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Adriamycin instillations as recurrence prophylaxis in superficial urinary bladder cancer.

Fourteen patients suffering from recurring superficial urinary bladder carcinoma were studied. 50 mg of adriamycin was instilled intravesically approximately once monthly over a period of more than 17 months. Recurrence index (RI) with adriamycin prophylaxis was statistically monthly significantly lower and per cystoscopy highly significantly lower than without prophylaxis. The recurrence rate (RR), as well as the mean annual recurrence rate (MARR) were similarly significantly lower with prophylaxis than without. The total response, an expression used earlier, was 86% following prophylactic instillation. 57% of the patients (8/14) suffered from bladder irritation and urinary tract infections occurred in three of them.

Aged↗

N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark.

A variable but often significant proportion of urinary bladder cancer in urban areas can be attributed to occupational and cultural (cigarette smoking) situations associated with exposures to various arylamines. The variable N-acetylation of carcinogenic arylamines by human hepatic enzyme systems, the known genetic regulation and polymorphic distribution of this enzyme activity in humans, and the known enhanced susceptibility of individuals with the genetically-distinct "slow acetylator" phenotype to various arylamine toxicities, has prompted examination of possible correlations between N-acetyltransferase phenotype and urinary bladder cancer risk in rural and urban populations. In this context, N-acetylation is viewed as a component of detoxication pathways with respect to arylamine bladder carcinogenesis. In preliminary utilizations of this approach, a population of urban urinary bladder cancer patients from Copenhagen, Denmark displayed a 13% excess (p = 0.065) of individuals with the slow acetylator phenotype (46/71 = 64.8%) when compared to a Danish control population (38/74 = 51.4%). These data are consistent with the possibility that arylamines may play an etiological role in bladder cancer in this locale and that slow acetylator individuals may be at higher relative risk (1.74) than rapid acetylator individuals. As 95% of patients reported histories of smoking, it was not possible to isolate and examine smoking factors. In contrast, a population of rural urinary bladder cancer patients from Lund, Sweden, where bladder cancer incidence (20/100,000) (1971) is lower than in Copenhagen (43.8/100,000) (1968-72), no difference in slow acetylator distribution was observed between bladder cancer (80/115 = 69.6%) and Swedish control (79/118 = 66.9%) populations, indicating a relative lack of involvement of arylamines in the etiology of rural bladder cancer. Populations of "spontaneous" bladder cancer patients would be expected to contain variable portions of disease related to arylamine exposure and would be less likely to display a detectable correlation than would an industrial population with documentable arylamine exposure. Consequently, confirmation of this hypothesis is being pursued by examination of industrial populations in an effort to obtain an empirical estimate of relative risk for slow and rapid acetylator phenotypes. These studies involve exposure-matched workmen both with and without bladder cancer.

Acetyltransferases↗

Anal profilometry correlated to colpo-cysto-urethrography in female urinary bladder suspension defects.

Of 40 women with urinary bladder suspension defects verified by CCU were investigated with anal profilometry, 25 had anterior suspension defects had 15 posterior suspension defects. The profiles were superimposed to demonstrate morphological changes. The slopes of the profiles were correlated to slopes of profiles from a normal material. There was significant difference between normal and pathological slopes. The morphological changes of the profiles in relation to the anatomy of the pelvic floor is discussed.

Anal Canal↗

The urinary bladder: An extremely rare location of pediatric neuroblastoma.

Pediatric malignant tumors in the urinary bladder are rare with a high prevalence of rhabdomyosarcomas. A 15-month-old patient was referred to the authors' center because of a urinary bladder tumor. Imaging studies disclosed a solid pelvic mass in the dome of the bladder confirmed by a cystoscopy. Surprisingly, the biopsy done during this procedure confirmed a neuroblastoma with a favorable Shimada classification. This tumor had no bad prognostic factors. But, vessel compression and local infiltration led to delayed surgery, and neoadjuvant chemotherapy was initiated. After chemotherapy, a complete surgical resection was accomplished. Currently, this patient is in complete continuous remission. Only 5 other cases have been reported. Thus, urinary neuroblastoma seems to be a very rare pediatric tumor, but it should be considered in the differential diagnoses of urinary bladder tumor.

Female↗

Promoting effect of monosodium aspartate, but not glycine, on renal pelvis and urinary bladder carcinogenesis in rat induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Although the incidences were relatively low, hyperplasias of the renal pelvis and the urinary bladder have been observed in Fischer-344 (F-344) rats after both sodium aspartate and glycine treatments in long-term 2-yr bioassays. In the present study, the effects of these amino acids on development of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary lesions were investigated in male and female F-344/DuCrj rats. F-344 rats of both sexes, 6 wk old at the commencement, were given 0.05% BBN for 4 wk and then treated with one of the amino acids at a level of 5.0% in the drinking water for the following 36 wk. Proliferative lesions in the renal pelvis often associated with necrosis and mineralization were increased in the group treated with BBN followed by sodium aspartate, but not by glycine, in both sexes. The same group demonstrated higher incidences of urinary bladder tumors with increased urinary pH and sodium concentration and decreased creatinine and uric acid, but not accompanying crystallization. These results showed a clear promoting effect of sodium aspartate for urinary carcinogenesis in rats. The mechanisms of the effect on the renal pelvis and urinary bladder might be different.

Animals↗

[Carcinoma in situ in the urinary bladder].

In this paper we have presented seven patients with carcinoma in situ of the urinary bladder, a rare intraepithelial form of transitional cell carcinoma of the urinary bladder, described first in 1952. In all patients malignant cells were detected in urine sediment, and the diagnosis was proven histopathologicaly by random biopsies of the urinary bladder. In five patients carcinoma in situ was associated with papillary bladder tumor, while two patients had primary carcinoma in situ. We have emphasized a high rate of irritative urinary symptoms, that can lead to diagnostic mistakes. Three patients had reduced bladder capacity. In all patients a complete response was achieved after local immunotherapy or local chemotherapy. After a follow-up lasting from 23 to 61 months in one patient a recurrent carcinoma in situ was diagnosed, while six patients show no signs of recurrent disease.

Adult↗

Pharmacological characterization of muscarinic receptors in mouse isolated urinary bladder smooth muscle.

The pharmacological characteristics of muscarinic receptors in the male mice urinary bladder smooth muscle were studied. (+)-Cis-dioxolane, oxotremorine-M, acetylcholine, carbachol and pilocarpine induced concentration-dependent contractions of the urinary bladder smooth muscle (pEC(50)=6.6+/-0.1, 6.9+/-0.1, 6.7+/-0.1, 5.8+/-0.1 and 5.8+/-0.1, E(Max)=3.2+/-0.8 g, 2.7+/-0.4 g, 1.0+/-0.1 g, 2.7+/-0.3 and 0.9+/-0.2 g, respectively, n=4). These contractions were competitively antagonized by a range of muscarinic receptor antagonists (pK(B) values): atropine (9.22+/-0.09), pirenzepine (6.85+/-0.08), 4-DAMP (8.42+/-0.14), methoctramine (5.96+/-0.05), p-F-HHSiD (7.48+/-0.09), tolterodine (8.89+/-0.13), AQ-RA 741 (7.04+/-0.12), s-secoverine (8.21+/-0.09), zamifenacin (8.30+/-0.17) and darifenacin (8.70+/-0.09). In this tissue, the pK(B) values correlated most favourably with pK(i) values for these compounds at human recombinant muscarinic M(3) receptors. A significant correlation was also noted at human recombinant muscarinic m5 receptors given the poor discriminative ability of ligands between M(3) and m5 receptors. In recontraction studies, in which the muscarinic M(3) receptor population was decreased, and conditions optimized to study M(2) receptor activation, methoctramine exhibited an affinity estimate consistent with muscarinic M(3) receptors (pK(B)=6.23+/-0.14; pA(2)=6.16+/-0.03). Overall, these data study suggest that muscarinic M(3) receptors are the predominant, if not the exclusive, subtype mediating contractile responses to muscarinic agonists in male mouse urinary bladder smooth muscle.

Acetylcholine↗

Acute effects of urinary bladder distention on the coronary circulation in patients with early atherosclerosis.

OBJECTIVES: We sought to examine whether distention of the urinary bladder, a physiologic stimulus, could induce impaired coronary circulation in patients with early atherosclerosis. BACKGROUND: Distention of the urinary bladder reflexively causes an increase in sympathetic activity. The effect of such distention on the coronary circulation in patients with early atherosclerosis remains unknown. METHODS: To assess the effect of bladder distention on coronary dynamic forces, epicardial and microvascular responses were measured with an intracoronary Doppler flow wire in 40 patients with early atherosclerosis (<50% diameter stenosis). Patients were randomized into two groups according to whether they did not (group 1, n = 20) or did have (group 2, n = 20) pretreatment with an alpha1-adrenergic receptor blocker (oral doxazosin, 2 mg). Coronary flow velocity was monitored by quantitative coronary angiography at baseline, during urinary bladder distention and after intracoronary nitroglycerin injection. RESULTS: Bladder distention significantly decreased the coronary diameter in the stenotic segments (p<0.001), decreased coronary blood flow (p<0.001) and increased coronary resistance (p<0.001), as compared with baseline values, in group 1 patients. In group 2 patients with bladder distention, the angiographic variables did not show significant changes, as compared with baseline values. No significant differences were noted between the groups in the responses of the angiographic variables after nitroglycerin administration. CONCLUSIONS: The present study shows, for the first time, that urinary bladder distention caused vasoconstriction of coronary conduit and resistance vessels involved mechanisms related to alpha1 adrenoceptors. Pretreated administration of doxazosin reversed the changes toward baseline. Vasoconstriction during bladder distention can be relieved after nitroglycerin administration, suggesting an unchanged responsiveness of vascular smooth muscle cells to such distention.

Blood Flow Velocity↗

cDNA cloning of a functional water channel from toad urinary bladder epithelium.

A cDNA was cloned from the epithelium of toad (Bufo marinas) urinary bladder, based on homology to the mammalian aquaporins (AQP). The cDNA [947 base pairs (bp), identified as AQP-t1] encoded a 272-amino acid protein with 76% identity to mammalian aquaporin-1 (AQP-1) and 88% identity to frog water channel FA-CHIP. AQP-t1 cDNA was nearly identical to a fragment of a nonfunctional cDNA cloned recently from toad bladder ["AQP-TB"; J. Siner, A. Paredes, C. Hosselet, T. Hammond, K. Strange, and H.W. Harris, Am. J. Physiol. 270 (Cell Physiol. 39): C372-C381, 1996], except for reading frame shifts at bp 253, 264, and 682, two single amino acid deletions, a different 3'-coding sequence downstream from bp 786, and a different 5' sequence upstream from bp 9. Water permeability (Pf) in Xenopus laevis oocytes expressing AQP-t1 cRNA was strongly increased from (0.83 +/- 0.06) x 10(-3) cm/s (water-injected control) to (17 +/- 4) x 10(-3) cm/s, with 80% inhibition by 0.3 mM HgCl2; glycerol and urea permeabilities were not increased. Northern blot analysis showed a single AQP-t1 mRNA of 2.8 kb in eye > lung > urinary bladder > skin > stomach approximately heart, brain, and intestine. AQP-t1 mRNA expression was not changed by a 3-day dehydration of toads or an 8-h stimulation of Pf in isolated bladders by forskolin. These results indicate that the epithelium of toad urinary bladder expresses a functional homologue of AQP-1 and FA-CHIP that is probably not vasopressin regulated.

Amino Acid Sequence↗

[125I]neurokinin A labels pharmacologically distinct populations of NK2 binding sites in hamster and rabbit urinary bladder.

The pharmacological profile of NK2 binding sites has been characterised in homogenates of rabbit urinary bladder and compared with that present in homogenates of hamster bladder. In both species, [125I]neurokinin A-specific binding to urinary bladder membranes was displaced by neurokinin A and the NK2 agonist [beta-Ala8]neurokinin A-(4-10) whilst the NK1 ligands [Sar9,Met(O2)11]substance P and (+/-)-CP-96,345, and the NK3 agonist, senktide, were only weak displacers or ineffective. At rabbit NK2 sites, the rank order of affinity of NK2 receptor-selective antagonists was; MEN 10,376 > MEN 10,207 > L-659,877 >> R 396. In contrast, the rank order of displacement of [125I]neurokinin A-specific binding to hamster bladder membranes was: L-659,877 > R 396 > MEN 10,376 > MEN 10,207. These data demonstrate that [125I]neurokinin A binds to pharmacologically distinct NK2 binding sites in hamster and rabbit urinary bladder.

Amino Acid Sequence↗

Urinary bladder cancer following cyclophosphamide therapy for Hodgkin's disease.

Urinary bladder cancers following prolonged cyclophosphamide therapy are being increasingly reported. We report a case of transitional cell carcinoma of the urinary bladder occurring 12 years after pulse intravenous therapy with cyclophosphamide for Hodgkin's disease. The mechanism of bladder carcinogenesis and the possible role of the uroprotector MESNA in preventing cyclophosphamide induced bladder cancer are discussed.

Cyclophosphamide↗

Species variations in the metabolism of N-butyl-N-(4-hydroxybutyl) nitrosamine and related compounds in relation to urinary bladder carcinogenesis.

Species variations in response to urinary bladder carcinogens, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN), and N,N-dibutylnitrosamine (DBN), were investigated in several animal species from the metabolic point of view. Since N-butyl-N-(3-carboxypropyl) nitrosamine (BCPN) and N-ethyl-N-(3-carboxypropyl) nitrosamine (ECPN) had been found to be the principal urinary metabolites which are responsible for the induction of bladder tumors by BBN or DBN and EHBN, respectively, in rats, acidic urinary metabolites with the N-nitroso moiety were isolated and determined by a colorimetric method after oral administration of these nitrosamines to rats, mice, hamsters, guinea pigs, and dogs. Qualitatively almost no species differences were observed among these animals in regard to the urinary metabolites except in the case of mice, in which the glycine conjugate of BCPN was isolated from the urine and identified as the principal metabolite of BBN and DBN. However, appreciable quantitative differences in the urinary excretion of BCPN or ECPN were found among these animal species, indicating that the differences in the susceptibilities of different animal species to urinary bladder carcinogenesis induced by BBN, DBN and EHBN may be closely related to the different extents of urinary excretion of the active metabolites of these nitrosamines.

Animals↗

Phase II clinical trial of carboplatin in canine transitional cell carcinoma of the urinary bladder.

Fourteen dogs with histologically-confirmed transitional cell carcinoma (TCC) of the urinary bladder were treated with 300 mg/m2 carboplatin every 3 weeks. Response to therapy was assessed with abdominal radiography, double contrast cystography, urinary bladder ultrasonography and thoracic radiography before therapy and at 6-week intervals during therapy. Dogs were monitored for hematologic toxicity with a CBC and platelet count performed immediately before and 10 to 14 days after carboplatin treatment. Tumor responses included progressive disease in 11 dogs and stable disease in 1 dog. Two dogs were euthanized due to carboplatin toxicity before assessment of tumor response. Toxicity included thrombocytopenia with or without neutropenia in 7 dogs and gastrointestinal toxicity in 6 dogs. Carboplatin therapy was not beneficial in the treatment of TCC in the 14 dogs in this study.

Animals↗

Review: tissue engineering of the urinary bladder: considering structure-function relationships and the role of mechanotransduction.

A variety of conditions encountered in urology result in bladder dysfunction and the need for bioengineered tissue substitutes. Traditionally, a number of synthetic materials and natural matrices have been used in experimental and clinical settings. However, the production of functional bladder tissue replacements remains elusive. The urinary bladder sustains considerable structural deformation during its normal function and represents an ideal model tissue in which to study the effects of biomechanical simulation on tissue morphogenesis, differentiation, and function. However, the actual role of mechanical forces within the bladder has received little attention. A strategy in which in vitro-generated tissue constructs are conditioned by exposure to the same mechanical forces as they would encounter in vivo could potentially be used both in the development of functional tissue replacements and to further study the role of biomechanical signalling. The purpose of this review is to examine the role and structure-function relationship of the urinary bladder and, through consultation of the literature available on mechanotransduction and tissue engineering of alternative tissues, to determine the factors that need to be considered when biomechanically engineering a functional bladder.

Animals↗

Lack of a modifying effect by the diuretic drug furosemide on the development of neoplastic lesions in rat two-stage urinary bladder carcinogenesis.

The effect of the diuretic drug furosemide on two-stage urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated with regard to possible promoting activity. BBN was administered at 2 doses, 0.01 or 0.05%, in drinking water for 4 wk, and thereafter furosemide was given by gavage 3 times weekly for 32 wk, 250 mg/kg body weight. Furosemide ingestion induced diuresis with an alkaline, hypotonic urine. No significant difference with regard to incidences of bladder lesions were apparent between furosemide and control groups. The present investigation indicated that neither furosemide nor its related polyuria acted as a promoter in two-stage urinary bladder carcinogenesis.

Animals↗

[The epidemiology and importance of metaplasia and dysplasia of the urinary bladder mucosa in autopsy material from a middle-size industrial city (study of Görlitz)].

This study had been conducted for the purpose of obtaining information on incidence and biological significance of metaplasia and dysplasia of the urinary bladder. Therefore, postmortem investigations were made of 1,117 urinary bladders, using optical light microscopy and mapping. They were related to a medium-size industrial town with an autopsy frequency of 98%. Metaplasia (58%) and dysplasia (13%) are no rare urinary bladder findings and occur particularly to individuals in somewhat advanced age, with no significant sex-related difference. Urocystitis was recorded from over 50% of all cases reviewed. More strongly pronounced inflammatory processes appeared to be risk factors for higher severity of dysplasia. Inconspicuous as well as metaplastic von Brunn's nests or squamous and glandular metaplasia without atypical cells should not be considered precarcinomas. However, atypical cells in terms of dysplasia were recordable from a small number of these metaplasias. Precancerous importance might be attributed to few of them, particularly in male patients with dysplastic squamous cell metaplasia. No reliable information, however, was available on premature development of dysplasia in lower age groups which would have meant a long-drawn process of carcinogenesis.

Adult↗

Detrusor collagen content in the denervated rat urinary bladder.

Neurogenic bladder dysfunction was created in male rats by removal of the pelvic ganglia. The bladders were then emptied manually once daily, and kept free from infection. After 10 days or six weeks the bladders were taken out and the mucosa-submucosa was removed. The detrusors were then weighed and used for collagen assay. Detrusor weight increased 4.5 and six times after 10 days and six weeks, respectively. Total detrusor collagen increased 2.3 and 3.7 times, but due to the increase in detrusor weight the concentration decreased to 60 per cent of normal. The electron microscopic investigation showed that the cross-sectional area of the smooth muscle cells had increased fourfold after six weeks. The collagen fibrils were found mainly in the interstitial tissue between the muscle bundles. As these increased in size following the neurogenic lesion, the collagen-rich tissue component decreased relatively. Our conclusion is that frequent emptying and the avoidance of bladder infection protects the denervated rat urinary bladder wall from injuries that would otherwise lead to an increased collagen concentration.

Animals↗

Adrenergic innervation of the ureters, urinary bladder, and urethra in pigs.

Studies were conducted on 4 sexually mature and 4 immature pigs. Scraps of the ureters, urinary bladder, and urethra were cut with a freezing microtome. Fluorescence method of Torre and Surgeon (1976) was used to reveal the adrenergic innervation. It was found that the ureters were weakly supplied with the adrenergic nerves; most of the nerves were located in the muscular and submucosal membranes. Apex of the urinary bladder possessed the weakest innervation. More nerves were found in particular layers of the bladder corpus whereas bladder trigonum and cervix possessed numerous nerves. Adrenergic innervation of the urethra was similar to that of the urinary bladder's cervix. Adrenergic nerves were present in the serous and muscular membranes of both the urinary bladder and the urethra. Part of the nerve fibres was connected with blood vessels of the organs under study.

Adrenergic Fibers↗