Bladder (San Francisco, Calif.)最新文献

Objectives: Non-invasive methods to objectively characterize overactive bladder (OAB) and other forms of voiding dysfunction using real-time ultrasound are currently under development but require accurate and precise serial measurements of bladder volumes during filling. This study's objective was to determine the most accurate and precise ultrasound-based method of quantifying serial bladder volumes during urodynamics (UD).

Methods: Twelve female participants with OAB completed an extended UD procedure with the addition of serial bladder ultrasound images captured once per minute. Bladder volume was measured using three ultrasound methods: (1) V_spheroid: two-dimensional (2D) method calculated assuming spheroid geometry; (2) V_bih: 2D correction method obtained by multiplying V_spheroid by a previously derived correction factor of 1.375; and (3) V_3D: three-dimensional (3D) method obtained by manually tracing the bladder outline in six planes automatically reconstructed into a solid rendered volume. These volumes were compared to a control (V_control) obtained by adding UD infused volume and the volume of estimated urine production.

Results: Based on linear regression analysis, both V_bih and V_3D were fairly accurate estimators of V_control, but V_3D was more precise. V_spheroid significantly underestimated V_control.

Conclusions: Although the V_bih and V_3D methods were more accurate than the more-commonly used V_spheroid method for measuring bladder volumes during UD, the V_3D method was the most precise and could best account for non-uniform bladder geometries. Therefore, the V_3D method may represent the best tool required for the continued development of non-invasive methods to diagnose OAB and other forms of voiding dysfunction.

Objectives: To investigate the effect of changing the bladder filling rate during cystometry in younger (2-3 months) and older (13-14 months) C57BL/6J male mice.

Methods: Cystometry was performed on mice under anesthesia. Voiding cycles were established in each mouse at a pump delivery rate of 17 μl/min. After 30 min, the rate was increased sequentially to 25, 33, 41 and 49 μl/min. Each rate was maintained for 30 min. The following cystometric parameters were quantified: peak pressure amplitude, intercontractile interval (ICI), compliance, micturition pressure threshold and voiding efficiency.

Results: Bladder weights were significantly greater in older mice (42 mg vs. 27 mg, P < 0.01), but functional capacities were not different. The pressure amplitudes did not change as filling rate increased, nor did they differ between the 4-month and 13-month-old males. ICIs were not significantly different between young and mature mice. However, both groups exhibited a non-linear reduction in ICI with increasing filling rate, best described by a power curve (R² > 0.93). Compliance was higher in the older mice at low filling rates (17 and 25 μl/min) but this difference diminished at higher rates. Compliance decreased with increasing flow rate in a non-linear manner, again with greater effects at low filling rates. Micturition pressure thresholds increased with increasing flow rate in a linear manner and older mice began voiding at higher pressures than younger. Both young and old mice exhibited voiding efficiencies of ~70%.

Conclusions: The rate of volume delivery has complex effects on the timing of voiding and compliance. These findings argue for greater standardization of cystometry protocols and further investigation into afferent signaling to higher centers at different filling rates.

The effect of radical cystectomy and extended pelvic lymph node dissection (RC/PLND) on the survival of patients with locally advanced and/or regionally metastatic bladder cancer is unknown. However, emerging evidence suggests that there may be survival benefit to a subset of select patients with this disease who demonstrate a response to chemotherapy. This article will review the current literature on the role of RC/PLND in the consolidative treatment of locally advanced and regionally metastatic bladder cancer.

Objective: Tight junctions are multicomponent structures, with claudin proteins defining paracellular permeability. Claudin 3 is a candidate for the exceptional "tightness" of human urothelium, being localised to the terminal tight junction (TJ) of superficial cells. Our aim was to determine whether claudin 3 plays an instigating and/or a functional role in the urothelial TJ.

Materials and methods: Normal human urothelial (NHU) cells maintained as non-immortalised cell lines were retrovirally-transduced to over-express or silence claudin 3 expression. Stable sublines induced to stratify or differentiate were assessed for TJ formation by immunocytochemistry and transepithelial electrical resistance (TER). Expression of claudin 3, ZO-1 and ZO-1α⁺ was examined in native urothelium by immunohistochemistry.

Results: Claudin 3 expression was associated with differentiation and development of a tight barrier and along with ZO-1 and ZO-1α⁺ was localised to the apical tight junction in native urothelium. Knockdown of claudin 3 inhibited formation of a tight barrier in three independent cell lines, however, overexpression of claudin 3 was not sufficient to induce tight barrier development in the absence of differentiation. A differentiation-dependent induction of the ZO-1α⁺ isoform was found to coincide with barrier formation. Whereas claudin 3 overexpression did not induce the switch to co-expression of ZO-1α^-/ZO-1α⁺, claudin 3 knockdown decreased localisation of ZO-1 to the TJ and resulted in compromised barrier function.

Conclusions: Urothelial cytodifferentiation is accompanied by induction of claudin 3 which is essential for the development of a terminal TJ. A coordinated switch to the ZO-1α⁺ isotype was also observed and for the first time may indicate that ZO-1α⁺ is involved in the structural assembly and function of the urothelial terminal TJ.