Faculty Bibliography

OBJECTIVE: To determine the clinical and urodynamic differences in the presentation and the value of simultaneous fluoroscopy in dysfunctional voiding (DV) and primary bladder neck obstruction (PBNO); the 2 most common causes of non-neurogenic "functional" bladder outlet obstruction in women. METHODS: A review of our urodynamic study database (March 2003 to August 2009) was conducted. DV was diagnosed when increased external sphincter activity was found during voluntary voiding on electromyography (EMG) or fluoroscopy. PBNO was diagnosed when a failure of bladder neck opening was noted on fluoroscopy during voiding. The demographics, symptoms, and urodynamic study parameters were collected. Comparisons were done using chi-square and 2-tailed t-tests. RESULTS: DV was diagnosed in 34 women and PBNO in 16. The patients with DV were younger than those with PBNO (40.9 vs 59.2 years, P < .001). Women with DV showed a clinical trend toward having more storage symptoms than those with PBNO and fewer voiding symptoms. Patients with DV had a greater mean maximal flow rate (12 vs 7 mL/s, P = .027) and lower mean postvoid residual urine volume (125 vs 400 mL, P = .012). No significant differences were found in maximal detrusor pressure, detrusor pressure at maximal flow rate, or detrusor overactivity. EMG showed increased activity during voiding in 79.4% of those with DV and 14.3% of those with PBNO (P < .001). CONCLUSION: Clinically, women with DV and PBNO had similar presentations, although those with PBNO had poorer emptying. The flow rates and patterns seemed to differ between those with DV and PBNO, although the voiding pressures were similar. EMG alone would have given the wrong diagnosis in 20.6% of those with DV (false negative) and 14.3% of those with PBNO (false positive). When fluoroscopy is used to define these entities, the accuracy of EMG to differentiate them is questionable.

Transurethral resection of the prostate (TURP) is the gold standard for treatment of symptomatic benign prostatic enlargement. Failure of TURP and other similar procedures may occur when a patient has poor bladder emptying postoperatively or has persistent or de novo bothersome postoperative lower urinary tract symptoms. Reasons for failure include inadequate resection, clot retention, anesthesia-related side effects, postoperative pain, hypo- or acontractile bladder, and/or poor patient selection. Patients initially can be managed conservatively or proactively. When clinically significant storage or voiding dysfunction persists, evaluation is necessary and may include cystoscopy and/or urodynamics. Depending on the diagnosis and etiology, patients can then be managed with an array of therapies, including urethral catheterization, oral medications, intravesical botulinum A toxin, neuromodulation, or further surgery as indicated. 2011 Springer Science+Business Media, LLC

The basic evaluation of suspected voiding dysfunction involves fundamental objective tools such as the pressure-flow study. Although accurate, the several drawbacks to this invasive study of bladder outlet obstruction (BOO) are discussed and evaluated. Other non-invasive and/or minimally invasive ways of diagnosing BOO continue to be the subject of investigation. The ultrasound-estimated bladder wall thickness and bladder wall mass indices are 2 parameters that may be useful for screening and diagnosing BOO. Preliminary results are presented from the prospective clinical trial comparing the diagnosing capabilities and results obtained with pressure-flow studies (the historic gold standard for BOO diagnosing) with that of ultrasound-estimated bladder weight

Phospholemman (PLM) is a 72-amino acid transmembrane protein thought to function in Na,K-ATPase regulation or assembly, similar to other members of the FXYD family of proteins. Unique to PLM among these regulatory proteins are sites for C-terminal phosphorylation by PKA and PKC, although a role for phosphorylation in PLM function remains unclear. To study PLM phosphorylation, we used PLM phosphopeptides to generate antibodies to specifically detect phosphorylated PLM. Peptide affinity chromatography isolated two populations of antibodies: one reacting with standard PLM, a collection of closely-spaced 15-kDa protein bands by SDS-PAGE. About 20% of PLM antibodies reacted specifically with a single distinct form of PLM. Levels of this second immunological form (PLM-b) were increased with overexpression of PLM cDNA, and also reacted with a monoclonal antibody against the PLM N-terminus. In complete contrast to standard PLM, however, PLM-b was quantitatively insoluble in nonionic detergents and was released from tight binding by colchicine. Antibodies to PLM-b were present in two different antisera raised to the phosphorylated C-terminal peptide (residues 57-70), but not in antiserum raised to the non-phosphorylated C-terminal peptide. Despite an apparent relationship between PLM-b and phosphorylated PLM, PLM-b levels were not affected by treatment of heart cells with isoproterenol. PLM-b appears to represent a cytoskeleton-attached detergent-insoluble form of PLM with distinctive C-terminal immunoreactivity that might have implications for PLM structure and function.

When evaluating patients with voiding dysfunction, noninvasive tests such as uroflowmetry and measurement of postvoid residual urine volume (PVR) can help to determine whether additional testing is warranted. PVR can be measured by 2 methods: catheterization or bedside bladder ultrasonography. Although both methods have advantages, the convenience, efficiency, and safety of bladder ultrasound makes its use beneficial in a wide variety of populations, including hospitalized patients, children, and the elderly. More recently, bladder ultrasound has been used for other procedures, such as suprapubic aspiration, evaluation of intravesical masses, and to determine bladder wall thickness and bladder wall mass, both of which have been associated with outflow obstruction

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

Urodynamics is the dynamic study of the transport, storage, and evacuation of urine by the urinary tract. It is comprised of several tests that, when used individually or collectively, can give information about lower urinary tract function. The components of the urodynamic study are uroflowmetry, cystometry, pressure-flow studies, electromyography, urethral pressure profilometry, leak point pressure measurement, videourodynamics, and ambulatory urodynamics. Familiarity with the recent advances and controversies of each component is essential when using urodynamics to diagnose and treat lower urinary tract dysfunction