Evaluation of Voiding Parameters in Healthy Women Using Sound Analysis.

OBJECTIVES: Sonouroflowmetry represents a novel method for estimating urinary flow parameters. The aim of this study was to compare the urinary flow parameters acquired using sonouroflowmetry with those of standard uroflowmetry in healthy female volunteers. METHODS: Thirty-six healthy female volunteers (aged 25-54 years) were subjected to standard uroflowmetry. Simultaneously, subjects dialed a dedicated number on a mobile phone and kept recording until urination was finished. Sound data were analyzed and compared to the uroflowmetry data. Of 218 recordings, 183 were included in the final analysis. Thirty-four measurements were excluded for voided volume <150 mL or technical problems during the recording. A linear model was fitted to calculate the urinary flow parameters and the voided volume from data obtained by sonouroflowmetry. Subsequently the matching datasets of UF and SUF were compared with respect to flow time, voided volume, maximum (Qmax ) and average (Qave ) flow rate. Pearson's correlation coefficient (PCC) was used to compare parameters recorded by uroflowmetry with those calculated based on sonouroflowmetry recordings. RESULTS: A strong correlation (PCC = 0.95) was noted between uroflowmetry recorded flow time and duration of the sonouroflowmetry sound signal. The voided volume measured by uroflowmetry showed a moderate correlation (PCC = 0.68) with the calculated area under the sonouroflowmetry curve. Qmax recorded using uroflowmetry and sonouroflowmetry recorded peak sound intensity showed a weak correlation (PCC = 0.38). CONCLUSIONS: This study validates the basic concept of using sound analysis to estimate urinary flow parameters and voided volume.

Validating of a Novel Method for Electronically Recording Overactive Bladder Symptoms in Men.

OBJECTIVE: The goal of this study was to compare a novel wireless phone and web based technology to record and store overactive bladder symptoms (OAB-S) to a traditional pen and paper micturition chart. METHODS: Overactive bladder symptoms were recorded over a period of 3 days using both an electronic micturition chart (EMC) and the standard pen and paper micturition chart (MC). Twenty-nine men, with lower urinary tract symptoms (LUTS), were included in the study. Dropout rate, patient's preference, and correlation between the quality of life measures (QoL) and symptoms recorded with EMC versus MC, were assessed and compared. RESULTS: Of the total number of 29 patients enrolled into the study, 24 completed the full 3-day trial using MC and 27 using EMC. MC was preferred by 50%, while EMC was preferred by 50% of participants. Using MC, 21% of patients forgot to record at least one episode of urgency, versus 17% using EMC, 17% forgot to record at least one micturition using MC versus 8% using EMC. A statistically significant correlation was found between lower severity of OAB-S and higher QoL, using both recording methods. CONCLUSIONS: In this study population, recording symptoms with EMC did not prove to be preferable compared to MC; however, EMC provided the same level of accuracy with the same or better adherence to the study protocol.

Comparison between uroflowmetry and sonouroflowmetry in recording of urinary flow in healthy men.

OBJECTIVES: To evaluate the accuracy of sonouroflowmetry in recording urinary flow parameters and voided volume. METHODS: A total of 25 healthy male volunteers (age 18-63 years) were included in the study. All participants were asked to carry out uroflowmetry synchronous with recording of the sound generated by the urine stream hitting the water level in the urine collection receptacle, using a dedicated cell phone. From 188 recordings, 34 were excluded, because of voided volume <150 mL or technical problems during recording. Sonouroflowmetry recording was visualized in a form of a trace, representing sound intensity over time. Subsequently, the matching datasets of uroflowmetry and sonouroflowmetry were compared with respect to flow time, voided volume, maximum flow rate and average flow rate. Pearson's correlation coefficient was used to compare parameters recorded by uroflowmetry with those calculated based on sonouroflowmetry recordings. RESULTS: The flow pattern recorded by sonouroflowmetry showed a good correlation with the uroflowmetry trace. A strong correlation (Pearson's correlation coefficient 0.87) was documented between uroflowmetry-recorded flow time and duration of the sound signal recorded with sonouroflowmetry. A moderate correlation was observed in voided volume (Pearson's correlation coefficient 0.68) and average flow rate (Pearson's correlation coefficient 0.57). A weak correlation (Pearson's correlation coefficient 0.38) between maximum flow rate recorded using uroflowmetry and sonouroflowmetry-recorded peak sound intensity was documented. CONCLUSIONS: The present study shows that the basic concept utilizing sound analysis for estimation of urinary flow parameters and voided volume is valid. However, further development of this technology and standardization of recording algorithm are required.

Acute lower urinary tract dysfunction (LUTD) following traumatic brain injury (TBI) in rats.

AIMS: The aim of this study was to assess experimental traumatic brain injury (TBI)-induced lower urinary tract dysfunction (LUTD) by monitoring systemic and urodynamic parameters using an implantable telemetry system. METHODS: A single lateral fluid percussion TBI (FP-TBI; 3.4 atm) was administered to 10 female rats. Pressure micro-catheters were implanted in the abdominal aorta and bladder dome for simultaneous data recording. Hemodynamic and urodynamic variables recorded 24 hr before and 24 hr after injury were analyzed and compared. RESULTS: TBI in the acute phase resulted in LUTD affecting bladder emptying, characterized by failure of voiding reflex, high capacity bladder, increased voided volume, prolonged intermicturition intervals, and loss of compliance. The dominant symptom was urinary retention (100%) and incontinence (60%). The effects followed a pattern of initial loss of bladder function followed by either altered recovery of reflex micturition or a period of incontinence. With a moderate injury symptoms were temporary in 90% of animals and permanent in 10% of animals. Injury produced only transient hypertension (≤1 hr) with a maximum systolic pressure of 172.64 ± 14.53 mmHg (70% of animals). CONCLUSIONS: The results demonstrate that experimental FP-TBI causes temporary bladder dysfunction that in more severe cases becomes permanent. Telemetry recordings revealed a sequence of events following injury that establishes moderate TBI as a risk factor for neurogenic bladder disorder. Results also suggest a correlation between lateral FP-TBI and incontinence.

Urinary bladder function in conscious rat pups: a developmental study.

Cystometric studies of bladder function in anesthetized neonatal rats have suggested specific changes in urodynamic parameters that coincide with the development of a mature bladder-to-bladder micturition reflex. Here, we used a conscious cystometry model that avoids the potentially confounding effects of anesthesia to characterize voiding patterns and urodynamic parameters during early postnatal development in healthy rat pups. Cystometry was performed on postnatal day (P)0, 3, 7, 14, and 21 rats with continuous intravesical instillation of NaCl via a bladder catheter. Micturition cycles were analyzed with respect to voiding pattern, nonvoiding contractions, infused volume, and basal, filling, threshold, and micturition pressures. Reproducible micturition patterns were obtained from all age groups. The time from stimulation to contraction was significantly longer (P ≤ 0.001) in ≤1-wk-old rats (∼10 s) than that in older rats (∼3 s). An interrupted voiding pattern was observed in ≤10-day-old subgroups. Micturition pressure progressively increased with age (from 21.77 ± 1.92 cmH(2)O at P0 to 35.47 ± 1.28 cmH(2)O at P21, P ≤ 0.001), as did bladder capacity. Nonvoiding contractions were prominent in the P3 age group (amplitude: 4.6 ± 1.3 cmH(2)O, frequency: ∼4.0 events/100 s). At P7, the pattern of spontaneous contractions became altered, acquiring a volume-related character that persisted in a less prominent manner through P21. Bladder compliance increased with age, i.e., maturation. In conclusion, conscious cystometry in rat pups resulted in reproducible micturition cycles that yielded consistent data. Our results revealed immature voiding and prolonged micturition contractions during the first 10 neonatal days and provide evidence for age-related changes in urodynamic parameters.

Recording urinary flow and lower urinary tract symptoms using sonouroflowmetry.

INTRODUCTION: To assess the accuracy of sonouroflow (SUF), an at-home, wireless-based acoustic system for recording lower urinary tract symptoms (LUTS) and urinary flow rate, and to compare test-to-test variability in flow parameters recorded using this new portable method with those obtained by conventional uroflowmetry. MATERIALS AND METHODS: An initial pilot study evaluated the technical feasibility of the SUF system. Subsequently, test-to-test variability was compared between sonourograms (SUFm) and standard uroflowmetry recordings. Uroflowmetry tests were performed at the urology office at pre-set times. SUF tests were performed at home on a schedule in keeping with the subjects' normal habits. RESULTS: In the initial feasibility study, 94% of SUFm recordings obtained from male volunteers displayed regular bell-shaped flow curves comparable to those recorded by standard uroflowmetry; significant variability was noted among female volunteers. In the comparative study, the coefficient of variation for SUFm-derived values was significantly lower for voiding time (p < 0.001) and significantly higher for average flow rate (p = 0.009) than that obtained from standard uroflowmetry recordings; maximum flow rate and time to maximum flow were not significantly different between methods. Box-and-whisker plots showed reduced test-to-test variability in the SUFm dataset for voiding time, maximum flow rate and time to maximum flow rate in 62.5%, 43.75% and 56%, respectively, of study subjects. CONCLUSIONS: The SUF system is easy to use and yields results comparable to those of standard uroflowmetry. Integration of recordings of LUTS with flow parameters and lower test-to-test variability suggest the potential of SUF for clinical applications.

Oxyhemoglobin-induced suppression of voltage-dependent K+ channels in cerebral arteries by enhanced tyrosine kinase activity.

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences. Oxyhemoglobin (oxyhb) has been implicated in SAH-induced cerebral vasospasm as it causes cerebral artery constriction and increases tyrosine kinase activity. Voltage-dependent, Ca(2+)-selective and K(+)-selective ion channels play an important role in the regulation of cerebral artery diameter and represent potential targets of oxyhb. Here we provide novel evidence that oxyhb selectively decreases 4-aminopyridine sensitive, voltage-dependent K(+) channel (K(v)) currents by approximately 30% in myocytes isolated from rabbit cerebral arteries but did not directly alter the activity of voltage-dependent Ca(2+) channels or large conductance Ca(2+)-activated (BK) channels. A combination of tyrosine kinase inhibitors (tyrphostin AG1478, tyrphostin A23, tyrphostin A25, genistein) abolished both oxyhb-induced suppression of K(v) channel currents and oxyhb-induced constriction of isolated cerebral arteries. The K(v) channel blocker 4-aminopyridine also inhibited oxyhb-induced cerebral artery constriction. The observed oxyhb-induced decrease in K(v) channel activity could represent either channel block, or a decrease in K(v) channel density on the plasma membrane. To explore whether oxyhb altered trafficking of K(v) channels to the plasma membrane, we used an antibody generated against an extracellular epitope of K(v)1.5 channels. In the presence of oxyhb, staining of K(v)1.5 on the plasma membrane surface was markedly reduced. Furthermore, oxyhb caused a loss of spatial distinction between staining with K(v)1.5 and the general anti-phosphotyrosine antibody PY-102. We propose that oxyhb-induced suppression of K(v) currents occurs via a mechanism involving enhanced tyrosine kinase activity and channel endocytosis. This novel mechanism may contribute to oxyhb-induced cerebral artery constriction following SAH.

Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis.

Corticotropin-releasing factor (CRF) is a prominent neuropeptide involved in micturition reflexes, and different roles in these reflexes have been suggested. These studies examined the expression of CRF in the urinary bladder and lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats. The expression of CRF receptors, CRF(1) and CRF(2), was examined in urinary bladder from control and CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from rats killed by isoflurane (4%) and thoracotomy. CRF protein expression in whole urinary bladders significantly (P < or = 0.01) increased with 48 h or chronic CYP treatment. CRF immunoreactivity (IR) was increased significantly (P < or = 0.01) in the urothelium and SPN after CYP treatment. CRF IR nerve fibers increased in density in the suburothelial plexus and detrusor smooth muscle whole mounts with CYP-induced cystitis. CRF(2) receptor transcript was expressed in the urothelium or detrusor smooth muscle, and CRF(2) receptor expression increased in whole bladder with CYP-treatment, whereas no CRF(1) receptor transcript was expressed in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF(2) IR in urinary bladder nerve fibers and urothelial cells from control animals, whereas no CRF(1) IR was observed. These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF(2)) expression in nerve fibers and urothelium in control rats. CRF may contribute to urinary bladder overactivity and altered sensory processing with CYP-induced cystitis.

Distribution and fate of cocaine- and amphetamine-regulated transcript peptide (CARTp)-expressing cells in rat urinary bladder: a developmental study.

We examined the distribution and fate of cocaine- and amphetamine-regulated transcript peptide (CARTp)(55-102)-immunoreactive (IR) structures in the neonatal and adult rat urinary bladder. Double-labeling studies examining CARTp with tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), or choline acetyltransferase (ChAT) were performed in wholemounts of urothelium or detrusor or cryostat sections of the bladder. In younger animals (postnatal day [P]1, P3), CARTp-IR cell bodies in detrusor smooth muscle were observed in large clusters ( approximately 100 cells/cluster) at the ureteral insertion and along thick bundles of nerve fibers at the bladder base. The total number of CARTp-IR cells was significantly reduced (by five-fold) at P14, and this reduced number persisted into adulthood. The decrease in the number of CARTp-expressing cells was complemented with positive staining for cleaved caspase-3, suggesting that apoptosis contributed to this decrease. At birth (P1), all CARTp-IR cells expressed the neuronal marker Hu. After birth, CARTp was expressed by some neurons (CARTp-IR, Hu-IR) that represent intramural ganglion cells and by cells that lacked a neuronal phenotype (CARTp-IR, Hu-) but did express TH. Neither of these cell populations expressed ChAT immunoreactivity in adult bladder. These cells (CARTp-IR, Hu-, TH-IR) may represent paraganglion or small intensely fluorescent (SIF) cells. The percentage of colocalization of CARTp-IR and nNOS or TH was dependent on postnatal age and showed an inverse relationship. At P1, 67.1 % of CARTp-IR cells expressed nNOS immunoreactivity. Decreased colocalization was observed with increasing postnatal age. In contrast, 19.5% of CARTp-IR cells expressed TH at P1, but colocalization increased with postnatal age. The suburothelial plexus lacked CARTp-IR nerve fibers until P14, when nerve fibers with varicosities were observed in the urethra and bladder neck region. In summary, we demonstrate 1) a decrease in the number of CARTp-IR cells in rat detrusor in early postnatal development; 2) apoptotic events in the bladder during early postnatal development; 3) rostral migration of CARTp-IR cells from the ureteral insertion toward the bladder body during postnatal development; 4) the presence of different populations of CARTp-IR cells, some with and others without a neuronal phenotype; and (5) age-dependent changes in chemical coding of CARTp-IR cells with postnatal development. This study demonstrates that CARTp-IR intramural ganglia and CARTp-IR paraganglion or SIF cells exist in the postnatal and adult rat bladder, although the role of these cell types remains to be determined.

Changes in pituitary adenylate cyclase activating polypeptide expression in urinary bladder pathways after spinal cord injury.

These studies examined changes in the pituitary adenylate cyclase activating polypeptide (PACAP) expression in micturition reflex pathways after spinal cord injury (SCI) of various durations. In spinal-intact animals, PACAP immunoreactivity (IR) was expressed in fibers in the superficial dorsal horn in all segmental levels examined (L1, L2, L4-S1). Bladder-afferent cells (35-45%) in the dorsal root ganglia (DRG; L1, L2, L6, S1) from spinal-intact animals also exhibited PACAP-IR. After SCI (6 weeks), PACAP-IR was dramatically increased in spinal segments and DRG (L1, L2, L6, S1) involved in micturition reflexes. The density of PACAP-IR was increased in the superficial laminae (I-II) of the L1, L2, L6, and S1 spinal segments. No changes in PACAP-IR were observed in the L4-L5 segments. Staining was also dramatically increased in a fiber bundle extending ventrally from Lissauer's tract (LT) in lamina I along the lateral edge of the dorsal horn to the sacral parasympathetic nucleus (SPN) in the L6-S1 spinal segments (lateral collateral pathway of Lissauer, LCP). After SCI (range 48 h to 6 weeks), PACAP-IR in cells in the L1, L2, L6, and S1 DRG significantly (P < or = 0.001) increased and the percentage of bladder-afferent cells expressing PACAP-IR also significantly (P < or = 0.001) increased (70-92%). No changes were observed in the L4-L5 DRG. PACAP-IR was reduced throughout the urothelium and detrusor smooth muscle whole mounts after SCI. These studies demonstrate changes in PACAP expression in micturition reflex pathways after SCI that may contribute to urinary bladder dysfunction or reemergence of primitive voiding reflexes after SCI.