Translation, cross-cultural adaptation and validation of the underactive bladder questionnaire to portuguese.

OBJECTIVE: The aim of the current study was to perform the translation, cross-cultural adaptation and validation of the Underactive Bladder Questionnaire (UAB-q). METHODS: The study design included the Portuguese translation, cross-cultural adaptation and validation of the UAB-q in 90 patients from a urology outpatient clinic following international methodology. The psychometric properties tested were the validity, reliability, internal consistency and stability of the instrument. RESULTS: The content validity index at the item (I-CVI) and scale level (S-CVI) were above 0.80 and did not require changes. Regarding the reliability analysis, Cronbach's alpha was 0.79. The internal consistency and the base time stability (test-retest) had excellent indexes; all were above 0.90. CONCLUSIONS: These results indicate that the UAB-q is a valid, reproducible and reliable instrument for screening underactive bladders and is a potentially useful tool to guide health actions and improve the care of underactive patients.

Use of Botulinum Toxin in Urologic Diseases.

OnabotulinumtoxinA (onaBoNTA) is approved by the US Food and Drug Administration for the treatment of urinary incontinence due to neurogenic detrusor overactivity and for the treatment of refractory overactive bladder. As a treatment for benign prostatic hyperplasia, onaBoNTA showed no difference over placebo in recently published studies. In contrast, treating interstitial cystitis/bladder pain syndrome with onaBoNTA has shown efficacy, and the current American Urological Association guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome lists onaBoNTA as fourth-line treatment. This comprehensive review will present all studied applications of onaBoNTA within the lower urinary tract.

Inhibitory role of the spinal galanin system in the control of micturition.

OBJECTIVE: To investigate the effect of intrathecal galanin on the micturition reflex in rats. METHODS: Continuous cystometrograms (0.04 mL/min infusion rate) were performed in female Sprague-Dawley rats (225-248 g) under urethane anesthesia. After stable micturition cycles were established, galanin was administered intrathecally to evaluate changes in bladder activity. Then, to examine the involvement of opioid systems in the galanin effects, galanin was administered intrathecally when the first bladder contraction was observed after intrathecal administration of naloxone, an opioid receptor antagonist. RESULTS: Intrathecal administration of galanin (1-10 µg) increased intercontraction intervals in a dose-dependent fashion. Intrathecal administration of galanin (1-10 µg) also increased pressure threshold in a dose-dependent fashion. These inhibitory effects of galanin (10 µg) were partially antagonized by intrathecal administration of naloxone (10 µg). CONCLUSION: These results indicate that in urethane-anesthetized rats, galanin delays the onset of micturition through activation of the opioid mechanism, suggesting the inhibitory role of galanin system in the control of the micturition reflex.

Future direction in pharmacotherapy for non-neurogenic male lower urinary tract symptoms.

BACKGROUND: The pathophysiology of male lower urinary tract symptoms (LUTS) is highly complex and multifactorial. The shift in perception that LUTS are not sex or organ specific has not been followed by significant innovations regarding the available drug classes. OBJECTIVE: To review pathophysiologic mechanisms and clinical and experimental data related to the development of new pharmacologic treatments for male LUTS. EVIDENCE ACQUISITION: The PubMed database was used to identify articles describing experimental and clinical studies of pathophysiologic mechanisms contributing to male LUTS and, supported by them, new pharmacotherapies with clinical or experimental evidence in the field. EVIDENCE SYNTHESIS: Several pathologic processes (eg, androgen signaling, inflammation, and metabolic factors) and targets (eg, the urothelium, prostate, interstitial cells, detrusor, neurotransmitters, neuromodulators, and receptors) have been implicated in male LUTS. Some newly introduced drugs, such as phosphodiesterase type 5 inhibitors and ß3-adrenergic agonists, have just started broad use in clinical practice. Drugs with potential benefit, such as vitamin D3 receptor analogs, gonadotropin-releasing hormone antagonists, cannabinoids, and drugs injected into the prostate, have been evaluated in experimental studies and have progressed to clinical trials. However, safety and efficacy data for these drugs are still scarce. Some compounds with interesting profiles have only been tested in experimental settings (eg, transient receptor potential channel blockers, Rho-kinase inhibitors, purinergic receptor blockers, and endothelin-converting enzyme inhibitors). CONCLUSIONS: New pathophysiologic mechanisms of male LUTS are described that lead to the continuous development of new pharmacotherapies. To date, few drugs have been added to the current armamentarium, and several are in various phases of clinical or experimental investigation.

Investigations into the presence of functional Beta1, Beta2 and Beta3-adrenoceptors in urothelium and detrusor of human bladder.

PURPOSE: We investigated the presence of functional Beta1, Beta2 and Beta3-adrenoceptor in urothelium and detrusor muscle of human bladder through in vitro pharmacology of selective Beta3 adrenoceptor agonist solabegron. MATERIALS AND METHODS: Expression of these adrenoceptors in surgically separated human urothelium and detrusor muscle were investigated using RT-PCR. The effects of activating these receptors were studied by determining the relaxation produced by Beta-adrenoceptors agonist in pre-contracted human detrusor strips. RESULTS: The results confirmed the presence of mRNA for Beta1, Beta2 and Beta3-adrenoceptor in both human urothelium and detrusor. In an in vitro functional bladder assay, Solabegron and other agonists for Beta-adrenoceptors such as procaterol and isoproterenol evoked potent concentration-dependent relaxation of isolated human bladder strips with pD2 values of 8.73 +/- 0.19, 5.08 +/- 0.48 and 6.28 +/- 0.54, respectively. CONCLUSIONS: Selective Beta3-adrenoceptor agonist may be a potential new treatment for the overactive bladder OAB syndrome. Existence of Beta3-adrenoceptor mRNA exists in the urothelium in addition to the detrusor muscle suggest multiple site of actions for the Beta3-adrenoceptor in the lower urinary tract.

Investigations into the presence of functional ß1, ß2 and ß3-adrenoceptors in urothelium and detrusor of human bladder

Purpose: We investigated the presence of functional ß1, ß2 and ß3-adrenoceptor in urothelium and detrusor muscle of human bladder through in vitro pharmacology of selective ß3 adrenoceptor agonist solabegron. Materials and Methods: Expression of these adrenoceptors in surgically separated human urothelium and detrusor muscle were investigated using RT-PCR. The effects of activating these receptors were studied by determining the relaxation produced by ß-adrenoceptors agonist in pre-contracted human detrusor strips. Results: The results confirmed the presence of mRNA for ß1, ß2 and ß3-adrenoceptor in both human urothelium and detrusor. In an in vitro functional bladder assay, Solabegron and other agonists for ß-adrenoceptors such as procaterol and isoproterenol evoked potent concentration-dependent relaxation of isolated human bladder strips with pD2 values of 8.73 ± 0.19, 5.08 ± 0.48 and 6.28 ± 0.54, respectively. Conclusions: Selective ß3-adrenoceptor agonist may be a potential new treatment for the overactive bladder OAB syndrome. Existence of ß3-adrenoceptor mRNA exists in the urothelium in addition to the detrusor muscle suggest multiple site of actions for the ß3-adrenoceptor in the lower urinary tract.

Green onions: potential mechanism for hepatitis A contamination.

The largest documented foodborne hepatitis A outbreak in U.S. history occurred in November 2003. The source of that outbreak was green onions from a farm in Mexico. Two biomarkers were used to determine ways in which hepatitis A virus (HAV) can contaminate onions. Fluorescent microspheres (1.0 to 10 microm) and HAV vaccine were placed on the soil and the surfaces of pot-grown onions and in the liquid medium of hydroponically cultivated onions. Reverse transcription PCR (RT-PCR) was used to identify HAV RNA. Microspheres were found on the outside and inside of the pot-grown onions for up to 60 days. RT-PCR revealed HAV RNA from the vaccine in well-washed green onions. In the hydroponically grown onions, microspheres were found throughout the onion after only 1 day. RT-PCR also revealed HAV RNA inside the hydroponically grown onions. Both biomarkers support the hypothesis that HAV can contaminate the inside of the growing onion and can be taken up intracellularly through the roots. Once inside, the particles are impossible to remove by cleaning.

The relationship between overactive bladder and sexual activity in women.

PURPOSE: We assessed the relationships between bladder symptoms, demographic, and medical history variables and sexual dysfunction in women with overactive bladder (OAB) disorder. MATERIALS AND METHODS: Seventy-eight women diagnosed with OAB completed self-administered questionnaires related to overall heath status, bladder function, and sexual function. Data were compiled for questionnaire responses, and multivariate logistic regression analyses were performed to determine predictors of sexual dysfunction. RESULTS: Bothersome bladder symptoms were reported by > or = 60% of the sample. Sixty-percent of the sample was sexually active in the past month. Difficulty with sexual arousal, orgasm, and sexual enjoyment were reported by about 25% of the women. Sexual partner status was the best predictor of sexual arousal, orgasm, and sexual enjoyment. Menopausal status emerged as an important predictor of arousal and sexual enjoyment. CONCLUSION: The majority of women with symptoms of OAB viewed these symptoms as bothersome. However, the extent of symptom bother did not predict aspects of female sexual dysfunction (FSD). Instead, menopausal and partner status emerged as the best predictors of FSD in our sample.

The relationship between overactive bladder and sexual activity in women

PURPOSE: We assessed the relationships between bladder symptoms, demographic, and medical history variables and sexual dysfunction in women with overactive bladder (OAB) disorder. MATERIALS AND METHODS: Seventy-eight women diagnosed with OAB completed self-administered questionnaires related to overall heath status, bladder function, and sexual function. Data were compiled for questionnaire responses, and multivariate logistic regression analyses were performed to determine predictors of sexual dysfunction. RESULTS: Bothersome bladder symptoms were reported by ³ 60 percent of the sample. Sixty-percent of the sample was sexually active in the past month. Difficulty with sexual arousal, orgasm, and sexual enjoyment were reported by about 25 percent of the women. Sexual partner status was the best predictor of sexual arousal, orgasm, and sexual enjoyment. Menopausal status emerged as an important predictor of arousal and sexual enjoyment. CONCLUSION: The majority of women with symptoms of OAB viewed these symptoms as bothersome. However, the extent of symptom bother did not predict aspects of female sexual dysfunction (FSD). Instead, menopausal and partner status emerged as the best predictors of FSD in our sample.

Treatment of stress urinary incontinence with duloxetine hydrochloride.

Currently, there are no approved medications for the treatment of stress urinary incontinence (SUI) in the United States. The effectiveness of duloxetine in the treatment of SUI is linked to its inhibition of presynaptic neuronal reuptake of serotonin and norepinephrine in the central nervous system, resulting in elevated levels of serotonin and norepinephrine in the synaptic cleft. In animal studies, this agent leads to an increase in nerve stimulation to the urethral striated sphincter muscle. A similar mechanism in women is believed to result in stronger urethral contractions, with improved sphincter tone during urine storage and physical stress. In 3 randomized, placebo-controlled clinical trials, patients receiving duloxetine had a statistically significant and clinically relevant reduction in the number of incontinence episodes and a corresponding improvement in quality of life. If this use of duloxetine is approved by the U.S. Food and Drug Administration, as it has been by the European regulatory agencies, it will be the first drug indicated for the treatment of SUI. This pharmacologic therapy is an additional option for women and is likely to become an integral component of patient management.

Gabapentin for overactive bladder and nocturia after anticholinergic failure

INTRODUCTION: We reviewed our experience with the use of gabapentin to treat symptoms of overactive bladder (OAB) and nocturia in patients who have failed conventional anticholinergic therapy. METHODS: Thirty-one patients referred to us with refractory (OAB) and/or nocturia were treated with oral gabapentin. All the patients had tried or remained on antimuscarinic drugs during treatment. Twenty-four of 31 complained of bothersome symptoms during day and night and the other seven had primary complaints of nocturia. Initial gabapentin doses ranged from 100-300 mg at bedtime. Dose was slowly titrated up to 3,000 mg based on patients' symptomatology and tolerability. RESULTS:The mean age was 51 years old (range 27-78). There were 13 men and 18 women. The median steady state dose chosen by the patient after initial titration was 600 mg/day. Fourteen of 31 patients reported subjective improvement of their frequency and 8 have been on the medication for over 12 months with persistent efficacy. For the 14 improved patients, mean frequency/24 hours decreased from 14.1 ± 2.2 to10.0 + 2.1. Three patients with primary nocturia reported improvement from a mean of 4.0 ± 1.3 to 1.0 ± 0.3 episodes/night. Six patients stopped taking the drug within one month due to side effects mostly described as drowsiness or lethargy. CONCLUSION: Fourteen of 31 patients with refractory (OAB) and nocturia improved with oral gabapentin. Gabapentin was generally well tolerated and can be considered in selective patients when conventional modalities have failed.

Gabapentin for overactive bladder and nocturia after anticholinergic failure.

INTRODUCTION: We reviewed our experience with the use of gabapentin to treat symptoms of overactive bladder (OAB) and nocturia in patients who have failed conventional anticholinergic therapy. METHODS: Thirty-one patients referred to us with refractory (OAB) and/or nocturia were treated with oral gabapentin. All the patients had tried or remained on antimuscarinic drugs during treatment. Twenty-four of 31 complained of bothersome symptoms during day and night and the other seven had primary complaints of nocturia. Initial gabapentin doses ranged from 100-300 mg at bedtime. Dose was slowly titrated up to 3,000 mg based on patients' symptomatology and tolerability. RESULTS: The mean age was 51 years old (range 27-78). There were 13 men and 18 women. The median steady state dose chosen by the patient after initial titration was 600 mg/day. Fourteen of 31 patients reported subjective improvement of their frequency and 8 have been on the medication for over 12 months with persistent efficacy. For the 14 improved patients, mean frequency/24 hours decreased from 14.1 +/- 2.2 to 10.0 +/- 2.1. Three patients with primary nocturia reported improvement from a mean of 4.0 +/- 1.3 to 1.0 +/- 0.3 episodes/night. Six patients stopped taking the drug within one month due to side effects mostly described as drowsiness or lethargy. CONCLUSIONS: Fourteen of 31 patients with refractory (OAB) and nocturia improved with oral gabapentin. Gabapentin was generally well tolerated and can be considered in selective patients when conventional modalities have failed.

Botulinum toxin treatment of urethral and bladder dysfunction.

There has been tremendous excitement with the use of botulinum toxin for the treatment of various urethral and bladder dysfunction over the past several years. Botulinum toxin is the most lethal naturally occurring toxin known to humankind. Why, then, would an urologist want to use this agent to poison the bladder or urethral sphincter? In this article, we will review the mechanisms underlying the effects of botulinum toxin treatment. We will discuss the current usage of this agent within the urologic community and will provide perspectives on future targets of botulinum toxin.