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Transient ventriculoperitoneal shunt dysfunction in children with myelodysplasia and urinary bladder infection. Report of three cases.

The authors present three children born with myelomeningocele and hydrocephalus. Each presented with symptoms/signs of ventriculoperitoneal shunt malfunction. All patients at the time of presentation exhibited significant urinary bladder infections and were appropriately treated for their infection. No patient was found to have an underlying shunt infection. All patients without medically threatening symptoms were carefully observed and noted to have resolution of their shunt dysfunction symptoms/signs following treatment of their urinary bladder infections and thus did not undergo a shunt operation. Based on the courses of these patients, we believe that significant urinary bladder infection in patients with myelodysplasia in whom a shunt has been placed may often be enough to bring a subclinical shunt malfunction to clinical attention or even to be the cause of temporary distal peritoneal shunt malabsorption. Although the exact mechanism for this dysfunction is unclear, treatment of the bladder infection may address the symptomatic shunt dysfunction in some patients so as to avoid operative intervention. We emphasize, however, that careful observation of these patients should be performed during hospitalization because they often rely on adequate cerebrospinal fluid diversion. Only patients with mild symptomatology should be observed first as the initial line of treatment.

Adolescent↗

[Undifferentiated small-cell carcinoma of the urinary bladder].

We report a case of undifferentiated small cell carcinoma of the urinary bladder in a 64-year-old male patient. Microscopically the tumor was similar to the intermediate type of small cell carcinoma of the lung, with some foci of transitional papillary carcinoma, adenocarcinoma and carcinoma in situ. Small cell carcinoma is seldom encountered in the urinary bladder. It is more aggressive and must be distinguished from poorly differentiated transitional cell carcinoma.

Adenocarcinoma↗

[Pharmacological studies on antispasmodics. V. Effect of 3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide (HSR-902) on the junctional transmission of pelvic nerve ending in isolated urinary bladder (author's transl)].

Effects of HSR-902, a new antispasmodic agent, on the junctional transmission of pelvic nerve ending in isolated urinary bladder was compared with those of atropine sulfate, butylscopolamine bromide, timepidium bromide and prifinium bromide. Tetrodotoxin (3 x 10(-8)g/ml) completely inhibited the contraction of isolated guinea pig urinary bladder induced by transmural stimulation (TM contraction), but hexamethonium chloride (1 x 10(-4)g/ml) and atropine sulfate (1 x 10(-5)g/ml) exhibited no inhibition and a slight inhibition, respectively. Neostigmine bromide (1 x 10(-7)g/ml) increased TM contraction, and the effect was completely inhibited by atropine sulfate (1 x 10(-5)g/ml). Antispasmodic agents (1 x 10(-7) - 1x 10(-5)g/ml), excluding HSR-902, showed slight inhibition on TM contraction. In contrast, HSR-902 (1 x 10(-6) - 1x10(-5)g/ml) increased TM contraction and/or resting tone (1 x 10(-5)g/ml). Phenoxybenzamine hydrochloride (1 x 10(-8)g/ml) and tolazoline hydrochloride (1 x 10(-5)g/ml), alpha-blocking agents, increased both TM contraction and resting tone. Increasing effects of HSR-902 on TM contraction and/or resting tone were completely inhibited by noradrenaline (1 x 10(-5)g/ml) with propranolol hydrochloride (1 x 10(-5)g/ml). These results suggested that these antispasmodic agents scarcely inhibited the junctional transmission in postganglionic cholinergic nerve ending induced by transmural stimulation of isolated guinea pig urinary bladder, and HSR-902 rather increased the transmission. Since it was also suggested that there was alpha-adrenoceptor inhibiting acetylcholine-release in the postganglionic cholinergic nerve terminal, the transmission increasing action of HSR-902 would be due to its alpha-blocking action.

Animals↗

Transitional cell hyperplasia and carcinomas in urinary bladders of transgenic mice with keratin 5 promoter-driven cyclooxygenase-2 overexpression.

The inducible form of cyclooxygenase (COX), COX-2, is up-regulated in many epithelial cancers and its prostaglandin products increase proliferation, enhance angiogenesis, and inhibit apoptosis in several tissues. Pharmacologic inhibition and genetic deletion studies showed a marked reduction of tumor development in colon and skin. COX-2 has also been strongly implicated in urinary bladder cancer primarily by studies with nonselective COX- and COX-2-selective inhibitors. We now show that forced expression of COX-2, under the control of a keratin 5 promoter, is sufficient to cause transitional cell hyperplasia (TCH) in 17% and 75% of the heterozygous and homozygous transgenic lines, respectively, in an age-dependent manner. TCH was strongly associated with inflammation, primarily nodules of B lymphocytes; some T cells and macrophage infiltration were also observed. Additionally, transitional cell carcinoma was observed in approximately 10% of the K5.COX-2 transgenic mice; no TCH or transitional cell carcinoma was observed in wild-type bladders. Immunohistochemistry for vascular proliferation and vascular endothelial growth factor showed significant increases above that in wild-type urinary bladders. Our results suggest that overexpression of COX-2 is sufficient to cause hyperplasia and carcinomas in the urinary bladder. Therefore, inhibition of COX-2 should continue to be pursued as a potential chemopreventive and therapeutic strategy.

Animals↗

On the functional role of muscarinic M2 receptors in cholinergic and purinergic responses in the rat urinary bladder.

The functional effects of muscarinic receptor and purinoceptor agonists and antagonists were studied on isolated strip preparations of the rat urinary bladder. The muscarinic "M3/M1-selective" receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) most conspicuously inhibited the carbachol-evoked contractile responses (pA2=9.8), while the muscarinic "M1-selective" receptor antagonist pirenzepine and the muscarinic "M2-selective" receptor antagonist methoctramine were less potent (pA2=7.0 and 6.5, respectively). Administration of 4-DAMP in combination with methoctramine in selective dosages gave no significant additional reduction of carbachol-evoked contractile responses. Adenosine 5'-triphosphate (ATP) elicited transient dose-dependent contractile responses and it caused relaxation of the carbachol-contracted detrusor strips. The relaxatory response was enhanced in the presence of methoctramine and furthermore, was attenuated by the adenosine receptor antagonist 8-p-sulfophenyltheophylline. Administration of 2-chloro-adenosine to pre-contracted strips tended to cause dose-dependent relaxations, which were significantly increased in the presence of methoctramine. The purinergic contractile response, on the other hand, was not affected by methoctramine. Thus, the results are consistent with the cholinergic contractile response in the rat urinary bladder being exerted via activation of muscarinic M3 receptors, while the muscarinic M2 receptors exerted a modulator effect on purine-evoked relaxations in the rat urinary bladder.

2-Chloroadenosine↗

ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes--a possible sensory mechanism?

1. The responses of rabbit urinary bladder to hydrostatic pressure changes and to electrical stimulation have been investigated using both the Ussing chamber and a superfusion apparatus. These experiments enabled us to monitor changes in both ionic transport across the tissue and cellular ATP release from it. 2. The urinary bladder of the rabbit maintains an electrical potential difference across its wall as a result largely of active sodium transport from the urinary (mucosal) to the serosal surface. 3. Small hydrostatic pressure differences produced by removal of bathing fluid from one side of the tissue caused reproducible changes in both potential difference and short-circuit current. The magnitude of these changes increases as the volume of fluid removed increases. 3. Amiloride on the mucosal (urinary), but not the serosal, surface of the membrane reduces the transepithelial potential difference and short-circuit current with an IC50 of 300 nM. Amiloride reduces the size of, but does not abolish, transepithelial potential changes caused by alterations in hydrostatic pressure. 4. Field electrical stimulation of strips of bladder tissue produces a reproducible release of ATP. Such release was demonstrated to occur largely from urothelial cells and is apparently non-vesicular as it increases in the absence of calcium and is not abolished by tetrodotoxin. 5. It is proposed that ATP is released from the urothelium as a sensory mediator for the degree of distension of the rabbit urinary bladder and other sensory modalities.

Adenosine Triphosphate↗

76 and 14 kDa polypeptides, two major components released from amphibian urinary bladder epithelium. Purification and characterization.

Exocytotic processes play a major role in the hormonal control of water permeability in the amphibian urinary bladder. Different treatments such as antidiuretic hormone (ADH) stimulation, incubation with phorbol ester or mild detergent and mechanical stretch of the bladder, consistently induce a liberation of two major polypeptides of 76 and 14 kDa molecular mass into the luminal medium. Each of these polypeptides represents 3 to 5% of the total protein of epithelial cell homogenates and 20 to 50% of the released material. Proportions of released 76 kDa polypeptide in urinary bladders of toads (Bufo marinus) and frogs (Rana esculenta) were similar but, in the frog extracts, two bands ("doublet") were resolved at the level of 76 kDa. In high performance liquid chromatography (HPLC), using gel filtration and ion exchange chromatography, the frog 76 kDa protein was resolved into two polypeptides of 80,000 to 100,000 and 60,000 to 80,000 daltons while the 14 kDa protein included two polypeptides, each with a molecular mass of approximately 14,000 daltons. Isoelectric focusing of the material released during a mechanical stretch of the tissue ("stretch extract") or of isolated purified proteins from the frog urinary bladder showed that the 14 kDa polypeptides were resolved in two major groups of polypeptides, one in the range of pH 7.4 to 7.8, the other at pH 5.6. The lower band of the 76 kDa doublet also comprised some diffuse bands (5.0 less than pI less than 5.2) while the other polypeptide of the doublet presented a sharp band at pH 6.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrical properties of smooth muscle in the guinea-pig urinary bladder.

1. The effects of transmural nerve stimulation were examined on preparations of detrusor smooth muscle from guinea-pig urinary bladder using intracellular recording techniques. Most recordings were made from preparations in which spontaneous and evoked action potentials had been inhibited by nifedipine (10 microM), a dihydropyridine that blocks L-type Ca2+ channels. 2. Supramaximal stimuli evoked excitatory junction potentials (EJPs) which could be divided into three basic types. Type 1 EJPs had short latencies (< 30 ms) and fast rise times (< 60 ms). Type 2 EJPs consisted of two components: a small depolarization that was followed by a second depolarization with a faster rise time. In a third type of cell, at high strengths of stimulation, EJPs resembled type 1 EJPs but at lower strengths of stimulation were similar in time course to type 2 EJPs. 3. All EJPs were abolished by tetrodotoxin (1 microM) and reduced by omega-conotoxin (0.1 microM), but were unaffected by hexamethonium (0.1 mM), suggesting that they result from the release of transmitter from post-ganglionic nerve fibres. All responses persisted in the presence of atropine (1 microM) but were abolished following the desensitization of P2-purinoceptors with alpha, beta-methylene ATP (m-ATP; 10 microM). 4. Spontaneous excitatory junction potentials (SEJPs) were also recorded from most cells. SEJPs were similar in appearance to fast single-component EJPs; however, in general they had a briefer time course. SEJPs persisted in the presence of tetrodotoxin (1 microM). 5. The electrical properties of urinary bladder smooth muscle were also examined. Voltage changes induced by point current injection into cells had fast rates of rise and decay (time constant, 5-20 ms). The input resistance of cells ranged between 12 and 108 M omega. When recordings were taken from cells near the point of current injection, resultant electrotonic potentials could be detected in only a small proportions of cells. 6. The results are discussed in relation to the idea that transmural nerve stimulation in the guinea-pig urinary bladder causes the activation of at least two different membrane conductances. Cells appear to be electrically coupled with one another. However, it is likely that coupling exists within discrete bundles of the smooth muscle.

Adenosine Triphosphate↗

[Inhibition of tumor induction by methylnitrosourea in resected urinary bladder].

In the present experiments the dependence of tumour induction upon the different phases of the cell cycle in the proliferating urinary bladder was examined. For stimulation of urothelial proliferation, a one-third resection of the bladder was performed in female Wistar rats. To synchronize the proliferating urothelial cells, hydroxyurea was given. The direct-acting urothelial carcinogen N-methyl-N-nitrosourea (MNU) was administered as a single intravesical dose during different cell cycle phases. The incidence of urothelial bladder tumors was 32.6% in the controls. By comparison, the tumour incidences were 18.9, 9.3, 21.7, 26.3, 25.0 and 30.0%, respectively, when MNU was instilled during the late Gi-, early and late S-, G2+M-, and early and late postmitotic phase. The results obtained from a total of 283 rats clearly document a cell cycle specific inhibition of tumour development in the proliferating urinary bladder particularly when the carcinogen was administered during the early S-phase. MNU has also been shown to produce mesenchymal tumours in the bladder (overall incidence: 4.9%) as well as urothelial tumours in the renal pelvis (3.2%) and ureters (1.4%).

Animals↗

Cellular changes in the toad urinary bladder in response to metabolic acidosis.

The urinary bladder of Bufo marinus excretes H+ and NH+4, and the H+ excretion is increased when the animal is placed in metabolic acidosis. The mitochondria-rich (MR) cells mediate the H+ excretion by the bladder. The purpose of this study was to determine if there is a change in MR cells of the bladder during metabolic acidosis. Bladders from normal toads and from toads that had been placed in metabolic acidosis were used. The bladders were mounted between plastic chambers and H+ excretion measured. The bladder was then fixed and prepared for scanning (SEM) and transmission (TEM) electron micrograph studies. SEM's at low magnification were used to count the various cell types and the TEM's were used to confirm the different cell types. Fields were randomly selected and a total of 2500 cells counted in each group. The bladders from toads in metabolic acidosis had a consistently higher ratio of MR cells to granular cell than did the normal bladders. These results indicate that during metabolic acidosis there is an increased number of MR cells in the bladder, and this increased the bladder's capacity to excrete H+.

Acidosis↗

Changes in contractile properties in hypertrophic rat urinary bladder.

Hypertrophy was induced in female rat urinary bladders by partial obstruction of the urethra. After 6 weeks the bladder weight had increased almost 7-fold compared to the matched controls. At this stage the animals were anesthetized and the pelvic nerves stimulated bilaterally at different bladder volumes. Isovolumetric pressures were measured by means of a catheter inserted via the urethra. For control (C) bladders maximum active pressure (104 +/- 11 cm. H2O, n = 5) was attained with 0.10 ml. content. For volumes above this a rapid progressive decrease in active pressure was noted. For hypertrophic (H) bladders maximum active pressure (92 +/- 14 cm. H2O, n = 6) was reached at 0.50 ml. Further filling decreased active pressure only slightly. By use of the law of Laplace the volume-active pressure relations were transformed to radius-force curves. The maximum active stress was similar for C and H bladders. The radius-force relation for H bladders was shifted to the right compared to the C curve (optimum radius for active force: C: 0.4 cm., H: greater than 0.9 cm.). This shift, responsible for the decreased ability to pressure production of the H bladders at small volumes indicates a dramatic remodelling of the smooth muscle in the hypertrophic bladder wall.

Animals↗

The significance of tumour grade in predicting disease progression in stage Ta transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To determine the significance of tumour grade in predicting disease progression in stage Ta transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: From August 1975 to January 1991, 140 patients (121 men and 19 women, mean age 64.2 years, range 30-83) with stage Ta TCC of the urinary bladder were treated at the Veterans General Hospital-Taipei by transurethral resection and post-operative adjuvant intravesical chemotherapy. There were 48 patients (34%) with grade 1, 78 patients (56%) with grade 2 and 14 patients (10%) with grade 3 tumours. Disease progression and muscle invasion were assessed during a mean follow-up of 74.3 months and related to grade, urine cytology and the number and location of tumours. RESULTS: A total of 10 patients (7%) had tumour recurrence which invaded the muscle, of whom one had grade 1, six had grade 2 and three had grade 3 tumours. The patient with a grade 1 tumour developed muscle invasion within 16 months of surgery. The mean interval to the development of muscle invasion was 49.2 months in patients with grade 2 and 39.4 months with grade 3 tumour. In patients with stage Ta TCC, a grade 3 tumour was more likely to progress to muscle invasion (21%) than was a grade 1 (2.1%; P < 0.05) or grade 2 (7.7%; P < 0.05) tumour. One patient with a grade 2 and one patient with grade 3 tumour developed distant metastases without muscle invasion. Overall, the disease progression rate was 8.6% (12/140) in stage Ta TCC. Disease progression was more common with grade 3 (28.5%) than with grade 2 (9.0%; P < 0.05) and grade 1 (2.1%; P < 0.05) tumours. CONCLUSION: Tumour grade may be used to predict disease progression after resection of stage Ta urinary bladder cancer. A higher grade of tumour was associated with a higher incidence of disease progression.

Administration, Intravesical↗

Low interleukin-1alpha messenger RNA levels predict decreased overall survival time of patients with urinary bladder carcinoma.

Due to our inability to exactly characterize tumours, many patients with urinary bladder cancer undergo unnecessary surgery or cytostatic therapy. We have here studied the expression of the cytokine interleukin-1alpha (IL-1alpha ) in 73 human bladder carcinomas in relation to patient survival, and examined possible relationships between IL-1alpha and urokinase plasminogen activator (uPA) expression. Expression levels of IL-1alpha and uPA mRNA were determined by RT-PCR using the quantitative TaqMan technique. The levels of IL-1alpha mRNA expression did not differ significantly between tumours of different grade or stage. Calculation of the overall survival rates showed a decreased overall survival time for patients with low levels of IL-1alpha mRNA in their tumours (log rank; P = 0.0002, median follow up: 37 months). Low tumoral IL-1alpha expression predicted decreased survival of patients with poorly differentiated tumours (P< 0.005) and of patients with invasive tumours (P = 0.02). uPA expression was about 4-fold increased in poorly differentiated tumours. High levels of uPA mRNA were associated with decreased overall survival times (log rank; P = 0.032, n = 60). We conclude that IL-1alpha is important for bladder cancer biology, and that measurements of this cytokine may be useful in pre-treatment characterization of urinary bladder cancer.

Cohort Studies↗

[Transitional cell carcinoma of the urinary bladder in adolescence: report of a case].

The patient is a 17 year-old girl who was admitted with the chief complaint of asymptomatic gross hematuria. Excretory urography showed a filling defect of the urinary bladder. Abdominal echography showed a papillary tumor of the urinary bladder. Cystoscopy showed a papillary bladder tumor on the posterior area of left ureteral orifice. Transurethral resection of the bladder tumor was performed for diagnosis and treatment. Pathological diagnosis was papillary transitional cell carcinoma (grade 1, pTa). Thirty cases of transitional cell tumor of the urinary bladder in childhood and adolescence have been reported in Japan including this case.

Adolescent↗

Distribution of intermediate filaments in epithelial cells of the amphibian urinary bladder: an immunofluorescence study.

The distribution of intermediate filaments in toad and frog urinary bladder was studied on frozen sections by indirect immunofluorescence microscopy using specific antiprekeratin antibodies. Our results show that in both species, epithelial cells lining the urinary bladder are very rich in cytokeratin, organized as a filamentous network. In granular cells, the most abundant cells facing the urinary lumen, vasopressin promotes fusion of the membranous tubular structures located in the luminal cytoplasm with the apical cell membrane. A role for intermediate filaments in the membrane rearragements induced by vasopressin in these cells, is proposed.

Animals↗

An aqueous garlic extract alleviates water avoidance stress-induced degeneration of the urinary bladder.

OBJECTIVE: To investigate the role of aqueous garlic extract (AGE) on the water-avoidance stress (WAS)-induced degeneration of the urinary bladder in a rat model. MATERIALS AND METHODS: Wistar albino rats were exposed to WAS for 2 h/day for 5 days (WAS group), after which, AGE (1 mL/kg) was injected intraperitoneally into the rats (WAS + AGE group). Urinary bladder samples were investigated with both light and scanning electron microscopy, and lipid peroxidation and glutathione levels were also measured in the samples. RESULTS: In the WAS group there was inflammatory cell infiltration, more mast cells and ulcerated areas in the mucosa. In the WAS + AGE group there was relatively normal urothelial alignment, moderate inflammatory cell infiltration and fewer mast cells in the mucosa. The increased lipid peroxidation and decreased glutathione levels in WAS rats were reversed by AGE treatment. CONCLUSIONS: These results show that AGE has a protective effect on WAS-induced degenerative changes in the urinary bladder.

Animals↗

Effects of outlet obstruction and its reversal on mitochondrial enzyme activity in rabbit urinary bladders.

PURPOSE: This study investigated the effects of outlet obstruction and its reversal on mitochondrial enzyme activity in the rabbit urinary bladder. MATERIALS AND METHODS: We induced mild bladder outlet obstruction in male New Zealand White rabbits. Following two weeks of obstruction, one group of animals (n = 6) was sacrificed, while outlet obstruction was relieved in three additional groups of animals, which were sacrificed one (n = 5), two (n = 5) and four (n = 5) weeks after relieving the obstruction. Seven sham operated rabbits served as controls. We extracted mitochondria from fresh detrusor and assayed activities of key mitochondrial enzymes in the citric acid cycle, citrate synthase and malate dehydrogenase, as well as those in the electron transport chain, succinate cytochrome c reductase, NADH-cytochrome c reductase and cytochrome c oxidase. With high performance liquid chromatography (HPLC) we determined the tissue content of phosphocreatine and the adenine nucleotides (ATP, ADP and AMP), which was used for calculating energy charge. Responses of detrusor strips to 500 microM bethanechol and 120 mM KCl provided the assessment of detrusor contractility. RESULTS: Contractile response of the detrusor strips to bethanechol stimulation was significantly reduced by outlet obstruction, nevertheless, it recovered gradually toward the control level after the relief of outlet obstruction. Outlet obstruction reduced the detrusor content of phosphocreatine, ATP and energy charge. After relieving the obstruction, however, these recovered gradually, reaching control levels 4 weeks later. The activities of all assayed enzymes were reduced by two weeks of outlet obstruction. Relieving the obstruction restored enzyme activity gradually but at different rates for different enzymes. Activities of the citric acid cycle enzymes citrate synthase and malate dehydrogenase recovered and were similar to control levels four weeks after relief of the obstruction. Of the enzymes in the electron transport chain, NADH cytochrome reductase activity recovered most quickly by one week after relief of the obstruction. The activity of cytochrome c oxidase improved more slowly, but 4 weeks after relieving the obstruction it, also, was restored and was similar to the control level. Succinate cytochrome reductase activity remained lower than the control over the entire four weeks of recovery. CONCLUSIONS: The close association between mitochondrial enzyme activity, energy metabolism and contractility of the detrusor indicates the important role of mitochondrial enzyme damage in decreasing energy production and impairing contractile function of the urinary bladders following outlet obstruction. Our findings also show that various mitochondrial enzymes exhibit different susceptibilities and reversibilities to pathological stress.

Adenine Nucleotides↗

The fine structure of the urinary bladder of the toad, Bufo marinus.

The urinary bladder of the toad (Bufo marinus) was studied with both the light and the electron microscope. The bladder wall consists of epithelium, submucosa, and serosa. In the epithelium, four different cell types were recognized on the basis of their fine structure and staining properties with several different dyes. These four were designated as granular cells, mitochondria-rich cells, mucous cells, and basal cells. In addition, migratory cells of a different type were found in the basal region of the epithelium. The luminal surface of the epithelial cells presents irregular microvilli and is coated by PAS-positive material which has been further investigated by histochemical procedures and radioautography. Included is a description of the fine structural details of cell membranes, cell junctions, and intracellular components. The submucosa consists of a delicate stroma of fibroblasts and collagen fibers and also contains blood and lymph vessels, unmyelinated nerves, migratory cells, and smooth muscle cells. The serosa consists of a single layer of serosal (mesothelial) cells which form an uninterrupted covering of the viscus. Possible pathways of sodium and water transport across the bladder wall are discussed.

Animals↗