of these variables is important as they are the driving force behind women seeking surgical treatment. Given the importance of HRQoL in determining need for treatment, as well as evaluating treatment success, this review provides an assessment of the degree to which HRQoL is impaired in women seeking surgical treatment.</p> <p>Methods</p> <p>PubMed searches for the terms "quality of life and distress and urinary incontinence" and "quality of life and bother and urinary incontinence" were performed with limits of English, human and female subjects through May 2008. All studies using validated instruments were included. No time limit was placed on the search.</p> <p>Results</p> <p>Of 178 articles retrieved, 21 met the inclusion criteria, and 17 reported methods of scoring. The studies used the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ). Wide ranges of mean and individual levels of severity of symptoms, UDI and IIQ scores were seen among women seeking surgical treatment. Fourteen studies reported baseline and post-surgical treatment distress and QoL data. Statistically significant improvements between baseline and post-surgical UDI and IIQ scores were reported in 12 studies. Reported cure rates ranged from 46% to 97%. Satisfaction with the procedure was reported in 4 studies and ranged from 84% to 91%. A minority of studies reported the relationship between reduction in symptoms and change in HRQoL.</p> <p>Conclusion</p> <p>HRQoL is the main reason women seek surgical treatment for incontinence and surgical treatment leads to a significant improvement in mean HRQoL scores. Assessment of HRQoL has proved less useful in identifying why individual women seek treatment for incontinence. Preliminary work has begun to characterize the interaction between severity of symptoms, distress or bother resulting from these urinary symptoms, impact on HRQoL, and treatment seeking behavior, but further research is needed. Greater standardization in the reporting of results of distress or bother and HRQoL would allow for comparison across studies.</p