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Ultra-structural morphological abnormalities of the urinary bladder in streptozotocin-induced diabetic female rats.

The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron microscopy in a female Wistar-rat model of streptozotocin-induced diabetes mellitus and compared to control samples. Numerous dark mitochondria with swollen cristae and electron lucent, large, calcified and degenerated mitochondria were observed first in the urothelium. Intraepithelial capillaries surrounded by thick collagen were also present. Gap junctions between myocytes were interrupted or extensively widened with reduced mitochondria and caveolae. Collagen accumulation, degenerated nerve fibres and myelin bodies were seen between myocytes with increased collagen content and frequent mast cells, phagocytes and lymphocyte aggregates in the stroma. All ultra-structural lesions became augmented with longer duration of diabetes. Diabetes induces time-dependent pathologic changes in the urinary bladder of rats that might account for bladder dysfunction.

Animals↗

Adrenergic and Cholinergic Nerves of the Human Urethra and Urinary Bladder. A histochemical study.

The occurrence and distribution of adrenergic and acetylcholine esterase (AChE) positive nerves in the human urethra and urinary bladder were studied histochemically with the fluorescence method of Falck and Hillarp, and the copper thiocholine method of Koelle and Friedenwald. Both types of nerves were mainly confined to the layers of smooth muscle cells in the walls of the organs. In all parts of the urethra, there was a scanty supply of adrenergic nerves. Few adrenergic nerves were also found in the urinary bladder, except in the trigone area, where they were abundant. AChE-positive nerves were uniformly and richly distributed in the urinary bladder. Throughout the urethra the distribution of AChE-positive nerve fibres was uniform, but the number was clearly less than in the urinary bladder. No intrmurally located adrenergic or AChE-Positive ganglion cells could be demonstrated.

Acetylcholinesterase↗

Monitoring urinary bladder temperature in the intensive care unit: state of the science.

Body temperature of patients in critical care units can be monitored with a variety of devices and at a variety of body sites. In recent years, monitoring of urinary bladder temperature has become more common. Temperature-sensing indwelling urinary catheters allow continuous drainage of urine and continuous measurement of body temperature. This article provides a comprehensive and critical review of research undertaken in intensive care units to compare body temperatures measured in the urinary bladder with temperatures measured at a core site, the pulmonary artery. The studies support the use of urinary bladder temperature as a reliable index of core temperature during times of thermal stability. For critically ill patients who are already under considerable stress and whose condition necessitates the use of an indwelling urinary catheter, bladder temperature monitoring is an easy and convenient method that eliminates the need to use alternative sites. Further studies on the effects of shivering and urinary flow rate on temperatures measured in the bladder in critical care patients are needed. The economics of monitoring urinary bladder temperature also should be studied.

Body Temperature↗

Increased expression of non-muscle myosin heavy chain-B in connective tissue cells of hypertrophic rat urinary bladder.

Expression of the non-muscle myosin heavy chain-B (NM-MHC-B, also denoted as the embryonic smooth muscle myosin heavy chain, SMemb) was examined in rat urinary bladder during growth in response to a partial urinary outflow obstruction. Following obstruction, the weight of the urinary bladder increased more than five-fold within 10 days. Immunohistochemistry with a polyclonal antiserum against the C-terminal sequence of NM-MHC-B revealed very few NM-MHC-B immunoreactive cells in the control urinary bladders. In hypertrophic bladders, the number of NM-MHC-B immunoreactive cells markedly increased. The majority of such cells were found in the interstitium surrounding smooth muscle bundles and also in the subserosal and submucosal layers. Western blot analysis showed that the NM-MHC-B expression was transient; the content of NM-MHC-B immunoreactive material had doubled 10 days after obstruction and then declined towards the control level after 6 weeks. Immunohistochemistry revealed co-localization of NM-MHC-B and vimentin within the same cells. NM-MHC-B did not co-localize with smooth muscle actin, suggesting that the source of NM-MHC-B is not a de-differentiated smooth muscle cell or myofibroblast but a non-muscle cell possibly reacting to tissue distension or stress. The NM-MHC-B-positive cells could have a role in the production of extracellular matrix and growth factors or be involved in modulation of spontaneous contractile activity.

Actins↗

Effect of temperature on apical membrane remodeling in ADH-stimulated toad urinary bladders.

Pretreatment and removal of vasopressin (ADH) in toad urinary bladder renal model tissues induces endocytosis at 25 degrees C. The objective of the current study is to determine if apical membrane remodeling, as well as transepithelial water flow, can be affected by lowering the temperature to 15 degrees C. Control toad urinary bladders in the presence of an osmotic gradient at either 25 degrees C or 15 degrees C when visualized by scanning electron microscopy (SEM) show a typical apical membrane surface with no apparent surface differences. ADH-treated tissues following 15-min stimulation at 25 degrees C or 15 degrees C revealed a propagation of apical microvilli on their surface membranes. After 15 min following removal of ADH, bladder tissues at 25 degrees C or 15 degrees C showed surface invaginations involving over 44% and 80% of granular cells, respectively. The rate of water flow in tissues at 15 degrees C remained elevated compared to tissues held at 25 degrees C. This was consistent with the observation that ADH-stimulated tissues following washout at 15 degrees C still had marked apical membrane surface involvement. However, at 30 min and 60 min postwashout, ADH-stimulated tissues at 15 degrees C recovered considerably, with a reduction in the number of shallow apical membrane invaginations involving fewer than 33% and 20% of granular cells respectively. This may indicate that the membrane undergoes continuous remodeling even at cold temperature conditions but with a different half-time. Control bladder tissues subjected to transmission electron microscopy (TEM) reveal a dense cytoplasmic profile with a scattered distribution of secretory granules, rough ER cisternae, mitochondria, and little or no vacuolation. In contrast, ADH-stimulated bladder tissues displayed a vacuolated cytoplasm, expanded rough ER cisternae, and ruffled basolateral membranes. These observations suggest that the apical membrane undergoes considerable reorganization following cessation of hormone action and that lowering the temperature reduces the rate of membrane remodeling and thus may provide a means to monitor the processes of endocytosis and the mechanisms responsible for water channel retrieval.

Animals↗

Management of patients with Bacilli Calmette-Guérin-refractory carcinoma in situ of the urinary bladder: cost implications of a clinical trial for valrubicin.

OBJECTIVE: This study was undertaken to identify the expected first- and second-year clinical costs associated with intravesical valrubicin therapy, using a decision analytic model, for patients with Bacilli Calmette-Guérin (BCG)-refractory carcinoma in situ (CIS) of the urinary bladder. BACKGROUND: Cancer of the urinary bladder is the fourth most common malignancy in men and the sixth most common noncutaneous carcinoma overall. One histopathologic stage of bladder cancer is CIS, for which BCG intravesical immunotherapy is the first-line therapy. Radical cystectomy has been recommended for patients with CIS who do not respond to or become refractory to therapy with BCG. Surgery, however, may not be appropriate for all patients, especially those who are ineligible for the lengthy procedure because of advanced age or comorbidities and those who prefer alternative nonsurgical management. For these groups, intravesical valrubicin therapy is a plausible alternative. METHODS: Models were developed and populated with data from 1 open-label study of 90 patients, information from the medical literature, and input from clinical experts. The analysis was conducted from the payor perspective for direct costs only. RESULTS: Our data indicate that first- and second-year expected costs for valrubicin therapy are $19,912 and $23,496, respectively. Expected cost for radical cystectomy was also evaluated, since some patients may have no other option if drug therapy fails. CONCLUSION: Our cost-consequence analysis and clinical data provide decision-makers with tools to aid in global budgetary projections of fractional and total expected health care costs associated with the management BCG-refractory CIS of the urinary bladder.

BCG Vaccine↗

Sarcomatoid carcinoma of the urinary bladder: a clinicopathologic and immunohistochemical analysis of 14 patients.

Sarcomatoid carcinoma of the urinary bladder is a rare entity, in which both the histogenesis and biological behavior remain controversial. We herein describe the clinicopathologic and immunohistochemical profiles of sarcomatoid carcinomas and discuss the significance of cell adhesion molecules in the development of this peculiar neoplasm. The authors examined formalin-fixed and paraffin-embedded tissue samples from 14 patients with sarcomatoid carcinoma of the urinary bladder. An immunohistochemical analysis was performed by using antibodies against epithelial and mesenchymal antigens as well as adhesion molecules. Most patients suffered from an advanced stage of the tumor, extending to the muscular layer (7 cases) or to the perivesical tissues (5 cases). Microscopically, all 14 tumors were composed predominantly of a carcomatoid component and an obviously carcinomatous component. The sarcomatoid component was composed of a mixture of spindle cells, round cells, and pleomorphic giant cells. The carcinomatous components consisted of papillary or nonpapillary high-grade transitional cell carcinoma (TCC). The zones of gradual transition between the carcinomatous and the sarcomatous elements were focally apparent in each tumor. The findings of an immunohistochemical examination indicated that both carcinomatous and sarcomatoid components expressed epithelial antigens (pankeratin or EMA), even though the staining pattern varied from case to case. As for cell adhesion molecules, the carcinomatous components were positive for E-cadherin (8 of 12), CD44s (8 of 12), and CD44v6 (6 of 12). Although the sarcomatoid components were also positive for E-cadherin (5 of 12), CD44s (4 of 12), and CD44v6 (3 of 12), these rates were lower than those in the carcinomatous components. Six patients died of their disease between 5 and 36 months after the diagnosis was made. The recognition of sarcomatoid carcinomas has important therapeutic and prognostic implications. It seems appropriate to treat these neoplasms in the same manner as conventional high-grade TCCs with similar degrees of invasion. We consider that sarcomatoid carcinomas should be regarded as a high-grade carcinoma that shows a prominent pseudosarcomatous dedifferentiation. The sarcomatoid component of sarcomatoid carcinomas may result from either anaplastic changes or dedifferentiation related to the process of losing cell adhesion molecules.

Aged↗

Comparative length-tension relationship of urinary bladder strips from hamsters, rats, guinea-pigs, rabbits and cats.

1. Comparative passive tension-active tension curves were constructed for urinary bladder body strips from hamster, rat, guinea-pig, rabbit and cat. 2. Equally sized strips from rabbit and cat bladders had a significantly greater mass and cross-sectional area than strips from other species. 3. There was a greater change in cross-sectional area of strips from rabbit and cat bladders with increasing length than in strips from other species. 4. Cat bladder strips developed a significantly greater absolute active tension than did strips from all other species at passive tensions greater than 5 g. 5. The length-tension relationships of the urinary bladder differs from skeletal or vascular smooth muscle in that there is no significant decrease in active tension at strip lengths greater than L0. 6. The ability of the urinary bladder to generate active tension at tissue lengths considerably greater than L0 is a prime importance in the physiological role of the urinary bladder to accommodate and store urine.

Animals↗

Frequent mutations of the p53 gene and infrequent H- and K-ras mutations in urinary bladder carcinomas of NON/Shi mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

To elucidate whether common genetic events in human urinary bladder carcinogenesis also occur in rodent models, we investigated the presence of p53, H- and K-ras mutations in 18 urinary bladder carcinomas induced by various concentrations of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male NON/Shi mice. Histopathologically, all were invasive, 11 being squamous cell carcinomas (SCCs) and the remaining seven being transitional cell carcinomas (TCCs). Using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis followed by DNA sequencing, p53, H- and K-ras mutations were observed in 14 (78%; exons 5-7), two (11%; one each on exons 1 and 2) and one (5.6%; exon 1) animals respectively. The frequencies of mutations in p53 exons 5, 6 and 7 were 7 (39%), 4 (22%), and 9 (50%) respectively, and no mutation was found in exon 8. All mutations involved one base-pair substitution with or without amino acid changes and the types of base-pair substitution were random. No evident association was observed between mutation sites and the histological phenotypes. In conclusion, p53 mutations are frequent in BBN-induced mouse invasive urinary bladder tumors, at similar levels to those observed for human high-grade invasive carcinomas, and this plus their distribution suggests their possible participation in this model of urinary bladder carcinogenesis.

Amino Acid Sequence↗

Primary malignant lymphoma of urinary bladder.

A case of primary malignant lymphoma of the urinary bladder is described. The classic presentation of gross hematuria and dysuria with a benign clinical course is illustrated. From a review of the literature and our experience, we conclude that localized primary lymphoma of the bladder, especially those with favorable histologic findings, often does not require medical or surgical intervention. Persistent irritative bladder symptoms can be palliated adequately with external beam radiotherapy, while surgical intervention is rarely indicated.

Aged↗

Cortical evoked potentials following stimulation of the urinary bladder in man.

Techniques are described for recording evoked potentials in humans in response to stimulation of the urinary bladder. Twenty patients with various disorders of their urinary function were investigated. Evoked cortical potentials following stimulation of the urinary bladder could be recorded from all patients except subjects with complete transverse spinal cord lesions. The response was most evident at the central site (Cz) and had its most prominent peaks at 45, 65, 82 and 102 msec. This technique may become a useful diagnostic tool in the study of neurogenic bladder dysfunctions.

Aged↗

Dissociation of magnitude of relaxation from cyclic AMP levels in rabbit urinary bladder smooth muscles.

The effects of forskolin and isoproterenol on contractile force and cyclic AMP levels were compared in smooth muscle strips from rabbit urinary bladder dome. Both of forskolin and isoproterenol produced the time- and the dose-dependent relaxation and the time- and the dose-dependent increases in cAMP levels. The relaxant response to forskolin caused more slowly than that to isoproterenol. The two agents caused almost the same relaxant responses at same concentration. However, cAMP levels induced by forskolin was much more than those induced by isoproterenol. These results that amounts of cAMP in urinary bladder don't correlate with the relaxation responses in urinary bladder smooth muscle strips suggest that some forms of functional compartmentalization of cAMP may exist in the urinary bladder.

Animals↗

Radiopaque markers transit and anorectal manometry in 16 patients with multiple sclerosis and urinary bladder dysfunction.

Fecal incontinence and/or constipation are frequent complaints in multiple sclerosis associated with urinary bladder dysfunction, incontinence, and/or retention. Total and segmental colonic transit were studied by determination of radiopaque markers, and anorectal function by anorectal manometry, in 16 multiple sclerosis patients clinically defined (with urinary bladder dysfunction shown by urodynamic examination). Fifteen multiple sclerosis patients had constipation and 14 had increased colonic transit time; ten multiple sclerosis patients had fecal incontinence and five had spontaneous rectal contractions. It is suggested that increased colonic transit and anorectal dysfunction were secondary to neurologic disorders just as urinary bladder dysfunction is due to neurologic disorders in multiple sclerosis.

Adult↗

Advanced adenocarcinoma of the urinary bladder successfully treated by the combination of cisplatinum, mitomycin-C, etoposide and tegafur-uracil chemotherapy.

Primary adenocarcinoma of the urinary bladder has shown an extremely poor response to radiation or chemotherapy. Therefore, radical surgery is the only therapeutic treatment for it. A case report is presented of a primary advanced adenocarcinoma of the urinary bladder invaded into the uterus with distant metastases which responded completely to systemic combination chemotherapy including tegafur-uracil. The patient was a 53-year-old woman with a history of asymptomatic macrohematuria. She was treated with the combination of cisplatinum, mitomycin-C, etoposide and tegafur-uracil chemotherapy. After four courses of the chemotherapy, computed tomography showed marked regression of the primary tumor of the urinary bladder and the complete disappearance of the distant metastases in the liver, lung and para-aortic lymph node. Subsequently, she underwent radical cystectomy and cutaneous ureterostomy. Pathologically, no viable cancer cells were detected. Three years after the operation, she has no evidence of disease recurrence. Treatment of advanced adenocarcinoma of the urinary bladder by this combination chemotherapy is of benefit.

Adenocarcinoma↗

Three-dimensional arrangement of collagen and elastin fibers in the human urinary bladder: a scanning electron microscopic study.

To clarify the arrangements of collagen and elastin fibers of the urinary bladder, we examined 9 human (male, aged 42 to 72) urinary bladders by scanning electron microscopy with chemical digestion methods. The mucosal layer was divided into 3 portions according to the collagen arrangement: the superficial portion interwoven densely by collagen fibrils, the middle portion layered by flat bundles of collagen fibrils and the deep portion made of a loose network of twisted collagen bundles. In the muscular layer, the smooth muscle fascicles were firmly covered with collagen sheets, while each muscle cell in a fascicle was accommodated by a thin sheath of collagen fibrils. The serosal layer consists of wavy collagen bundles piled up in a sheet, which was intercalated by clusters of adipose cells. Elastic fibers were, on the other hand, sparse throughout the bladder wall, except for denser networks around the blood vessels and muscle fascicles and beneath the peritoneal mesothelium. The arrangements of these components were discussed in relation to the mechanical function and compliance of the urinary bladder.

Adipose Tissue↗

Modification by alpha-tocopherol, propyl gallate and tertiary butylhydroquinone of urinary bladder carcinogenesis in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The promoting activity of 3 antioxidants, alpha-tocopherol (alpha-TP), propyl gallate (PG) and tertiary butylhydroquinone (TBHQ) in urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male F344 rats was examined. Rats, 6-week-old, were treated with 0.05% BBN in the drinking water for 4 weeks and then administered 1.50, 0.75 or 0.38% alpha-TP, 1.0% PG or 2.0% TBHQ in the diet for 32 weeks. The urinary bladder of all animals was examined histologically after the total 36 experimental weeks. The incidence of papillary or nodular hyperplasia (PN hyperplasia) of the urinary bladder was significantly higher in the rats treated with BBN followed by 2.0% dietary TBHQ that in controls initiated with 0.05% BBN followed by control diet. This result indicates that TBHQ has weak promoting activity in urinary bladder carcinogenesis. alpha-TP and PG did not demonstrate a promoting effect for urinary bladder lesions.

Animals↗

Pseudosarcomatous myofibroblastic proliferations in the urinary bladder of children.

Ten examples of a pseudosarcomatous myofibroblastic proliferation occurring in the urinary bladder of children (aged 2 to 16 years) are reported. The lesions appeared as polypoid nodular masses of variable size with myxoid and hemorrhagic areas. They consisted of compact fascicles of elongated spindle cells with minimal atypia. Myxoid areas of variable extension and scattered inflammatory cells were constant features, whereas diffuse collagen deposition was not common. Despite the striking cellularity of some of the lesions, most showed minimal mitotic activity. Ultrastructurally, the predominant cells had features of myofibroblasts. Six cases studied by immunocytochemical methods expressed vimentin and muscle-specific actin. In addition, two of these cases expressed desmin and two others cytokeratin. Infiltration into the muscularis propria of the urinary bladder was demonstrated in six cases and into the perivesical soft tissues in two. However, none of the eight patients for whom follow-up information is available has had local recurrence or metastasis develop 18 months to 6 years after surgical excision.

Actins↗

Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type arising in the urinary bladder: report of 4 cases with molecular genetic analysis.

CONTEXT: Primary lymphoma of the urinary bladder is rare. Only 84 cases have been reported in the English literature to date, and none of these cases has had molecular confirmation of clonal immunoglobulin gene rearrangement. OBJECTIVES: To review all cases with primary urinary bladder lymphoma in our records, to classify them using the REAL classification, to confirm their immunophenotype and genotype, and to determine their outcome. DESIGN: We identified 4 cases of primary urinary bladder lymphoma in our medical records from a 30-year period. Immunohistochemical detection of immunoglobulin light chains and molecular analysis of immunoglobulin heavy-chain genes using the polymerase chain reaction were performed on paraffin-embedded material. RESULTS: All patients were older than 60 years. The male-female ratio was 1:3. All patients had a history of chronic cystitis. Histologic features of mucosa-associated lymphoid tissue lymphoma with centrocyte-like cells, plasmacytoid B cells, or both were observed in all cases. Monoclonality of B cells was demonstrated by immunohistochemistry, polymerase chain reaction, or both methods in every case. All patients presented with stage IAE disease, were treated with radiotherapy alone, and have been in continuous complete remission for 2 to 13 years. CONCLUSIONS: Primary bladder lymphomas are usually of low-grade mucosa-associated lymphoid tissue type. They are more common in females and are associated with a history of chronic cystitis. Lymphoepithelial lesions are seen only in association with areas of cystitis glandularis. B-cell clonality is readily demonstrable by immunohistochemistry and/or polymerase chain reaction analysis. Local radiotherapy appears to confer long-term control.

Aged↗