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Sequential studies of rat urinary bladder epithelial lesions induced by ifosfamide (Z4942).

Urinary bladder damage caused by ifosfamide in male F344 rats was studied by light microscopy and scanning electron microscopy. Ifosfamide was injected intraperitoneally at doses of 30, 60 and 120 mg. per kg. body weight, and rats were killed at several intervals following treatment. The changes in the epithelium observed by light microscopy and scanning electron microscopy following ifosfamide injection were compared to those observed following cyclophosphamide injection. Necrosis and exfoliation of the urinary bladder epithelium occurred after day 1 of ifosfamide treatment and were followed by regenerative hyperplasia. This hyperplasia was reversible. A dose response was evident in the number and size of lesions induced and the time of regeneration and repair. Scanning electron microscopy disclosed short, uniform microvilli on the luminal surface of cells during the early phases of hyperplasia. These microvilli persisted for only 1 day, from days 1 to 7, and days 1 to 12 respectively, following injection of 30, 60 and 120 mg. per kg. of ifosfamide. The hyperplastic lesions also contained cells with pleomorphic microvilli and ropy or leafy microridges on their surfaces. These findings after ifosfamide administration were similar to those reported to be induced in the urinary bladder by cyclophosphamide.

Animals↗

Effects of morphine in the isolated mouse urinary bladder.

Acute morphine increased the responses to acetylcholine of the isolated mouse urinary bladder. A chronic morphine treatment did not change the responses of the urinary bladder to acetylcholine or ATP. The acute administration of morphine did not modify the contractile response to ATP in the urinary bladders from untreated or chronically morphine treated mice. Methadone and ketocyclazocine decreased the responses to the electrical stimulation of the urinary bladder. These depressant effects were not modified by naloxone. The results suggest the nonexistence of opiate receptors in the mouse urinary bladder and the lack of direct effects of morphine on the neuroeffector junction.

Acetylcholine↗

[Signet-ring cell carcinoma of the urinary bladder].

The signet-ring cell carcinoma of the urinary bladder as a rare histopathological variant of the adenocarcinoma is demonstrated with the help of clinical, cytological and histological findings of a case (29-year-old male) and it is referred to etiopathogenetic as well as clinical particularities which render possible a delimitation from the carcinoma of the epithelium of the urinary tract. Half of all 28 cases published up to now issued from the remaining parts of the urachus, particularly when localized in the parietal region. The from the first deeply infiltrating growth in the wall of the urinary bladder demands larger surgical interventions, in which cases the partial resection of the urinary bladder represents still the most insignificant operative procedure with clearly better prognosis. For improving the therapeutic situation and the dubious prognosis urachus carriers should be operated on in time, whereby for their recognition modern picture-producing diagnostic method such as sonography should be utilized.

Adenocarcinoma, Mucinous↗

Effects of gender, age and hypertension on beta-adrenergic receptor function in rat urinary bladder.

beta-Adrenoceptors mediate urinary bladder relaxation, and gender, age and hypertension have been linked to bladder dysfunction. Therefore, we have studied whether any of these factors affects the ability of beta-adrenoceptor agonists to relax rat bladder detrusor muscle in vitro. For this purpose we have compared male and female Wistar rats, young and old male Wistar rats, and male normotensive and spontaneously hypertensive rats (SHR). Comparisons were done using KCl-precontracted bladder strips (length about 15-20 mm) and the endogenous agonist noradrenaline, the synthetic non-subtype-selective agonist isoprenaline, and the prototypical beta(3)-adrenoceptor agonists BRL 37,344 and CGP 12,177. While all agonists yielded numerically weaker relaxation in female as compared to male rats (for example for noradrenaline E(max) 40+/-4% vs 53+/-6% relaxation, pEC(50) 5.41+/-0.13 vs 5.60+/-0.14), this difference reached statistical significance only for the weak partial agonist CGP 12,177. Responses to all agonists were attenuated in old as compared to young rats, largely due to a reduced maximum effect, although the difference did not reach statistical significance for isoprenaline. The maximum relaxation responses to noradrenaline and isoprenaline were significantly lower in SHR than in normotensive rats, but both strains exhibited similar responses to the partial agonist BRL 37,344. We conclude that factors associated with bladder dysfunction, such as gender, age and hypertension, can be associated with impaired beta-adrenoceptor-mediated bladder relaxation. However, these alterations are not always consistent across various agonists, and the extent of the differences can be small. Therefore, we propose that beta-adrenoceptor dysfunction may contribute to the pathophysiology of such conditions, but is unlikely to be the only or even the major factor in this regard. We speculate that beta-adrenoceptor agonists may be effective in the treatment of bladder dysfunction under all of these conditions.

Adrenergic beta-3 Receptor Agonists↗

Promoting effects of dimethylarsinic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in rats.

Arsenicals are epidemiologically significant chemicals in relation to induction of urinary bladder cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMA), a major metabolite of inorganic arsenicals in mammals, for rat urinary bladder carcinogenesis. In experiment 1, 6-week-old male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then given one of several concentrations of DMA in their drinking water (groups 1-6: 0, 2, 10, 25, 50 and 100 p.p.m.) for 32 weeks. The development of preneoplastic lesions and tumors (papillomas and carcinomas) in the urinary bladder was enhanced by treatment with DMA in a dose-dependent manner. A significant increase in multiplicity of tumors (papillomas and carcinomas) was observed even at a low concentration of DMA (10 p.p.m.). On the other hand, no preneoplastic lesions and tumors were observed in the rats treated with DMA alone. In experiment 2, different concentrations of DMA (groups 1-4: 0, 10, 25 and 100 p.p.m.) in drinking water were administered to the rats for 8 weeks without prior initiation by BBN. A significant increase in the 5-bromo-2'-deoxyuridine labeling index and alteration of the surfaces of the urinary bladder epithelial cells, as revealed by scanning electron microscopy, provided evidence of a dose-dependent increase in cell proliferation due to the DMA treatment. These results suggest that DMA has the potential to promote rat urinary bladder carcinogenesis and one of the mechanisms involved is its stimulation of cell proliferation in the urinary bladder epithelium.

Animals↗

Protective effect of taurine against cyclophosphamide-induced urinary bladder toxicity in rats.

1. In the present study, the effect of taurine, on cyclophosphamide (CP)-induced urinary bladder toxicity was investigated. 2. Administration of a single dose of CP (150 mg/kg, i.p.) induced cystitis, as manifested by marked congestion, oedema and extravasation in rat urinary bladder, as well as a marked desquamative damage to the urothium, severe inflammation in the lamina propria, focal erosions and polymorphonuclear leucocytes associated with occasional lymphocyte infiltration as determined by macroscopic and histopathological examination. 3. A significant decrease in the endogenous anti-oxidant compound glutathione and elevation of lipid peroxidation also resulted in rat urinary bladder tissue. 4. Cyclophosphamide-induced cystitis markedly affected the contractile function of the urinary bladder, as revealed by a significant inhibition of tissue responsiveness to acetylcholine (ACh) at different molar concentrations in vitro. 5. Conversely, pretreatment with taurine (1% in drinking water to reach a dose of 1 g/kg per day) for 7 days before and 1 day after CP injection produced a significant decrease in urinary bladder weight (oedema) and a marked decrease in vascular congestion and haemorrhage, as well as a profound improvement in histological structure. Moreover, taurine pretreatment resulted in a significant decrease in lipid peroxide in urinary bladder tissue and glutathione content was greatly restored. 6. Urinary bladder rings isolated from rats treated concurrently with taurine and CP showed a significant increase in their responsiveness to ACh compared with the CP group. 7. These results suggest that taurine offers a protective effect against CP-induced urinary bladder toxicity and may, therefore, decrease the limitation on its clinical application. These results merit extension and further investigation of the impact of taurine on CP antitumour activity.

Animals↗

[The presence of nitric oxide synthase in mucosal epithelial cells of the frog urinary bladder].

In experiments on frog Rana temporaria L. urinary bladder, we investigated localization of NO-synthase (NOS) in urinary bladder slices and measured NOS activity in the suspension of mucosal epithelial cells. Intensive NADPH-diaphorase staining which is widely used as an indicator of NOS activity was found in mucosal epithelium. Almost all mucosal epithelial cells isolated in Ca2+ -free conditions demonstrated positive NADPH-diaphorase reactivity. Direct measurement of NOS activity in suspension of mucosal cells determined by the rate of conversion of L-arginine to L-citrullin showed that the enzyme activity was reduced in absence of external Ca2+ and was inhibited by L-NAME: non-specific NOS inhibitor, and 1400 W: a highly selective iNOS inhibitor (control: 754 +/- 184; L-NAME, 1 mM 329 +/- 87; 1400 W, 20 mM: 547 +/- 25; Ca2+ -free/EDTA: 490 +/- 184 cpm [3H]-citrullin/10(6) cells per 45 min, p < 0.05, n = 7-8). The data obtained demonstrate that frog urinary bladder mucosa epithelial cells provided antidiuretic hormone-induced increase of osmotic water permeability contain nitric oxide synthase. The presence of inducible (iNOS) as well as constitutive isoform(s) revealed in these cells allows to suggest involvement of NOS in intracellular signaling pathways regulated water transport across the epithelium.

Animals↗

Urine cytology: early diagnosis of induced carcinoma of the rat urinary bladder.

Transitional cell carcinoma of the urinary bladder was induced in F344 rats by intragastric intubation of the animals with the known bladder carcinogen N-nitroso-N-methyl-N-dodecylamine (NMDA). Urinary cytology was used to follow the development of bladder lesions. As early as 8 weeks after the beginning of NMDA exposure, small, but distinct, differences could be detected between the morphology of exfoliated transitional cells found in the urine if animals treated with NMDA and those of control animals. Atypia was noted in the cells from some of the NMDA treated animals at about 20 weeks, and after 32 weeks definitely malignant transitional cells were identified in the urine of all NMDA treated animals. When the NMDA treated animals were killed, at 55-60 weeks after the beginning of NMDA treatment, transitional cell carcinoma of the urinary bladder was confirmed in all animals. No abnormal cells were noted in urine from any of the control animals. Urine cytology is an excellent technique for early detection of experimental urinary bladder cancer, and may be especially useful in screening industrial workers exposed to suspect bladder carcinogens.

Animals↗

The ontogeny of the autonomic innervation and contractile response of the rabbit urinary bladder.

Although there has been considerable research on urinary bladder innervation, physiology and response to pharmacological agent, very little information is available concerning the ontogeny of bladder innervation and the contractile response to autonomic agents. The developmental aspects of urinary bladder innervation and function have been studied in the rabbit utilizing the following techniques: histochemical methodology to demonstrate autonomic innervation; in vitro responses to autonomic agents to demonstrate contractile responses; and ratio-ligand binding assays to determine specific receptor densities. The results of these studies can be summarized as follows: 1) at birth, the density of adrenergic fibers in the rabbit urinary bladder is very sparse, whereas there is a dense cholinergic innervation present. Over the first 6 weeks of postnatal development, there is a rapid progressive increase in the density of adrenergic fibers, whereas there is no significant change in the cholinergic innervation; 2) at birth, isolated strips of bladder respond poorly to methoxamine (alpha adrenergic agonist) and isoproterenol (beta-adrenergic agonist), but well to bethanechol (muscarinic cholinergic) and ATP (purinergic); 3) at birth, the density of adrenergic alpha and beta receptors is low; over the first 6 weeks of postnatal development, the density increases progressively to adult levels. The muscarinic receptor density is high at birth and does not change significantly over the first 6 weeks of postnatal development.

Animals↗

[Three-dimentional echography in diagnosis and staging of urinary bladder cancer].

The role of USI and three-dimentional volumetric reconstruction was studied in diagnosis of urinary bladder cancer diagnosis. 69 UBC patients were examined. Examination included renal USI of the kidneys, urinary bladder, prostate, echoureterography, cystoscopy, CT, MRT. The number of the tumors, volume, area, invasion were studied in 3D mode. US angiography assessed resistance index and tumor vascularization by degrees 0-3. USI findings were compared with those of MRT, cystoscopy, histomorphology of the biopsies. 2D USI technique proved effective in detection of urinary bladder cancer at stage T1 in 66%, 3D in 100. At stage T2a-b informative value of both techniques reached 87%. Overall informative value of 2D in detection of urinary bladder cancer was 81%, three-dimentional echography--96%. USI proved effective in diagnosis and staging of urinary bladder cancer. Use of 3D ultrasonic angiography facilitates the choice of more effective surgical policy in the treatment of urinary bladder cancer patients.

Aged↗

Cerebro-cortical innervation of the urinary bladder.

In this report cerebro-cortical innervation of the urinary bladder has been investigated in man by the use of electroencephalography and in the cat by the application of the evoked potential technique. Electroencephalographic monitoring during bladder filling while the patient was asleep was a useful method to determine cerebral response to stimulation of bladder sensory receptors. Bladder filling was performed during stage IV sleep. In the intact individual detrusor reflex contraction or attainment of bladder capacity was followed by prompt arousal and desynchronization of EEg rhythms. In patients with interruption of bladder sensory pathways in the periphery or in the spinal cord there was loss of impairment of the EEG response to bladder filling. In the cat, anesthetized with sodium pentobarbital, electrical stimulation of the nerve supply to the urinary detrusor muscle and to the pudendal nerve innervation to the periurethral striated muscle and anal sphincter, evoked a diphasic response in the cerebral cortex of the frontal lobe. All responses were grouped in the same area and were of short latency. Similar potentials have been evoked in man. These studies demonstrate that the peripheral, spinal and cerebral innervation of the urinary bladder in man are definable by electrophysiologic techniques. As a result, these electrophysiologic techniques are applicable to defining neuropathic changes in the urinary bladder innervation in man.

Animals↗

Malakoplakia of urinary bladder following cadaveric renal transplantation.

Malakoplakia of the urinary bladder following cadaveric renal transplantation in a twenty-two-year-old woman is reported. Urinary tract infection with Escherichia coli persisted postoperatively. Three years later, gross hematuria and fever occurred. Yellow-tan mucosal plaques or nodules were observed cystoscopically, and histologic examination revealed malakoplakia of the urinary bladder with characteristic foamy histiocytes containing Michaelis-Gutmann bodies.

Adult↗

Diagnosing the location of carcinoma in situ (CIS) of the urinary bladder using pirarubicin hydrochloride.

INTRODUCTION: No established technique for locating solitary carcinoma in situ (CIS) of the urinary bladder or CIS accompanying bladder cancer has been determined. Here we investigated whether the location of CIS of the urinary bladder can be macroscopically ascertained by instilling pirarubicin hydrochloride (THP) into the urinary bladder. PATIENTS AND METHODS: We dissolved 50 mg of THP in 50 ml of distilled water, and instilled the resulting solution into the urinary bladder. After 5 min, the urinary bladder is examined using a cystoscope. The study group consisted of 30 subjects (23 men and 7 women). RESULTS: THP uptake was seen in 19 flat (nontumorous) areas of the bladder mucosa in 13 patients. Of these, 11 lesions in 6 patients were confirmed to be CIS. THP uptake was also seen in flat malignant lesions such as bladder cancer invasion into the prostatic urethra, and in benign lesions such as chronic cystitis and urothelial hyperplasia. CONCLUSIONS: The present method can be useful to find easily and macroscopically the location of flat malignant lesions such as CIS.

Administration, Intravesical↗

Bladder preservation in small cell carcinoma of the urinary bladder: an institutional experience and review of the literature.

AIMS: Primary small cell carcinoma (SCC) of the urinary bladder is rare, accounting for less than 1% of all primary bladder malignancies. Metastases are often present at the time of diagnosis, prognosis is poor and there is no established optimum treatment strategy. Small cell carcinoma of the lung (SCLC) shares many clinicopathological features with SCC of the bladder, and there is good evidence supporting the use of combination chemotherapy in SCLC. In addition, consolidation thoracic irradiation and prophylactic cranial irradiation (PCI) both increase 3-year absolute survival by 5.4% in SCLC patients with limited disease and a complete response to chemotherapy. Therefore, we adopted a similar staging and treatment strategy for SCC of the bladder. We report our clinical experience using this strategy, and review published studies. MATERIALS AND METHODS: All cases of SCC of the bladder referred to Velindre Hospital between 1998 and 2005 were identified and data collected retrospectively on demographic details, stage, performance status, treatment and response to treatment. For the review, the electronic databases MEDLINE, EMBASE and Cancerlit were searched, along with hand searching of journals, relevant books and review papers. RESULTS: Seven patients were identified. In total, six out of seven had platinum-based chemotherapy. Four patients received consolidation radiotherapy (CRT) to the bladder after a complete response to chemotherapy, and none have locally relapsed to date. The three patients with limited disease remain alive and disease free 14, 30 and 36 months after diagnosis. CONCLUSIONS: Combined modality therapy using platinum-based combination chemotherapy and consolidation radiotherapy may provide effective local control and allow a bladder-preserving approach to the management of SCC of the bladder. The role of PCI is controversial, and should be discussed with patients on an individual basis.

Aged↗

Investigation about the penetration depth in the normal bladder wall and tumor by local instillation of mitomycin into the urinary bladder.

The penetration depth of mitomycin into the normal urinary bladder wall and tumor was determined in 21 bladder tumor patients. Either 20 mg mitomycin/20 ml distilled water or 40 mg/40 ml distilled water was locally instilled into the bladder with a catheter after emptying it and was left for about 25-l20 min. The individual concentrations of mitomycin within the various bladder layers (epithelial, lamina propria, up to the middle of the musculature) were determined with a thin-layer cup method specially modified for these investigations. The results show a high scatter of resorption from 2 up to 442 micrograms of mitomycin/g dry weight. With this method, mitomycin could be determined in the bladder musculature.

Administration, Topical↗

[Lung sarcoidosis following instillation of mitomycin C in the urinary bladder].

Intravesical prophylaxis against recurrence of urinary bladder carcinomas using mitomycin C (MMC) has proved to be and effective treatment with few side effects. Previously only two cases of lung toxicity after instillation of MMC into the urinary bladder has been described. We report a 65-year-old man in whom lung sarcoidosis occurred after intravesical administration of MMC. This association has not been reported to date. The clinical picture and the pathogenesis of this lung disease are discussed.

Administration, Intravesical↗