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Comparative physiology and pharmacology of the cat and rabbit urinary bladder.

The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in-vivo studies of spinal and supra-spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in-vitro study of bladder function. In order to determine if the results obtained using one species can be applied to another, we have compared the in-vitro physiology and pharmacology of the cat and rabbit bladder using isolated strips and whole bladder preparations. The results can be summarized as follows: 1) The cat displays significant spontaneous activity during in-vitro cystometry, but the rabbit shows no such activity (whole bladder studies). 2) Although the bladder weights of the cat and rabbit are similar, the rabbit bladder has a capacity three times that of the cat. 3) The maximal response to field stimulation was obtained at one gram of passive tension for the rabbit isolated strips, whereas five grams of passive tension was required for the cat strips. 4) Atropine inhibited the response of isolated strips of cat bladder to field stimulation by approximately 13% whereas the response of rabbit bladder strips was inhibited by approximately 45%. 5) The magnitude of the response of rabbit bladder strips to ATP was similar to the response to field stimulation in the presence of atropine; the response of cat bladder strips to ATP was only 20% of the response of that of the rabbit bladder strips, and approximately 10% of the response of the cat strips to field stimulation in the presence of atropine. 6) Field stimulation produced a 10fold greater rise in intravesical pressure in the cat isolated bladder than in the isolated rabbit bladder; in response to bethanechol, the cat bladder generated a 6-fold greater response than the rabbit bladder. It is clear that the in-vitro pharmacological responses of the cat urinary bladder are qualitatively and quantitatively different from that of the rabbit bladder.

Adenosine Triphosphate↗

Condylomata acuminata of the urinary bladder. Natural history, viral typing, and DNA content.

Three patients with condylomata acuminata of the urinary bladder are reported. Two of the patients were immunosuppressed, and one had longstanding extensive condylomata acuminata of the external genitalia and adjacent areas. All lesions recurred at least once and were difficult to treat. The diagnosis was confirmed by in situ hybridization on archival material with human papillomavirus (HPV) DNA probes under stringent conditions. In two of the patients, probes for HPV types 6 and 11 were positive; HPV 11 only was identified in one patient. Probes for HPV types 16 and 18 and pBR322 vector controls were negative. In one patient with a strong hybridization signal, the lesion was also positive for common papillomavirus antigen. DNA content measured by cytophotometry of Feulgen-stained whole nuclei isolated from lesions in two patients revealed a markedly aneuploid DNA pattern. Whether this is a factor in the behavior of the lesions is not known at this time. Although rare, HPV infection of the urinary bladder may result in widespread condylomatosis and may mimic giant condylomas of Buschke-Löwenstein or even verrucous carcinomas, sometimes necessitating radical treatment. Nevertheless, until there is proof to the contrary, the lesions must be considered benign and should not be confused with squamous cancer of the bladder.

Adult↗

Comparison of the bladder tumour antigen test with photodynamic diagnosis in patients with pathologically confirmed recurrent superficial urinary bladder tumours.

OBJECTIVE: To verify the sensitivity of the bladder tumour antigen (BTAstat, Bard Urological, Covington, GA) test against the sensitive procedure of photodynamic diagnosis (PDD), in which 5-aminolaevulinic acid (5-ALA, a precursor of fluorescent porphyrins) is absorbed by the tumour and detected by ultraviolet cystoscopy, in the early diagnosis of urinary bladder tumours. PATIENTS AND METHODS: Forty-three patients (31 men and 12 women, age range 21-87 years) were assessed after transurethral resection of their bladder tumour using the BTAstat test and PDD. Sixty-nine biopsies from suspect areas of bladder mucosa were taken during cystoscopy under ultraviolet light and all suspect lesions electrocoagulated. RESULTS: Thirty-five patients (81%) had a positive BTAstat test; in these patients PDD detected malignant lesions (17 Ta1G1-2, two T1G2, two T1G3 and 14 Tis). In eight patients (19%) the BTAstat was negative but PDD detected three malignant lesions (two Tis and one TaG1). CONCLUSIONS: PDD is valuable for detecting bladder malignancy and can identify small lesions not detected by the BTAstat test.

Adult↗

Urothelial hyperplasia of the urinary bladder of the rat induced by mechanical perforation and phenacetin treatment.

Mechanical perforation of the urinary bladder of Sprague-Dawley rats and subsequent administration of phenacetin in the diet induced urothelial hyperplasia in 11 of 12 rats. No pathological changes were found in the bladders of the control rats only submitted to mechanical perforation or phenacetin treatment only. The hyperplastic changes varied from mild focal urothelial hyperplasia after one week to severe focal and diffuse nodular and papillary hyperplasia after 3 weeks.

Animals↗

Primary malignant melanoma of the urinary bladder.

A melanin-synthesizing tumor of the urinary bladder was studied by light and electron microscopy. Careful clinical evaluation did not reveal evidence for a primary melanoma elsewhere in the patient. The clinical presentation, course of the disease, and demonstration of melanocytes in the bladder epithelium and malignant melanocytes comprising the tumor by light and electron microscopy indicated that the neoplasm was a primary malignant melanoma arising in the bladder.

Aged↗

Effects of streptozotocin-induced diabetes mellitus on intracellular calcium and contraction of longitudinal smooth muscle from rat urinary bladder.

PURPOSE: To examine the effect of diabetes on [Ca2+]i and contractility in longitudinal smooth muscle of the urinary bladder. MATERIALS AND METHODS: Longitudinal smooth muscle strips were isolated from the urinary bladders of rats with STZ-induced diabetes as well as age matched controls. Force and [Ca2+]i were measured simultaneously in muscle strips loaded with the calcium indicator, fura-2. Contractions were initiated by electrical field stimulation (EFS) at various frequencies, as well as by high K+, carbachol (CCh) and cyclopiazonic acid (CPA) in the presence of varying concentrations of extracellular Ca2+. RESULTS: In unstimulated muscles, there was no significant difference in resting [Ca2+]i between the control and diabetic groups. However, the muscle strips from the diabetic animals produced higher force levels in response to EFS, high K+, CCh and CPA than those from control animals. The higher force development in the diabetic muscles was not associated with greater increases in [Ca2+]i, which in fact tended to be lower during stimulation in the diabetic tissues. When stimulated by CCh in the presence of nifedipine, both control and diabetic muscles exhibited a nifedipine-resistant component of contraction, however, this was significantly larger in the diabetic muscles. CONCLUSION: The results suggest that there are no major impairments in either intracellular calcium regulation or contractile function in bladder smooth muscle after 8-weeks of STZ-induced diabetes. However, a non-specific enhancement of force production was seen, which was not associated with increases in [Ca2+]i. These changes imply that the apparent sensitivity to [Ca2+]i is enhanced in bladder smooth muscle from diabetic rats.

Animals↗

Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases.

The existence of a papillary lesion of the urinary bladder with a benign clinical course and recognizable morphologic features that merit the benign categorization "papilloma" has been controversial. The clinical aspects and histologic features of these lesions remain to be fully elucidated. We have studied the clinicopathologic features of 26 patients with urothelial papillomas and correlated them with outcome. Papillomas occurred in two distinct clinical settings: (1) de novo neoplasms (23/26) or (2) those occurring in patients with a known clinical history of bladder cancer ("secondary" papillomas; 3/26). Follow-up information was available in 14/23 of the de novo cases (mean = 39 mo) and in 3/3 secondary cases (mean = 24 mo). Patients with de novo papillomas had a mean age of 46 years; 16 were male and 7 were female. Twelve of 14 had a benign clinical course with no recurrences; 1 developed a recurrent papilloma at 3 years, and 1 developed a pT3a high-grade papillary urothelial carcinoma at 4 years. Patients with secondary papillomas had a mean age of 66 years; two were male and one was a female. One of these patients developed two additional recurrences, and two patients had no new recurrences. Morphologically, the papillary architecture ranged from a common simple, nonhierarchical arrangement to, infrequently, more complex anastomosing papillae with budding. The individual papillae ranged from small (most common), with scant stroma and slender fibrovascular cores, to large, with marked stromal edema and/or cystitis cystica-like urothelial invaginations. Common to all was a lining of normal-appearing urothelium without hyperplasia, maintenance of normal polarity, and frequent prominence of the umbrella cell layer. Overall, no patient with a diagnosis of papilloma died of disease; only one patient with a de novo lesion (7.0%) had a recurrent papilloma, and 1/14 (7.0%) progressed to a higher grade and stage of disease, although this patient was on immunosuppressive therapy secondary to a renal transplant. De novo urothelial papillomas occur in younger patients and usually have a benign course. Urothelial papillomas are histologically and probably biologically distinctive tumors and merit distinction from other higher risk papillary neoplasms of the urinary bladder.

Adult↗

[Indications for one-stage and delayed urethrectomy after radical cystectomy in patients with invasive cancer of the urinary bladder].

Our aim was to determine indications for urethrectomy in patients with muscle-invasive cancer of the urinary bladder (UBC) which is essential for choice of urine derivation. A total of 51 patients with invasive UBC at the age of 33-78 years (mean age 60 years) were treated: 7 patients with pT2bN0M0, 1 patient with pT2bN1M0, 18 patients with pT3aN0M0, 3 patients with pT3aN1M0, 14 patients with pT3bN0M0, 6 patients with pT4aN0M0, 2 patients with pT4bN0M0. Urethrectomy was indicated for men with involvement of the prostatic urethra (stage t4a) and urinary bladder cervix, multiple tumors of the bladder, pelvic lymph node lesions, detection of tumor cells by instant biopsy in the free urethral edge, poor differentiation of the tumor (G3) in combination with one of the above factors, emergence of urethrorrhagia late after cystectomy; for women with involvement of the bladder cervix and Lieutaud's triangle in combination with poor differentiation of the tumor cells (G3). Cystectomy was followed by urine derivation of the following type: uretero-ureteroanastomosis with nephrostomy (n = 2), ureterocutaneostomy (n = 3), Briker's operation (n = 22), ureterosygmoanastomosis with creation of sigmoid reservoir (method Mainz pouch II) (n = 21), Studer orthotopic plastic reconstruction (n = 2) and Hautmann plastic surgery (n = 1). Urethrectomy was made in 16 patients. One-stage operation was conducted in 14 patients (suprapubic approach--8 males, perineal one--in 6 females). Delayed urethrectomy was made in 2 patients. Intra- and postoperative complications caused by urethral removal were absent. Corrected 2-year survival for all 51 patients was 70.8 +/- 11.3%. Among the deceased were 2 patients who had undergone urethrectomy at the stage T2b and T4a 5 and 8 months after primary operation, respectively. Thus, we believe that urethrectomy must be made in the above indications and poor differentiation of the tumor cells (G3).

Adult↗

Contractile responses and calcium mobilization induced by muscarinic agonists in the rat urinary bladder: effects of age.

In the current study, the contractile responses to muscarinic stimulation of urinary bladder strips from young rats and aged rats were compared. 1. The EC50 values of the two groups in response to bethanechol were similar. 2. The magnitude and the velocity of tension generation was significantly lower in strips from the aged group. 3. The magnitude as well as the velocity of tension generation in response to high K+ solution of the two models were similar. 4. The time to peak [Ca2+]i in response to bethanechol was prolonged in strips from the aged group as compared with the young group. 5. 45Ca2+ influx in response to bethanechol was significantly reduced in the aged group as compared with the young group. It is concluded that the reduced contractile response to muscarinic stimulation of isolated urinary bladder strips from aged rats is mediated at least in part by a decreased rate of Ca2+ entry.

Age Factors↗

Carcinomas of the urinary bladder simulating malignant lymphoma. A report of five cases.

We report five carcinomas of the urinary bladder, four of them transitional cell carcinomas and one undifferentiated carcinoma, with unusual features that have received little or no comment in the literature and may be the cause of diagnostic difficulty because of their possible confusion with malignant lymphoma. Four patients were male and one female. They ranged from 61 to 76 years of age. Three tumors from these patients had a prominent (2 cases) or massive (1 case) lymphoid infiltrate that partially obscured the invasive carcinoma in two cases and largely obscured it in the third case, which closely resembled a lymphoepithelioma. The diagnosis of malignant lymphoma was only excluded with confidence in the last case after thorough immunohistochemical study. The lymphoid infiltrate was composed of numerous T-cells (UCHL-1 and Leu 22 positive) and polytypic plasma cells with admixed eosinophils; occasional germinal centers were present in one case. The tumors were deeply invasive in two patients, one of whom is alive with no evidence of disease 4 years after treatment with chemotherapy and radiation therapy; the other two cases are too recent for meaningful follow-up. Two other transitional cell carcinomas had diffuse patterns that simulated lymphoma or plasmacytoma. Recognition of these patterns of vesical carcinoma is important in order to avoid the misdiagnosis of the very rare malignant lymphoma of the urinary bladder.

Aged↗

[Changes in tissue and blood polyamine levels following chemotherapy in rats with urinary bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl) nitosamine in rats].

BACKGROUND: Polyamines are recognized as cell growth factors. We attempted to determine whether alterations in the levels of tissue and blood polyamines were useful biochemical makers for monitoring the efficacy of the chemotherapy for bladder tumors. METHODS: The concentrations of three polyamines of diamine, spermidine and spermine in urinary bladder and blood were determined in male F344 rats with urinary bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), following chemotherapy with cisplatin, methotrexate and pirarubicin. RESULTS: Bladder carcinoma was observed in 5 of 20 rats of the chemotherapeutic group, and 16 of 20 rats of the control group given saline alone. The levels of spermidine, spermine and total polyamine in both bladder and blood of the treated rats were significantly lower than those of the control rats. CONCLUSION: The study suggested that the levels of tissue and blood polyamines could be used as biochemical markers for monitoring the efficacy of the chemotherapy for bladder tumors.

Animals↗

Mechanoinhibitory effect of estradiol in guinea pig urinary bladder smooth muscles.

The mechanoinhibitory effect of estradiol on the myogenic activity of guinea pig urinary bladder detrusor muscles was studied. In detrusor muscles tonically contracted with 80 mmol/lKCl, 17 beta-estradiol and the nonestrogenic isomer 17 alpha-estradiol at 30 mumol/l reduced the contraction by 64 +/- 3 and 59 +/- 1%, respectively. In detrusor muscles maintained in Ca(2+)-free media and depolarized with 80 mmol/lKCl, the contractile response of muscles to the reintroduction of Ca2+ was inhibited in a dose-dependent manner by 17 beta-estradiol, suggesting that 17 beta-estradiol blocked entry of extracellular Ca2+ into bladder smooth muscle cells and reduced the rise of intracellular Ca2+ required for contraction. In detrusor muscles mildly depolarized with 15 mmol/lKCl, 17 beta-estradiol reduced the myogenic activity with an IC50 of 6.8 +/- 1.3 mumol/l. The higher activity of 17 beta-estradiol in this latter test indicated that estradiol could also possess some K+ channel opening activity. Glibenclamide at 1 mumol/l did not affect the relaxant activity of 17 beta-estradiol in detrusor muscles stimulated with 15 mmol/l; however, this activity was diminished in a dose-dependent manner by iberiotoxin. Collectively, these results have demonstrated that in addition to the Ca2+ antagonist activity, 17 beta-estradiol possesses K+ channel opening activity in guinea pig urinary bladder smooth muscles, activating probably not the adenosine triphosphate sensitive, but the Ca(2+)-dependent large-conductance K+ channels.

Adenosine Triphosphate↗

Effects of pH on the carcinogenicity of o-phenylphenol and sodium o-phenylphenate in the rat urinary bladder.

The effects of an alkalizer or an acidifier on bladder carcinogenesis induced by OPP or OPP-Na were examined. Groups of 31 male F344/DuCrj rats were given 1.25% OPP in the diet (group 1), 1.25% OPP in the diet plus 0.4% sodium bicarbonate (NaHCO3) in drinking-water (group 2), 2% OPP-Na in the diet (group 3) or 2% OPP-Na in the diet plus 1% ammonium chloride (NH4Cl) in drinking-water (group 4) for 26 wk. Urinary bladder tumours, papilloma and carcinoma occurred in 12/31 (39%) of group 1, 20/31 (65%) of group 2, 22/31 (71%) of group 3 and 3/31 (10%) of group 4. Values of urinary pH after 25 wk of treatment were correlated with the tumour incidences. The results indicate that the administration of an alkalizer enhanced the carcinogenicity of OPP and the administration of an acidifer inhibited the carcinogenicity of OPP-Na to the rat urinary bladder. This suggests that the earlier finding that OPP-Na was more carcinogenic than OPP resulted from the higher alkalinity of OPP-Na.

Animals↗

Stimulation of urinary bladder tumorigenesis by carcinogen-exposed stroma.

There is evidence to suggest that control mechanisms, either growth-stimulatory, inhibitory or inductive, may play a role in carcinogenesis. To test the hypothesis that treatment of rat urinary bladder with carcinogen induces alterations in the stroma which result in modified epithelial-stromal interactions, experiments were conducted using a rat model specifically designed for the study. Following exposure of Fischer F344 rats in drinking water to the urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) for four weeks, bladders were removed and subjected to a brief detergent treatment to completely remove epithelium. The bladders without epithelium ("stroma" bladder) were heterotopically transplanted to syngeneic recipients. Four days later, the denuded mucosa surface was resurfaced with intraluminal instillation of urothelial cells, either untreated or treated with BHBN for six weeks (6w-BHBN) or 10 weeks (10w-BHBN). Examination at 12 weeks posttransplant of the "stroma" bladders that had received 6w-BHBN urothelial cells showed a higher tumor incidence of carcinoma in the BHBN-exposed "stroma" bladders as compared with the incidence in the carcinogen-unexposed "stroma" bladders (p less than 0.05). Examination at 18 weeks posttransplant showed 100% incidence of tumors in all "stroma" bladders irrespective of the lengths of BHBN exposure of urothelial cells. However, among the bladders that had received 6w-BHBN urothelial cells, carcinogen-exposed "stroma" bladders proved to be better "soil" for neoplastic cells to proliferate; the mean tumor volume as well as the mean total tumor volume per bladder were significantly higher than in the control "stroma" bladders (p less than 0.01 for each comparison). Similarly, among the bladders that had been resurfaced with 10w-BHBN urothelial cells, the mean total tumor volume per bladder was greater in the carcinogen-treated "stroma" bladders than in the controls (p less than 0.05). No proliferative or neoplastic changes were observed in the BHBN exposed "stroma" bladders which had been resurfaced with normal urothelial cells. Our data indicate that neoplastic growth of carcinogen treated urothelium is enhanced when such cells interact with the stroma which has also been exposed to carcinogen.

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[Inflammatory pseudotumor of the urinary bladder. Study of 4 cases and review of the literature].

INTRODUCTION: Inflammatory pseudotumour (IPT) of the urinary bladder is a benign proliferative lesion which can simulate clinically and histologically a sarcoma. Aim of this study is to report four new cases and to review the literature. CASES: Two patients were male, aged 2 and 4 years respectively (cases 1 and 2); cases 3 was a 26 year old woman and case 4 was a 40 year old man. Three patients presented with gross haematuria. One patient (case 4) presented with abdominal pain. On cystoscopy all the lesions presented as polypoid masses, ranging from 0.5 to 3 cm. in greatest axis. All patients were treated with conservative surgery. Case 1 died of unrelated causes 7 years later; at autopsy no evidence of residual bladder lesion was found. All the remaining three patients are alive and free of disease 8, 4, and 3 years respectively. RESULTS: On histology all the lesions had similar features. They were characterized by a submucosal growth of spindle cells with little pleomorphism, immersed in abundant myxoid stroma. In all cases immunoreactivity with vimentin was obtained; smooth muscle actin was focally positive in two cases and cytokeratin in one case. Bladder muscular wall was involved in three cases. CONCLUSION: The present four cases showed same histological and immunohistochemical feature of the IPTs previously described in the literature. IPT of the urinary bladder must be differentiated from malignant lesions such as rhabdomyosarcoma, leiomyosarcoma, inflammatory fibrosarcoma, sarcomatoid carcinoma. Differential diagnosis is based mainly on the characteristic histological picture of IPT. Immunohistochemistry can be misleading as IPT shares in common with those malignant conditions, positivity with some markers, such as desmin with rhabdomyosarcoma and cytokeratin with sarcomatoid carcinoma.

Adult↗

The urinary bladder, a consistent source of Borrelia burgdorferi in experimentally infected white-footed mice (Peromyscus leucopus).

White-footed mice, Peromyscus leucopus, were experimentally infected in the laboratory with Borrelia burgdorferi, the causative agent of Lyme disease. After mice were infected by intraperitoneal or subcutaneous inoculation or by tick bite, attempts were made to culture spirochetes from the urinary bladder, spleen, kidney, blood, and urine. Spirochetes were most frequently isolated from the bladder (94%), followed by the kidney (75%), spleen (61%), and blood (13%). No spirochetes were isolated from the urine. Tissue sectioning and immunofluorescence staining of the urinary bladder demonstrated spirochetes within the bladder wall. The results demonstrate that cultivation of the urinary bladder is very effective at isolating B. burgdorferi from experimentally infected white-footed mice and that culturing this organ may be productive when surveying wild rodents for infection with this spirochete.

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Rat urinary bladder hyperplasia induced by oral administration of carbonic anhydrase inhibitors.

The carbonic anhydrase inhibitors, acetazolamide and MK-0927, were given by oral route to male Sprague-Dawley rats at 200 mg/kg/day and 25 mg/kg/day, respectively, for up to 4 weeks. Sequential necropsies were performed and urinary bladders were examined by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Similar urinary bladder changes were seen with both compounds. SEM evidenced slight multifocal urothelial changes consisting of cell swelling, dissociation, degeneration, and exfoliation after 3 and 5 days of treatment. After 2 and 4 weeks of treatment, elevated or leafy microridges on the luminal cell surfaces were seen together with foci of swollen cells. After a 2-month-recovery-period, the urothelial surfaces were normal. LM and TEM showed multifocal vacuolation of the urothelium associated with inflammation of the underlying lamina propria after 3 and 5 days of treatment. Cellular hypertrophy and hyperplasia of the transitional epithelium was seen after a 5-day treatment, persisted without increasing severity after 2 and 4 weeks of treatment, and totally regressed after the recovery period. It was concluded that, in the rat urinary bladder, oral administration of acetazolamide and MK-0927 induced early degeneration and inflammation followed by epithelial regeneration, resulting in a reversible hyperplasia of the transitional epithelium.

Acetazolamide↗