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[Studies of tryptophan metabolism in cancer of the urinary bladder].

In 100 patients suffering from urinary bladder cancer (pTA-4, Nx, M0-1, G0-3) we created an oral tryptophan load administering 5 g of L-type tryptophan. Thereafter the amount of both xanthurenic acid and kynurenin was determined quantitatively in the 24-hour urine. 16 patients revealed pathological test results and excretion pattern of tryptophan metabolites via kynurenin were similar to vitamin B6-dependent xanthurenic aciduria both in its homocygotic and heterocygotic pattern. It has not been possible to prove a direct correlation between xanthurenic aciduria and urinary bladder cancer. However, xanthurenic aciduria may be of significance as a risk factor in the etiopathogenesis of urinary bladder cancer.

Humans↗

[Chronic interstitial cystitis (Hunner) associated verrucous carcinoma of the urinary bladder].

A verrucous carcinoma of the urinary bladder (pT4N0M0, G1) developed in a 66-year-old woman who had been suffering from interstitial cystitis with Hunner's ulcer for 10 years. Up to now, only 7 cases of verrucous carcinoma of the urinary bladder unassociated with bilharzial cystitis have been reported. Although the development of a verrucous carcinoma as a complication of interstitial cystitis has not been reported so far, the authors regard the chronic irritation of the bladder to be the most important etiologic factor for the malignant transformation. After conservative management had failed, a radical cystectomy with supravesical urinary diversion was performed. The characteristics of interstitial cystitis, verrucous carcinoma and surgical management are discussed.

Aged↗

Nontraumatic spontaneous rupture of the urinary bladder.

Rupture of the urinary bladder without a history of recent trauma or instrumentation is rare; it is usually associated with bladder disease or outlet obstruction. The patient is usually seen as an emergency case and has an atypical clinical picture. The four patients in this report were initially seen and treated by a general surgeon; in only two was the diagnosis established preoperatively and confirmed by retrograde cystography. Awareness on the part of the consulting surgeon that bladder rupture is possible in a predisposed patient may lead to a correct preoperative diagnosis. In this series, early operation--removing urine from the peritoneal cavity or retropubic space, closing the rupture and securing good vesical drainage--resulted in resumption of vesical function in all four patients and there were no deaths.

Adult↗

Effect of coffee drinking on cell proliferation in rat urinary bladder epithelium.

A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis was investigated in male Wistar rats using cell proliferation in urinary bladder epithelium as the indicator of tumour promotion. Male rats were given either undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil, known to induce cell proliferation in urinary bladder epithelium, was included in the study as a positive control. In rats receiving 100% coffee, body weights, liquid intake and urinary volume were decreased. Neither histopathological examination of urinary bladder tissue nor the bromodeoxyuridine labelling index revealed biologically significant differences between rats receiving coffee and the tap water controls. Uracil increased the labelling index and induced hyperplasia of the urinary bladder epithelium, as expected. It was concluded that these results produced no evidence that drinking coffee predisposes to tumour development in the urinary bladder.

Animals↗

Malignant neurofibroma of the urinary bladder.

Malignant neurofibroma of the urinary bladder is a very rare entity and usually associated with von Recklinghausen's disease. We present the first case of sporadic malignant neurofibroma of the urinary bladder and a review of the literature.

Aged↗

Autonomic nervous influence of the female guinea-pig urinary bladder during the oestrus cycle.

The mammalian urinary bladder receives dual innervation. The excitatory innervation is considered to be partly cholinergic and partly mediated via NANC-receptors. Several (co-)transmitters have been suggested. The adrenergic inhibitory innervation is mediated via alpha- and beta-receptors. Female sex hormones could change autonomic influence of urogenital organs. It was considered to be of interest to characterize the spontaneous and nerve stimulation-induced muscular activity in the urinary bladder of the female guinea-pig during the oestrus cycle. Both the spontaneous activity and nerve-induced activity varied according to the hormonal status of the animal. An alpha-adrenergic inhibitory influence was identified. It was further confirmed that the excitatory innervation could not be blocked by the cholinergic antagonist scopolamine, while alpha-beta-methylene ATP partly inhibited nerve stimulation-induced smooth muscle response, most prominent at cycle day 6. Indomethacin did not impair spontaneous activity or nerve stimulation-induced activity. Nitric oxide reduced nerve stimulation-induced responses on cycle day 12. Imperative urinary bladder contractions are reported to diminish after oestrogen use and in the female a hormonal effect of the nervous influence on the urinary bladder smooth muscle is suggested.

Adenosine Triphosphate↗

A clinical diagnosis of urinary bladder (extra-adrenal) phaeochromocytoma.

Urinary bladder (extra-adrenal) pheochromocytoma is a catecholamine-producing tumor that arises from chromaffin cells in the extra-adrenal paraganglion system of the urinary bladder. The symptoms and signs result from the release of epinephrine and/or non-epinephrine, which is more prominent during micturition. The most serious consequences of the disease are paroxysmal hypertension during micturition and malignant degeneration. Thus, proper treatment is mandatory.

Humans↗

Kinin B1 receptor-mediated motor responses in normal or inflamed rat urinary bladder in vivo.

The rat urinary bladder is one of the few in vivo preparations in which kinin B1 receptor-mediated contractile responses have been described, but the nature (local or reflex) of these responses has not been characterized. We have investigated the motor effects of i.v. or topical (onto the bladder serosa) administration of the selective kinin B1 receptor agonist [des-Arg9]-bradykinin ([des-Arg9]-BK) in the normal or inflamed (cyclophosphamide-induced) urinary bladder in urethane-anaesthetized rats. In both normal and inflamed bladders [des-Arg9]-BK produced a tonic contraction of low amplitude (< 15 mmHg) with phasic contractions of high amplitude (> or = 15 mmHg) superimposed (micturition reflex contractions). In inflamed bladders, the response to [des-Arg9]-BK was more prominent than in controls. Similar observations were made after the topical administration of [des-Arg9]-BK. In order to evaluate any time-dependency in the expression of B1 receptor-mediated bladder responses, [des-Arg9]-BK was administered in separate groups of control animals at 30 and 240 min after the completion of surgical procedures required for set-up of the preparation: no bladder contraction was detected at 30 min whereas both local and reflex contractions could be elicited by [des-Arg9]-BK at 240 min after the set up. In ganglionectomized rats, the response to [des-Arg9]-BK or the selective tachykinin NK2 receptor agonist [betaAla8]NKA(4-10) was evaluated at 30 and 240 min after the set up in inflamed or in control animals. The response to [des-Arg9]-BK was greater after inflammation although a time-dependent increase was evident in both groups; in contrast, the response to [betaAla8]NKA(4-10) was similar in both groups and remained constant over the observation period. After induction of inflammation, the tonic contraction induced by [des-Arg9]-BK in ganglionectomized rats was dose-dependently reduced by the kinin B1 receptor antagonist [desArg10]Hoe 140. The contractile response (number of micturition reflex contractions) induced by [des-Arg9]-BK in normal rats with intact pelvic nerves at 240 min from the set up was not changed after the administration of the selective B2 receptor antagonist Hoe 140. These results indicate that stimulation of bladder kinin B1 receptors evokes a local, tonic-type contraction with reflex contractions superimposed in both normal and inflamed bladders, but in the latter situation the motor responses are magnified.

Administration, Topical↗

Intravesical wire as foreign body in urinary bladder.

Foreign bodies in the urinary bladder are frequently the objects of jokes among doctors, but they may sometimes cause serious implications to the patients. Here we present our experiences in 3 such cases where long segments of wire were introduced into the urinary bladder through the urethra.

Adolescent↗

Upregulation of retinoic acid-inducible gene-I in T24 urinary bladder carcinoma cells stimulated with interferon-gamma.

Urinary bladder epithelial cells play an important role in the host defense against urinary tract infections. Interferon-gamma (IFN-gamma) is a potent cytokine that regulates immune responses by inducing multiple genes in many types of cells including urinary bladder epithelial cells. Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH-box family, which is involved in various reactions related to RNA metabolism, and is induced in leukemic cells by retinoic acid or in endothelial cells by lipopolysaccharide. We have studied the expression of RIG-I in T24 cells, a cell line derived from human urinary bladder epithelial carcinoma cells. IFN-gamma stimulated T24 cells to express RIG-I mRNA and protein in concentration- and time-dependent manners. Immunohistochemical analysis revealed the expression of RIG-I in the urinary bladder epithelium from a patient with chronic urinary tract infection and in a bladder epithelial carcinoma. We conclude that RIG-I may play some role in inflammatory reactions in the urinary tract epithelium.

Antineoplastic Agents↗

Modifying factors in urinary bladder carcinogenesis.

N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is a potent carcinogen in the urinary bladder of animals. The BBN model of bladder cancer is an excellent model of human urinary bladder cancer and has already led to a greater knowledge of its pathogenesis. In our studies, histogenesis and morphological characteristics of BBN urinary bladder cancer were analyzed in different animal species such as rats, mice, hamsters and guinea pigs and also in different rat strains. Papillary or nodular hyperplasia (PN hyperplasia) is found to be a preneoplastic lesion of the rat urinary bladder. Therefore, the promoting and inhibitory effects of various chemicals in two-stage urinary bladder carcinogenesis were judged by measuring PN hyperplasia in rats. Dose-dependent and organ-specific effects of the urinary bladder promoter, saccharin, in the induction of PN hyperplasia were shown in rats after initiation by BBN. The promoting effect of saccharin was seen more clearly in the urinary bladder of rats after potent initiation. A strain difference in susceptibility of the urinary bladder to the promoter was also shown. These results suggest that the above various factors may also have modifying activities on urinary bladder carcinogenesis in man.

Animals↗

Negative feedback regulation of nerve-mediated contractions by KCa channels in mouse urinary bladder smooth muscle.

When the urinary bladder is full, activation of parasympathetic nerves causes release of neurotransmitters that induce forceful contraction of the detrusor muscle, leading to urine voiding. The roles of ion channels that regulate contractility of urinary bladder smooth muscle (UBSM) in response to activation of parasympathetic nerves are not well known. The present study was designed to characterize the role of large (BK)- and small-conductance (SK) Ca(2+)-activated K(+) (K(Ca)) channels in regulating UBSM contractility in response to physiological levels of nerve stimulation in UBSM strips from mice. Nerve-evoked contractions were induced by electric field stimulation (0.5-50 Hz) in isolated strips of UBSM. BK and SK channel inhibition substantially increased the amplitude of nerve-evoked contractions up to 2.45 +/- 0.12- and 2.99 +/- 0.25-fold, respectively. When both SK and BK channels were inhibited, the combined response was additive. Inhibition of L-type voltage-dependent Ca(2+) channels (VDCCs) in UBSM inhibited nerve-evoked contractions by 92.3 +/- 2.0%. These results suggest that SK and BK channels are part of two distinct negative feedback pathways that limit UBSM contractility in response to nerve stimulation by modulating the activity of VDCCs. Dysfunctional regulation of UBSM contractility by alterations in BK/SK channel expression or function may underlie pathologies such as overactive bladder.

Animals↗

Rhabdomyosarcoma (botryoid sarcoma) of the urinary bladder in a Maltese.

A urinary bladder tumour was diagnosed in a two-year-old female Maltese with haematuria and pollakiuria on the basis of ultrasonography and pneumocystography findings. The mass was resected, and the bladder was preserved at surgery. Histological and immunohistochemical examination confirmed the tumour to be a rhabdomyosarcoma, which has rarely been reported in small breeds of dog. There was no recurrence of the tumour at the original site in the urinary bladder two months later, when the dog died due to metastasis to the liver. This is believed to be the first report of bladder rhabdomyosarcoma in a Maltese.

Animals↗

[Urinary bladder xanthoma. A cystoscopic finding].

Urinary bladder xanthoma (UBX) is an infrequent lesion that has been very rarely referred to in medical literature. We describe a case of UBX that was associated with a low-grade transitional cell carcinoma of the urinary bladder. The cystoscopic aspect of this lesion was so characteristic that diagnosis could be suggested at cystoscopy, while histological examination confirmed this.

Aged↗

High-risk superficial bladder cancer: intravesical therapy for T1 G3 transitional cell carcinoma of the urinary bladder.

The ideal treatment for T1 G3 transitional cell carcinoma (TCC) of the urinary bladder remains controversial. Therapeutic options after the initial transurethral (TUR) resection are observation, intravesical therapy, a repeat resection, radiation therapy, and cystectomy. Because more than half of patients with T1 G3 TCC of the urinary bladder do not progress, initial cystectomy can represent overtreatment. However, observation alone following TUR for T1 G3 TCC of the urinary bladder is associated with a progression rate of 48%. Intravesical immunotherapy has been shown to decrease recurrence and progression in high-grade Ta carcinoma in situ and T1 bladder cancer. When patients with T1 G3 tumors are well selected, intravesical therapy following the initial TUR can significantly improve survival and quality of life. Persistence or recurrence of high-grade tumor mandates consideration of cystectomy.

Adjuvants, Immunologic↗

Characterization of hyperpolarization-activated current (Ih) in dorsal root ganglion neurons innervating rat urinary bladder.

Afferent pathways innervating the urinary bladder consist of myelinated Adelta-fibers and unmyelinated C-fibers. Normal voiding is dependent on mechanoceptive Adelta-fiber bladder afferents that respond to bladder distention. However, the mechanisms for controlling the excitability of Adelta-fiber bladder afferents are not fully understood. We therefore used whole cell patch-clamp techniques to investigate the properties of hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents (I(h)) in dorsal root ganglion (DRG) neurons innervating the urinary bladder of rats. The neurons were identified by axonal tracing with a fluorescent dye, Fast Blue, injected into the bladder wall. Hyperpolarizing voltage step pulses from -40 to -130 mV produced voltage- and time-dependent inward I(h) currents in bladder afferent neurons. The amplitude and current density of I(h) at a holding potential of -130 mV was significantly larger in medium-sized bladder afferent neurons (diameter: 37.8 +/- 0.3 microm), a small portion (19%) of which were sensitive to capsaicin (1 microM), than in uniformly capsaicin-sensitive small-sized (27.6 +/- 0.5 microm) bladder neurons. In medium-sized bladder neurons, a selective HCN channel inhibitor, ZD7288, dose-dependently inhibited I(h) currents. ZD7288 (10 microM) also increased the time constant of the slow depolarization phase of spike after-hyperpolarization from 91.8 to 233.0 ms. These results indicate that I(h) currents are predominantly expressed in medium-sized bladder afferent neurons innervating the bladder and that inhibition of I(h) currents delayed recovery from the spike after-hyperpolarization. Thus, it is assumed that I(h) currents could control excitability of mechanoceptive Adelta-fiber bladder afferent neurons, which are usually capsaicin-insensitive and larger in size than capsaicin-sensitive C-fiber bladder afferent neurons.

Action Potentials↗

Dose-dependent amplification by L-ascorbic acid of NaHCO3 promotion of rat urinary bladder carcinogenesis.

The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO3 was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which received basal diet (Oriental MF) containing AsA at 0, 1, 2, 3.5, or 5% plus 1.5% NaHCO3 for 32 wk. Relative urinary bladder weights in the 5% AsA group were significantly increased as compared to the 0 or 1% group values due to the development of tumors. Both the incidence and number of microscopic urinary bladder lesions (tumors and preneoplastic lesions) showed dose-dependent increases. Furthermore, the sizes of the urinary bladder tumors (carcinomas and papillomas) were significantly increased with the highest dose, 5-bromo-2'-deoxyuridine labeling indices showed slightly increased proliferation in preneoplastic lesions of the urinary bladder epithelium with 5% AsA treatment. In a separate experiment, scanning electron microscopic observation revealed that administration of 5% AsA plus 1.5% NaHCO3 for 8 wk, without BBN, altered the urinary bladder surface. Elevation of urinary bladder epithelium AsA content, as well as urinary AsA, was also noted. Ornithine decarboxylase (ODC) activity and ODC messenger RNA levels in urinary bladder epithelium of rats treated with 1.5% NaHCO3 plus 5% AsA for 8 wk showed no statistically significant differences as compared to the control group. The results indicate that AsA amplifies the rat urinary bladder carcinogenesis promotion activity of NaHCO3 and that its intensity of action depends on the dose, particularly at high dose.

Animals↗