Murine bladder wall biomechanics following partial bladder obstruction

Evaluation of bladder wall mechanical behavior is important in understanding the functional changes that occur in response to pathologic processes such as partial bladder outlet obstruction (pBOO). In the murine model, the traditional approach of cystometry to describe bladder compliance can prove difficult secondary to small bladder capacity and surgical exposure of the bladder. Here, we explore an alternative technique to characterize murine mechanical properties by applying biaxial mechanical stretch to murine bladders that had undergone pBOO. 5–6 week old female C57/Bl6 mice were ovariectomized and subjected to pBOO via an open surgical urethral ligation and sacrificed after 4 weeks (n=12). Age matched controls (n=6) were also analyzed. Bladders were separated based on phenotype of fibrotic (n=6) or distended (n=6) at the time of harvest. Biaxial testing was performed in modified Kreb's solution at 37 °C. Tissue was preconditioned to 10 cycles and mechanical response was evaluated by comparing axial strain at 50 kPa. The normal murine bladders exhibited anisotropy and were stiffer in the longitudinal direction. All mice showed a loss of anisotropy after 4 weeks of pBOO. The two phenotypes observed after pBOO, fibrotic and distended, exhibited less and more extensibility, respectively. These proof-of-principle data demonstrate that pBOO creates quantifiable changes in the mechanics of the murine bladder that can be effectively quantified with biaxial testing.     

DNA ploidy of bladder cancer using bladder biopsy supernate specimens

OBJECTIVE: To perform DNA image cytometry on 119 bladder biopsy supernate (BBS) specimens of transitional cell carcinoma (TCC) bladder to: (1) test the suitability of this cytologic specimen for use in DNA ploidy analysis, and (2) assess the value of DNA ploidy measured on this specimen as to the risk of tumor recurrence and survival. STUDY DESIGN: The histologic grade and cytologic grade were correlated, and the DNA ploidy produced was determined by image analysis of Feulgen-stained nuclei. Kaplan-Meier curves related age, sex, grade and DNA ploidy to recurrence of tumor and survival. Log rank analyses were used to ascertain the difference between the curves for each categorical variable. RESULTS: Urothelial cells derived from the BBS specimen were demonstrated to be representative of the tumor. The tumor recurrence rate was significantly higher (P = .0001) and the survival rate significantly lower (P = .0002) for patients with aneuploid tumors compared to those with diploid tumors. Patients with TCC 2 tumors had a significantly shorter time to recurrence (P = .003), although the relationship between ploidy and survival in this group was of marginal significance. CONCLUSION: The specimen was free of many of the problems associate with the other specimen types used for measuring DNA ploidy. The results show that the BBS specimen is diagnostically useful and suitable for DNA analysis, providing prognostically relevant information.     

Cytology of bladder papilloma

Eighty-four urinary cytology specimens from 51 patients known to have bladder papilloma were reviewed and compared with 30 specimens from patients without neoplastic urologic disease, 12 specimens from patients later found to have papillomas that were unsuspected at the time of examination and 6 specimens from patients with a history of papilloma but no present evidence of the disease. No specific findings were identified that could be used to make a cytologic diagnosis of papilloma. However, the specimens from patients with papilloma were likely to contain an increased number of exfoliated epithelial cells, including atypically shaped cells that were small and round or, less frequently, elongated; they were also likely to contain a small number of red blood cells. This combination of cytologic findings yielded a pattern that can be described as consistent with or suggestive of papilloma in the appropriate clinical setting. It is not diagnostic since the absence of this cytologic pattern does not rule out papilloma, and the same cytologic features can be found (less frequently) in patients with other urologic diseases.     

The aging bladder

Although it is well established that lower urinary tract symptoms increase in frequency with aging, there are few studies of the mechanisms that underlie bladder dysfunction. Age-related reduction in bladder capacity, uninhibited contractions, decreased urinary flow rate, diminished urethral pressure profile, and increased postvoid residual volume warrant investigation and require differentiation between symptoms associated with aging and those related to comorbid conditions. Here, the current data are reviewed, including those from muscle bath investigations of bladder tissue contractility, in vivo studies using animal models, and clinical studies in the aging population.     

Neuroendocrine tumor of the bladder

Small cell carcinoma (SCC) of the bladder is a rare and aggressive tumor associated with a poor prognosis. It often presents at a later stage than urothelial carcinoma of the bladder, and comprises less than 1% of bladder malignancies. A number of treatment algorithms have been used to treat bladder SCC, including cystectomy, partial cystectomy, radiotherapy, chemoradiotherapy, chemotherapy alone, and neoadjuvant/adjuvant chemotherapy. Presented is a case of SCC of the bladder, and the epidemiology, prognosis, and current treatment algorithms for patients with bladder SCC are reviewed.     

Metabolism of depleted turtle bladder

Summary Oxygen consumption, glycogen content, transmural potential difference (PD), and short-circuit current (SCC) were measured in fresh turtle hemibladder sacs and in matching sacs depleted by 18 hr of incubation in aerated, substrate-free Ringer's solution. Percent of original values after depletion were: oxygen consumption, 61%; glycogen content, 36%; PD, 28%; SCC, 19%. PD and SCC responded to addition of substrate (5.5mm glucose plus 2mm pyruvate) by a lag period of approximately 2 hr followed by progressive increases lasting for many hours. Other experiments utilized split bladders. The epithelium and adhering connective tissue (mucosal fraction) were separated from the underlying smooth muscle and connective tissue (serosal fraction) and the oxygen consumption and glycogen content of slices of the two fractions determined. Mucosal oxygen consumption declined to 48% of the original value during depletion while serosal oxygen consumption (initially much lower than mucosal) was well-maintained at 95% of the original value. Substantial net synthesis of glycogen took place in both fractions of depleted bladders after addition of substrate. The ratio of moles of oxygen consumed to moles of glucose (from glycogen) disappearing during the 18-hr depletion period was approximately 5.5 for serosal tissue and within the range 30 to 61 for mucosal tissue. The mucosal ratio was incompatible with the utilization of glycogen as the major endogenous substrate during depletion under aerobic conditions. It is suggested that the oxidation of lipid supports most of the endogenous metabolism in the mucosal tissue of the turtle bladder.     

Neurogenic inflammation of Guinea-pig bladder

Capsaicin, substance P, and ovalbumin, instilled into the bladders of naive and ovalbumin (OVA) sensitized guineapigs caused inflammation, as indicated by increased vascular permeability. Histological changes after exposure to these compounds progressed with time from intense vasodilatation to marginalization of granulocytes followed by interstitial migration of leukocytes. In vitro incubation of guinea-pig bladder tissue with substance P and ovalbumin stimulated release of prostaglandin D(2) and leukotrienes. In vitro incubation of bladder tissue with capsaicin, OVA, prostaglandin D(2), leukotriene C(4), histamine, or calcium ionophore A-23587 all stimulated substance P release. These data suggest that bladder inflammation initiated by a variety of stimuli could lead to a cyclic pattern of release of inflammatory mediators and neuropeptides, which could result in amplification and persistence of cystitis after the inciting cause has subsided.     

Cytochemical markers of bladder carcinogenesis

Summary Enzyme cytochemical and immunocytochemical techniques at the light and electron microscope levels were used to study the distribution of potential markers of chemical transformation in rodent bladders. In rat tumours induced byin vivo treatment with methylnitrosourea, alkaline phosphatase localization was normal on the external surface of the plasma membranes of some cells but abnormal in others where reaction product was seen only on intracellular membranes. 5-Nucleotidase localization was abnormal in all cells, being seen on endoplasmic reticulum and nuclear membranes only, while in normal bladders only ectoenzyme localization was seen. Heterogeneity of alkaline phosphatase and 5-nucleotidase localization was seen on the plasma membranes of these tumours after 15 days in organ culture. Some cells produced enzyme and others did not; in other cells only parts of the membrane reacted heavily, while other regions were negative.In transformed cell cultures and tumours of mouse bladder derived byin vitro treatment of explants with dimethylbenz (a) anthracene, a bimodal pattern of alkaline phosphatase localization was seen. Cells had either normal ectoenzyme reaction product or abnormal intracellular membrane reaction product. 5-Nucleotidase and ADPase were lost after transformation while cAMP-phosphodiesterase was retained as an ectoenzyme. Mg.ATPase and a cAMP-independent, calcium-insensitive protein phosphatase were induced in transformed cell cultures. An epithelial antigen was detected in the cytoplasm of both normal and transformed cells associated with reticular cytoplasmic ground substance, plasma membrane vesicles and cytoskeletal elements.