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Sample records for 5-ht-induced bladder contraction

  1. Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

    PubMed

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-01-30

    Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign

  2. Role of "Aplysia" Cell Adhesion Molecules during 5-HT-Induced Long-Term Functional and Structural Changes

    ERIC Educational Resources Information Center

    Han, Jin-Hee; Lim, Chae-Seok; Lee, Yong-Seok; Kandel, Eric R.; Kaang, Bong-Kiun

    2004-01-01

    We previously reported that five repeated pulses of 5-HT lead to down-regulation of the TM-apCAM isoform at the surface of "Aplysia" sensory neurons (SNs). We here examined whether apCAM down-regulation is required for 5-HT-induced long-term facilitation. We also analyzed the role of the cytoplasmic and extracellular domains by overexpressing…

  3. Prostanoid receptors mediating contraction in rat, macaque and human bladder smooth muscle in vitro.

    PubMed

    Root, James A; Davey, Dorren A; Af Forselles, Kerry J

    2015-12-15

    Selective prostaglandin EP1 antagonists have been suggested for the treatment of bladder dysfunction. This study assessed the contractile prostanoid receptor subtypes in human and non-human bladder in vitro. Classical tissue bath studies were conducted using bladder strips exposed to prostanoid agonists and antagonists. Prostaglandin E2 (PGE2) contracted rat, macaque and human bladder smooth muscle strips (pEC50 7.91±0.06 (n=7), 6.40±0.13 (n=7), and 6.07±0.11 (n=5), respectively). The EP1 receptor antagonist, PF2907617 (300nM), caused a rightward shift of the PGE2 concentration-response curve in the rat bladder only (pKB 8.40±0.15, n=3). PGE2 responses in rat and macaque bladders, but not human, were antagonised by the EP3 antagonist CJ24979 (1µM). Sulprostone, a mixed EP1/EP3/FP receptor agonist, induced potent contractions of rat bladder muscle (pEC50 7.94±0.31, n=6). The FP receptor agonist, prostaglandin F2α (PGF2α), induced bladder contraction in all species tested, but with a lower potency in rat. The selective FP receptor agonist latanoprost caused potent contractions of macaque and human bladder strips only. SQ29548, a selective TP antagonist, and GW848687X, a mixed EP1/TP antagonist caused rightward shifts of the concentration-response curves to the selective TP agonist, U46619 (pKB estimates 8.53±0.07 and 7.56±0.06, n=3, respectively). Responses to U46619 were absent in rat preparations. These data suggest significant species differences exist in bladder contractile prostanoid receptor subtypes. We conclude that the EP1 subtype does not represent the best approach to the clinical treatment of bladder disorders targeting inhibition of smooth muscle contraction.

  4. 5-hydroxytryptamine induced relaxation in the pig urinary bladder neck

    PubMed Central

    Recio, Paz; Barahona, María Victoria; Orensanz, Luis M; Bustamante, Salvador; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Prieto, Dolores; Hernández, Medardo

    2009-01-01

    Background and purpose 5-Hydroxytryptamine (5-HT) is one of the inhibitory mediators in the urinary bladder outlet region. Here we investigated mechanisms involved in 5-HT-induced relaxations of the pig bladder neck. Experimental approach Urothelium-denuded strips of pig bladder were mounted in organ baths for isometric force recordings of responses to 5-HT and electrical field stimulation (EFS). Key results After phenylephrine-induced contraction, 5-HT and 5-HT receptor agonists concentration-dependently relaxed the preparations, with the potency order: 5-carboxamidotryptamine (5-CT) > 5-HT = RS67333 > (±)-8-hydroxy-2-dipropylaminotetralinhydrobromide > m-chlorophenylbiguanide > α-methyl-5-HT > ergotamine. 5-HT and 5-CT relaxations were reduced by the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulphonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride and potentiated by (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide dihydrochloride (WAY 100135) and cyanopindolol, 5-HT1A and 5-HT1A/1B receptor antagonists respectively. Inhibitors of 5-HT1B/1D, 5-HT2, 5-HT2B/2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT6 receptors failed to modify 5-HT responses. Blockade of monoamine oxidase A/B, noradrenergic neurotransmission, α-adrenoceptors, muscarinic and purinergic receptors, nitric oxide synthase, guanylate cyclase and prostanoid synthesis did not alter relaxations to 5-HT. Inhibitors of Ca2+-activated K+ and ATP-dependent K+ channels failed to modify 5-HT responses but blockade of neuronal voltage-gated Na+-, Ca2+-and voltage-gated K+ (Kv)-channels potentiated these relaxations. Adenylyl cyclase activation and cAMP-dependent protein kinase (PKA) inhibition potentiated and reduced, respectively, 5-HT-induced responses. Under non-adrenergic, non-cholinergic, non-nitrergic conditions, EFS induced neurogenic, frequency-dependent, relaxations which were resistant to WAY 100135 and cyanopindolol. Conclusions and implications 5-HT relaxed

  5. Influence of hypercapnia and hypocapnia on bladder contractions and their respiratory consequences.

    PubMed

    Bartlett, D; Knuth, S L

    2003-03-28

    Rhythmic contractions of the detrusor muscle, induced by gradual filling of the urinary bladder in decerebrate or anesthetized cats, are accompanied by decreased inspiratory activity in motor nerves to respiratory muscles, particularly those of the upper airway. We have examined the influence of hypercapnia and hypocapnia on these contractions and the accompanying activities of the phrenic and hypoglossal nerves in decerebrate, vagotomized, paralyzed and ventilated cats, some of which had denervated carotid chemoreceptors. Hypercapnia slowed, and then reversibly abolished bladder contractions in most animals, regardless of the state of the carotid chemoreceptors. Bladder contractions were well maintained in progressive hypocapnia, even at end-tidal CO(2) levels below the 'apneic' thresholds of the hypoglossal and phrenic activities. The reductions of the nerve activities in response to bladder contractions were not significantly altered by hypercapnia or hypocapnia. The abolition of bladder contractions by hypercapnia is unlikely to reflect a direct effect of CO(2) or H+ ion on the contractile mechanism of the detrusor muscle, but may be based on inhibition of stretch receptors in the bladder wall and/or an effect of CO(2) or H+ in or near the micturition centers in the brain stem.

  6. Delineating the inner bladder surface using uniform contractions from the outer surface under variable bladder filling conditions

    PubMed Central

    Bayley, Andrew; Catton, Charles; Chung, Peter; Currie, Geoffrey; Heaton, Robert; Wheat, Janelle; Milosevic, Michael

    2015-01-01

    Objective: To evaluate the methods to delineate the inner bladder (IB) surface using a uniform contraction from the outer bladder (OB) surface, assuming the bladder wall (BW) is either of constant thickness, constant volume or variable volume. Methods: 14 prostate intensity-modulated radiotherapy patients with 2 planning CTs were identified. For both CTs, OB was delineated using model-based segmentation. IB was delineated manually. Then, using uniform contractions from OB, the position of IB was approximated using a: 2.5-mm contraction, patient-specific contraction, patient-specific constant wall volume method and variable wall volume method. The structures created using those strategies were compared against the manual IB contours using geometric and dosimetric indices. Results: In the presence of variable bladder filling, use of a generic or patient-specific constant contraction resulted in a significant overestimation of IB volume (+12 and +13 cm3, respectively; p < 0.001) that was inversely correlated with the difference in urine volume between the scans (R2 > 0.86). Mean differences across 95% of IB surfaces were ≤2 mm for methods using either constant or variable wall volume. Mean dose–volume histogram (DVH) differences were <1 cm3 across the whole BW DVH when using the method that assumed a variable wall volume. Conclusion: The variable volume BW model provided the best approximation of the IB surface position under varying filling conditions, based on geometric and dosimetric indices. Advances in knowledge: Use of the equation derived in this research provides a quick and accurate method to delineate the hollow BW on serial imaging for the purposes of dose reconstruction. PMID:26206519

  7. Effects of thienorphine on the contraction of isolated ureter and bladder of guinea pigs.

    PubMed

    Zhou, Peilan; Li, Yulei; Yong, Zheng; Yan, Hui; Su, Ruibin; Gong, Zehui

    2016-10-15

    Opioid analgesics are widely used in moderate to severe pain including renal colic. Morphine is believed to cause spasm of ureter and affect the bladder contractions. Thienorphine is a partial opioid agonist that is a good candidate for the treatment of opioid dependence and pain. This study examined the effects of thienorphine on the guinea pig isolated ureter and bladder. The contractile amplitude of isolated ureter induced by KCl (40mM) was not influenced by thienorphine or buprenorphine, whereas morphine increased the amplitude of the isolated ureter. Thienorphine, buprenorphine or naloxone concentration-dependently antagonized the isolated ureter contraction induced by morphine. Thienorphine (1.0-32.0μM) or buprenorphine (1.0-32.0μM) had no effects on the spontaneous or acetylcholine (Ach) induced contractions of isolated bladder, but decreased the amplitude of the contractions of isolated bladder at 100μM concentration. Morphine (0.1-3.2mM) concentration dependently increased the spontaneous movement and Ach (1μM) induced contractions of isolated bladder. The mRNA levels of μ receptor in the ureter and bladder was as the same as that in the frontal cortex. In comparison, the mRNA levels of κ receptor, δ receptor and N/OFQ receptor was fewer than that in the frontal cortex. In summary, thienorphine has little influence on the guinea pig isolated ureter and bladder compared with morphine, which may result in a lack of adverse renal colic effects. PMID:27445237

  8. Detecting the onset of urinary bladder contractions using an implantable pressure sensor.

    PubMed

    Melgaard, J; Rijkhoff, N J M

    2011-12-01

    This study investigates whether signals obtained from an implantable pressure sensor placed in the urinary bladder wall could be used to detect the onset of bladder contractions. The sensor assembly was custom made using a small piezoresistive sensor die. The die was mounted on ceramic substrate (8 mm × 8 mm) and encapsulated in silicone by a two-part moulding process. The final sensor was lens shaped with a diameter of 13.6 mm and height of 2.0 mm. Experiments were performed in six pigs that had one or more sensors placed in the bladder wall. An external reference sensor was used to simultaneously monitor intravesical pressure via a transurethral catheter. Bladder contractions were evoked by unilateral electrical stimulation of the pelvic nerve. Onset latency was computed using both signals. In addition, the correlation between wall pressure and intravesical pressure was calculated. On average, the onset latency was - 307 ms using the wall sensors compared to the intravesical pressure, i.e., the detection occurred earlier using the wall sensors than the intravesical sensor. In 91 of 114 recordings the correlation coefficient was above 0.90. In conclusion, the implantable sensor performs similar to the reference sensor when used to detect the onset of bladder contractions. PMID:21997323

  9. Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway

    SciTech Connect

    Weng, T.I.; Chen, W.J.; Liu, S.H. . E-mail: shliu@ha.mc.ntu.edu.tw

    2005-10-15

    Uropathogenic Escherichia coli is a common cause of urinary tract infection. We determined the effects of intravesical instillation of E. coli lipopolysaccharide (LPS, endotoxin) on muscle contractions, protein kinase C (PKC) translocation, and inducible nitric oxide synthase (iNOS) expression in rat urinary bladder. The contractions of the isolated rat detrusor muscle evoked by electrical field stimulations were measured short-term (1 h) or long-term (24 h) after intravesical instillation of LPS. One hour after LPS intravesical instillation, bladder PKC-{alpha} translocation from cytosolic fraction to membrane fraction and endothelial (e)NOS protein was elevated, and detrusor muscle contractions were significantly increased. PKC inhibitors chelerythrine and Ro32-0432 inhibited this LPS-enhanced contractile response. Application of PKC activator {beta}-phorbol-12,13-dibutyrate enhanced the muscle contractions. Three hours after intravesical instillation of LPS, iNOS mRNA was detected in the bladder. Immunoblotting study also demonstrated that the induction of iNOS proteins is detected in bladder in which LPS was instilled. 24 h after intravesical instillation of LPS, PKC-{alpha} translocation was impaired in the bladder; LPS did not affect PKC-{delta} translocation. Muscle contractions were also decreased 24 h after LPS intravesical instillation. Aminoguanidine, a selective iNOS inhibitor, blocked the decrease in PKC-{alpha} translocation and detrusor contractions induced by LPS. These results indicate that there are different mechanisms involved in the alteration of urinary bladder contractions after short-term and long-term treatment of LPS; an iNOS-regulated PKC signaling may participate in causing the inhibition of muscle contractions in urinary bladder induced by long-term LPS treatment.

  10. Bladder contractions alter inspiratory termination by superior laryngeal and intercostal nerve stimulation.

    PubMed

    Bartlett, D; Knuth, S L

    1999-08-01

    Gradual distension of the urinary bladder evokes spontaneous bladder contractions (SBCs), which are associated with reduced inspiratory activity in the phrenic and other inspiratory motor nerves. We examined the influence of isovolumetric SBCs on the threshold for termination of phrenic inspiration by electrical stimulation of superior laryngeal and/or mid-thoracic intercostal nerves (ICN) in decerebrate, vagotomized, paralyzed, ventilated cats. Although SBCs reduced phrenic inspiratory activity, the threshold for inspiratory termination by nerve stimulation was increased. The results emphasize the complexity of the synaptic connections among brain stem neurons governing micturition and breathing.

  11. Induced gall-bladder contraction accelerates fragment clearance after extracorporeal shockwave lithotripsy.

    PubMed

    Ziegenhagen, D J; Zehnter, E; Kruis, W; Pohl, C

    1993-01-01

    At the end of extracorporeal shockwave lithotripsy (ESWL) gallstone fragments are dispersed throughout the gall-bladder. In this state they should be expelled more easily than when later sedimented to the gall-bladder fundus. Thus, a randomized study was performed to evaluate the clinical benefit of induced gall-bladder contraction after ESWL. One hundred and five patients with radiolucent gallstones (1-3 stones, diameter < or = 30 mm) were randomized to received either saline or an infusion of 0.2 micrograms/kg ceruletide. Stone clearance rates and incidence of biliary symptoms were recorded. Clearance rates at 6 weeks and 3 months after ESWL were significantly (P < 0.025) improved by the ceruletide infusion. This effect, resulting in shortened bile acid therapy, was limited to patients with small solitary stones and dependent on a good initial fragmentation. Major side effects attributable to ceruletide were not observed. These results suggest that induced gall-bladder contraction can be successfully applied as an adjuvant treatment in a subgroup of patients with small solitary gallstones.

  12. Pudendal but not tibial nerve stimulation inhibits bladder contractions induced by stimulation of pontine micturition center in cats.

    PubMed

    Lyon, Timothy D; Ferroni, Matthew C; Kadow, Brian T; Slater, Richard C; Zhang, Zhaocun; Chang, Victor; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-02-15

    This study examined the possibility that pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS) inhibits the excitatory pathway from the pontine micturition center (PMC) to the urinary bladder. In decerebrate cats under α-chloralose anesthesia, electrical stimulation of the PMC (40 Hz frequency, 0.2-ms pulse width, 10-25 s duration) using a microelectrode induced bladder contractions >20 cmH2O amplitude when the bladder was filled to 60-70% capacity. PNS or TNS (5 Hz, 0.2 ms) at two and four times the threshold (2T and 4T) to induce anal or toe twitch was applied to inhibit the PMC stimulation-induced bladder contractions. Propranolol, a nonselective β-adrenergic receptor antagonist, was administered intravenously (1 mg/kg i.v.) to determine the role of sympathetic pathways in PNS/TNS inhibition. PNS at both 2T and 4T significantly (P < 0.05) reduced the amplitude and area under the curve of the bladder contractions induced by PMC stimulation, while TNS at 4T facilitated the bladder contractions. Propranolol completely eliminated PNS inhibition and TNS facilitation. This study indicates that PNS, but not TNS, inhibits PMC stimulation-induced bladder contractions via a β-adrenergic mechanism that may occur in the detrusor muscle as a result of reflex activity in lumbar sympathetic nerves. Neither PNS nor TNS activated a central inhibitory pathway with synaptic connections to the sacral parasympathetic neurons that innervate the bladder. Understanding the site of action involved in bladder neuromodulation is important for developing new therapies for bladder disorders. PMID:26676253

  13. Modulation of nerve-evoked contractions by β3-adrenoceptor agonism in human and rat isolated urinary bladder.

    PubMed

    Rouget, Céline; Rekik, Moèz; Camparo, Philippe; Botto, Henry; Rischmann, Pascal; Lluel, Philippe; Palea, Stefano; Westfall, Timothy D

    2014-02-01

    Activation of β3-adrenoceptors has been shown to have a direct relaxant effect on urinary bladder smooth muscle from both rats and humans, however there are very few studies investigating the effects of β3-adrenoceptor agonists on nerve-evoked bladder contractions. Therefore in the current study, the role of β3-adrenoceptors in modulating efferent neurotransmission was evaluated. The effects of β3-adrenoceptor agonism on neurogenic contractions induced by electrical field stimulation (EFS) were compared with effects on contractions induced by exogenous acetylcholine (Ach) and αβ-methylene adenosine triphosphate (αβ-meATP) in order to determine the site of action. Isoproterenol inhibited EFS-induced neurogenic contractions of human bladder (pD2=6.79; Emax=65%). The effect of isoproterenol was selectively inhibited by the β3-adrenoceptor antagonist L-748,337 (pKB=7.34). Contractions induced by exogenous Ach (0.5-1μM) were inhibited 25% by isoproterenol (3μM) while contractions to 10Hz in the same strip were inhibited 67%. The selective β3-adrenoceptor agonist CL-316,243 inhibited EFS-induced neurogenic contractions of rat bladder (pD2=7.83; Emax=65%). The effects of CL-316,243 were inhibited in a concentration dependent manner by L-748,337 (pA2=6.42). Contractions induced by exogenous Ach and αβ-meATP were significantly inhibited by CL-316,243, 29% and 40%, respectively. These results demonstrate that the activation of β3-adrenoceptors inhibits neurogenic contractions of both rat and human urinary bladder. Contractions induced by exogenously applied parasympathetic neurotransmitters are also inhibited by β3-agonism however the effect is clearly less than on neurogenic contractions (particularly in human), suggesting that in addition to a direct effect on smooth muscle, activation of prejunctional β3-adrenoceptors may inhibit neurotransmitter release.

  14. Phorbol 12,13-Dibutyrate-Induced, Protein Kinase C-Mediated Contraction of Rabbit Bladder Smooth Muscle

    PubMed Central

    Wang, Tanchun; Kendig, Derek M.; Trappanese, Danielle M.; Smolock, Elaine M.; Moreland, Robert S.

    2012-01-01

    Contraction of bladder smooth muscle is predominantly initiated by M3 muscarinic receptor-mediated activation of the Gq/11-phospholipase C β-protein kinase C (PKC) and the G12/13-RhoGEF-Rho kinase (ROCK) pathways. However, these pathways and their downstream effectors are not well understood in bladder smooth muscle. We used phorbol 12,13-dibutyrate (PDBu), and 1,2-dioctanoyl-sn-glycerol (DOG), activators of PKC, in this investigation. We were interested in dissecting the role(s) of PKC and to clarify the signaling pathways in bladder smooth muscle contraction, especially the potential cross-talk with ROCK and their downstream effectors in regulating myosin light chain phosphatase activity and force. To achieve this goal, the study was performed in the presence or absence of the PKC inhibitor bisindolylmaleimide-1 (Bis) or the ROCK inhibitor H-1152. Phosphorylation levels of Thr38-CPI-17 and Thr696/Thr850 myosin phosphatase target subunit (MYPT1) were measured during PDBu or DOG stimulation using site specific antibodies. PDBu-induced contraction in bladder smooth muscle involved both activation of PKC and PKC-dependent activation of ROCK. CPI-17 as a major downstream effector, is phosphorylated by PKC and ROCK during PDBu and DOG stimulation. Our results suggest that Thr696 and Thr850-MYPT1 phosphorylation are not involved in the regulation of a PDBu-induced contraction. The results also demonstrate that bladder smooth muscle contains a constitutively active isoform of ROCK that may play an important role in the regulation of bladder smooth muscle basal tone. Together with the results from our previous study, we developed a working model to describe the complex signaling pathways that regulate contraction of bladder smooth muscle. PMID:22232602

  15. Effects of hypoxia and glucose-removal condition on muscle contraction of the smooth muscles of porcine urinary bladder.

    PubMed

    Nagai, Yuta; Kaneda, Takeharu; Miyamoto, Yasuyuki; Nuruki, Takaomi; Kanda, Hidenori; Urakawa, Norimoto; Shimizu, Kazumasa

    2016-01-01

    To elucidate the dependence of aerobic energy metabolism and utilization of glucose in contraction of urinary bladder smooth muscle, we investigated the changes in the reduced pyridine nucleotide (PNred) fluorescence, representing glycolysis activity, and determined the phosphocreatine (PCr) and ATP contents of the porcine urinary bladder during contractions induced by high K(+) or carbachol (CCh) and with and without hypoxia (achieved by bubbling N2 instead of O2) or in a glucose-free condition. Hyperosmotic addition of 65 mM KCl (H-65K(+)) and 1 µM CCh induced a phasic contraction followed by a tonic contraction. A glucose-free physiological salt solution (PSS) did not change the subsequent contractile responses to H-65K(+) and CCh. However, hypoxia significantly attenuated H-65K(+)- and CCh-induced contraction. H-65K(+) and CCh induced a sustained increase in PNred fluorescence, representing glycolysis activity. Hypoxia enhanced H-65K(+)- and CCh-induced increases in PNred fluorescence, whereas glucose-free PSS decreased these increases, significantly. In the presence of H-65K(+), hypoxia decreased the PCr and ATP contents; however, the glucose-free PSS did not change the PCr contents. In conclusion, we demonstrated that high K(+)- and CCh-induced contractions depend on aerobic metabolism and that an endogenous substrate may be utilized to maintain muscle contraction in a glucose-free PSS in the porcine urinary bladder.

  16. Enhancement of rat bladder contraction by artificial sweeteners via increased extracellular Ca{sup 2+} influx

    SciTech Connect

    Dasgupta, Jaydip; Elliott, Ruth A. . E-mail: rae5@leicester.ac.uk; Doshani, Angie; Tincello, Douglas G.

    2006-12-01

    Introduction: Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfame K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips. Methods: Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS) in the absence and presence of atropine, and with {alpha},{beta} methylene ATP, potassium, calcium and carbachol. Results: Sweeteners 10{sup -7} M to 10{sup -2} M enhanced the contractile response to 10 Hz EFS compared to control (p < 0.01). The atropine-resistant response to EFS was marginally increased by acesulfame K 10{sup -6} M, aspartame 10{sup -7} M and sodium saccharin 10{sup -7} M. Acesulfame K 10{sup -6} M increased the maximum contractile response to {alpha},{beta} methylene ATP by 35% ({+-} 9.6%) (p < 0.05) and to KCl by 12% ({+-} 3.1%) (p < 0.01). Sodium saccharin also increased the response to KCl by 37% ({+-} 15.2%) (p < 0.05). These sweeteners shifted the calcium concentration-response curves to the left. Acesulfame K 10{sup -6} M increased the log EC{sub 5} from -2.79 ({+-} 0.037) to -3.03 ({+-} 0.048, p < 0.01) and sodium saccharin 10{sup -7} M from -2.74 ({+-} 0.03) to 2.86 ({+-} 0.031, p < 0.05). The sweeteners had no significant effect on the contractile response to carbachol but they did increase the amplitude of spontaneous bladder contractions. Discussion: These results suggest that low concentrations of artificial sweeteners enhanced detrusor muscle contraction via modulation of L-type Ca{sup +2} channels.

  17. Smooth muscle modeling and experimental identification: application to bladder isometric contraction

    NASA Astrophysics Data System (ADS)

    Laforêt, Jérémy; Guiraud, David; Andreu, David; Taillades, Hubert; Azevedo Coste, Christine

    2011-06-01

    This paper presents an original smooth muscle model based on the Huxley microscopic approach. This model is the main part of a comprehensive lower urinary track model. The latter is used for simulation studies and is assessed through experiments on rabbits, for which a subset of parameters is estimated, using intravesical pressure measurements in isometric conditions. Bladder contraction is induced by electrical stimulation that determines the onset and thus synchronizes simulation and experimental data. Model sensitivity versus parameter accuracy is discussed and allows the definition of a subset of four parameters that must be accurately identified in order to obtain good fitting between experimental and acquired data. Preliminary experimental data are presented as well as model identification results. They show that the model is able to follow the pressure changes induced by an artificial stimulus in isometric contractions. Moreover, the model gives an insight into the internal changes in calcium concentration and the ratio of the different chemical species present in the muscle cells, in particular the bounded and unbounded actin and myosin and the normalized concentration of intracellular calcium.

  18. Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder.

    PubMed

    Isogai, Ayu; Lee, Ken; Mitsui, Retsu; Hashitani, Hikaru

    2016-09-01

    We investigated the role of TRPV4 channels (TRPV4) in regulating the contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was examined by fluorescence immunohistochemistry. Changes in the contractility of DSM and MM bundles were measured using isometric tension recording. Intracellular Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) imaging, while membrane potential changes were recorded using intracellular microelectrode technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM), a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated with a cessation of spontaneous phasic contractions in a manner sensitive to HC-067047 (10 μM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 μM), large conductance Ca(2+)-activated K(+) (BK) channel blockers restored the spontaneous contractions in GSK. The sustained contractions in DSM and MM were reduced by nifedipine (10 μM), a blocker of L-type voltage-dependent Ca(2+) channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+) levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca(2+) influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility during its storage phase. Despite the membrane hyperpolarization in GSK, Ca(2+) entry mainly through TRPV4 develops the tonic contraction. PMID:27497848

  19. [Clinical use of sodium hypochlorite for local treatment and prevention of urinary tract infections and therapy of contracted bladders (author's transl)].

    PubMed

    Eisen, M; Jurcovic, K; Pfeiffer, E; Skoluda, D; Busse, K

    1976-01-01

    A stable commercial electrolytic sodium hypochlorite solution was tested in 63 urologic patients. The complete germicidal action against all sorts of bacteria was shown in suspension-tests. Irrigation studies of the infected bladder were performed. It was found that continued bladder irrigations were necessary to stop bacterial ascension from the infected urethra. Bladder capacity was increased in 6 of 8 patients with nonmalignant contracted bladder or interstitial cystitis. Desinfection with sodium hypochlorite in urologic practice is cheap, easy to perform and diminishes the risk of hospitalism. Clinical studies confirmed the absence of general or local toxicity.

  20. Distribution of serotonin 5-HT1A-binding sites in the brainstem and the hypothalamus, and their roles in 5-HT-induced sleep and ingestive behaviors in rock pigeons (Columba livia).

    PubMed

    dos Santos, Tiago Souza; Krüger, Jéssica; Melleu, Fernando Falkenburger; Herold, Christina; Zilles, Karl; Poli, Anicleto; Güntürkün, Onur; Marino-Neto, José

    2015-12-15

    Serotonin 1A receptors (5-HT1ARs), which are widely distributed in the mammalian brain, participate in cognitive and emotional functions. In birds, 5-HT1ARs are expressed in prosencephalic areas involved in visual and cognitive functions. Diverse evidence supports 5-HT1AR-mediated 5-HT-induced ingestive and sleep behaviors in birds. Here, we describe the distribution of 5-HT1ARs in the hypothalamus and brainstem of birds, analyze their potential roles in sleep and ingestive behaviors, and attempt to determine the involvement of auto-/hetero-5-HT1ARs in these behaviors. In 6 pigeons, the anatomical distribution of [(3)H]8-OH-DPAT binding in the rostral brainstem and hypothalamus was examined. Ingestive/sleep behaviors were recorded (1h) in 16 pigeons pretreated with MM77 (a heterosynaptic 5-HT1AR antagonist; 23 or 69 nmol) for 20 min, followed by intracerebroventricular ICV injection of 5-HT (N:8; 150 nmol), 8-OH-DPAT (DPAT, a 5-HT1A,7R agonist, 30 nmol N:8) or vehicle. 5-HT- and DPAT-induced sleep and ingestive behaviors, brainstem 5-HT neuronal density and brain 5-HT content were examined in 12 pigeons, pretreated by ICV with the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (N:6/group). The distribution of brainstem and diencephalic c-Fos immunoreactivity after ICV injection of 5-HT, DPAT or vehicle (N:5/group) into birds provided with or denied access to water is also described. 5-HT1ARs are concentrated in the brainstem 5-HTergic areas and throughout the periventricular hypothalamus, preoptic nuclei and circumventricular organs. 5-HT and DPAT produced a complex c-Fos expression pattern in the 5-HT1AR-enriched preoptic hypothalamus and the circumventricular organs, which are related to drinking and sleep regulation, but modestly affected c-Fos expression in 5-HTergic neurons. The 5-HT-induced ingestivebehaviors and the 5-HT- and DPAT-induced sleep behaviors were reduced by MM77 pretreatment. 5,7-DHT increased sleep per se, decreased tryptophan

  1. Synthesis and structure-activity relationships of a novel series of tricyclic dihydropyridine-based KATP openers that potently inhibit bladder contractions in vitro.

    PubMed

    Carroll, William A; Agrios, Konstantinos A; Altenbach, Robert J; Buckner, Steven A; Chen, Yiyuan; Coghlan, Michael J; Daza, Anthony V; Drizin, Irene; Gopalakrishnan, Murali; Henry, Rodger F; Kort, Michael E; Kym, Philip R; Milicic, Ivan; Smith, Jamie C; Tang, Rui; Turner, Sean C; Whiteaker, Kristi L; Zhang, Henry; Sullivan, James P

    2004-06-01

    Structure-activity relationships were investigated on a novel series of tricyclic dihydropyridine-containing K(ATP) openers. This diverse group of analogues, comprising a variety of heterocyclic rings fused to the dihydropyridine nucleus, was designed to determine the influence on activity of hydrogen-bond-donating and -accepting groups and their stereochemical disposition. Compounds were evaluated for K(ATP) activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a subset of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation.

  2. Involvement of interleukin-6-regulated nitric oxide synthase in hemorrhagic cystitis and impaired bladder contractions in young rats induced by acrolein, a urinary metabolite of cyclophosphamide.

    PubMed

    Wang, Ching-Chia; Weng, Te-I; Wu, En-Ting; Wu, Mei-Hwan; Yang, Rong-Sen; Liu, Shing-Hwa

    2013-01-01

    Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, a chemotherapeutic alkylating agent. Acrolein is a urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis. Here, we investigated the effects and mechanisms of acrolein by intravesical instillation on urinary bladder muscle contractions and pathological alterations in rats. Acrolein instillation significantly increased the muscle contractions of rat bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions after 24 h. Acrolein increased phosphorylated protein kinase C (pan-PKC) expressions in bladders after 1 and 6 h but inhibited it after 24 h. Inducible nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in bladders 24 h after acrolein treatment. Twenty-four-hour acrolein instillation increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary bladder. The iNOS inhibitors significantly inhibited the acrolein-increased nitrite/nitrate levels, but not IL-6 levels. IL-6-neutralizing antibodies effectively inhibited the acrolein-increased NOx levels. The increased detrusor contractions by 1-h acrolein treatment were significantly reversed by the PKC inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing antibody. Both the iNOS inhibitor and IL-6-neutralizing antibody effectively reversed the increased iNOS expression, decreased PKC phosphorylation, increased bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment. Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates in the acrolein-triggered detrusor contraction inhibition and hemorrhagic cystitis. These findings may help us to find a new strategy to treat cyclophosphamide-induced hemorrhagic cystitis.

  3. Nerve-released acetylcholine contracts urinary bladder smooth muscle by inducing action potentials independently of IP3-mediated calcium release.

    PubMed

    Nausch, Bernhard; Heppner, Thomas J; Nelson, Mark T

    2010-09-01

    Nerve-released ACh is the main stimulus for contraction of urinary bladder smooth muscle (UBSM). Here, the mechanisms by which ACh contracts UBSM are explored by determining Ca(2+) and electrical signals induced by nerve-released ACh. Photolysis of caged inositol 1,4,5-trisphosphate (IP(3)) evoked Ca(2+) release from the sarcoplasmic reticulum. Electrical field stimulation (20 Hz) induced Ca(2+) waves within the smooth muscle that were present only during stimulus application. Ca(2+) waves were blocked by inhibition of muscarinic ACh receptors (mAChRs) with atropine and depletion of sarcoplasmic reticulum Ca(2+) stores with cyclopiazonic acid (CPA), and therefore likely reflect activation of IP(3) receptors (IP(3)Rs). Electrical field stimulation also increased excitability to induce action potentials (APs) that were accompanied by Ca(2+) flashes, reflecting Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCCs) during the action potential. The evoked Ca(2+) flashes and APs occurred as a burst with a lag time of approximately 1.5 s after onset of stimulation. They were not inhibited by blocking IP(3)-mediated Ca(2+) waves, but by blockers of mAChRs (atropine) and VDCCs (diltiazem). Nerve-evoked contractions of UBSM strips were greatly reduced by blocking VDCCs, but not by preventing IP(3)-mediated Ca(2+) signaling with cyclopiazonic acid or inhibition of PLC with U73122. These results indicate that ACh released from nerve varicosities induces IP(3)-mediated Ca(2+) waves during stimulation; but contrary to expectations, these signals do not appear to participate in contraction. In addition, our data provide compelling evidence that UBSM contractions evoked by nerve-released ACh depend on increased excitability and the resultant Ca(2+) entry through VDCCs during APs.

  4. The purinergic component of human bladder smooth muscle cells’ proliferation and contraction under physiological stretch

    SciTech Connect

    Wazir, Romel; Luo, De-Yi; Tian, Ye; Yue, Xuan; Li, Hong; Wang, Kun-Jie

    2013-07-26

    Highlights: •Stretch induces proliferation and contraction. •Optimum applied stretch in vitro is 5% and 10% equibiaxial stretching respectively. •Expression of P2X1 and P2X2 is upregulated after application of stretch. •P2X2 is possibly more susceptible to stretch related changes. •Purinoceptors functioning may explain conditions with atropine resistance. -- Abstract: Objective: To investigate whether cyclic stretch induces proliferation and contraction of human smooth muscle cells (HBSMCs), mediated by P2X purinoceptor 1 and 2 and the signal transduction mechanisms of this process. Methods: HBSMCs were seeded on silicone membrane and stretched under varying parameters; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (Frequency: 0.05 Hz, 0.1 Hz, 0.2 Hz, 0.5 Hz, 1 Hz). 5-Bromo-2-deoxyuridine assay was employed for proliferative studies. Contractility of the cells was determined using collagen gel contraction assay. After optimal physiological stretch was established; P2X1 and P2X2 were analyzed by real time polymerase chain reaction and Western Blot. Specificity of purinoceptors was maintained by employing specific inhibitors; (NF023 for P2X1, and A317491for P2X2), in some experiments. Results: Optimum proliferation and contractility were observed at 5% and 10% equibiaxial stretching respectively, applied at a frequency of 0.1 Hz; At 5% stretch, proliferation increased from 0.837 ± 0.026 (control) to 1.462 ± 0.023%, p < 0.05. Mean contraction at 10% stretching increased from 31.7 ± 2.3%, (control) to 78.28 ±1.45%, p < 0.05. Expression of P2X1 and P2X2 was upregulated after application of stretch. Inhibition had effects on proliferation (1.232 ± 0.051, p < 0.05 NF023) and (1.302 ± 0.021, p < 0.05 A314791) while contractility was markedly reduced (68.24 ± 2.31, p < 0.05 NF023) and (73.2 ± 2.87, p < 0.05 A314791). These findings shows that mechanical stretch can promote magnitude-dependent proliferative and contractile modulation of HBSMCs in

  5. Neurogenic bladder

    MedlinePlus

    ... of underactive bladder: Full bladder and possibly urine leakage Inability to tell when the bladder is full ... Constant urine leakage can cause skin to break down and lead to pressure sores Kidney damage may occur if the bladder ...

  6. Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission.

    PubMed

    Fernandes, Vítor S; Xin, Wenkuan; Petkov, Georgi V

    2015-07-15

    Hydrogen sulfide (H2S) is a key signaling molecule regulating important physiological processes, including smooth muscle function. However, the mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are not well understood. This study investigates the cellular and tissue mechanisms by which H2S regulates DSM contractility, excitatory neurotransmission, and large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels in freshly isolated guinea pig DSM. We used a multidisciplinary experimental approach including isometric DSM tension recordings, colorimetric ACh measurement, Ca(2+) imaging, and patch-clamp electrophysiology. In isolated DSM strips, the novel slow release H2S donor, P-(4-methoxyphenyl)-p-4-morpholinylphosphinodithioic acid morpholine salt (GYY4137), significantly increased the spontaneous phasic and nerve-evoked DSM contractions. The blockade of neuronal voltage-gated Na(+) channels or muscarinic ACh receptors with tetrodotoxin or atropine, respectively, reduced the stimulatory effect of GYY4137 on DSM contractility. GYY4137 increased ACh release from bladder nerves, which was inhibited upon blockade of L-type voltage-gated Ca(2+) channels with nifedipine. Furthermore, GYY4137 increased the amplitude of the Ca(2+) transients and basal Ca(2+) levels in isolated DSM strips. GYY4137 reduced the DSM relaxation induced by the BK channel opener, NS11021. In freshly isolated DSM cells, GYY4137 decreased the amplitude and frequency of transient BK currents recorded in a perforated whole cell configuration and reduced the single BK channel open probability measured in excised inside-out patches. GYY4137 inhibited spontaneous transient hyperpolarizations and depolarized the DSM cell membrane potential. Our results reveal the novel findings that H2S increases spontaneous phasic and nerve-evoked DSM contractions by activating ACh release from bladder nerves in combination with a direct inhibition of DSM BK channels.

  7. Bladder Cancer

    MedlinePlus

    ... organ in your lower abdomen that stores urine. Bladder cancer occurs in the lining of the bladder. It ... urinate Low back pain Risk factors for developing bladder cancer include smoking and exposure to certain chemicals in ...

  8. Bladder cancer

    MedlinePlus

    ... removing the rest of the bladder Chemotherapy or immunotherapy placed directly into the bladder Stage II and ... IV), chemotherapy is usually given by vein (intravenously). IMMUNOTHERAPY Bladder cancers are often treated with immunotherapy. In ...

  9. Bladder Diseases

    MedlinePlus

    ... frequent, urgent urination Bladder cancer Doctors diagnose bladder diseases using different tests. These include urine tests, x- ... National Institute of Diabetes and Digestive and Kidney Diseases

  10. Doxazosin selectively potentiates contraction to serotonin via 5-HT₂A receptors in longitudinal muscle strips of the rabbit gastric body.

    PubMed

    Zhao, Yan; Cao, Xue-Bin; Ren, Lei-Ming

    2014-03-01

    The aims of this study were to examine the effects of doxazosin on contractile responses to 5-hydroxytryptamine (5-HT), carbachol, and histamine, and to compare them with those of prazosin, alfuzosin, and terazosin, and then characterize a pharmacological profile of the 5-HT-induced contractile response using preparations of isolated longitudinal muscle strips from the rabbit gastric body. The results from these preparations showed that the contraction response to 5-HT, but not to carbachol or histamine, was found to be dose-dependently potentiated by doxazosin and its enantiomers. The specific potentiation effect on 5-HT was not observed in the preparations that were treated with prazosin, terazosin, or alfuzosin. The contractile response to 5-HT and its potentiation by doxazosin were not affected by treatment with phenoxybenzamine. However, 5-HT-induced contraction was competitively antagonized by nefazodone (with pA₂ value of 8.64 ± 0.17), and was almost completely inhibited by treatment with indomethacin. In conclusion, doxazosin, but not prazosin, alfuzosin, or terazosin, selectively potentiates 5-HT-induced contraction in the rabbit gastric body strips via an α₁-adrenoceptor-independent mechanism, without chiral recognition of its enantiomers. Additionally, the contraction to 5-HT was found to be mediated via 5-HT(₂) receptors, and was similar to PGs synthesis in the preparations.

  11. Contractions

    MedlinePlus

    ... feel tightening of your uterus muscles at irregular intervals or a squeezing sensation in your lower abdomen ... beginning of childbirth. These contractions come at regular intervals, usually move from the back to the lower ...

  12. Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers: discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent K(ATP) opener that selectively inhibits spontaneous bladder contractions.

    PubMed

    Carroll, William A; Altenbach, Robert J; Bai, Hao; Brioni, Jorge D; Brune, Michael E; Buckner, Steven A; Cassidy, Christopher; Chen, Yiyuan; Coghlan, Michael J; Daza, Anthony V; Drizin, Irene; Fey, Thomas A; Fitzgerald, Michael; Gopalakrishnan, Murali; Gregg, Robert J; Henry, Rodger F; Holladay, Mark W; King, Linda L; Kort, Michael E; Kym, Philip R; Milicic, Ivan; Tang, Rui; Turner, Sean C; Whiteaker, Kristi L; Yi, Lin; Zhang, Henry; Sullivan, James P

    2004-06-01

    Structure-activity relationships were investigated on a novel series of sulfonyldihydropyridine-containing K(ATP) openers. Ring sizes, absolute stereochemistry, and aromatic substitution were evaluated for K(ATP) activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a select group of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation. In an anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)-cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at plasma concentrations lower than those that affected hemodynamic parameters. Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and supports the concept that bladder-selective K(ATP) channel openers may have utility in the treatment of overactive bladder.

  13. Bladder Health

    MedlinePlus

    ... life (the person’s level of health, comfort, and happiness). In fact, people with bladder problems may have a lower quality of life than people with diabetes, heart disease, or high blood pressure. Bladder problems ...

  14. Bladder stones

    MedlinePlus

    Stones - bladder; Urinary tract stones; Bladder calculi ... Benway BM, Bhayani SM. Lower urinary tract calculi. In: Wein AJ, ed. Campbell-Walsh Urology . 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 89. Sharma R, Dill CE, Gelman DY. Urinary ...

  15. In vivo roles for myosin phosphatase targeting subunit-1 phosphorylation sites T694 and T852 in bladder smooth muscle contraction

    PubMed Central

    Chen, Cai-Ping; Chen, Xin; Qiao, Yan-Ning; Wang, Pei; He, Wei-Qi; Zhang, Cheng-Hai; Zhao, Wei; Gao, Yun-Qian; Chen, Chen; Tao, Tao; Sun, Jie; Wang, Ye; Gao, Ning; Kamm, Kristine E; Stull, James T; Zhu, Min-Sheng

    2015-01-01

    Force production and maintenance in smooth muscle is largely controlled by different signalling modules that fine tune myosin regulatory light chain (RLC) phosphorylation, which relies on a balance between Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) activities. To investigate the regulation of MLCP activity in vivo, we analysed the role of two phosphorylation sites on MYPT1 (regulatory subunit of MLCP) that biochemically inhibit MLCP activity in vitro. MYPT1 is constitutively phosphorylated at T694 by unidentified kinases in vivo, whereas the T852 site is phosphorylated by RhoA-associated protein kinase (ROCK). We established two mouse lines with alanine substitution of T694 or T852. Isolated bladder smooth muscle from T852A mice displayed no significant changes in RLC phosphorylation or force responses, but force was inhibited with a ROCK inhibitor. In contrast, smooth muscles containing the T694A mutation showed a significant reduction of force along with reduced RLC phosphorylation. The contractile responses of T694A mutant smooth muscle were also independent of ROCK activation. Thus, phosphorylation of MYPT1 T694, but not T852, is a primary mechanism contributing to inhibition of MLCP activity and enhancement of RLC phosphorylation in vivo. The constitutive phosphorylation of MYPT1 T694 may provide a mechanism for regulating force maintenance of smooth muscle. Key points Force production and maintenance in smooth muscle is largely controlled by myosin regulatory light chain (RLC) phosphorylation, which relies on a balance between Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) activities. MYPT1 is the regulatory subunit of MLCP that biochemically inhibits MLCP activity via T694 or T852 phosphorylation in vitro. Here we separately investigated the contribution of these two phosphorylation sites in bladder smooth muscles by establishing two single point

  16. Neurogenic Bladder

    PubMed Central

    Dorsher, Peter T.; McIntosh, Peter M.

    2012-01-01

    Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

  17. Bladder Monitor

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Diagnostic Ultrasound Corporation's Bladder Scan Monitor continuously records and monitors bladder fullness and alerts the wearer or caretaker when voiding is required. The sensor is held against the lower abdomen by a belt and connected to the monitor by a cable. The sensor obtains bladder volume data from sound waves reflecting off the bladder wall. The device was developed by Langley Research Center, the Ames Research Center and the NASA Technology Applications Team. It utilizes Langley's advanced ultrasound technology. It is licensed to the ARC for medical applications, and sublicensed to Diagnostics Ultrasound. Central monitoring systems are planned for the future.

  18. The other bladder syndrome: underactive bladder.

    PubMed

    Miyazato, Minoru; Yoshimura, Naoki; Chancellor, Michael B

    2013-01-01

    Detrusor underactivity, or underactive bladder (UAB), is defined as a contraction of reduced strength and/or duration resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span. UAB can be observed in many neurologic conditions and myogenic failure. Diabetic cystopathy is the most important and inevitable disease developing from UAB, and can occur silently and early in the disease course. Careful neurologic and urodynamic examinations are necessary for the diagnosis of UAB. Proper management is focused on prevention of upper tract damage, avoidance of overdistension, and reduction of residual urine. Scheduled voiding, double voiding, al-blockers, and intermittent self-catheterization are the typical conservative treatment options. Sacral nerve stimulation may be an effective treatment option for UAB. New concepts such as stem cell therapy and neurotrophic gene therapy are being explored. Other new agents for UAB that act on prostaglandin E2 and EP2 receptors are currently under development. The pharmaceutical and biotechnology industries that have a pipeline in urology and women's health may want to consider UAB as a potential target condition. Scientific counsel and review of the current pharmaceutical portfolio may uncover agents, including those in other therapeutic fields, that may benefit the management of UAB.

  19. Inhibition of native 5-HT3 receptor-evoked contractions in guinea pig and mouse ileum by antimalarial drugs.

    PubMed

    Kelley, Stephen P; Walsh, Jacqueline; Kelly, Mark C; Muhdar, Simerjyot; Adel-Aziz, Mohammed; Barrett, Iain D; Wildman, Scott S

    2014-09-01

    Quinine, chloroquine and mefloquine are commonly used to treat malaria, however, with associated gastrointestinal (GI) side-effects. These drugs act as antagonists at recombinant 5-HT3 receptors and modulate gut peristalsis. These gastrointestinal side effects may be the result of antagonism at intestinal 5-HT3 receptors. Ileum from male C57BL/6 mice and guinea pigs was mounted longitudinally in organ baths. The concentration-response curves for 5-HT and the selective 5-HT3 agonist 2-Me-5-HT were obtained with 5-HT (pEC50 = 7.57 ± 0.33, 12) more potent (P = 0.004) than 2-Me-5-HT (pEC50 = 5.45 ± 0.58, n = 5) in mouse ileum. There was no difference in potency of 5-HT (pEC50 = 5.42 ± 0.15, n = 8) and 2-Me-5-HT (pIC50 = 5.01 ± 0.55, n = 11) in guinea pig ileum (P > 0.05). Quinine, chloroquine or mefloquine was applied for 10 min and inhibitions prior to submaximal agonist application. In mouse ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50 = 4.9 ± 0.17, n = 7; 4.76 ± 0.14, n = 5; 6.21 ± 0.2, n = 4, correspondingly) with mefloquine most potent (P < 0.05). Quinine, chloroquine and mefloquine antagonised 2-me-5-HT-induced contractions (pIC50 = 6.35 ± 0.11, n = 8; 4.64 ± 0.2, n = 7; 5.11 ± 0.22, n = 6, correspondingly) with quinine most potent (P < 0.05). In guinea-pig ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50 = 5.02 ± 0.15, n = 6; 4.54 ± 0.1, n = 7; 5.32 ± 0.13, n = 5) and 2-me-5-HT-induced contractions (pIC50 = 4.62 ± 0.25, n = 5; 4.56 ± 0.14, n = 6; 5.67 ± 0.12, n = 4) with chloroquine least potent against 5-HT and mefloquine most potent against 2-me-5-HT (P < 0.05). These results support previous studies identifying anti-malarial drugs as antagonists at recombinant 5-HT3 receptors and may also demonstrate the ability of these drugs to influence native 5-HT3 receptor-evoked contractile responses which may account for their associated GI side-effects. PMID:24886883

  20. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    PubMed

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions.

  1. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    PubMed

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. PMID:25056352

  2. Overactive Bladder.

    PubMed

    White, Nicola; Iglesia, Cheryl B

    2016-03-01

    Overactive bladder (OAB) is a condition affecting millions of individuals in the United States. Anticholinergics are the mainstay of treatment. Bladder botulinum toxin injections have shown an improvement in symptoms of OAB equivalent to anticholinergic therapy. Percutaneous tibial nerve stimulation can decrease symptoms of urinary frequency and urge incontinence. Sacral neuromodulation for refractory patients has been approved by the Food and Drug Administration for treatment of OAB, urge incontinence, and urinary retention. Few randomized, head-to-head comparisons of the different available alternatives exist; however, patients now have increasing options to manage their symptoms and improve their quality of life.

  3. Pharmacologic management of overactive bladder.

    PubMed

    Lam, Sum; Hilas, Olga

    2007-01-01

    Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.

  4. Mechanisms of 5-hydroxytryptamine-induced contraction of isolated rat intrapulmonary bronchi.

    PubMed

    Szarek, J L; Zhang, J Z; Gruetter, C A

    1995-12-01

    Previous studies in our laboratory and others suggested that activation of 5-HT2 receptors mediates 5-hydroxytryptamine (5-HT)-induced contraction of airway smooth muscle and that this response is dependent in part on endogenous acetylcholine (ACh). The purpose of the present study was to confirm a role for 5-HT2 receptors and endogenous ACh in 5-HT-induced contraction of rat bronchi. In this study, we examined the effects of 5-HT2 receptor antagonists (ketanserin and LY53857), acetylcholinesterase inhibitors (physostigmine and neostigmine), and a muscarinic receptor alkylating agent [propylbenzilylcholine mustard (PBCM)] on contractile responses evoked by 5-HT and the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT). Concentration-response curves generated in isolated rat intrapulmonary bronchi in response to 5-HT and alpha-Me-5-HT were superimposable. Inhibition of acetylcholinesterase by physostigmine or neostigmine potentiated contractile responses elicited by 5-HT and alpha-Me-5-HT. Alkylation of muscarinic receptors with PBCM decreased maximal responses elicited by 5-HT or alpha-Me-5-HT in a concentration-dependent manner. Maximum contraction attained with exogenous ACh was decreased by PBCM in a concentration-dependent manner and, at the highest concentration evaluated, ACh-induced contractions were abolished. 5-Hydroxytryptamine-induced contraction was inhibited competitively by low concentrations of the 5-HT2-receptor selective antagonist, ketanserin; higher concentrations abolished contractile responses to the amine. The inhibition of 5-HT-induced contractile responses by another 5-HT2-receptor selective antagonist, LY53857, was non-competitive in nature. Together, the results suggest that 5-HT contracts rat airways directly by activating 5-HT2 receptors located on airway smooth muscle and indirectly by activation of 5-HT2 receptors on parasympathetic nerve endings to cause release of ACh. The potential physiological implication of

  5. Bladder Cancer Advocacy Network

    MedlinePlus

    ... future bladder cancer research through the Patient Survey Network. Read More... The JPB Foundation 2016 Bladder Cancer ... 2016 Young Investigator Awardees The Bladder Cancer Advocacy Network (BCAN) has announced the recipients of the 2016 ...

  6. Bladder emptying by intermittent electrical stimulation of the pudendal nerve

    NASA Astrophysics Data System (ADS)

    Boggs, Joseph W.; Wenzel, Brian J.; Gustafson, Kenneth J.; Grill, Warren M.

    2006-03-01

    Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with α-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 ± 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 ± 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 ± 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 ± 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.

  7. The underactive bladder: detection and diagnosis.

    PubMed

    Osman, Nadir; Mangera, Altaf; Hillary, Christopher; Inman, Richard; Chapple, Christopher

    2016-01-01

    The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the "underactive bladder" (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration. PMID:27081483

  8. The underactive bladder: detection and diagnosis.

    PubMed

    Osman, Nadir; Mangera, Altaf; Hillary, Christopher; Inman, Richard; Chapple, Christopher

    2016-01-01

    The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the "underactive bladder" (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration.

  9. Participation of 5-HT1-like and 5-HT2A receptors in the contraction of human temporal artery by 5-hydroxytryptamine and related drugs.

    PubMed Central

    Verheggen, R.; Freudenthaler, S.; Meyer-Dulheuer, F.; Kaumann, A. J.

    1996-01-01

    1. We investigated the hypothesis that, as in some other large human arteries, 5-HT-induced contraction of the temporal artery is mediated through two co-existing receptor populations, 5-HT1-like- and 5-HT2A. Temporal arterial segments were obtained from patients undergoing brain surgery and rings prepared set up to contract with 5-HT and related agents. Fractions of maximal 5-HT responses mediated through 5-HT1-like and 5-HT2A receptors, f1 and f2 = 1-f1, were estimated by use of the 5-HT2A-selective antagonist ketanserin. 2. In rings with intact endothelium 5-HT evoked contractions with a -log EC50, M of 7.0. Ketanserin (10-1000 nM) antagonized part of the 5-HT-induced contractions. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M of 6.9 and f1 of 0.17 (100 nM ketanserin) and -log EC50, M of 6.4 and f1 of 0.20 (1000 nM ketanserin). 3. In rings with endothelial function attenuated by enzymatic treatment, 5-HT caused contractions with a -log EC50, M of 7.2 that were partially blocked by ketanserin. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M 7.4 and f1 of 0.16 (100 nM ketanserin) and -log EC50, M of 7.5 and f1 of 0.14 (1000 nM ketanserin). 4. The ketanserin-resistant component of 5-HT-evoked contraction was blocked by methiothepin (100-1000 nM) consistent with mediation through 5-HT1-like receptors. 5. In rings with intact endothelium the 5-HT1-like-selective agonist, sumatriptan, caused small contractions with a -log EC50, M of 6.5 and intrinsic activity of 0.21 with respect to 5-HT that were resistant to blockade by 1000 nM ketanserin but antagonized by 100 nM methiothepin. 6. In rings with intact endothelium the 5-HT2A receptor partial agonist SK&F 103829 (2,3,4,5-tetrahydro-8[methyl sulphonyl]-1H3-benzazepin-7-ol methensulphonate) contracted rings with a -log EC50, M of 5.0 and an intrinsic activity of 0.49 with respect to 5-HT; the effects were antagonized by ketanserin 1000

  10. Bladder function - neurological control

    MedlinePlus Videos and Cool Tools

    ... with urine, sensory nerves send impulses to the brain indicating that the bladder is full. The sensory ... cord to relay this information. In turn, the brain sends impulses back to the bladder instructing the ...

  11. Possible site of action of 2-methylserotonin in inducing relaxation of acetylcholine-induced contraction in the molluscan (Mytilus edulis) smooth muscle.

    PubMed

    Murakami, H; Kizawa, Y; Sano, M; Edamura, N; Maruyama, C; Yamazaki, A

    1992-02-01

    1. The present study investigated the presence of 5-HT3 receptor using 2-methylserotonin (2-Me-5-HT) in the smooth muscle of Mytilus ABRM. 2. 2-Me-5-HT relaxed the acetylcholine-induced contraction in a dose-dependent manner ranging from 10(-6) to 3 x 10(-4) M (pD2 = 5.55 +/- 0.32). 3. 2-Me-5-HT-induced relaxation was antagonized by 3 x 10(-5) M ketanserin in a competitive manner (pA2 = 5.14 +/- 0.1), but not by cypropheptadine, mianserin, MDL 72222 or ICS 205-930 at a concentration of 3 x 10(-5) M. 4. 2-Me-5-HT (3 x 10(-4) M) did not alter the content of cyclic AMP and cyclic GMP in the ABRM. 5. These findings suggested that the 2-Me-5-HT-induced relaxation was mediated through 5-HT2-like receptors and was not linked to cyclic AMP or GMP systems, and, further, that 5-HT3 receptor subtype was not present in the ABRM.

  12. Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.

    PubMed

    Sung, Dong Jun; Noh, Hyun Ju; Kim, Jae Gon; Park, Sang Woong; Kim, Bokyung; Cho, Hana; Bae, Young Min

    2013-01-01

    Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K(+) (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca(2+)-activated K(+), inward rectifier K(+) and ATP-sensitive K(+) channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca(2+) channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, α-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway. PMID:24336234

  13. Neoadjuvant Intravesical Vaccine Therapy in Treating Patients With Bladder Carcinoma Who Are Undergoing Cystectomy

    ClinicalTrials.gov

    2014-12-22

    Bladder Adenocarcinoma; Bladder Squamous Cell Carcinoma; Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Bladder Cancer; Stage II Bladder Cancer; Stage III Bladder Cancer; Stage IV Bladder Cancer

  14. Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter

    PubMed Central

    Hernández, Medardo; Barahona, María Victoria; Simonsen, Ulf; Recio, Paz; Rivera, Luis; Martínez, Ana Cristina; García-Sacristán, Albino; Orensanz, Luis M; Prieto, Dolores

    2003-01-01

    This study was designed to investigate the effect of 5-hydroxytryptamine (5-HT) and to characterize the 5-HT receptors involved in 5-HT responses in the pig intravesical ureter. 5-HT (0.01–10 μM) concentration-dependently increased the tone of intravesical ureteral strips, whereas the increases in phasic contractions were concentration-independent. The 5-HT2 receptor agonist α-methyl 5-HT, mimicked the effect on tone whereas weak or no response was obtained with 5-CT, 8-OH-DPAT, m-chlorophenylbiguanide and RS 67333, 5-HT1, 5-HT1A, 5-HT3 and 5-HT4 receptor agonists, respectively. 5-HT did not induce relaxation of U46619-contracted ureteral preparations. Pargyline (100 μM), a monoaminooxidase A/B activity inhibitor, produced leftward displacements of the concentration-response curves for 5-HT. 5-HT-induced tone was reduced by the 5-HT2 and 5-HT2A receptor antagonists ritanserine (0.1 μM) and spiperone (0.2 μM), respectively. However, 5-HT contraction was not antagonized by cyanopindolol (2 μM), SDZ–SER 082 (1 μM), Y-25130 (1 μM) and GR 113808 (0.1 μM), which are respectively, 5-HT1A/1B, 5-HT2B/2C, 5-HT3, and 5-HT4 selective receptor antagonists. Removal of the urothelium did not modify 5-HT-induced contractions. Blockade of neuronal voltage-activated sodium channels, α-adrenergic receptors and adrenergic neurotransmission with tetrodotoxin (1 μM), phentolamine (0.3 μM) and guanethidine (10 μM), respectively, reduced the contractions to 5-HT. However, physostigmine (1 μM), atropine (0.1 μM) and suramin (30 μM), inhibitors of cholinesterase activity, muscarinic- and purinergic P2-receptors, respectively, failed to modify the contractions to 5-HT. These results suggest that 5-HT increases the tone of the pig intravesical ureter through 5-HT2A receptors located at the smooth muscle. Part of the 5-HT contraction is indirectly mediated via noradrenaline release from sympathetic nerves. PMID:12522083

  15. Mouse bladder wall injection.

    PubMed

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  16. Drugs Approved for Bladder Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Bladder Cancer This page lists cancer ... in bladder cancer that are not listed here. Drugs Approved for Bladder Cancer Atezolizumab Cisplatin Doxorubicin Hydrochloride ...

  17. Purinergic and cholinergic components of bladder contractility and flow.

    PubMed

    Theobald, R J

    1995-01-01

    The role of ATP as a neurotransmitter/neuromodulator in the urinary tract has been the subject of much study, particularly whether ATP has a functional role in producing urine flow. Recent studies suggested significant species variation, specifically a variation between cat and other species. This study was performed to determine the in vivo response of cat urinary bladder to pelvic nerve stimulation (PNS) and to the exogenous administration of cholinergic and purinergic agents. In anesthetized cats, bladder contractions and fluid expulsion was measured in response to PNS and to the exogenous administration of cholinergic and purinergic agents. Fluid was instilled into the bladder and any fluid expelled by bladder contractions induced by PNS or exogenous agents was collected in a beaker. The volume was measured in a graduated cylinder and recorded. PNS, carbachol and APPCP produced sustained contractions with significant expulsion of fluid. ATP, ACh and hypogastric nerve stimulation did not produce any significant expulsion of fluid. Atropine, a cholinergic antagonist, inhibited PNS contractions and fluid expulsion with no effect on purinergic actions. There was a significant relationship between the magnitude of the contraction, duration of the contractions and volume of fluid expelled. The data and information from other studies, strongly suggests a functional role for ATP as a cotransmitter in the lower urinary tract different from ACh's role. ATP stimulation of a specific purinergic receptor plays a role in initiation of bladder contractions and perhaps in the initiation of urine flow from the bladder. ACh's role is functionally different and appears to be more involved in maintenance of contractile activity and flow. PMID:7830505

  18. Electrical propagation in the renal pelvis, ureter and bladder.

    PubMed

    Hammad, F T

    2015-02-01

    Under normal conditions, following the passage of urine from the collecting duct, the urine is stored briefly in the renal pelvis before being transported through the ureter to the bladder where the urine is stored for a longer time (hours) before being voided through the urethra. The transport of urine from the renal pelvis to the bladder occurs spontaneously due to contractions of the muscles in the wall of the pelvis and ureter. Spontaneous contractions also occur in the detrusor muscle and are responsible for maintaining the bladder shape during the filling phase. These muscle contractions occur as result of electrical impulses, which are generated and propagated through different parts of the urinary tract. The renal pelvis and the ureter differ from the bladder in relation to the origin, characteristics and propagation of these electrical impulses. In the ureter, the electrical impulses originate mainly at the proximal region of the renal pelvis and are transmitted antegradely down the length of the ureter. The electrical impulses in the bladder, on the other hand, originate at any location in the bladder wall and can be transmitted in different directions with the axial direction being the prominent one. In this manuscript, an overview of the current state of research on the origin and propagation characteristics of these electrical impulses in the normal and pathological conditions is provided. PMID:25204732

  19. The underactive bladder: detection and diagnosis

    PubMed Central

    Osman, Nadir; Mangera, Altaf; Hillary, Christopher; Inman, Richard; Chapple, Christopher

    2016-01-01

    The inability to generate a voiding contraction sufficient to allow efficient bladder emptying within a reasonable time frame is a common problem seen in urological practice. Typically, the symptoms that arise are voiding symptoms, such as weak and slow urinary flow. These symptoms can cause considerable bother to patients and impact upon quality of life. The urodynamic finding of inadequate detrusor contraction has been termed detrusor underactivity (DUA). Although a definition is available for this entity, there are no widely accepted diagnostic criteria. Drawing parallels to detrusor overactivity and the overactive bladder, the symptoms arising from DUA have been referred to as the “underactive bladder” (UAB), while attempts to crystallize the definition of UAB are now ongoing. In this article, we review the contemporary literature pertaining to the epidemiology and etiopathogenesis of DUA as well as discuss the definitional aspects that are currently under consideration. PMID:27081483

  20. The defunctionalized bladder.

    PubMed

    Adeyoju, A B; Lynch, T H; Thornhill, J A

    1998-01-01

    Supravesical urinary diversion without cystectomy is a common procedure performed to manage a variety of lower urinary tract pathologies. The purpose of this article is to review the complications associated with the bladder left in situ and to relate this to the female patient. Complications related to the defunctionalized bladder include pyocystis, hemorrhage, pain/spasm and neoplastic transformation. The defunctionalized bladder also has implications for sexual function, pregnancy and undiversion. The risk factors for complications are chronic infection, inadequate drainage, interstitial cystitis and previous irradiation. The incidence of neoplastic change in the defunctionalized bladder is low, but long-term follow-up is advised, as carcinoma could develop many decades after diversion. Sexual function following urinary diversion is better preserved when the bladder is retained.

  1. P2X2 and P2X5 Receptors Mediate Bladder Hyperesthesia in ICC in Female Overactive Bladder.

    PubMed

    Meng, Mingsen; Zheng, Ji; Yan, Junan; Li, Qianwei; Fang, Qiang; Li, Weibing

    2015-06-01

    This study was set to explore the role of P2X2 and P2X5 as the important molecules in sensory afferent of bladder in female overactive bladder (OAB) patients with the bladder hyperesthesia. Sixty-eight OAB patients admitted in Southwest Hospital affiliated to the Third Military Medical University during September, 2011-December, 2012 were selected and included in the experimental group (OAB group) and 30 healthy volunteers during the same period were included as the control group. We recorded voiding diary and urodynamic results, and immunohistochemistry analysis was used to detect P2X2 and P2X5 receptor in interstitial cell of Caja (ICC) in bladder tissue of female OAB patients and healthy volunteers, to tentatively explore the effect of P2X2 and P2X5 in bladder hyperesthesia. Urodynamic study has important diagnostic value in the diagnosis and differential diagnosis of OAB. P2X2 receptor was significantly up-regulated in bladder ICC in OAB group. The blockage of P2X2 receptor could significantly inhibit the contraction of bladder muscle strips, decrease the bladder pressure and the electric discharge of pelvic nerve. PET and urodynamic study showed that micturition desire sense in PAG area of pons in OAB patients was significantly increased compared with the control group. The up-regulation of P2X2 in ICC is an important factor to cause bladder hyperesthesia in OAB patients. PET and urodynamic study indicate that the bladder-originated nervous impulses are important cause of OAB. This study provides a basis for the study of P2X2 receptor in ICC in bladder hyperesthesia of OAB patients.

  2. Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats.

    PubMed

    Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-01-01

    This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (P < 0.05). Propranolol treatment also significantly (P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity.

  3. Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats.

    PubMed

    Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-01-01

    This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (P < 0.05). Propranolol treatment also significantly (P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity. PMID:25394827

  4. Neural network based forward prediction of bladder pressure using pudendal nerve electrical activity.

    PubMed

    Geramipour, A; Makki, S; Erfanian, A

    2015-01-01

    Individuals with spinal cord injury or neurological disorders have problems in urinary bladder storage and in voiding function. In these people, the detrusor of bladder contracts at low volume and this causes incontinence. The goal of bladder control is to increase the bladder capacity by electrical stimulation of relative nerves such as pelvic nerves, sacral nerve roots or pudendal nerves. For this purpose, the bladder pressure has to be monitored continuously. In this paper, we propose a method for real-time estimating the bladder pressure using artificial neural network. The method is based upon measurements of electroneurogram (ENG) signal of pudendal nerve. This approach yields synthetic bladder pressure estimates during bladder contraction. The experiments were conducted on three rats. The results show that neural predictor can provide accurate estimation and prediction of bladder pressure with good generalization ability. The average error of 1-second and 5-second ahead prediction of bladder pressure are 9.62% and 10.54%, respectively. PMID:26737354

  5. Urinary Incontinence: Bladder Training

    MedlinePlus

    ... following ways: Lengthen the amount of time between bathroom trips. Increase the amount of urine your bladder ... Kegel exercises may also help control urges. Scheduled bathroom trips: Some people control their incontinence by going ...

  6. Ultrasound: Bladder (For Parents)

    MedlinePlus

    ... bladder area and images are recorded on a computer. The black-and-white images show the internal ... the images can be seen clearly on the computer screen. A technician (sonographer) trained in ultrasound imaging ...

  7. Neuromodulation in neurogenic bladder

    PubMed Central

    Sanford, Melissa T.

    2016-01-01

    While neuromodulation is a well-established treatment option for patients with non-neurogenic overactive bladder and urinary retention, its applicability to the neurogenic bladder population has only recently been examined more in depth. In this article we will discuss the outcomes, contraindications, and special considerations of sacral and percutaneous tibial nerve stimulation (PTNS) in patients with neurogenic lower urinary tract dysfunction. PMID:26904417

  8. Botulinum toxin treatment of urethral and bladder dysfunction.

    PubMed

    Chuang, Yao-Chi; Smith, Christopher P; Somogyi, George T; Chancellor, Michael B

    2003-01-01

    Botulinum toxin (BTX) is the most lethal naturally occurring toxin known to mankind. Injection of BTX into the urethral sphincter or bladder is an effective treatment for lower urinary tract dysfunction. We reviewed the literature on the mechanisms of action and clinical efficacy of BTX treatment in urologic diseases, with a focus on lower urinary tract dysfunction. Injection of BTX is safe and effective in the treatment of detrusor-sphincter dyssynergia, non-neurogenic pelvic floor spasticity, and refractory overactive bladder. Urodynamic assessment after sphincter injection with BTX reveals a decrease of bladder voiding pressure, urethral pressure profile, and post-void residual urine. An increase of the functional bladder capacity and a decrease of the bladder voiding pressure can be seen after bladder injection with BTX. Clinical improvement was found in a moderate percentage of treated patients in most reported series and lasted for 3 to 14 months without significant adverse effects. In addition, BTX-A treatment inhibits afferent-nerve-mediated bladder contraction. This analgesic effect may expand the application of BTX in the localized genitourinary tract pain syndrome, such as interstitial cystitis and prostatodynia. In conclusion, application of BTX is a promising treatment for lower urinary tract dysfunction with profound basic and clinical implications.

  9. [Experimental studies in animals on the bladder function following sacral blockade with alkohol (author's transl)].

    PubMed

    Fischer, D; Gerbershagen, H U; Wenzel, K G; Stockamp, K; Baar, H A

    1975-03-01

    Caudal anesthesia was achieved with Xylocain-R in 13 dogs and with ethanol (99,2 percent) in 8 dogs. Urinary bladder function was studied before and after block. The results obtained are in agreement with the functional changes after rhizotomy of S1--S3: bladder capacity increases after cuadal block and pressures measured at equal volumes decrease. Urinary overflow was observed; 80 percent of the filling volume, however, remains within the bladder. An autonomous bladder contraction induced by smypathetic nerve activity could not be proven within our observation period of 7 days.

  10. Traumatic injury of the bladder and urethra

    MedlinePlus

    Injury - bladder and urethra; Bruised bladder; Urethral injury; Bladder injury; Pelvic fracture; Urethral disruption ... Types of bladder injuries include: Blunt trauma (such as a blow to the body) Penetrating wounds (such as bullet or stab wounds) The ...

  11. Radiochemotherapy for bladder cancer.

    PubMed

    Ott, O J; Rödel, C; Weiss, C; Wittlinger, M; St Krause, F; Dunst, J; Fietkau, R; Sauer, R

    2009-09-01

    Standard treatment for muscle-invasive bladder cancer is cystectomy. Multimodality treatment, including transurethral resection of the bladder tumour, radiation therapy, chemotherapy and deep regional hyperthermia, has been shown to produce survival rates comparable with those of cystectomy. With these programmes, cystectomy has been reserved for patients with incomplete response or local relapse. During the past two decades, organ preservation by multimodality treatment has been investigated in prospective series from single centres and co-operative groups, with more than 1000 patients included. Five-year overall survival rates in the range of 50-60% have been reported, and about three-quarters of the surviving patients maintained their bladder. Clinical criteria helpful in determining patients for bladder preservation include such variables as small tumour size (<5 cm), early tumour stage, a visibly and microscopically complete transurethral resection, absence of ureteral obstruction, and no evidence of pelvic lymph node metastases. On multivariate analysis, the completeness of transurethral resection of a bladder tumour was found to be one of the strongest prognostic factors for overall survival. Patients at greater risk of new tumour development after initial complete response are those with multifocal disease and extensive associated carcinoma in situ at presentation. Close co-ordination among all disciplines is required to achieve optimal results. Future investigations will focus on optimising radiation techniques, including all possibilities of radiosensitisation (e.g. concurrent radiochemotherapy, deep regional hyperthermia), and incorporating more effective systemic chemotherapy, and the proper selection of patients based on predictive molecular makers.

  12. The use of cystometry in small rodents: a study of bladder chemosensation.

    PubMed

    Uvin, Pieter; Everaerts, Wouter; Pinto, Silvia; Alpízar, Yeranddy A; Boudes, Mathieu; Gevaert, Thomas; Voets, Thomas; Nilius, Bernd; Talavera, Karel; De Ridder, Dirk

    2012-01-01

    The lower urinary tract (LUT) functions as a dynamic reservoir that is able to store urine and to efficiently expel it at a convenient time. While storing urine, however, the bladder is exposed for prolonged periods to waste products. By acting as a tight barrier, the epithelial lining of the LUT, the urothelium, avoids re-absorption of harmful substances. Moreover, noxious chemicals stimulate the bladder's nociceptive innervation and initiate voiding contractions that expel the bladder's contents. Interestingly, the bladder's sensitivity to noxious chemicals has been used successfully in clinical practice, by intravesically infusing the TRPV1 agonist capsaicin to treat neurogenic bladder overactivity. This underscores the advantage of viewing the bladder as a chemosensory organ and prompts for further clinical research. However, ethical issues severely limit the possibilities to perform, in human subjects, the invasive measurements that are necessary to unravel the molecular bases of LUT clinical pharmacology. A way to overcome this limitation is the use of several animal models. Here we describe the implementation of cystometry in mice and rats, a technique that allows measuring the intravesical pressure in conditions of controlled bladder perfusion. After laparotomy, a catheter is implanted in the bladder dome and tunneled subcutaneously to the interscapular region. Then the bladder can be filled at a controlled rate, while the urethra is left free for micturition. During the repetitive cycles of filling and voiding, intravesical pressure can be measured via the implanted catheter. As such, the pressure changes can be quantified and analyzed. Moreover, simultaneous measurement of the voided volume allows distinguishing voiding contractions from non-voiding contractions. Importantly, due to the differences in micturition control between rodents and humans, cystometric measurements in these animals have only limited translational value. Nevertheless, they are

  13. General Information about Bladder Cancer

    MedlinePlus

    ... Research Bladder Cancer Treatment (PDQ®)–Patient Version General Information About Bladder Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  14. Bladder Dysfunction in Mice with Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Altuntas, Cengiz Z.; Daneshgari, Firouz; Liu, Guiming; Fabiyi, Adebola; Kavran, Michael; Johnson, Justin M.; Gulen, M. Fatih; Jaini, Ritika; Li, Xiaoxia; Frenkl, Tara L.; Tuohy, Vincent K.

    2009-01-01

    The vast majority of patients with multiple sclerosis (MS) develop bladder control problems including urgency to urinate, urinary incontinence, frequency of urination, and retention of urine. Over 60% of MS patients show detrusor-sphincter dyssynergia, an abnormality characterized by obstruction of urinary outflow as a result of discoordinated contraction of the urethral sphincter muscle and the bladder detrusor muscle. In the current study we examined bladder function in female SWXJ mice with different defined levels of neurological impairment following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of central nervous system inflammation widely used in MS research. We found that EAE mice develop profound bladder dysfunction characterized by significantly increased micturition frequencies and significantly decreased urine output per micturition. Moreover, we found that the severity of bladder abnormalities in EAE mice was directly related to the severity of clinical EAE and neurologic disability. Our study is the first to show and characterize micturition abnormalities in EAE mice thereby providing a most useful model system for understanding and treating neurogenic bladder. PMID:18703233

  15. Postmenopausal overactive bladder

    PubMed Central

    2014-01-01

    Bladder storage symptoms have a severe impact on many areas as regards the quality of life including health-related, social, psychological and working functions. Pharmacotherapy of lower urinary tract stores (LUTS) has been developed to optimize neural control of the lower urinary tract in pathologic states. The bladder can be overactive or underactive. Overactive bladder (OAB) is highly prevalent and is associated with considerable morbidity, especially in aging population. Therefore, an effective treatment of OAB must result in a meaningful reduction in urinary symptoms. Pharmacotherapy for the OAB must be individualized based on the degree of bother, medication side-effect profile, concomitant comorbidities and current medication regimen. Antimuscarinic agents will continue to represent the current gold standard for the first-line pharmacological management of OAB. Alternatively to antimuscarinic therapy, β3-adrenergic receptor agonists, due to their efficacy and favorable adverse event profile, are a novel and attractive option of pharmacological treatment of overactive bladder symptoms. A combination of selective antimuscarinic and β3-adrenergic receptor agonists, agents with the different mechanism of action, gives a new treatment option for the patient with OAB according to its harms profile. A number of putative novel therapeutic agents is under clinical evaluations that may ultimately provide alternative or combination treatment options for OAB in the nearest future. PMID:26327873

  16. Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice

    PubMed Central

    Claudino, Mário Angelo; Leiria, Luiz Osório Silveira; da Silva, Fábio Henrique; Alexandre, Eduardo Costa; Renno, Andre; Mónica, Fabiola Zakia; de Nucci, Gilberto; Fertrin, Kleber Yotsumoto; Antunes, Edson; Costa, Fernando Ferreira; Franco-Penteado, Carla Fernanda

    2015-01-01

    Background Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking. Objective Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo, in the Berkeley SCD murine model (SS). Methods Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10μM) and contractile response to (carbachol (CCh; 1 nM-100μM), KCl (1 mM-300mM), CaCl2 (1μM-100mM), α,β-methylene ATP (1, 3 and 10 μM) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100μM) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder. Results SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying (ex vivo), compared to control animals. In DSM, relaxation in response to a selective β3-adrenergic agonist (mirabegron) and to a non-selective β-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration. Conclusions Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in

  17. Is the Poly (L- Lactide- Co– Caprolactone) Nanofibrous Membrane Suitable for Urinary Bladder Regeneration?

    PubMed Central

    Kowalczyk, Tomasz; Warda, Karolina; Rasmus, Marta; Buchholz, Lukasz; Krzyzanowska, Sandra; Nakielski, Pawel; Chmielewski, Tomasz; Bodnar, Magdalena; Marszalek, Andrzej; Debski, Robert; Frontczak-Baniewicz, Malgorzata; Mikułowski, Grzegorz; Nowacki, Maciej; Kowalewski, Tomasz A.; Drewa, Tomasz

    2014-01-01

    The purpose of this study was to compare: a new five-layered poly (L–lactide–co–caprolactone) (PLC) membrane and small intestinal submucosa (SIS) as a control in rat urinary bladder wall regeneration. The five-layered poly (L–lactide–co–caprolactone) membrane was prepared by an electrospinning process. Adipose tissue was harvested from five 8-week old male Wistar rats. Adipose derived stem cells (ADSCs) were seeded in a density of 3×106 cells/cm2 onto PLC membrane and SIS scaffolds, and cultured for 5-7 days in the stem cell culture medium. Twenty male Wistar rats were randomly divided into five equal groups. Augmentation cystoplasty was performed in a previously created dome defect. Groups: (I) PLC+ 3×106ADSCs; (II) SIS+ 3×106ADSCs; (III) PLC; (IV) SIS; (V) control. Cystography was performed after three months. The reconstructed urinary bladders were evaluated in H&E and Masson's trichrome staining. Regeneration of all components of the normal urinary bladder wall was observed in bladders augmented with cell-seeded SIS matrices. The urinary bladders augmented with SIS matrices without cells showed fibrosis and graft contraction. Bladder augmentation with the PLC membrane led to numerous undesirable events including: bladder wall perforation, fistula or diverticula formation, and incorporation of the reconstructed wall into the bladder lumen. The new five-layered poly (L–lactide–co–caprolactone) membrane possesses poorer potential for regenerating the urinary bladder wall compared with SIS scaffold. PMID:25162451

  18. Urinary Bladder Smooth Muscle Engineered from Adipose Stem Cells and a Three Dimensional Synthetic Composite

    PubMed Central

    Jack, Gregory S.; Zhang, Rong; Lee, Min; Xu, Yuhan; Wu, Ben; Rodríguez, Larissa V.

    2009-01-01

    Human adipose stem cells were cultured in smooth muscle inductive media and seeded into synthetic bladder composites to tissue engineer bladder smooth muscle. 85:15 poly-lactic-glycolic acid bladder dome composites were cast using an electropulled microfiber luminal surface combined with an outer porous sponge. Cell seeded bladders expressed smooth muscle actin, myosin heavy chain, calponinin, and caldesmon via RT-PCR and immunoflourescence. Nude rats (n=45) underwent removal of half their bladder and repair using: (i) augmentation with the adipose stem cell seeded composites, (ii) augmentation with a matched acellular composite, or (iii) suture closure. Animals were followed for 12 weeks post-implantation and bladders were explanted serially. Results showed that bladder capacity and compliance were maintained in the cell seeded group throughout the 12 weeks, but deteriorated in the acellular scaffold group sequentially with time. Control animals repaired with sutures regained their baseline bladder capacities by week 12, demonstrating a long term limitation of this model. Histological analysis of explanted materials demonstrated viable adipose stem cells and increasing smooth muscle mass in the cell seeded scaffolds with time. Tissue bath stimulation demonstrated smooth muscle contraction of the seeded implants but not the acellular implants after 12 weeks in vivo. Our study demonstrates the feasibility and short term physical properties of bladder tissue engineered from adipose stem cells. PMID:19345408

  19. Real-Time Classification of Bladder Events for Effective Diagnosis and Treatment of Urinary Incontinence.

    PubMed

    Karam, Robert; Bourbeau, Dennis; Majerus, Steve; Makovey, Iryna; Goldman, Howard B; Damaser, Margot S; Bhunia, Swarup

    2016-04-01

    Diagnosis of lower urinary tract dysfunction with urodynamics has historically relied on data acquired from multiple sensors using nonphysiologically fast cystometric filling. In addition, state-of-the-art neuromodulation approaches to restore bladder function could benefit from a bladder sensor for closed-loop control, but a practical sensor and automated data analysis are not available. We have developed an algorithm for real-time bladder event detection based on a single in situ sensor, making it attractive for both extended ambulatory bladder monitoring and closed-loop control of stimulation systems for diagnosis and treatment of bladder overactivity. Using bladder pressure data acquired from 14 human subjects with neurogenic bladder, we developed context-aware thresholding, a novel, parameterized, user-tunable algorithmic framework capable of real-time classification of bladder events, such as detrusor contractions, from single-sensor bladder pressure data. We compare six event detection algorithms with both single-sensor and two-sensor systems using a metric termed Conditional Stimulation Score, which ranks algorithms based on projected stimulation efficacy and efficiency. We demonstrate that adaptive methods are more robust against day-to-day variations than static thresholding, improving sensitivity and specificity without parameter modifications. Relative to other methods, context-aware thresholding is fast, robust, highly accurate, noise-tolerant, and amenable to energy-efficient hardware implementation, which is important for mapping to an implant device. PMID:26292331

  20. Bladder leiomyoma presenting as dyspareunia

    PubMed Central

    Xin, Jun; Lai, Hai-ping; Lin, Shao-kun; Zhang, Qing-quan; Shao, Chu-xiao; Jin, Lie; Lei, Wen-hui

    2016-01-01

    Abstract Introduction: Leiomyoma of the bladder is a rare tumor arising from the submucosa. Most patients with bladder leiomyoma may present with urinary frequency or obstructive urinary symptoms. However, there are a few cases of bladder leiomyoma coexisting with uterine leiomyoma presenting as dyspareunia. We herein report an unusual case of coexisting bladder leiomyoma and uterine leiomyoma presenting as dyspareunia. Case presentation: A 44-year-old Asian female presented to urologist and complained that she had experienced dyspareunia over the preceding several months. A pelvic ultrasonography revealed a mass lesion located in the trigone of urinary bladder. The mass lesion was confirmed on contrast-enhanced computed tomography (CT). The CT scan also revealed a lobulated and enlarged uterus consistent with uterine leiomyoma. Then, the biopsies were then taken with a transurethral resection (TUR) loop and these biopsies showed a benign proliferation of smooth muscle in a connective tissue stroma suggestive of bladder leiomyoma. An open local excision of bladder leiomyoma and hysteromyomectomy were performed successfully. Histological examination confirmed bladder leiomyoma coexisting with uterine leiomyoma. Conclusion: This case highlights a rare presentation of bladder leiomyoma, dyspareunia, as the chief symptom in a patient who had coexisting uterine leiomyoma. Bladder leiomyomas coexisting with uterine leiomyomas are rare and can present with a wide spectrum of complaints including without symptoms, irritative symptoms, obstructive symptoms, or even dyspareunia. PMID:27428187

  1. Pachydermoperiostosis and bladder cancer.

    PubMed

    Famularo, Guiseppe; Stasolla, Alessandro; Gasbarrone, Laura

    2015-06-01

    Pachydermoperiostosis or the Touraine-Soulente-Golé syndrome is a rare monogenetic disorder characterized by pachydermia, periostosis and digital clubbing accounts for approximately 3∼5% of all patients with hypertrophic osteoarthropathy. Missense mutations in SLCO2A1 and HPGD genes could plausibly underlie the pathogenesis of pachydermoperiostosis. Patients have usually a favorable outcome with very few cases associated with cancer. Herein, we report the first case of a patient with pachydermoperiostosis associated with bladder cancer. PMID:26158372

  2. Endoscopic Management of Bladder Diverticula.

    PubMed

    Pham, Khanh N; Jeldres, Claudio; Hefty, Thomas; Corman, John M

    2016-01-01

    A 50-year-old man with benign prostatic hyperplasia and urinary retention had a very large diverticulum on the posterior wall of the bladder. The patient was managed with transurethral resection of the prostate and endoscopic fulguration of the bladder diverticulum mucosa using the Orandi technique. There was near-complete resolution of the bladder diverticulum following endoscopic management, obviating the need for bladder diverticulectomy. The patient now empties his bladder, with a postvoid residual < 50 mL and the absence of urinary tract infection after 6-month follow-up. We report the successful treatment of a large bladder diverticulum with endoscopic fulguration to near-complete resolution. This minimally invasive technique is a useful alternative in patients unfit for a more extensive surgical approach. PMID:27601971

  3. Endoscopic Management of Bladder Diverticula

    PubMed Central

    Pham, Khanh N.; Jeldres, Claudio; Hefty, Thomas; Corman, John M.

    2016-01-01

    A 50-year-old man with benign prostatic hyperplasia and urinary retention had a very large diverticulum on the posterior wall of the bladder. The patient was managed with transurethral resection of the prostate and endoscopic fulguration of the bladder diverticulum mucosa using the Orandi technique. There was near-complete resolution of the bladder diverticulum following endoscopic management, obviating the need for bladder diverticulectomy. The patient now empties his bladder, with a postvoid residual < 50 mL and the absence of urinary tract infection after 6-month follow-up. We report the successful treatment of a large bladder diverticulum with endoscopic fulguration to near-complete resolution. This minimally invasive technique is a useful alternative in patients unfit for a more extensive surgical approach. PMID:27601971

  4. Pharmacogenomics in bladder cancer

    PubMed Central

    Dancik, Garrett M.; Theodorescu, Dan

    2014-01-01

    Bladder cancer is a common cancer worldwide. For patients presenting with muscle-invasive disease, the five year survival rate is approximately 50%. Cisplatinum-based combination chemotherapy is recommended in the neoadjuvant setting prior to cystectomy and is also the first line in the metastatic setting. However, the survival benefit of such therapy is modest. The identification of pharmacogenomic biomarkers would enable the rational and personalized treatment of patients by selecting those patients that would benefit most from such therapies sparing others the unnecessary toxicity. Conventional therapies would be recommended for an expected responder while a non-responder would be considered for alternative therapies selected on the basis of the individual’s molecular profile. Although few effective bladder cancer therapies have been introduced in the past 30 years, several targeted therapies against the molecular drivers of bladder cancer appear promising. This review summarizes pharmacogenomic biomarkers that require further investigation and/or prospective evaluation, publicly available tools for drug discovery and biomarker identification from in vitro data, and targeted agents that have been evaluated in preclinical models. PMID:24360659

  5. Bladder Cancer and Genetic Mutations.

    PubMed

    Zhang, Xiaoying; Zhang, Yangde

    2015-09-01

    The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder

  6. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction.

  7. Temporal changes in micturition and bladder contractility after sucrose diuresis and streptozotocin-induced diabetes mellitus in rats.

    PubMed

    Tammela, T L; Leggett, R E; Levin, R M; Longhurst, P A

    1995-06-01

    Studies were done to compare the acute effects of streptozotocin-induced diabetes and sucrose consumption on micturition, bladder mass and contractile responses of bladder strips to field stimulation and contractile agonists. Micturition changes occurred gradually in diabetic rats, reached maximal values within 7 to 14 days, and were accompanied by significant increases in bladder mass after 7 days. Bladder strips from diabetics responded to field stimulation, carbachol and KCl with significantly greater contractions than did those from controls within 7 days. Sucrose-drinking rats had maximal increases in fluid consumption and micturition frequency on the first night after starting treatment. Increases in micturition volumes were slower to develop than in diabetics. Bladder mass was significantly increased 30 and 60 days after starting sucrose treatment. Bladder strips from sucrose-drinking rats responded to field stimulation and carbachol with significantly greater contractions than did those from controls only after 60 days. Monitoring of drinking and micturition patterns established that diabetic rats drink and urinate during both the dark and light cycles. In contrast, control and sucrose-drinking rats drink and urinate principally at night. The results demonstrate that differences in bladder function between diabetic and sucrose drinking rats are apparent during the first month after treatment begins. The data suggest that the effects of diabetes and sucrose consumption on contractile bladder function are related to the diuresis-induced increases in bladder mass.

  8. [Morphologic and functional heterogeneous changes of the urinary bladder different parts at rats with infravesical obstruction of the urinary tracts].

    PubMed

    Kudriavtsev, Iu V; Kirpatovskiĭ, V I; Mudraia, I S; Khromov, R A; Kudriavtseva, L V

    2012-01-01

    Infravesical obstruction of the lower urinary tracts of 30 rats was carried out by the measured constriction of the urethral prevesical parts. Morphologic and functional changes of the urinary bladder different parts were studied in 1 week and in 3 months. Compensatory hypertrophy of the detrusor was accompanied increasing of hypertrophied, atrophic and native forms of leiomyocytes, as so their transformation into myofibroblasts with connective tissue formation between the muscle fibers mainly in the neck of urinary bladder Contractility of the detrusor decreased with their tonus increasing mainly in the neck of urinary bladder too. Weakening effect of adrenalin in 3 month after obstruction significantly decreased, while in the body and neck of urinary bladder it virtually disappeared. Blockade of alpha-adrenoreceptors after noradrenalin stimulation resulted in enchancement of the hypertrophic detrusor contraction when tonus of the urinary neck decreased. On the contrary, in the intact urinary bladder the similarly influence resulted in weakening of contraction.

  9. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

    PubMed

    Kullmann, F Aura; Wells, Grace I; Langdale, Christopher L; Zheng, Jihong; Thor, Karl B

    2013-01-01

    Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS) activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5%) to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion) was precisely repeated every 30 minutes. Administration of vehicle (saline i.v.) occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v.) after the 8(th). Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function. PMID:24040064

  10. A microchannel neuroprosthesis for bladder control after spinal cord injury in rat.

    PubMed

    Chew, Daniel J; Zhu, Lan; Delivopoulos, Evangelos; Minev, Ivan R; Musick, Katherine M; Mosse, Charles A; Craggs, Michael; Donaldson, Nicholas; Lacour, Stéphanie P; McMahon, Stephen B; Fawcett, James W

    2013-11-01

    A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness. We designed a closed-loop neuroprosthetic interface that measures bladder fullness and prevents spontaneous voiding episodes without the need for dorsal rhizotomy in a rat model. To obtain bladder sensory information, we implanted teased dorsal roots (rootlets) within the rat vertebral column into microchannel electrodes, which provided signal amplification and noise suppression. As long as they were attached to the spinal cord, these rootlets survived for up to 3 months and contained axons and blood vessels. Electrophysiological recordings showed that half of the rootlets propagated action potentials, with firing frequency correlated to bladder fullness. When the bladder became full enough to initiate spontaneous voiding, high-frequency/amplitude sensory activity was detected. Voiding was abolished using a high-frequency depolarizing block to the ventral roots. A ventral root stimulator initiated bladder emptying at low frequency and prevented unwanted contraction at high frequency. These data suggest that sensory information from the dorsal root together with a ventral root stimulator could form the basis for a closed-loop bladder neuroprosthetic. PMID:24197736

  11. Botulinum toxin as a treatment for refractory overactive bladder.

    PubMed

    Harris, Shatril; Rizzolo, Denise

    2016-02-01

    Detrusor overactivity is the most common cause of overactive bladder (OAB) and refers to demonstrable involuntary detrusor contractions during urodynamic studies. The number of adults age 40 years or older suffering from idiopathic urge incontinence ranges from 13% in men to 30% in women. For patients whose symptoms are refractory to conventional therapy, intradetrusor botulinum toxin injection offers a safe and effective outpatient treatment with high rates of improvement of OAB symptoms.

  12. Simple cyst of urinary bladder.

    PubMed

    Bo, Yang

    2014-07-01

    Simple cysts are rare in the urinary bladder and can pose a diagnostic dilemma to both the urologist and the histopathologist. No case study was found in the database of Elsevier Science Direct, Spring-Link, or PubMed. We present two cases of subserous cyst in the bladder and discuss the diagnosis and treatment of the condition. The cystic lesion at bladder dome was detected by radiologic examination and confirmed by cystoscopy. In case 1, transurethral resection was first performed which was followed by partial cystectomy; In case 2, the cyst was removed with the urachus using laparoscopic surgery. The patients recovered uneventfully and the histopathology showed cysts in subserous layer of urinary bladder. The bladder cyst should be distinguished from urachal tumor, and laparoscopic partial cystectomy is the preferred operative procedure.

  13. Emerging Immunotargets in Bladder Cancer.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Vau, Nuno; Santoni, Matteo; Montironi, Rodolfo; Cheng, Liang; Marques, Rita C; Scarpelli, Marina; Fonseca, Jorge; Matrana, Marc R; Holger, Moch; Cascinu, Stefano; Tortora, Giampaolo; Lopez-Beltran, Antonio

    2016-01-01

    Bladder cancer treatment, namely systemic therapy, was dominated in the last three decades due to the absence of newer therapeutic options other than chemotherapy regimens. Chemotherapy, by itself, both in first and second-line seems to have achieved the modest plateau of its possibilities at the cost of non-negligible toxicity. Targeted therapies, which changed the therapy of many different tumors, seem rather ineffective in bladder cancer. More recently, a new generation of Immunotherapy based regimens represent the most promising avenue for the future systemic treatment of bladder cancer. Checkpoint inhibition, namely PD1/PD-L1 pathway inhibition, showed impressive results in many other tumor types and are expected to become a major player in the treatment of bladder cancer. Other immunotherapy strategies such as fusion proteins represent distant, although promising, options. A brief overview of the current status of bladder cancer immunotherapy is presented.

  14. Overexpression of Aquaporin-1 and Caveolin-1 in the Rat Urinary Bladder Urothelium Following Bladder Outlet Obstruction

    PubMed Central

    Song, Seung Hee; Park, Kwangsung; Kwon, Dongdeuk

    2013-01-01

    Purpose This study was designed to investigate the effect of detrusor overactivity induced by partial bladder outlet obstruction (BOO) on the expression of aquaporin 1 (AQP1) and caveolin 1 (CAV1) in the rat urinary bladder, and to determine the role of these molecules in detrusor overactivity. Methods Female Sprague-Dawley rats were divided into control (n=30) and experimental (n=30) groups. The BOO group underwent partial BOO, and the control group underwent a sham operation. After 4 weeks, an urodynamic study was performed to measure the contraction interval and contraction pressure. The expression and cellular localization of AQP1 and CAV1 were determined by western blot and immunofluorescence experiments in the rat urinary bladder. Results In cystometrograms, the contraction interval was significantly lower in the BOO group (2.9±1.5 minutes) than in the control group (6.7±1.0 minutes) (P<0.05). Conversely, the average contraction pressure was significantly higher in the BOO group (21.2±3.3 mmHg) than in the control group (13.0±2.5 mmHg) (P<0.05). AQP1 and CAV1 were coexpressed in the capillaries, arterioles, and venules of the suburothelial layer. AQP1 and CAV1 protein expression was significantly increased in the BOO rats compared to the control rats (P<0.05). Conclusions Detrusor overactivity induced by BOO causes a significant increase in the expression of AQP1 and CAV1, which were coexpressed in the suburothelial microvasculature. This finding suggests that AQP1 and CAV1 might be closely related to bladder signal activity and may have a functional role in BOO-associated detrusor overactivity. PMID:24466464

  15. Chemoprevention of bladder cancer.

    PubMed

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

  16. Chemoprevention of bladder cancer.

    PubMed

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

  17. Chronic treatment with resveratrol improves overactive bladder in obese mice via antioxidant activity.

    PubMed

    Alexandre, Eduardo C; Calmasini, Fabiano B; de Oliveira, Mariana G; Silva, Fábio H; da Silva, Carmem P V; André, Diana M; Leonardo, Flávia C; Delbin, Maria A; Antunes, Edson

    2016-10-01

    The objective of the present work was to evaluate whether oral intake with resveratrol ameliorates overactive bladder in high-fat fed mice. Male C57BL6 mice fed with standard chow or high-fat diet to induce obesity received a two-week therapy with resveratrol (100mg/kg, given as a daily gavage). Weight and metabolic profile, together with cystometry and in vitro bladder contractions were evaluated. Measurements of gp91phox and SOD1 mRNA expressions and reactive-oxygen species (ROS) in bladder tissues, and serum TBARS were performed. Obese mice exhibited increases in body weight and epididymal fat mass, which were significantly reduced by oral treatment with resveratrol. Cystometric study in obese mice showed increases in non-voiding contractions, post-voiding pressure and voiding frequency that were reversed by resveratrol treatment. Likewise, the in vitro bladder overactivity in response to electrical-field stimulation (80V, 1-32Hz) or carbachol (1nM to 10mM) were normalized by resveratrol. The gp91phox and SOD1 mRNA expressions in bladder tissues were markedly higher in obese mice compared with lean group. In addition, ROS levels in bladder tissues and serum lipid peroxidation (TBARS assay) were markedly higher in obese compared with lean mice, all of which were reduced by resveratrol treatment. In lean group, resveratrol had no effect in any parameter evaluated. Our results show that two-week therapy of obese mice with resveratrol reduces the systemic and bladder oxidative stress, and greatly ameliorated the cystometry alterations and in vitro bladder overactivity. Resveratrol treatment could be an option to prevent obesity-associated overactive bladder.

  18. Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

    PubMed Central

    Schnegelsberg, Birthe; Sun, Tung-Tien; Cain, Gary; Bhattacharya, Anindya; Nunn, Philip A.; Ford, Anthony P. D. W.; Vizzard, Margaret A.

    2010-01-01

    NGF has been suggested to play a role in urinary bladder dysfunction by mediating inflammation, as well as morphological and functional changes, in sensory and sympathetic neurons innervating the urinary bladder. To further explore the role of NGF in bladder sensory function, we generated a transgenic mouse model of chronic NGF overexpression in the bladder using the urothelium-specific uroplakin II (UPII) promoter. NGF mRNA and protein were expressed at higher levels in the bladders of NGF-overexpressing (NGF-OE) transgenic mice compared with wild-type littermate controls from postnatal day 7 through 12–16 wk of age. Overexpression of NGF led to urinary bladder enlargement characterized by marked nerve fiber hyperplasia in the submucosa and detrusor smooth muscle and elevated numbers of tissue mast cells. There was a marked increase in the density of CGRP- and substance P-positive C-fiber sensory afferents, neurofilament 200-positive myelinated sensory afferents, and tyrosine hydroxylase-positive sympathetic nerve fibers in the suburothelial nerve plexus. CGRP-positive ganglia were also present in the urinary bladders of transgenic mice. Transgenic mice had reduced urinary bladder capacity and an increase in the number and amplitude of nonvoiding bladder contractions under baseline conditions in conscious open-voiding cystometry. These changes in urinary bladder function were further associated with an increased referred somatic pelvic hypersensitivity. Thus, chronic urothelial NGF overexpression in transgenic mice leads to neuronal proliferation, focal increases in urinary bladder mast cells, increased urinary bladder reflex activity, and pelvic hypersensitivity. NGF-overexpressing mice may, therefore, provide a useful transgenic model for exploring the role of NGF in urinary bladder dysfunction. PMID:20032263

  19. Contribution of opioid and metabotropic glutamate receptor mechanisms to inhibition of bladder overactivity by tibial nerve stimulation.

    PubMed

    Matsuta, Yosuke; Mally, Abhijith D; Zhang, Fan; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2013-07-15

    The contribution of metabotropic glutamate receptors (mGluR) and opioid receptors to inhibition of bladder overactivity by tibial nerve stimulation (TNS) was investigated in cats under α-chloralose anesthesia using LY341495 (a group II mGluR antagonist) and naloxone (an opioid receptor antagonist). Slow infusion cystometry was used to measure the volume threshold (i.e., bladder capacity) for inducing a large bladder contraction. After measuring the bladder capacity during saline infusion, 0.25% acetic acid (AA) was infused to irritate the bladder, activate the nociceptive C-fiber bladder afferents, and induce bladder overactivity. AA significantly (P < 0.0001) reduced bladder capacity to 26.6 ± 4.7% of saline control capacity. TNS (5 Hz, 0.2 ms) at 2 and 4 times the threshold (T) intensity for inducing an observable toe movement significantly increased bladder capacity to 62.2 ± 8.3% at 2T (P < 0.01) and 80.8 ± 9.2% at 4T (P = 0.0001) of saline control capacity. LY341495 (0.1-5 mg/kg iv) did not change bladder overactivity, but completely suppressed the inhibition induced by TNS at a low stimulus intensity (2T) and partially suppressed the inhibition at high intensity (4T). Following administration of LY341495, naloxone (0.01 mg/kg iv) completely eliminated the high-intensity TNS-induced inhibition. However, without LY341495 treatment a 10 times higher dose (0.1 mg/kg) of naloxone was required to completely block TNS inhibition. These results indicate that interactions between group II mGluR and opioid receptor mechanisms contribute to TNS inhibition of AA-induced bladder overactivity. Understanding neurotransmitter mechanisms underlying TNS inhibition of bladder overactivity is important for the development of new treatments for bladder disorders. PMID:23576608

  20. Bladder Injury During Cesarean Delivery

    PubMed Central

    Tarney, Christopher M.

    2013-01-01

    Cesarean section is the most common surgery performed in the United States with over 30% of deliveries occurring via this route. This number is likely to increase given decreasing rates of vaginal birth after cesarean section (VBAC) and primary cesarean delivery on maternal request, which carries the inherent risk for intraoperative complications. Urologic injury is the most common injury at the time of either obstetric or gynecologic surgery, with the bladder being the most frequent organ damaged. Risk factors for bladder injury during cesarean section include previous cesarean delivery, adhesions, emergent cesarean delivery, and cesarean section performed at the time of the second stage of labor. Fortunately, most bladder injuries are recognized at the time of surgery, which is important, as quick recognition and repair are associated with a significant reduction in patient mortality. Although cesarean delivery is a cornerstone of obstetrics, there is a paucity of data in the literature either supporting or refuting specific techniques that are performed today. There is evidence to support double-layer closure of the hysterotomy, the routine use of adhesive barriers, and performing a Pfannenstiel skin incision versus a vertical midline subumbilical incision to decrease the risk for bladder injury during cesarean section. There is also no evidence that supports the creation of a bladder flap, although routinely performed during cesarean section, as a method to reduce the risk of bladder injury. Finally, more research is needed to determine if indwelling catheterization, exteriorization of the uterus, and methods to extend hysterotomy incision lead to bladder injury. PMID:24876830

  1. Biomarkers in overactive bladder.

    PubMed

    Bhide, Alka A; Cartwright, Rufus; Khullar, Vik; Digesu, G Alessandro

    2013-07-01

    A biomarker is an indicator of a particular disease. It is generally used to define the presence (diagnostic biomarker), severity, progression (prognostic biomarker) of a condition and/or its response to a specific treatment (predictive biomarker). Biomarkers can be specific cells, enzymes, hormones, genes or gene products, which can be detected and measured in parts of the body such as blood, urine or tissue. Therefore, biomarkers have been suggested to play an important role in both the clinical assessment and the management of patients, as well as in the research setting. Recently, interest has gathered in urinary biomarkers as a tool to assess overactive bladder (OAB), potentially playing a role in the diagnosis, disease progression and monitoring response to treatment. Urinary biomarkers identified so far include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), prostaglandins, cytokines and C-reactive protein. The aim of this review was to review the published literature on biomarkers in OAB. A literature review using Pub Med, clinicaltrials.gov and the controlled trials online registries was performed from 1970 up to June 2012. The search keywords were: the International Continence Society (ICS) definition of "OAB", "nerve growth fac- tor" (NGF), "brain derived growth factor" (BDNF), "prostaglandins," "cytokines," "genetic biomarkers" and "C reactive protein".The results were limited for fully published English-language articles. The search was then subsequently expanded to include urinary biomarkers in interstitial cystitis and bladder pain where relevant. Each of the studies/articles was reviewed, interpreted and discussed to consider the role of urinary biomarkers in OAB. Using the search criteria, a total of 20 studies (animal and human) that investigated the role of urinary biomarkers in OAB were identified. Full text versions of these articles were obtained and reviewed. Studies on NGF suggested that urinary levels were higher in OAB

  2. Underactive Bladder in Older Adults.

    PubMed

    Chuang, Yao-Chi; Plata, Mauricio; Lamb, Laura E; Chancellor, Michael B

    2015-11-01

    Overactive bladder is one of the most common bladder problems, but an estimated 20 million Americans have underactive bladder (UAB), which makes going to the bathroom difficult, increases the risk of urinary tract infections, and even leads to institutionalization. This article provides an overview of UAB in older adults, and discusses the prevalence, predisposing factors, cause, clinical investigations, and treatments. At present, there is no effective therapy for UAB. A great deal of work still needs to be done on understanding the pathogenesis and the development of effective therapies. PMID:26476113

  3. Underactive Bladder in Older Adults.

    PubMed

    Chuang, Yao-Chi; Plata, Mauricio; Lamb, Laura E; Chancellor, Michael B

    2015-11-01

    Overactive bladder is one of the most common bladder problems, but an estimated 20 million Americans have underactive bladder (UAB), which makes going to the bathroom difficult, increases the risk of urinary tract infections, and even leads to institutionalization. This article provides an overview of UAB in older adults, and discusses the prevalence, predisposing factors, cause, clinical investigations, and treatments. At present, there is no effective therapy for UAB. A great deal of work still needs to be done on understanding the pathogenesis and the development of effective therapies.

  4. Bladder diverticulitis: a case report.

    PubMed

    Silberman, Michael; Jeanmonod, Rebecca

    2011-01-01

    Bladder diverticulum, an outpouching of the mucosa through the muscular wall of the bladder, is a multifactorial disease process that can be either acquired or congenital. Although small diverticuli are usually asymptomatic, a large diverticulum may result in hematuria, urinary tract infection, acute abdomen due to its rupture, acute urinary retention, or neoplasm formation. We describe the case of an elderly gentleman who presented to the emergency department with abdominal pain and was ultimately diagnosed with bladder diverticulitis, a disease not previously described in the literature.

  5. Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel

    PubMed Central

    Herrera, Gerald M; Pozo, Maria J; Zvara, Peter; Petkov, Georgi V; Bond, Chris T; Adelman, John P; Nelson, Mark T

    2003-01-01

    Small conductance, calcium-activated potassium (SK) channels have an important role in determining the excitability and contractility of urinary bladder smooth muscle. Here, the role of the SK isoform SK3 was examined by altering expression levels of the SK3 gene using a mouse model that conditionally overexpresses SK3 channels (SK3T/T). Prominent SK3 immunostaining was found in both the smooth muscle (detrusor) and urothelium layers of the urinary bladder. SK currents were elevated 2.4-fold in isolated myocytes from SK3T/T mice. Selective suppression of SK3 expression by dietary doxycycline (DOX) decreased SK current density in isolated myocytes, increased phasic contractions of isolated urinary bladder smooth muscle strips and exposed high affinity effects of the blocker apamin of the SK isoforms (SK1–3), suggesting an additional participation from SK2 channels. The role of SK3 channels in urinary bladder function was assessed using cystometry in conscious, freely moving mice. The urinary bladders of SK3T/T had significantly greater bladder capacity, and urine output exceeded the infused saline volume. Suppression of SK3 channel expression did not alter filling pressure, threshold pressure or bladder capacity, but micturition pressure was elevated compared to control mice. However, SK3 suppression did eliminate excess urine production and caused a marked increase in non-voiding contractions. The ability to examine bladder function in mice in which SK3 channel expression is selectively altered reveals that these channels have a significant role in the control of non-voiding contractions in vivo. Activation of these channels may be a therapeutic approach for management of non-voiding contractions, a condition which characterizes many types of urinary bladder dysfunctions including urinary incontinence. PMID:12813145

  6. Increased bladder permeability in interstitial cystitis/painful bladder syndrome

    PubMed Central

    Greenwood-Van Meerveld, Beverley; Wisniewski, Amy B.; VanGordon, Samuel; Lin, HsuehKung; Kropp, Bradley P.; Towner, Rheal A.

    2015-01-01

    The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system. PMID:26751576

  7. Phaeochromocytomas of the bladder.

    PubMed Central

    Khan, O; Williams, G; Chisholm, G D; Welbourn, R B

    1982-01-01

    Phaeochromocytomas of the bladder are rare, only about 100 cases having been reported previously. Four adults with these lesions have been managed at Hammersmith Hospital in the past 10 years. Three patients had hypertension, together with syncopal attacks and/or headaches, induced by micturition. The fourth patient presented with haematuria. After control of blood pressure and localization of the tumours by various combinations of cystoscopy, intravenous urography, venous sampling, ultrasound, angiography and computerized coaxial tomography (CT scanning), 3 patients underwent partial cystectomy, and the fourth pelvic exenteration. Two patients were apparently cured of the disease, but 2 were not. One developed modal metastases and recurrence of hypertension after 18 months and one rapidly developed metastases in the lungs and elsewhere. Effective therapy probably requires a high index of suspicion in diagnosing the condition and possibly an aggressive surgical and radiotherapeutic policy. PMID:7057406

  8. Ct2 Bladder Cancer.

    PubMed

    Soloway, Mark S

    2016-09-01

    The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach.

  9. Ct2 Bladder Cancer.

    PubMed

    Soloway, Mark S

    2016-09-01

    The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach. PMID:27457483

  10. Drugs Approved for Bladder Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  11. Augmentation cystoplasty in neurogenic bladder.

    PubMed

    Çetinel, Bülent; Kocjancic, Ervin; Demirdağ, Çetin

    2016-09-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  12. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  13. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... chemicals. Studies suggest that chronic bladder inflammation, a parasitic infection called schistosomiasis, and some medications used to treat ... Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Patient Support and Advocacy Resources (2 links) American Cancer ...

  14. [Melanosis of the urinary bladder].

    PubMed

    Wöllner, J; Janzen, J; Pannek, J

    2016-01-01

    Melanosis of the bladder is rare. Only 10 cases have been described in the literature. We present the case of an 80-year-old woman with neurogenic lower urinary tract dysfunction due to spinal paralysis. During the diagnostic work-up which included cystoscopy, black spots in the bladder wall were observed. Histopathological evaluation revealed a benign suburothelial melanosis. Thus, with cystoscopic suspicion of a malignancy (melanoma), a biopsy is mandatory and regular cystoscopic follow-up is recommended. PMID:26358438

  15. Paraganglioma of the urinary bladder.

    PubMed

    Adraktas, Dionesia; Caserta, Melanie; Tchelepi, Hisham

    2014-09-01

    Extra-adrenal paragangliomas of the urinary bladder are rare. Typically, patients present with symptoms related to catecholamine hypersecretion or mass effect, but these tumors can also be encountered incidentally on imaging studies obtained for a different purpose. It is important to recognize the key imaging features of this entity so that it may be suggested as a possible differential diagnosis in the setting of a newly identified bladder mass.

  16. Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder

    PubMed Central

    Kim, Aram; Yu, Hwan Yeul; Heo, Jinbeom; Song, Miho; Shin, Jung-Hyun; Lim, Jisun; Yoon, Soo-Jung; Kim, YongHwan; Lee, Seungun; Kim, Seong Who; Oh, Wonil; Choi, Soo Jin; Shin, Dong-Myung; Choo, Myung-Soo

    2016-01-01

    Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-β signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1 × 106) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy. PMID:27481042

  17. Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder.

    PubMed

    Kim, Aram; Yu, Hwan Yeul; Heo, Jinbeom; Song, Miho; Shin, Jung-Hyun; Lim, Jisun; Yoon, Soo-Jung; Kim, YongHwan; Lee, Seungun; Kim, Seong Who; Oh, Wonil; Choi, Soo Jin; Shin, Dong-Myung; Choo, Myung-Soo

    2016-01-01

    Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-β signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1 × 10(6)) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy. PMID:27481042

  18. Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat.

    PubMed

    Oger-Roussel, Stephanie; Behr-Roussel, Delphine; Caisey, Stephanie; Kergoat, Micheline; Charon, Christine; Audet, Annick; Bernabé, Jacques; Alexandre, Laurent; Giuliano, Francois

    2014-01-15

    Despite the fact that urogenito-sexual complications significantly impact the quality of life of diabetic patients, a robust in vivo experimental model is lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK) rat and responses to standard-of-care treatments for each disorder have been assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats (n = 23), characterized for their metabolic parameters, were used. Bladder function was assessed by cystometry in conscious rats treated by intravenous solifenacin (1 mg/kg). Subsequently, erectile function was assessed under anesthesia following electrical stimulation of the cavernous nerve in presence of intravenous sildenafil (0.3 mg/kg). GK rats displayed detrusor overactivity with a significant increase in frequency/amplitude of nonvoiding contractions during the filling phase, together with an increase in bladder capacity, intercontraction interval, voided volume, and maximal pressure of voiding contraction. Solifenacin significantly decreased parameters characterizing voiding contractions without modifying voiding efficiency. Erectile function in GK rats was markedly impaired and remained so after sildenafil treatment despite a significant improvement. GK rats display both bladder and erectile dysfunctions and respond at least partially to standard-of-care treatments for each disorder, thus representing a suitable model to investigate the pathophysiology and assess the efficacy of new therapeutic agents for Type 2 diabetes-associated bladder and erectile complications. PMID:24305064

  19. Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat.

    PubMed

    Oger-Roussel, Stephanie; Behr-Roussel, Delphine; Caisey, Stephanie; Kergoat, Micheline; Charon, Christine; Audet, Annick; Bernabé, Jacques; Alexandre, Laurent; Giuliano, Francois

    2014-01-15

    Despite the fact that urogenito-sexual complications significantly impact the quality of life of diabetic patients, a robust in vivo experimental model is lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK) rat and responses to standard-of-care treatments for each disorder have been assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats (n = 23), characterized for their metabolic parameters, were used. Bladder function was assessed by cystometry in conscious rats treated by intravenous solifenacin (1 mg/kg). Subsequently, erectile function was assessed under anesthesia following electrical stimulation of the cavernous nerve in presence of intravenous sildenafil (0.3 mg/kg). GK rats displayed detrusor overactivity with a significant increase in frequency/amplitude of nonvoiding contractions during the filling phase, together with an increase in bladder capacity, intercontraction interval, voided volume, and maximal pressure of voiding contraction. Solifenacin significantly decreased parameters characterizing voiding contractions without modifying voiding efficiency. Erectile function in GK rats was markedly impaired and remained so after sildenafil treatment despite a significant improvement. GK rats display both bladder and erectile dysfunctions and respond at least partially to standard-of-care treatments for each disorder, thus representing a suitable model to investigate the pathophysiology and assess the efficacy of new therapeutic agents for Type 2 diabetes-associated bladder and erectile complications.

  20. Effect of bladder wall thickness on miniature pneumatic artificial muscle performance.

    PubMed

    Pillsbury, Thomas E; Kothera, Curt S; Wereley, Norman M

    2015-09-28

    Pneumatic artificial muscles (PAMs) are actuators known for their high power to weight ratio, natural compliance and light weight. Due to these advantages, PAMs have been used for orthotic devices and robotic limbs. Small scale PAMs have the same advantages, as well as requiring greatly reduced volumes with potential application to prostheses and small scale robotics. The bladder of a PAM affects common actuator performance metrics, specifically: blocked force, free contraction, hysteresis, and dead-band pressure. This paper investigates the effect that bladder thickness has on static actuation performance of small scale PAMs. Miniature PAMs were fabricated with a range of bladder thicknesses to quantify the change in common actuator performance metrics specifically: blocked force, free contraction, and dead-band pressure. These PAMs were then experimentally characterized in quasi-static conditions, where results showed that increasing bladder wall thickness decreases blocked force and free contraction, while dead-band pressure increases. A nonlinear model was then applied to determine the structure of the stress-strain relationship that enables accurate modeling and the minimum number of terms. Two nonlinear models are compared and the identified parameters are analyzed to study the effect of the bladder thickness on the model.

  1. Bladder Dysfunction and Vesicoureteral Reflux

    PubMed Central

    Sillén, Ulla

    2008-01-01

    In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR) in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB) and the dysfunctional voiding (DV), have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome), most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES) are more severe than the genuine filling phase dysfunction (OAB), with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed. PMID:19009037

  2. Improved bladder emptying in urinary retention by electrical stimulation of pudendal afferents

    NASA Astrophysics Data System (ADS)

    Peng, Chih-Wei; Chen, Jia-Jin Jason; Cheng, Chen-Li; Grill, Warren M.

    2008-06-01

    Urinary retention is the inability to empty the bladder completely, and may result from bladder hypocontractility, increases in outlet resistance or both. Chronic urinary retention can lead to several urological complications and is often refractory to pharmacologic, behavioral and surgical treatments. We sought to determine whether electrical stimulation of sensory fibers in the pudendal nerve could engage an augmenting reflex and thereby improve bladder emptying in an animal model of urinary retention. We measured the efficiency of bladder emptying with and without concomitant electrical stimulation of pudendal nerve afferents in urethane-anesthetized rats. Voiding efficiency (VE = voided volume/initial volume) was reduced from 72 ± 7% to 29 ± 7% following unilateral transection of the sensory branch of the pudendal nerve (UST) and from 70 ± 5% to 18 ± 4% following bilateral transection (BST). Unilateral electrical stimulation of the proximal transected sensory pudendal nerve during distention-evoked voiding contractions significantly improved VE. Low-intensity stimulation at frequencies of 1-50 Hz increased VE to 40-51% following UST and to 39-49% following BST, while high-intensity stimulation was ineffective at increasing VE. The increase in VE was mediated by increases in the duration of distention-evoked voiding bladder contractions, rather than increases in contraction amplitude. These results are consistent with an essential role for pudendal sensory feedback in efficient bladder emptying, and raise the possibility that electrical activation of pudendal nerve afferents may provide a new approach to restore efficient bladder emptying in persons with urinary retention.

  3. Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors

    PubMed Central

    Blaha, Igor; Recio, Paz; Martínez, María Pilar; López-Oliva, María Elvira; Ribeiro, Ana S. F.; Agis-Torres, Ángel; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Fernandes, Vítor S.; Hernández, Medardo

    2016-01-01

    Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR. PMID:27285468

  4. Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors.

    PubMed

    Blaha, Igor; Recio, Paz; Martínez, María Pilar; López-Oliva, María Elvira; Ribeiro, Ana S F; Agis-Torres, Ángel; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Fernandes, Vítor S; Hernández, Medardo

    2016-01-01

    Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.

  5. Effect of neocuproine, a copper(i) chelator, on rat bladder function.

    PubMed

    Göçmen, Cemil; Giesselman, Ben; de Groat, William C

    2005-03-01

    The effects of a specific copper(I)-chelator, neocuproine (NC), and a selective copper(II)-chelator, cuprizone, on nonadrenergic-noncholinergic transmitter mechanisms in the rat urinary bladder were studied by measuring nerve-evoked contractions of bladder strips and voiding function under urethane anesthesia. After blocking cholinergic and adrenergic transmission with atropine and guanethidine, electrical field stimulation induced bimodal contractions of bladder strips. An initial, transient contraction that was blocked by the purinergic antagonist, suramin, was significantly enhanced by NC (20 and 200 microM applied sequentially) but not affected by cuprizone. The facilitating effect, which was blocked by suramin and reversible after washout of the drug, did not occur following administration of neocuproine-copper(I) complex (NC-Cu). NC (20 microM) significantly increased the second, more sustained contraction, whereas 200 microM decreased this response. These effects of NC on the sustained contractions were not elicited by NC-Cu and not blocked by suramin. The nitric oxide synthase inhibitor, l-nitroarginine, did not alter the responses to NC. NC (20 microM) elicited a marked increase in basal tone of the strips. This effect was less prominent after the second application of 200 microMNC or with NC-Cu treatment or in the presence of suramin. In anesthetized rats, during continuous infusion cystometry, intravesical infusion of 50 microM NC but not NC-Cu or cuprizone significantly decreased the intercontraction interval (ICI) without changing contraction amplitude. The ICI returned to normal after washout of NC. Suramin blocked this effect. These results indicate that NC enhances bladder activity by facilitating purinergic excitatory responses and that copper(I)-sensitive mechanisms tonically inhibit purinergic transmission in the bladder.

  6. The overactive bladder progression to underactive bladder hypothesis.

    PubMed

    Chancellor, Michael B

    2014-09-01

    The overactive bladder (OAB) is a well-known and common urologic condition. However, the apparent opposite syndrome to the OAB, the underactive bladder (UAB), remains an enigma. Underactive bladder syndrome is complex condition that shares symptoms with other prevalent urologic diagnoses. UAB is not a pure condition-it is not the result of any single factor, but rather, it is multifactorial. As a result, UAB may overlap with OAB, bladder outlet obstruction, or even occur with no symptoms or associated diseases. To make it yet more challenging, in the elderly, detrusor hyperreflexia/impaired contractility (DHIC) is a condition that has the pathological elements of both OAB and UAB and is also common. I hypothesize that UAB and OAB may not be an entirely separate disease entity. Instead, chronic untreated or treatment refractory OAB--due to neurological diseases such as diabetes, bladder outlet obstruction or aging sarcopenia and frailty--may progress to DHIC and, finally, UAB. The progression of OAB to UAB hypothesis suggests that early education, behavioral modification and medical treatment may alter and/or prevent progression to UAB.

  7. Overactive bladder in children.

    PubMed

    Franco, Israel

    2016-09-01

    Overactive bladder (OAB) is a ubiquitous syndrome that is defined by urinary urgency with, or without urinary incontinence. OAB is observed in all parts of the world, with a prevalence of 5-12% in children (5-10 years of age) and a prevalence of 0.5% in older adolescents (16-18 years of age). Published data indicate that around a third of children with OAB are likely to become adults with similar complaints. Studies in children and in adults with OAB indicate that these individuals are more likely to also have anxiety, depression and attention deficit problems, and that appropriate treatment of these comorbidities can often improve the patient's OAB symptoms. Furthermore, data from twin studies and familial surveys seem to indicate a genetic component of OAB. Pharmacological treatments of OAB in children have improved in the past 5 years, moving beyond anticholinergic agents and including the off-label use of α-blockers, β3-agonists and intravesical botulinum toxin. Use of several different electrical stimulation techniques is also effective, both as first-line treatments, and for patients with treatment-refractory symptoms. Overall the outlook of children with OAB seems to be improving, with a greater understanding of the pathophysiology of this syndrome. Treatment modalities that target the source of the underlying problem, especially in children, are likely to provide the best patient outcomes.

  8. Overactive bladder in children.

    PubMed

    Franco, Israel

    2016-09-01

    Overactive bladder (OAB) is a ubiquitous syndrome that is defined by urinary urgency with, or without urinary incontinence. OAB is observed in all parts of the world, with a prevalence of 5-12% in children (5-10 years of age) and a prevalence of 0.5% in older adolescents (16-18 years of age). Published data indicate that around a third of children with OAB are likely to become adults with similar complaints. Studies in children and in adults with OAB indicate that these individuals are more likely to also have anxiety, depression and attention deficit problems, and that appropriate treatment of these comorbidities can often improve the patient's OAB symptoms. Furthermore, data from twin studies and familial surveys seem to indicate a genetic component of OAB. Pharmacological treatments of OAB in children have improved in the past 5 years, moving beyond anticholinergic agents and including the off-label use of α-blockers, β3-agonists and intravesical botulinum toxin. Use of several different electrical stimulation techniques is also effective, both as first-line treatments, and for patients with treatment-refractory symptoms. Overall the outlook of children with OAB seems to be improving, with a greater understanding of the pathophysiology of this syndrome. Treatment modalities that target the source of the underlying problem, especially in children, are likely to provide the best patient outcomes. PMID:27530266

  9. A healthy bladder: a consensus statement

    PubMed Central

    Lukacz, E S; Sampselle, C; Gray, M; MacDiarmid, S; Rosenberg, M; Ellsworth, P; Palmer, M H

    2011-01-01

    A panel of experts in urology, urogynecology, nursing, and behavioral therapy convened in 2010 to discuss the importance of a healthy bladder on overall health. They determined that a consensus statement was necessary to raise awareness among the general public, healthcare providers, payors, and policymakers, with the goals of minimizing the impact of poor bladder health and stimulating primary prevention of bladder conditions. In this statement, ‘healthy’ bladder function is described, as well as internal and external factors that influence bladder health. It is suggested that primary prevention strategies should be aimed at providing education regarding normal lower urinary tract structures and functioning to the public, including patients and healthcare providers. This education may promote the achievement of optimal bladder health by increasing healthy bladder habits and behaviors, awareness of risk factors, healthcare seeking, and clinician engagement and reducing stigma and other barriers to treatment. Promoting optimal bladder health may reduce the personal, societal and economic impact of bladder conditions, including anxiety and depression and costs associated with conditions or diseases and their treatment. While adopting healthy bladder habits and behaviors and behaviors may improve or maintain bladder health, it is important to recognize that certain symptoms may indicate the presence of conditions that require medical attention; many bladder conditions are treatable with a range of options for most bladder conditions. Lastly, the authors propose clinical directives based on persuasive and convergent research to improve and maintain bladder health. The authors hope that this statement will lead to promotion and achievement of optimal bladder health, which may improve overall health and help minimize the effects of bladder conditions on the public, healthcare professionals, educators, employers, and payors. The advisors are in consensus regarding the

  10. Functional and biochemical characteristics of urinary bladder muscarinic receptors in long-term alloxan diabetic rats

    PubMed Central

    Rocha, Jeová Nina

    2015-01-01

    Objective To re-examine the function of the urinary bladder in vivo as well as to determine the functional and biochemical characteristics of bladder muscarinic receptors in long-term alloxan-induced diabetes rats. Methods Two-month-old male Wistar rats were injected with alloxan and the animals showing blood glucose levels >300mg/dL together with age-paired untreated animals were kept for 11 months. Body weight, bladder weight, blood glucose, and urinary volume over a period of 24 hours were determined in both groups of animals. A voiding cystometry in conscious control and diabetic rats was performed to determine maximal micturition pressure, micturition contraction interval and duration as well as voided and post-voiding residual volume. In addition, concentration-response curves for bethanechol in isolated bladder strips, as well as [3H]-N methyl-scopolamine binding site characteristics in bladder homogenates were determined. Results Mean bladder weight was 162.5±21.2mg versus 290±37.9mg in control and treated animals, respectively (p<0.05). Micturition contraction amplitude (34.6±4.7mmHg versus 49.6±2.5mmHg), duration (14.5±1.7 seconds versus 23.33±4.6 seconds) and interval (87.5±17.02 seconds versus 281.11±20.24 seconds) were significantly greater in alloxan diabetic rats. Voided urine volume per micturition contraction was also significantly higher in diabetic animals. However the post-voiding residual volume was not statistically different. Bethanechol potency (EC50 3µM versus 5µM) and maximal effect (31.2±5.9g/g versus 36.1±6.8g/g) in isolated bladder strips as well as number (169±4fmol/mg versus 176±3fmol/mg protein) and affinity (0.69±0.1nM versus 0.57±0.1nM) of bladder muscarinic receptors were also not statistically different. Conclusion Bladder function in vivo is altered in chronic alloxan-induced diabetes rats without changes in functional and biochemical characteristics of bladder muscarinic receptors. PMID:26466064

  11. Kidney transplantation in abnormal bladder

    PubMed Central

    Mishra, Shashi K.; Muthu, V.; Rajapurkar, Mohan M.; Desai, Mahesh R.

    2007-01-01

    Structural urologic abnormalities resulting in dysfunctional lower urinary tract leading to end stage renal disease may constitute 15% patients in the adult population and up to 20-30% in the pediatric population. A patient with an abnormal bladder, who is approaching end stage renal disease, needs careful evaluation of the lower urinary tract to plan the most satisfactory technical approach to the transplant procedure. Past experience of different authors can give an insight into the management and outcome of these patients. This review revisits the current literature available on transplantation in abnormal bladder and summarizes the clinical approach towards handling this group of difficult transplant patients. We add on our experience as we discuss the various issues. The outcome of renal transplant in abnormal bladder is not adversely affected when done in a reconstructed bladder. Correct preoperative evaluation, certain technical modification during transplant and postoperative care is mandatory to avoid complications. Knowledge of the abnormal bladder should allow successful transplantation with good outcome. PMID:19718334

  12. Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder.

    PubMed

    Tempest, Heidi; Stoneham, Mark; Frampton, Claire; Noble, Jeremy

    2011-01-01

    The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy. PMID:22696635

  13. [Occupational hazards and bladder cancer].

    PubMed

    Nizamova, R S

    1991-01-01

    Occupational exposure to health hazards was studied in 258 industrial workers who had developed cancer of the bladder against 454 matched controls. All the test subjects and controls were residents of the Tambov Province centers of chemical industry. Statistical significance (relative risk-4.7) was established for exposure to aromatic amines. For those contacting with aniline dyes the relative risk (RR) made up 2.4. The risk to develop bladder cancer in powder shops (RR-3.2) was attributed to the hazards of dyes and diphenylamine. In leather-shoe and textile industry the exposure to dyes was not safe (RR-6.1), neither was it to chemicals, oil products, pesticides, overheating (RR-3.2, 1.6, 3.2 and 2.9, respectively). It is stated that in line with a significant risk to develop bladder cancer at exposure to aromatic amines there exist a number of occupational factors contributing to this risk.

  14. Implantable Bladder Sensors: A Methodological Review.

    PubMed

    Dakurah, Mathias Naangmenkpeong; Koo, Chiwan; Choi, Wonseok; Joung, Yeun-Ho

    2015-09-01

    The loss of urinary bladder control/sensation, also known as urinary incontinence (UI), is a common clinical problem in autistic children, diabetics, and the elderly. UI not only causes discomfort for patients but may also lead to kidney failure, infections, and even death. The increase of bladder urine volume/pressure above normal ranges without sensation of UI patients necessitates the need for bladder sensors. Currently, a catheter-based sensor is introduced directly through the urethra into the bladder to measure pressure variations. Unfortunately, this method is inaccurate because measurement is affected by disturbances in catheter lines as well as delays in response time owing to the inertia of urine inside the bladder. Moreover, this technique can cause infection during prolonged use; hence, it is only suitable for short-term measurement. Development of discrete wireless implantable sensors to measure bladder volume/pressure would allow for long-term monitoring within the bladder, while maintaining the patient's quality of life. With the recent advances in microfabrication, the size of implantable bladder sensors has been significantly reduced. However, microfabricated sensors face hostility from the bladder environment and require surgical intervention for implantation inside the bladder. Here, we explore the various types of implantable bladder sensors and current efforts to solve issues like hermeticity, biocompatibility, drift, telemetry, power, and compatibility issues with popular imaging tools such as computed tomography and magnetic resonance imaging. We also discuss some possible improvements/emerging trends in the design of an implantable bladder sensor.

  15. Implantable Bladder Sensors: A Methodological Review

    PubMed Central

    Dakurah, Mathias Naangmenkpeong; Koo, Chiwan; Choi, Wonseok; Joung, Yeun-Ho

    2015-01-01

    The loss of urinary bladder control/sensation, also known as urinary incontinence (UI), is a common clinical problem in autistic children, diabetics, and the elderly. UI not only causes discomfort for patients but may also lead to kidney failure, infections, and even death. The increase of bladder urine volume/pressure above normal ranges without sensation of UI patients necessitates the need for bladder sensors. Currently, a catheter-based sensor is introduced directly through the urethra into the bladder to measure pressure variations. Unfortunately, this method is inaccurate because measurement is affected by disturbances in catheter lines as well as delays in response time owing to the inertia of urine inside the bladder. Moreover, this technique can cause infection during prolonged use; hence, it is only suitable for short-term measurement. Development of discrete wireless implantable sensors to measure bladder volume/pressure would allow for long-term monitoring within the bladder, while maintaining the patient’s quality of life. With the recent advances in microfabrication, the size of implantable bladder sensors has been significantly reduced. However, microfabricated sensors face hostility from the bladder environment and require surgical intervention for implantation inside the bladder. Here, we explore the various types of implantable bladder sensors and current efforts to solve issues like hermeticity, biocompatibility, drift, telemetry, power, and compatibility issues with popular imaging tools such as computed tomography and magnetic resonance imaging. We also discuss some possible improvements/emerging trends in the design of an implantable bladder sensor. PMID:26620894

  16. Implantable Bladder Sensors: A Methodological Review.

    PubMed

    Dakurah, Mathias Naangmenkpeong; Koo, Chiwan; Choi, Wonseok; Joung, Yeun-Ho

    2015-09-01

    The loss of urinary bladder control/sensation, also known as urinary incontinence (UI), is a common clinical problem in autistic children, diabetics, and the elderly. UI not only causes discomfort for patients but may also lead to kidney failure, infections, and even death. The increase of bladder urine volume/pressure above normal ranges without sensation of UI patients necessitates the need for bladder sensors. Currently, a catheter-based sensor is introduced directly through the urethra into the bladder to measure pressure variations. Unfortunately, this method is inaccurate because measurement is affected by disturbances in catheter lines as well as delays in response time owing to the inertia of urine inside the bladder. Moreover, this technique can cause infection during prolonged use; hence, it is only suitable for short-term measurement. Development of discrete wireless implantable sensors to measure bladder volume/pressure would allow for long-term monitoring within the bladder, while maintaining the patient's quality of life. With the recent advances in microfabrication, the size of implantable bladder sensors has been significantly reduced. However, microfabricated sensors face hostility from the bladder environment and require surgical intervention for implantation inside the bladder. Here, we explore the various types of implantable bladder sensors and current efforts to solve issues like hermeticity, biocompatibility, drift, telemetry, power, and compatibility issues with popular imaging tools such as computed tomography and magnetic resonance imaging. We also discuss some possible improvements/emerging trends in the design of an implantable bladder sensor. PMID:26620894

  17. [Rare cases of bladder stones].

    PubMed

    Sampalmieri, Gregorio; Moretti, Antonello; Sampalmieri, Matteo

    2014-01-01

    We present here two special cases of urolithiasis. The first one shows a giant bladder lithiasis resulting in severe renal insufficiency in a 63-year-old patient, who had previously had nicturia (2-3 times), occasional episodes of urinary frequency and burning micturition, in the absence of renal colic, hematuria or interrupted urination. The second case referes to an 85-year-old man suffering from prostatic enlargement and bladder stones, hospitalized to undergo intervention of trans-vesical prostatic adenomectomy, during which two star-shaped stones were found without obvious symptoms.

  18. Urinary markers for bladder cancer

    PubMed Central

    Smith, Zachary L.

    2013-01-01

    Bladder cancer has the fifth highest incidence of all malignancies in the United States, with a propensity to recur, requiring lifelong surveillance after diagnosis. Urinary markers of disease have been of extreme interest in this field in an effort to simplify surveillance schedules and improve early detection of tumors. Many markers have been described, but most remain investigational. However, some markers have undergone clinical trials and are approved for clinical use. In this review, urinary markers and their application for screening and surveillance of bladder cancer are discussed. PMID:23864929

  19. Do antibiotics clear bladder infections?

    PubMed

    Reid, G

    1994-09-01

    An examination of transitional bladder epithelial cells from 69 urine specimens from 23 spinal cord injury patients showed the presence of adherent bacterial biofilms in 66 cases (96%). All patients were receiving antimicrobial therapy, primarily trimethoprim-sulfamethoxazole (41 of 69), without any apparent effect on the bladder colonization. The large number of bacteria that emerged with highly virulent and potentially multi-drug resistant characteristics, especially Enterococcus faecalis (33% of isolates), was of concern. These findings raise questions about the proved efficacy and effectiveness of antibiotics against uropathogenic biofilms adherent to tissues.

  20. Dose Distribution in Bladder and Surrounding Normal Tissues in Relation to Bladder Volume in Conformal Radiotherapy for Bladder Cancer

    SciTech Connect

    Majewski, Wojciech; Wesolowska, Iwona; Urbanczyk, Hubert; Hawrylewicz, Leszek; Schwierczok, Barbara; Miszczyk, Leszek

    2009-12-01

    Purpose: To estimate bladder movements and changes in dose distribution in the bladder and surrounding tissues associated with changes in bladder filling and to estimate the internal treatment margins. Methods and Materials: A total of 16 patients with bladder cancer underwent planning computed tomography scans with 80- and 150-mL bladder volumes. The bladder displacements associated with the change in volume were measured. Each patient had treatment plans constructed for a 'partially empty' (80 mL) and a 'partially full' (150 mL) bladder. An additional plan was constructed for tumor irradiation alone. A subsequent 9 patients underwent sequential weekly computed tomography scanning during radiotherapy to verify the bladder movements and estimate the internal margins. Results: Bladder movements were mainly observed cranially, and the estimated internal margins were nonuniform and largest (>2 cm) anteriorly and cranially. The dose distribution in the bladder worsened if the bladder increased in volume: 70% of patients (11 of 16) would have had bladder underdosed to <95% of the prescribed dose. The dose distribution in the rectum and intestines was better with a 'partially empty' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm{sup 3} for the intestines, respectively) than with a 'partially full' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 28%, 24%, and 18% for the rectum and 180, 158, 136 cm{sup 3} for the intestines, respectively). The change in bladder filling during RT was significant for the dose distribution in the intestines. Tumor irradiation alone was significantly better than whole bladder irradiation in terms of organ sparing. Conclusion: The displacements of the bladder due to volume changes were mainly related to the upper wall. The internal margins should be nonuniform, with the largest margins cranially and anteriorly. The changes in bladder

  1. Intraspinal stimulation for bladder voiding in cats before and after chronic spinal cord injury

    NASA Astrophysics Data System (ADS)

    Pikov, Victor; Bullara, Leo; McCreery, Douglas B.

    2007-12-01

    The long-term objective of this study is to develop neural prostheses for people with spinal cord injuries who are unable to voluntarily control their bladder. This feasibility study was performed in 22 adult cats. We implanted an array of microelectrodes into locations in the sacral spinal cord that are involved in the control of micturition reflexes. The effect of microelectrode stimulation was studied under light Propofol anesthesia at monthly intervals for up to 14 months. We found that electrical stimulation in the sacral parasympathetic nucleus at S2 level or in adjacent ventrolateral white matter produced bladder contractions insufficient for inducing voiding, while stimulation at or immediately dorsal to the dorsal gray commissure at S1 level produced strong (at least 20 mmHg) bladder contractions as well as strong (at least 40 mm Hg) external urethral sphincter relaxation, resulting in bladder voiding in 14 animals. In a subset of three animals, spinal cord transection was performed. For several months after the transection, intraspinal stimulation continued to be similarly or even more effective in inducing the bladder voiding as before the transection. We speculate that in the absence of the supraspinal connections, the plasticity in the local spinal circuitry played a role in the improved responsiveness to intraspinal stimulation.

  2. Architect's Contract.

    ERIC Educational Resources Information Center

    Ohio State Board of Education, Columbus.

    An actual contract form used for architectural services is presented. Fees, duties, and services are included. Services are listed in the following phases--(1) schematic design, (2) design development, (3) contract document, and (4) construction. Extra services are listed, and owner's responsibility with regard to cost estimates is given.…

  3. Performance Contracting.

    ERIC Educational Resources Information Center

    Allen, Tom

    The management team at Minooka (Illinois) School District 201 is actively pursuing school improvement measures by establishing Performance Contracts to increase productivity. The format of the Performance Contract highlights yearly short-term and long-term goals, which are presented in the form of Job Improvement Targets stating the goal itself, a…

  4. Student Contracts.

    ERIC Educational Resources Information Center

    Aldridge, Hal

    1971-01-01

    Discussion of the nature of student-teacher contracts pertaining to academic work to be performed by the student and evaluated by the teacher covers a wide range of related issues in this article. The nature of contracts, evaluation procedures, instructional materials, community attitudes, and the individualization of instruction are commented on…

  5. Modulation of bladder function by luminal adenosine turnover and A1 receptor activation

    PubMed Central

    Prakasam, H. Sandeep; Herrington, Heather; Roppolo, James R.; Jackson, Edwin K.

    2012-01-01

    The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed that the concentration of extracellular adenosine at the mucosal surface of the uroepithelium was regulated by ecto-adenosine deaminase and by equilibrative nucleoside transporters, whereas adenosine kinase and equilibrative nucleoside transporters modulated serosal levels. We further observed that enriching endogenous adenosine by blocking its routes of metabolism or direct activation of mucosal A1 receptors with 2-chloro-N6-cyclopentyladenosine (CCPA), a selective agonist, stimulated bladder activity by lowering the threshold pressure for voiding. Finally, CCPA did not quell bladder hyperactivity in animals with acute cyclophosphamide-induced cystitis but instead exacerbated their irritated bladder phenotype. In conclusion, we find that adenosine levels at both surfaces of the uroepithelium are modulated by turnover, that blocking these pathways or stimulating A1 receptors directly at the luminal surface promotes bladder contractions, and that adenosine further stimulates voiding in animals with cyclophosphamide-induced cystitis. PMID:22552934

  6. Glutathione S-transferase P1 ILE105Val polymorphism in occupationally exposed bladder cancer cases.

    PubMed

    Kopps, Silke; Angeli-Greaves, Miriam; Blaszkewicz, Meinolf; Prager, Hans-Martin; Roemer, Hermann C; Lohlein, Dietrich; Weistenhofer, Wobbeke; Bolt, Hermann M; Golka, Klaus

    2008-01-01

    The genotype glutathione S-transferase P1 (GSTP1) influences the risk for bladder cancer among Chinese workers occupationally exposed to benzidine. Studies of Caucasian bladder cancer cases without known occupational exposures showed conflicting results. Research was thus conducted to define the role of GSTP1 genotypes in Caucasian bladder cancer cases with an occupational history of exposure to aromatic amines. DNA from 143 cases reported to the Industrial Professional Associations (Berufsgenossenschaften) in Germany from 1996 to 2004, who had contracted urothelial cancer due to occupational exposure, and 196 patients from one Department of Surgery in Dortmund, without known malignancy in their medical history, were genotyped using real-time polymerase chain reaction (PCR) (LightCycler) in relation to GSTP1 A1578G (Ile105Val) polymorphism. Among the subjects with bladder cancer, 46% presented the AA genotype, 39% the AG genotype, and 15% the GG genotype. In the surgical (noncancer) control group analyzed, 42% presented the AA genotype, 42% the AG genotype, and 16% the GG genotype. A subgroup of bladder cancer cases, represented by 46 painters, showed a distribution of 41% of the AA genotype, 48% of the AG genotype, and 11% of the GG genotype. Data indicated that in Caucasians exposed to aromatic amines the GSTP1 A1578G polymorphism did not appear to play a significant role as a predisposing factor for bladder cancer incidence.

  7. Viscoelastic properties of the normal human bladder.

    PubMed

    Andersson, S; Kronström, A; Bjerle, P

    1989-01-01

    Continuous and stepwise cystometry were performed through suprapubic catheters in 12 healthy young subjects in order to assess passive viscoelastic variables of the normal human bladder during the collection phase. Elastic contants increased non-linearly with bladder distension. Relative elastic modulus and relaxation time of the bladder wall increased or tended to increase with bladder distension and infusion rate. There was considerable interindividual variation in all variables suggesting that discrimination between normal and abnormal bladder wall viscoelasticity may be difficult in routine clinical practice.

  8. Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats.

    PubMed

    Reese, Jeremy N; Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-04-15

    This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity ∼80% of saline control capacity. PNS significantly (P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly (P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly (P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex.

  9. Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats.

    PubMed

    Reese, Jeremy N; Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-04-15

    This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity ∼80% of saline control capacity. PNS significantly (P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly (P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly (P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex. PMID:25673810

  10. Overactive bladder - 18 years - Part II.

    PubMed

    Truzzi, Jose Carlos; Gomes, Cristiano Mendes; Bezerra, Carlos A; Plata, Ivan Mauricio; Campos, Jose; Garrido, Gustavo Luis; Almeida, Fernando G; Averbeck, Marcio Augusto; Fornari, Alexandre; Salazar, Anibal; Dell'Oro, Arturo; Cintra, Caio; Sacomani, Carlos Alberto Ricetto; Tapia, Juan Pablo; Brambila, Eduardo; Longo, Emilio Miguel; Rocha, Flavio Trigo; Coutinho, Francisco; Favre, Gabriel; Garcia, Jose Antonio; Castano, Juan; Reyes, Miguel; Leyton, Rodrigo Eugenio; Ferreira, Ruiter Silva; Duran, Sergio; Lopez, Vanda; Reges, Ricardo

    2016-01-01

    Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics - pillars of the overactive bladder pharmacotherapy - started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning - as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder - 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder. PMID:27176185

  11. Cancer of the Urinary Bladder

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 76,960 % of All New Cancer Cases 4.6% Estimated Deaths in 2016 16,390 % of All Cancer ... of This Cancer : In 2013, there were an estimated 587,426 people living with bladder cancer in ...

  12. Urothelial Bladder Cancer Urinary Biomarkers

    PubMed Central

    Noon, Aidan P

    2014-01-01

    Abstract Urothelial bladder cancer is the fourth most prevalent male malignancy in the United States and also one of the ten most lethal. Superficial or non-muscle-invasive bladder cancer has a high rate of recurrence and can progress to muscle invasive disease. Conventional surveillance requires regular cystoscopy and is used often with urinary cytology. Unfortunately, the cystoscopy procedure is invasive for patients and costly for health care providers. Urinary biomarkers have the potential to improve bladder cancer diagnosis, the efficiency and also the cost-effectiveness of follow up. It may also be possible for urinary biomarkers to help prognosticate particularly for patients with high-grade bladder cancer who may want enhanced assessment of their risk of disease progression. In this review the important historical urinary biomarkers and the newly emerging biomarkers are discussed. As will be presented, although many of the tests have good performance characteristics, unfortunately no single test can fulfill all the roles currently provided by cystoscopy and cytology. It is likely that in the future, urinary biomarker testing will be used selectively in a personalized manner to try and improve prognostication or reduce the necessity for invasive cystoscopy in patients understanding the limits of the test.

  13. [Specific types of bladder cancer].

    PubMed

    Bertz, S; Hartmann, A; Knüchel-Clarke, R; Gaisa, N T

    2016-02-01

    Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review. PMID:26782034

  14. Bladder Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Stem Cells in Functional Bladder Engineering

    PubMed Central

    Smolar, Jakub; Salemi, Souzan; Horst, Maya; Sulser, Tullio; Eberli, Daniel

    2016-01-01

    Conditions impairing bladder function in children and adults, such as myelomeningocele, posterior urethral valves, bladder exstrophy or spinal cord injury, often need urinary diversion or augmentation cystoplasty as when untreated they may cause severe bladder dysfunction and kidney failure. Currently, the gold standard therapy of end-stage bladder disease refractory to conservative management is enterocystoplasty, a surgical enlargement of the bladder with intestinal tissue. Despite providing functional improvement, enterocystoplasty is associated with significant long-term complications, such as recurrent urinary tract infections, metabolic abnormalities, stone formation, and malignancies. Therefore, there is a strong clinical need for alternative therapies for these reconstructive procedures, of which stem cell-based tissue engineering (TE) is considered to be the most promising future strategy. This review is focused on the recent progress in bladder stem cell research and therapy and the challenges that remain for the development of a functional bladder wall. PMID:27781020

  16. Original Research: Combined model of bladder detrusor smooth muscle and interstitial cells.

    PubMed

    Rosenberg, Josef; Byrtus, Miroslav; Stengl, Milan

    2016-10-01

    Although patients with lower urinary tract symptoms constitute a large and still growing population, understanding of bladder detrusor muscle physiology remains limited. Understanding the interactions between the detrusor smooth muscle cells and other bladder cell types (e.g. interstitial cells, IC) that may significantly contribute to coordinating and modulating detrusor contractions represents a considerable challenge. Computer modeling could help to elucidate some properties that are difficult to address experimentally; therefore, we developed in silico models of detrusor smooth muscle cell and interstitial cells, coupled through gap junctions. The models include all of the major ion conductances and transporters described in smooth muscle cell and interstitial cells in the literature. The model of normal detrusor muscle (smooth muscle cell and interstitial cells coupled through gap junctions) completely reproduced the experimental results obtained with detrusor strips in the presence of several pharmacological interventions (ryanodine, caffeine, nimodipine), whereas the model of smooth muscle cell alone (without interstitial cells) failed to reproduce the experimental results. Next, a model of overactive bladder, a highly prevalent clinical condition in both men and women with increasing incidence at older ages, was produced by modifying several processes as reported previously: a reduction of Ca(2+)-release through ryanodine receptors and a reduction of Ca(2+)-dependent K(+)-conductance with augmented gap junctional coupling. This model was also able to reproduce the pharmacological modulation of overactive bladder. In conclusion, a model of bladder detrusor muscle was developed that reproduced experimental results obtained in both normal and overactive bladder preparations. The results indicate that the non-smooth muscle cells of the detrusor (interstitial cells) contribute significantly to the contractile behavior of bladder detrusor muscle and should not be

  17. Effect of detrusor overactivity on the expression of aquaporins and nitric oxide synthase in rat urinary bladder following bladder outlet obstruction

    PubMed Central

    Kim, Sun-Ouck; Choi, Dongjune; Song, Seung Hee; Ahn, Kyu Youn; Kwon, Dongdeuk; Park, Kwangsung; Ryu, Soo Bang

    2013-01-01

    Background: Aquaporins (AQPs) have recently been reported to be expressed in rat and human urothelium. Nitric oxide (NO) is thought to play a role in the bladder overactivity related to bladder outlet obstruction (BOO). The purpose of this study is to investigate the effect of BOO on the expression of AQP2-3 and nitric oxide synthase (NOS) isoforms in rat urothelium. Methods: Female Sprague-Dawley rats (230–240 g, n = 60) were divided into 2 groups. The control group (n = 30) and the partial bladder outlet obstruction (BOO) group (n = 30). After 4 weeks, we performed a urodynamic study to measure the contraction interval and contraction pressure. The expression and cellular localization of AQP2-3, endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) were determined by Western blot and immunohistochemistry. Results: On the cystometrogram, the estimated contraction interval time (minutes, mean ± SE) was significantly lower in the BOO group (3.0 ± 0.9) than in the control group (6.3 ± 0.4; p < 0.05). AQP2 was localized in the cytoplasm of the epithelium, whereas AQP3 was found only in the cell membrane of the epithelium. The protein expression of AQP2-3, eNOS and nNOS was significantly increased in the BOO group. Conclusion: Detrusor overactivity induced by BOO causes a significant increase in the expression of AQP2-3, eNOS, and nNOS in rat urinary bladder. This may imply that the AQPs and NOS isoforms have a functional role in the bladder dysfunction that occurs in association with BOO. PMID:23766828

  18. Assessment of bladder wall thickness in women with overactive bladder

    PubMed Central

    Üçer, Oktay; Gümüş, Bilal; Albaz, Ali Can; Pekindil, Gökhan

    2016-01-01

    Objective To compare bladder wall thickness (BWT) between female patients with overactive bladder (OAB) and aged-matched healthy controls. Material and methods Thirty-six female patients with OAB and 31 healthy women were enrolled in the present prospective observational study. Qmax and Qave were measured by using uroflowmetry in all of the women in the patient and control groups, and also maximum bladder capacity (MBC), post- void residual urine (PVRU), prevoiding and postvoiding BWT were measured by using transabdominal ultrasound. Lower urinary tract symptoms of the participants were assessed by using Overactive Bladder Version-8 (OAB-V8) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). All of the data were statistically compared between the patient and control groups. In the patient group, the relationships between parameters were evaluated correlation analysis. Results The mean age of the patients and controls were similar (respectively, 45.58±12.35 and 44.21±11.60 years (p=0.68). The mean pre- and post-voiding BWT, OAB-V8 and ICIQ-SF scores of the patients were significantly higher than the controls. In the patient group, the moderate positive correlations between BWT with Qmax (p=0.02) and Qave (p=0.02) were found. Conclusion This study showed that the BWTs of the female patients with OAB are higher than those of healthy women. Further studies should investigate the changes in BWT of patients with OAB after treatment of OAB. PMID:27274895

  19. Metabolic phenotype of bladder cancer.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme

  20. Metabolic phenotype of bladder cancer.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme

  1. Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity

    PubMed Central

    Anderson, U A; Carson, C; Johnston, L; Joshi, S; Gurney, A M; McCloskey, K D

    2013-01-01

    Background and Purpose The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility. Experimental Approach KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors. Key Results KCNQ subtypes 1–5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity. Conclusions and Implications These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder. PMID:23586426

  2. AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis

    PubMed Central

    Zhang, Xiling; Yao, Jian; Gao, Kun; Chi, Yuan; Mitsui, Takahiko; Ihara, Tatsuya; Sawada, Norifumi; Kamiyama, Manabu; Fan, Jianglin; Takeda, Masayuki

    2016-01-01

    Bladder voiding dysfunction is closely related to local oxidation, inflammation, and enhanced channel activities. Given that the AMP-activated protein kinase (AMPK) has anti-oxidative, anti-inflammatory and channel-inhibiting properties, we examined whether and how AMPK affected bladder activity. AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation. Downregulation of CREB with siRNA increased Cx43 expression. A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity. AMPK also counteracted the IL-1β- and TNFα-induced increase in Cx43 in BSMCs. In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction. Further analysis comparing the responses of the wild-type (Cx43+/+) and heterozygous (Cx43+/−) Cx43 mice to cyclophosphamide revealed that the Cx43+/− mice retained a relatively normal micturition pattern compared to the Cx43+/+ mice. Taken together, our results indicate that AMPK inhibits Cx43 in BSMCs and improves bladder activity under pathological conditions. We propose that strategies that target AMPK can be developed as novel therapeutic approaches for treating bladder dysfunction. PMID:26806558

  3. TRANSPORT OF SALT AND WATER IN RABBIT AND GUINEA PIG GALL BLADDER.

    PubMed

    DIAMOND, J M

    1964-09-01

    A simple and reproducible method has been developed for following fluid transport by an in vitro preparation of mammalian gall bladder, based upon weighing the organ at 5 minute intervals. Both guinea pig and rabbit gall bladders transport NaCl and water in isotonic proportions from lumen to serosa. In the rabbit bicarbonate stimulates transport, but there is no need for exogenous glucose. The transport rate is not affected by removal of potassium from the bathing solutions. Albumin causes a transient weight loss from the gall bladder wall, apparently by making the serosal smooth muscle fibers contract. Active NaCl transport can carry water against osmotic gradients of up to two atmospheres. Under passive conditions water may also move against its activity gradient in the presence of a permeating solute. The significance of water movement against osmotic gradients during active solute transport is discussed. PMID:14212148

  4. Emulating a Fish Swim Bladder

    NASA Astrophysics Data System (ADS)

    Vesenka, James; Meredith, Dawn; Bolker, Jessica; Schubert, Christopher; Kraut, Gertrud

    2009-10-01

    The University of New Hampshire and the University of New England are developing biologically relevant physics laboratories for their predominantly health science audiences. Buoyancy plays an important role in a variety of biological processes. We describe an inexpensive laboratory activity based on the Cartesian Diver that allows students to quantitatively emulate the swim bladder of a fish. Inflation of the ``bladder'' is externally controlled through an external gas syringe or squeezing on the plastic water containment vessel (a 2L soda bottle). The students can accurately determine the volume of a ``fish'' at the point of neutral buoyancy by visual measurement of the trapped air pocket. A simple electronic gas pressure sensor allows the hydrostatic pressure on the fish to be analyzed simultaneously.

  5. Research Findings on Overactive Bladder

    PubMed Central

    Patra, Phani B.; Patra, Sayani

    2015-01-01

    Several physiopathologic conditions lead to the manifestation of overactive bladder (OAB). These conditions include ageing, diabetes mellitus, bladder outlet obstruction, spinal cord injury, stroke and brain injury, Parkinson's disease, multiple sclerosis, interstitial cystitis, stress and depression. This review has discussed research findings in human and animal studies conducted on the above conditions. Several structural and functional changes under these conditions have not only been observed in the lower urinary tract, but also in the brain and spinal cord. Significant changes were observed in the following areas: neurotransmitters, prostaglandins, nerve growth factor, Rho-kinase, interstitial cells of Cajal, and ion and transient receptor potential channels. Interestingly, alterations in these areas showed great variation in each of the conditions of the OAB, suggesting that the pathophysiology of the OAB might be different in each condition of the disease. It is anticipated that this review will be helpful for further research on new and specific drug development against OAB. PMID:26195957

  6. [Oral anticholinergics in overactive bladder].

    PubMed

    Madersbacher, H

    2006-07-01

    Behavioural therapy and anticholinergics are the mainstays in the treatment of symptoms of overactive bladder in patients with idiopathic and neurogenic detrusor overactivity; they are the first-line treatment. Oxybutynin, propiverine, tolterodine and trospium chloride as well as the "newcomers" solifenacin and darifenacin are comparable in regards to their efficacy. However, based on different pharmacokinetics and pharmacodynamics with different resorption velocity, different metabolisation and different CNS penetration, the profile of adverse events is different, qualitatively and quantitatively. Substances that are resorbed slowly or available as slow-release formulations are tolerated better. Lipophilic anticholinergics which pass the blood-brain barrier may compromise cognitive functions, especially in geriatric patients, who are already on cholinesterase inhibitors due to memory disorders. The following article gives an overview of the anticholinergics currently prescribed in patients with symptoms of overactive bladder with special attention to the influence of pharmacokinetics/pharmacodynamics on the adverse events profile including possible CNS side effects.

  7. [Neurogenic bladder, 20 years later].

    PubMed

    Perrigot, M

    1995-10-28

    The therapeutic armamentarium--physical therapy, drugs, surgery--developed over the last 20 years now gives us the means of providing curative care to nearly all patients with manifestations of neuropathic bladder, meaning that the clinical examination and complementary tests must be conducted under strictly controlled conditions to identify the underlying mechanism. The examination of the perineum almost always reveals a defect when the origin is neurological but is often normal when gynaecologic or urologic factors are involved. Motor command, tonus, reflexes and sensitivity should all be carefully explored to distinguish between central and peripheral causes. Much progress has been made in complementary examinations. For example, nearly 100% of the neurological aetiologies can be identified with precision. Tests include electromyography of the perineum, measurement of the latency of the bulbocavernous reflex and that of the distal part of the internal pudental nerve. Complementary tests evaluating bladder and sphincter function include urine sediment with cytology, intravenous pyelography and echography of the urinary tract. Pressure measurements with cystomanometry, sphincterometry and flowmetry add further precisions. Whether the underlying mechanism of bladder dysfunction is purely neurological as is the case in many young patients with multiple sclerosis, spina bifida or caudia equina syndrome, results from several causes as in patients with Parkinson's disease and enlargement of the prostate, or is among the increasing number of post-radiation sequellae, the essential step is careful clinical examination and detailed interpretation of complementary examinations. Thus the wide range of techniques now available for the management of the neuropathic bladder can be adapted to each individual case according to the pathological processes causing the clinical manifestations. PMID:8545359

  8. Variation in swim bladder drumming sounds from three doradid catfish species with similar sonic morphologies.

    PubMed

    Boyle, Kelly S; Riepe, Ségolène; Bolen, Géraldine; Parmentier, Eric

    2015-09-01

    A variety of teleost fishes produce sounds for communication by vibrating the swim bladder with fast contracting muscles. Doradid catfishes have an elastic spring apparatus (ESA) for sound production. Contractions of the ESA protractor muscle pull the anterior transverse process of the 4th vertebra or Müllerian ramus (MR) to expand the swim bladder and elasticity of the MR returns the swim bladder to the resting state. In this study, we examined the sound characteristics and associated fine structure of the protractor drumming muscles of three doradid species: Acanthodoras cataphractus, Platydoras hancockii and Agamyxis pectinifrons. Despite large variations in size, sounds from all three species had similar mean dominant rates ranging from 91 to 131 Hz and showed frequencies related to muscle contraction speed rather than fish size. Sounds differed among species in terms of waveform shape and their rate of amplitude modulation. In addition, multiple distinguishable sound types were observed from each species: three sound types from A. cataphractus and P. hancockii, and two sound types from A. pectinifrons. Although sounds differed among species, no differences in muscle fiber fine structure were observed at the species level. Drumming muscles from each species bear features associated with fast contractions, including sarcoplasmic cores, thin radial myofibrils, abundant mitochondria and an elaborated sarcoplasmic reticulum. These results indicate that sound differences between doradids are not due to swimbladder size, muscle anatomy, muscle length or Müllerian ramus shape, but instead result from differences in neural activation of sonic muscles. PMID:26206358

  9. Role of angiogenesis in urothelial bladder carcinoma

    PubMed Central

    Górnicka, Barbara

    2016-01-01

    Introduction Bladder cancer is the most common urinary tract malignancy in western countries. In recent years, extensive research has suggested that angiogenesis plays an important role in bladder cancer biology, contributing to tumor growth and progression. Material and methods In this review, we discuss general mechanisms of angiogenesis and highlight the influence of pro- and anti-angiogenic factors, and cancer stem cells on bladder cancer biology, their relation to disease progression, and potential use in novel targeted therapies. Results Expression of a number of proangiogenic factors, including HIF-1, VEGF, bFGF, IL-8 and MMPs, as well as anti-angiogenic factor TSP-1, was found to be altered in bladder tumors. Involvement of cancer stem cells in bladder cancer development was also proposed. Conclusions High expression of most pro-angiogenic factors correlated with disease progression and shorter patient survival, but discrepancies between studies urge us to continue evaluating the significance of angiogenesis in bladder cancer. PMID:27729991

  10. UTIs in patients with neurogenic bladder.

    PubMed

    Jahromi, Mona S; Mure, Amanda; Gomez, Christopher S

    2014-09-01

    Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy. PMID:25113150

  11. [Overactive bladder syndrome in children].

    PubMed

    Persson de Geeter, C

    2004-07-01

    According to recent terminology, the symptom complex of frequency and urgency with or without urge incontinence in childhood is called overactive bladder. The main etiologic factor seems to be a delayed maturation of complex neuroanatomic structures responsible for normal bladder control. Afflicted children show a typical pattern of reflex voiding with different degrees of severity. In many cases nocturnal incontinence is the main complaint and this may lead to the wrong diagnosis of nocturnal enuresis with resulting false treatment. The diagnostic work-up consists of standardized evaluation of children with enuresis and voiding dysfunction and should concentrate on the exclusion of any possible underlying neurological disorder. Treatment focuses primarily on behavioral modification and cognitive education with regard to bladder sensation and voluntary micturition. Muscarinic receptor antagonists are very useful as supportive medical treatment with a rather low rate of adverse effects. Children who fail to respond to treatment or children suffering from side effects can profit from alternative treatment modalities including biofeedback programs, pelvic floor stimulation, or acupuncture.

  12. Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2

    PubMed Central

    Guan, Na N; Svennersten, Karl; de Verdier, Petra J; Wiklund, N Peter; Gustafsson, Lars E

    2015-01-01

    Background and Purpose We have described a urothelium-dependent release of PGD2-like activity which had inhibitory effects on the motility of guinea pig urinary bladder. Here, we have pharmacologically characterized the receptors involved and localized the sites of PGD2 formation and of its receptors. Experimental Approach In the presence of selective DP and TP receptor antagonists alone or combined, PGD2 was applied to urothelium-denuded diclofenac-treated urinary bladder strips mounted in organ baths. Antibodies against PGD2 synthase and DP1 receptors were used with Western blots and for histochemistry. Key Results PGD2 inhibited nerve stimulation -induced contractions in strips of guinea pig urinary bladder with estimated pIC50 of 7.55 ± 0.15 (n = 13), an effect blocked by the DP1 receptor antagonist BW-A868C. After blockade of DP1 receptors, PGD2 enhanced the contractions, an effect abolished by the TP receptor antagonist SQ-29548. Histochemistry revealed strong immunoreactivity for PGD synthase in the urothelium/suburothelium with strongest reaction in the suburothelium. Immunoreactive DP1 receptors were found in the smooth muscle of the bladder wall with a dominant localization to smooth muscle membranes. Conclusions and Implications In guinea pig urinary bladder, the main effect of PGD2 is an inhibitory action via DP1 receptors localized to the smooth muscle, but an excitatory effect via TP receptors can also be evoked. The urothelium with its suburothelium might signal to the smooth muscle which is rich in PGD2 receptors of the DP1 type. The results are important for our understanding of regulation of bladder motility. PMID:25917171

  13. Ultrasound and Biomarker Tests in Predicting Cancer Aggressiveness in Tissue Samples of Patients With Bladder Cancer

    ClinicalTrials.gov

    2016-06-09

    Bladder Papillary Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma

  14. Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs.

    PubMed

    Palea, Stefano; Guilloteau, Véronique; Rekik, Moéz; Lovati, Emanuela; Guerard, Marc; Guardia, Maria-Alba; Lluel, Philippe; Pietra, Claudio; Yoshiyama, Mitsuharu

    2016-01-01

    Introduction. Tachykinins potently contract the isolated urinary bladder from a number of animal species and play an important role in the regulation of the micturition reflex. On the guinea-pig isolated urinary bladder we examined the effects of a new potent and selective NK1 receptor antagonist (netupitant) on the contractions induced by a selective NK1 receptor agonist, SP-methylester (SP-OMe). Moreover, the effects of netupitant and another selective NK1 antagonist (L-733,060) were studied in anesthetized guinea-pigs using two experimental models, the isovolumetric bladder contractions and a model of bladder overactivity induced by intravesical administration of acetic acid (AA). Methods and Results. Detrusor muscle strips were mounted in 5 mL organ baths and isometric contractions to cumulative concentrations of SP-OME were recorded before and after incubation with increasing concentrations of netupitant. In anesthetized female guinea-pigs, reflex bladder activity was examined under isovolumetric conditions with the bladder distended with saline or during cystometry using intravesical infusion of AA. After a 30 min stabilization period, netupitant (0.1-3 mg/kg, i.v.) or L-733,060 (3-10 mg/kg, i.v.) were administered. In the detrusor muscle, netupitant produced a concentration-dependent inhibition (mean pKB = 9.24) of the responses to SP-OMe. Under isovolumetric conditions, netupitant or L-733,060 reduced bladder contraction frequency in a dose-dependent manner, but neither drug changed bladder contraction amplitude. In the AA model, netupitant dose-dependently increased intercontraction interval (ICI) but had no effect on the amplitude of micturition (AM). L-733,060 dose-dependently increased ICI also but this effect was paralleled by a significant reduction of AM. Conclusion. Netupitant decreases the frequency of reflex bladder contractions without altering their amplitude, suggesting that this drug targets the afferent limb of the micturition reflex circuit

  15. Netupitant, a Potent and Highly Selective NK1 Receptor Antagonist, Alleviates Acetic Acid-Induced Bladder Overactivity in Anesthetized Guinea-Pigs

    PubMed Central

    Palea, Stefano; Guilloteau, Véronique; Rekik, Moéz; Lovati, Emanuela; Guerard, Marc; Guardia, Maria-Alba; Lluel, Philippe; Pietra, Claudio; Yoshiyama, Mitsuharu

    2016-01-01

    Introduction. Tachykinins potently contract the isolated urinary bladder from a number of animal species and play an important role in the regulation of the micturition reflex. On the guinea-pig isolated urinary bladder we examined the effects of a new potent and selective NK1 receptor antagonist (netupitant) on the contractions induced by a selective NK1 receptor agonist, SP-methylester (SP-OMe). Moreover, the effects of netupitant and another selective NK1 antagonist (L-733,060) were studied in anesthetized guinea-pigs using two experimental models, the isovolumetric bladder contractions and a model of bladder overactivity induced by intravesical administration of acetic acid (AA). Methods and Results. Detrusor muscle strips were mounted in 5 mL organ baths and isometric contractions to cumulative concentrations of SP-OME were recorded before and after incubation with increasing concentrations of netupitant. In anesthetized female guinea-pigs, reflex bladder activity was examined under isovolumetric conditions with the bladder distended with saline or during cystometry using intravesical infusion of AA. After a 30 min stabilization period, netupitant (0.1–3 mg/kg, i.v.) or L-733,060 (3–10 mg/kg, i.v.) were administered. In the detrusor muscle, netupitant produced a concentration-dependent inhibition (mean pKB = 9.24) of the responses to SP-OMe. Under isovolumetric conditions, netupitant or L-733,060 reduced bladder contraction frequency in a dose-dependent manner, but neither drug changed bladder contraction amplitude. In the AA model, netupitant dose-dependently increased intercontraction interval (ICI) but had no effect on the amplitude of micturition (AM). L-733,060 dose-dependently increased ICI also but this effect was paralleled by a significant reduction of AM. Conclusion. Netupitant decreases the frequency of reflex bladder contractions without altering their amplitude, suggesting that this drug targets the afferent limb of the micturition reflex

  16. Gall-Bladder Agenesis and Associated Anomalies

    PubMed Central

    Shorey, Brian; Spigelman, Allan D.

    1995-01-01

    Congenital absence of the gall-bladder is a rare condition. It is sometimes associated with other congenital defects. We report here two cases of gall-bladder agenesis discovered at laparoscopy. Both had a history of skeletal and cardiovascular anomalies. The investigation of patients with absent gall-bladder can be very difficult. Ultrasound scanning is usually inconclusive and further noninvasive tests should be performed to establish the diagnosis and prevent an unnecessary operation. The presence of other congenital defects should alert the clinician to the possibility of gall-bladder agenesis. PMID:18612357

  17. Intravesical drug delivery for dysfunctional bladder.

    PubMed

    Hsu, Chun-Chien; Chuang, Yao-Chi; Chancellor, Michael B

    2013-06-01

    The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ-specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug-delivery.

  18. [Conservative and surgical therapy of urinary incontinence and bladder complaints in the man].

    PubMed

    Danuser, H; Burkhard, F C; John, H

    2003-05-01

    Treatment of incontinence and bladder complaints in the male should be directed to the cause whenever possible. Frequently, however, only symptomatic therapy is possible. Urge incontinence or overactive bladder due to obstruction should primarily be treated by eliminating the obstruction. Medical and surgical treatment methods are available for benign prostatic hyperplasia, bladder neck hypertrophy and prostatic cancer. In contrast, bladder neck sclerosis and uretheral strictures can only be treated surgically. Anticholinergics are primarily indicated if urge symptoms/incontinence persist after obstruction has been relieved or if urge incontinence occurs without obstruction. Seldom, in special cases injection of Botulinustoxin A or augmentation of the bladder may be indicated. Another possible cause of urge symptoms is urinary tract infection. This should be adequately treated according to resistance studies and the cause of the infection determined. In cases of overflow incontinence the infravesicle obstruction must be sought and treated. If limited detrusor contractability is the cause of overflow incontinence and the bladder cannot be emptied through pressmicturition, parasympathicometics may be of help. By insufficient effect, the procedure of intermittent self-catheterization must be taught. If this is not possible, the last resort is placement of a transuretheral or percutaneous catheter for continuous drainage. Stress incontinence is a rare complication in men, usually following prostatic surgery. It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis. Supravesicular urinary diversion is occasionally necessary after conservative and less invasive surgical measures have been exhausted and symptomatic suffering persists. Neurogenic disturbances in bladder capacity and/or emptying

  19. Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

    PubMed Central

    2014-01-01

    The physiological functions of the urinary bladder are to store and periodically expel urine. These tasks are facilitated by the contraction and relaxation of the urinary bladder smooth muscle (UBSM), also known as detrusor smooth muscle, which comprises the bladder wall. The large-conductance voltage- and Ca2+-activated K+ (BK, BKCa, MaxiK, Slo1, or KCa1.1) channel is highly expressed in UBSM and is arguably the most important physiologically relevant K+ channel that regulates UBSM function. Its significance arises from the fact that the BK channel is the only K+ channel that is activated by increases in both voltage and intracellular Ca2+. The BK channels control UBSM excitability and contractility by maintaining the resting membrane potential and shaping the repolarization phase of the spontaneous action potentials that determine UBSM spontaneous rhythmic contractility. In UBSM, these channels have complex regulatory mechanisms involving integrated intracellular Ca2+ signals, protein kinases, phosphodiesterases, and close functional interactions with muscarinic and β-adrenergic receptors. BK channel dysfunction is implicated in some forms of bladder pathologies, such as detrusor overactivity, and related overactive bladder. This review article summarizes the current state of knowledge of the functional role of UBSM BK channels under normal and pathophysiological conditions and provides new insight toward the BK channels as targets for pharmacological or genetic control of UBSM function. Modulation of UBSM BK channels can occur by directly or indirectly targeting their regulatory mechanisms, which has the potential to provide novel therapeutic approaches for bladder dysfunction, such as overactive bladder and detrusor underactivity. PMID:24990859

  20. Atezolizumab in Treating Patients With Recurrent BCG-Unresponsive Non-muscle Invasive Bladder Cancer

    ClinicalTrials.gov

    2016-09-12

    Recurrent Bladder Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma

  1. Treatment of overactive bladder in the aging population: focus on darifenacin.

    PubMed

    Jha, Swati; Parsons, Matthew

    2006-01-01

    Anticholinergics are commonly used in primary and secondary care settings for the treatment of overactive bladder syndrome. The number of anticholinergic drugs available on the market is increasing and various studies, both observational and randomized controlled trials, have evaluated effectiveness of the different preparations available. When anticholinergic therapy is prescribed, there is still uncertainty about which anticholinergic drugs are most effective, at which dose, and by which route of administration. There is also uncertainty about the role of anticholinergic drugs in different patient groups, particularly in the elderly. The rationale for using anticholinergic drugs in the treatment of overactive bladder syndrome is to block the parasympathetic acetylcholine pathway and thus abolish or reduce the intensity of detrusor muscle contraction. There are currently five recognized subtypes of muscarinic receptor; the M1, M2, and M3 subtypes are of interest in bladder activity. Muscarinic receptors are found in other parts of the body, eg, in the gut, salivary glands, tear ducts. Side effects associated with non-selective antimuscarinics can be particularly distressing in the elderly. The development of bladder selective M3 specific antagonists has the advantage of providing increased efficacy with minimal side effects. Darifenacin is one such preparation. The aim of this review is to assess the pharmacology, interactions and the safety and tolerability of darifenacin in the treatment of overactive bladder in the elderly population with particular reference to clinical trial data available.

  2. Overactive Bladder Syndrome and the Potential Role of Prostaglandins and Phosphodiesterases: An Introduction

    PubMed Central

    Rahnama'i, Mohammad Sajjad; Van Koeveringe, Gommert A.; Van Kerrebroeck, Philip E.

    2013-01-01

    In this paper, a general introduction is given, presenting the overactive bladder syndrome (OAB) and its impact on the quality of life and economical burden in patients affected. Moreover, the anatomy, physiology and histology of the lower urinary tract are discussed, followed by a brief overview on the possible role of prostaglandin (PG) and phosphodiesterase type 5 (PDE5) in the urinary bladder. The current literature on the role and distribution of PGE2 and its receptors in the urinary bladder is discussed. In both animal models and in human studies, high levels of signaling molecules such as PG and cGMP have been implicated, in decreased functional bladder capacity and micturition volume, as well as in increased voiding contraction amplitude. As a consequence, inhibition of prostanoid production, the use of prostanoid receptor antagonists, or PDE inhibitors might be a rational way to treat patients with detrusor overactivity. Similarly, prostanoid receptor agonists, or agents that stimulate their production, might have a function in treating bladder underactivity. PMID:24350100

  3. Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods.

    PubMed

    Takeda, M; Obara, K; Mizusawa, T; Tomita, Y; Arai, K; Tsutsui, T; Hatano, A; Takahashi, K; Nomura, S

    1999-03-01

    The purpose of the present study was to confirm the presence of beta3-adrenoceptor subtype in the relaxation of human urinary bladder detrusor tissue by reverse transcription-polymerase chain reaction (PCR); direct sequencing of the PCR product, in situ hybridization; and isometric contraction. Using reverse transcription-PCR, the mRNAs of three receptor subtypes (beta1, beta2, and beta3) were expressed in the human urinary bladder detrusor tissue. Direct sequencing of the PCR product of the above beta3-adrenoceptor revealed no mutation in the amplified regions. In situ hybridization with digoxygenin-labeled oligonucleotide probe revealed the presence of the mRNA of beta3-adrenoceptor subtype in the smooth muscle of the urinary bladder. The relaxant effects of isoproterenol (a nonselective beta-adrenoceptor agonist); ZD7114, BRL37344, and CGP12177A (putative selective beta3-adrenoceptor agonists); and SR59230A (a putative selective beta3-adrenoceptor antagonist) were tested using an isometric contraction technique. Isoproterenol in either the presence or absence of both atenolol (a beta1-adrenoceptor-selective antagonist) and butoxamine (a beta2-adrenoceptor-selective antagonist) revealed a relaxant effect on the carbachol-induced contraction of the human urinary bladder detrusor. Both BRL37344 and CGP12177A also revealed relaxant effects on the human urinary bladder detrusor, but ZD7114 did not elicit any relaxation. These results suggest that beta3-adrenoceptor may have some role in urine storage in the human urinary bladder. PMID:10027879

  4. Urinary Bladder Cancer in Yemen

    PubMed Central

    Al-Samawi, Abdullah Saleh; Aulaqi, Saleh Mansoor

    2013-01-01

    Objectives The aims of this study are to highlight the clinicopathological features of urinary bladder cancer in Yemen, and to describe the histological grading of urothelial neoplasms according to the World Health Organization and International Society of Urologic pathology (WHO/ISUP 1998) classification. Methods This is a descriptive record-based study of 316 cases of bladder cancer diagnosed by two pathologists at the Department of pathology, Sana'a University from 1st January 2005 to 30th April 2009. The diagnoses were made on hematoxylin and eosin stained sections and categorized according to WHO/ISUP 1998 classification. Results Out of 316 urinary bladder cancers, 248 (78%) were urothelial neoplasms, 53 (17%) were squamous cell carcinoma, 7 (2%) were adenocarcinoma, and 3 (1%) were rhabdomyosarcoma. The remaining cases were metastatic carcinomas (n=3), small cell carcinoma (n=1), and non-Hodgkin's lymphoma (n=1). The urothelial neoplasms observed were carcinoma in situ 4 (2%), papilloma 7 (3%), papillary urothelial neoplasm of low malignant potential 26 (11%), papillary urothelial carcinoma of low grade 107 (43%), papillary urothelial carcinoma of high grade 18 (7%), and non-papillary urothelial carcinoma of high grade 85 (34%), with 60 years mean age for males and 58 years for females; along with a male to female ratio of 4:1. The peak incidence was observed in the 61-70 years age group. Conclusion This study documents a high frequency of urothelial neoplasms, mostly papillary urothelial carcinoma of low grade and non-papillary urothelial carcinoma of high grade with male preponderance and peak incidence in 6th decade of age. PMID:24044060

  5. Calcium transport in turtle bladder

    SciTech Connect

    Sabatini, S.; Kurtzman, N.A. )

    1987-12-01

    Unidirectional {sup 45}Ca fluxes were measured in the turtle bladder under open-circuit and short-circuit conditions. In the open-circuited state net calcium flux (J{sup net}{sub Ca}) was secretory (serosa to mucosa). Ouabain reversed J{sup net}{sub Ca} to an absorptive flux. Amiloride reduced both fluxes such that J{sup net}{sub Ca} was not significantly different from zero. Removal of mucosal sodium caused net calcium absorption; removal of serosal sodium caused calcium secretion. When bladders were short circuited, J{sup net}{sub Ca} decreased to approximately one-third of control value but remained secretory. When ouabain was added under short-circuit conditions, J{sup net}{sub Ca} was similar in magnitude and direction to ouabain under open-circuited conditions (i.e., absorptive). Tissue {sup 45}Ca content was {approx equal}30-fold lower when the isotope was placed in the mucosal bath, suggesting that the apical membrane is the resistance barrier to calcium transport. The results obtained in this study are best explained by postulating a Ca{sup 2+}-ATPase on the serosa of the turtle bladder epithelium and a sodium-calcium antiporter on the mucosa. In this model, the energy for calcium movement would be supplied, in large part, by the Na{sup +}-K{sup +}-ATPase. By increasing cell sodium, ouabain would decrease the activity of the mucosal sodium-calcium exchanger (or reverse it), uncovering active calcium transport across the serosa.

  6. Bladder cancer documentation of causes: multilingual questionnaire, 'bladder cancer doc'.

    PubMed

    Golka, Klaus; Abreu-Villaca, Yael; Anbari Attar, Rowshanak; Angeli-Greaves, Miriam; Aslam, Muhammad; Basaran, Nursen; Belik, Rouslana; Butryee, Chaniphun; Dalpiaz, Orietta; Dzhusupov, Keneshbek; Ecke, Thorsten H; Galambos, Henrieta; Galambos, Henrieta; Gerilovica, Helena; Gerullis, Holger; Gonzalez, Patricia Casares; Goossens, Maria E; Gorgishvili-Hermes, Lela; Heyns, Chris F; Hodzic, Jasmin; Ikoma, Fumihiko; Jichlinski, Patrice; Kang, Boo-Hyon; Kiesswetter, Ernst; Krishnamurthi, Kannan; Lehmann, Marie-Louise; Martinova, Irina; Mittal, Rama Devi; Ravichandran, Beerappa; Romics, Imre; Roy, Bidyut; Rungkat-Zakaria, Fransiska; Rydzynski, Konrad; Scutaru, Cristian; Shen, Jianhua; Soufi, Maria; Toguzbaeva, Karlygash; Vu Duc, Trinh; Widera, Agata; Wishahi, Mohamed; Hengstler, Jan G

    2012-06-01

    There is a considerable discrepancy between the number of identified occupational-related bladder cancer cases and the estimated numbers particularly in emerging nations or less developed countries where suitable approaches are less or even not known. Thus, within a project of the World Health Organisation Collaborating Centres in Occupational Health, a questionnaire of the Dortmund group, applied in different studies, was translated into more than 30 languages (Afrikaans, Arabic, Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German, Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz, Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese, Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish, Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite questionnaire asks for relevant medical information in the physician's part and for the occupational history since leaving school in the patient's part. Furthermore, this questionnaire is asking for intensity and frequency of certain occupational and non-occupational risk factors. The literature regarding occupations like painter, hairdresser or miner and exposures like carcinogenic aromatic amines, azo dyes, or combustion products is highlighted. The questionnaire is available on www.ifado.de/BladderCancerDoc.

  7. Clinical Impact of Overactive Bladder

    PubMed Central

    Nitti, Victor W

    2002-01-01

    Overactive bladder (OAB) is a medical condition with the symptoms of urinary frequency and urgency, with or without urge incontinence. Traditionally, epidemiologic studies have focused on the symptom of incontinence, and therefore the prevalence and clinical impact have been grossly underestimated. Recently, several population-based studies have been conducted that have provided insight into the true magnitude of OAB. This article will review the latest data on the prevalence of OAB and discuss the impact of the condition on quality of life. Furthermore, it will examine some of the comorbidities associated with OAB and look at the potential economic impact of OAB. PMID:16986018

  8. Spectroscopic Imaging of Bladder Cancer

    SciTech Connect

    Demos, S G; Gandour-Edwards, R; Ramsamooj, R; deVere White, R

    2003-01-01

    The feasibility of developing bladder cancer detection methods using intrinsic tissue optical properties is the focus of this investigation. In vitro experiments have been performed using polarized elastic light scattering in combination with tissue autofluorescence in the NIR spectral region under laser excitation in the green and red spectral regions. The experimental results obtained from a set of tissue specimens from 25 patients reveal the presence of optical fingerprint characteristics suitable for cancer detection with high contrast and accuracy. These photonic methods are compatible with existing endoscopic imaging modalities which make them suitable for in-vivo application.

  9. Contract sanctity

    SciTech Connect

    Seeley, R.S.

    1995-10-01

    Increased competition and the pressure to keep rates low is driving utilities and independent power producers alike to consider more options to keep costs down. While an important strategy for them, the results are creating some conflicts. The April 12, 1995 Federal Energy Regulatory Commission (FERC) decision against New York State Electric & Gas (NYSEG) attempt to breach contracts with two independent power producers, observers say, is one of the most important decisions on contract disputes between independents and utilities. It reveals the complex issues and compelling arguments on both sides. It opens the question of utilities` ability to pay, and the future direction of independent power. The conflicts create a problem for utilities and independents alike.

  10. Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model.

    PubMed

    Chai, Xiangfei; van Herk, Marcel; Betgen, Anja; Hulshof, Maarten; Bel, Arjan

    2012-06-21

    In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

  11. Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model

    NASA Astrophysics Data System (ADS)

    Chai, Xiangfei; van Herk, Marcel; Betgen, Anja; Hulshof, Maarten; Bel, Arjan

    2012-06-01

    In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

  12. Heterogeneity of morphological and functional changes in various compartments of rat urinary bladder in infravesical obstruction of the urinary tract.

    PubMed

    Kirpatovskii, V I; Kudryavtsev, Yu V; Mudraya, I S; Belik, S M; Khromov, R A

    2009-01-01

    Infravesical obstruction of the lower urinary tract was simulated in rats by dosed constriction of the prevesical portion of the urethra. The functional and morphological changes in various urinary bladder compartments were evaluated after 1 week and 3 months. The development of compensatory hypertrophy of the detrusor was associated with an increase in the number of hypertrophic, atrophic, and young leiomyocyte forms and their transformation into myofibroblasts, with the formation of connective tissue laminae between myofibril bundles mainly in the zone of urinary urinary bladder neck. Specific contractility of the detrusor strips decreased with increasing their tone, which was most pronounced in the neck zone. The relaxing effect of norepinephrine was significantly lower after 3 months of obstruction and virtually disappeared in the zone of the urinary bladder body and neck. Blockade of a-adrenoceptors after adrenostimulation with norepinephrine stimulated contractions of the hypertrophic detrusor against the background of reduced tone of the urinary bladder neck, in contrast to intact urinary bladder where this treatment reduced contractions.

  13. Neurogenic bladder in spinal cord injury patients

    PubMed Central

    Taweel, Waleed Al; Seyam, Raouf

    2015-01-01

    Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

  14. Optimization of the current self-assembled urinary bladder model: Organ-specific stroma and smooth muscle inclusion

    PubMed Central

    Orabi, Hazem; Rousseau, Alexandre; Laterreur, Veronique; Bolduc, Stephane

    2015-01-01

    Introduction: Due to the complications associated with the use of non-native biomaterials and the lack of local tissues, bioengineered tissues are required for surgical reconstruction of complex urinary tract diseases, including those of the urinary bladder. The self-assembly method of matrix formation using autologous stromal cells obviates the need for exogenous biomaterials. We aimed at creating novel ex-vivo multilayer urinary tissue from a single bladder biopsy. Methods: After isolating urothelial, bladder stromal and smooth muscle cells from bladder biopsies, we produced 2 models of urinary equivalents: (1) the original one with dermal fibroblasts and (2) the new one with bladder stromal cells. Dermal fibroblasts and bladder stromal cells were stimulated to form an extracellular matrix, followed by sequential seeding of smooth muscle cells and urothelial cells. Stratification and cellular differentiation were assessed by histology, immunostaining and electron microscopy. Barrier function was checked with the permeability test. Biomechanical properties were assessed with uniaxinal tensile strength, elastic modulus, and failure strain. Results: Both urinary equivalents could be handled easily and did not contract. Stratified epithelium, intact basement membrane, fused matrix, and prominent muscle layer were detected in both urinary equivalents. Bladder stromal cell-based constructs had terminally differentiated urothelium and more elasticity than dermal fibroblasts-based equivalents. Permeation studies showed that both equivalents were comparable to native tissues. Conclusions: Organ-specific stromal cells produced urinary tissues with more terminally differentiated urothelium and better biomechanical characteristics than non-specific stromal cells. Smooth muscle cells could be incorporated into the self-assembled tissues effectively. This multilayer tissue can be used as a urethral graft or as a bladder model for disease modelling and pharmacotherapeutic

  15. Progressive changes in detrusor function and micturition patterns with chroinc bladder ischemia

    PubMed Central

    Zhao, Zuohui; Azad, Roya; Yang, Jing-Hua; Siroky, Mike B.

    2016-01-01

    Purpose Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia. Materials and Methods Iliac artery atherosclerosis and bladder ischemia were produced in male Sprague-Dawley rats. At 8 and 16 weeks after ischemia, micturition patterns and cystometrograms were recorded in conscious rats then bladder blood flow and nonvoiding spontaneous contractions were measured under general anesthesia. Bladder tissues were processed for Western blotting, immunostaining, and transmission electron microscopy. Results Bladder responses to ischemic insult depended on the duration of ischemia. Micturition patterns and cystometric changes at 8-week ischemia suggested detrusor overactivity, while voiding behavior and cystometrograms at 16-week ischemia implied abnormal detrusor function resembling underactivity. Upregulation of muscarinic M2 receptor was found after 8- and 16 weeks of ischemia. Downregulation of M3 and upregulation of M1 were detected at 16-week ischemia. Neural structural damage and marked neurodegeneration were found after 8 and 16 weeks of ischemia, respectively. Conclusions Prolonged ischemia may be a mediating variable in progression of overactive bladder to dysfunctional patterns similar to detrusor underactivity. The mechanism appears to involve differential expression of M1, M2, and M3 receptors, neural structural injury, and progressive loss of nerve fibers. PMID:27437534

  16. Overactive bladder, differential diagnosis, and clinical utility of fesoterodine

    PubMed Central

    Wyndaele, Jean-Jacques

    2012-01-01

    Overactive bladder is a symptom syndrome with urgency, frequency and, in many cases, nocturia. Urge incontinence is not present in all. There is no direct correlation with detrusor overactivity, an objective finding during urodynamic testing where involuntary contractions can be noticed. In the pathophysiology, much more attention has been given to the afferent/sensory arm of the micturition reflex in the last decade. Anatomical and infectious causes have to be diagnosed or ruled out. Diagnosis of overactive bladder is made mostly by history-taking, but other tests can be necessary in specific patients. Treatment consists of behavioral measures, a good explanation of the condition, training, and pelvic floor physiotherapy. Drugs are often used. Until recently, antimuscarinic drugs have been the mainstay of pharmacological therapy. Fesoterodine is a newer antimuscarinic agent which is more pharmacodynamically stable then tolterodine. Fesoterodine has been extensively researched using different dosages and compared with placebo and tolterodine, in different age groups, and under different conditions. Fesoterodine is superior to placebo and to tolterodine in the short term and long term. Its safety is very acceptable. PMID:23204858

  17. The neurogenic bladder: introducing four contributions.

    PubMed

    Proesmans, Willem

    2008-04-01

    Neurogenic bladder dysfunction in children is frequently seen in patients with meningomyelocele (MMC). The disorder carries a high risk for all kinds of complications, with renal damage being the most important. More than 95% of MMC patients have a neurogenic bladder, the paramount manifestation of which is a disturbed coordination between detrusor and sphincter muscles. This vesicourethral dysfunction leads to defective filling and emptying of the urinary bladder. Voiding at will is almost never possible. According to the location and extent of the neural tube lesion, patients have either an atonic or a hypertonic pelvic floor and either an atonic or a hypertonic detrusor, leading to four classic combinations. Hypertonic sphincter and detrusor hyperactivity lead to the most dangerous form of neurogenic bladder, referred to as the "unsafe" bladder. The presence of residual urine in a high-pressure container causes either decompensation of the detrusor with vesicoureteral reflux or deterioration of the bladder wall with hypertrophy and stiffness resulting in uterovesical obstruction. The subsequent insufficient drainage of the upper urinary tract leads to decompensation of the ureters and finally to chronic renal disease, the process being accelerated by urinary tract infections. The aim of treatment is to restore as much as possible both essential functions: urine storage and timely emptying of the reservoir. What should and can be achieved is a more or less adequate, low-pressure, functional capacity of the bladder that is emptied as completely as possible by clean intermittent catheterization (CIC). MMC leads to the prototype of neurogenic bladder in childhood. What we know and what we do for MMC patients can roughly be applied to all other forms of neurogenic bladder, either congenital or acquired.

  18. [Classification and natural history of bladder tumors].

    PubMed

    Allory, Yves

    2014-12-01

    Urinary bladder tumors are mainly of urothelial type. Classifications include stage and grade to provide with the required prognostic factors and help to select the most adequate treatment. Though somatic mutations in bladder tumors are known, their used for targeted therapy are restricted to clinical trials. Upper urinary tract tumors are classified as urinary bladder tumor at histological level, but tumor staging is specified according to calyx, renal pelvis or ureter location; in young patients with upper urinary tract tumor, a Lynch syndrome should be eliminated. PMID:25668829

  19. Bladder exstrophy: current management and postoperative imaging.

    PubMed

    Pierre, Ketsia; Borer, Joseph; Phelps, Andrew; Chow, Jeanne S

    2014-07-01

    Bladder exstrophy is a rare malformation characterized by an infra-umbilical abdominal wall defect, incomplete closure of the bladder with mucosa continuous with the abdominal wall, epispadias, and alterations in the pelvic bones and muscles. It is part of the exstrophy-epispadias complex, with cloacal exstrophy on the severe and epispadias on the mild ends of the spectrum. Bladder exstrophy is the most common of these entities and is more common in boys. The goal of this paper is to describe common methods of repair and to provide an imaging review of the postoperative appearances. PMID:24939762

  20. Inflammatory pseudotumor of the urinary bladder.

    PubMed

    Rosado, Elsa; Pereira, José; Corbusier, Florence; Demeter, Pieter; Bali, Maria Antonietta

    2015-01-01

    We report a case of an inflammatory pseudotumor of the urinary bladder in a 31 year-old woman. She presented at the emergency room with low abdominal pain and urinary symptoms. Abdominal ultrasound, computed tomography and magnetic resonance imaging were performed and revealed asymmetric thickening of the urinary bladder wall. Cystoscopy with urinary cytology revealed a benign nature of the process. The patient underwent partial cystectomy and the pathologic examination of the specimen revealed an inflammatory pseudotumor. We reviewed the clinical, imaging and pathological features of the inflammatory pseudotumor of the urinary bladder and discussed its differential diagnosis.

  1. Inflammatory Pseudotumor of the Urinary Bladder

    PubMed Central

    Rosado, Elsa; Pereira, José; Corbusier, Florence; Demeter, Pieter; Bali, Maria Antonietta

    2015-01-01

    We report a case of an inflammatory pseudotumor of the urinary bladder in a 31 year-old woman. She presented at the emergency room with low abdominal pain and urinary symptoms. Abdominal ultrasound, computed tomography and magnetic resonance imaging were performed and revealed asymmetric thickening of the urinary bladder wall. Cystoscopy with urinary cytology revealed a benign nature of the process. The patient underwent partial cystectomy and the pathologic examination of the specimen revealed an inflammatory pseudotumor. We reviewed the clinical, imaging and pathological features of the inflammatory pseudotumor of the urinary bladder and discussed its differential diagnosis. PMID:25926919

  2. Bladder reconstruction: The past, present and future

    PubMed Central

    EL-TAJI, OMAR M.S.; KHATTAK, ALTAF Q.; HUSSAIN, SYED A.

    2015-01-01

    Ileal conduit urinary diversion is the gold standard treatment for urinary tract reconstruction following cystectomy. This procedure uses gastrointestinal segments for bladder augmentation, a technique that is often associated with significant complications. The substantial progression in the fields of tissue engineering and regenerative medicine over the previous two decades has resulted in the development of techniques that may lead to the construction of functional de novo urinary bladder substitutes. The present review identifies and discusses the complications associated with current treatment options post-cystectomy. The current techniques, achievements and perspectives of the use of biomaterials and stem cells in the field of urinary bladder reconstruction are also reviewed. PMID:26170968

  3. [Management of metastatic bladder cancer].

    PubMed

    Gauthier, Hélène; Serrate, Camille; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

    2014-12-01

    The management of patients with metastatic bladder cancer is mainly based on cytotoxic chemotherapy. The reference molecule is cisplatin. In 2014, first-line regimens include gemcitabine and cisplatin (GC protocol) or methotrexate, vinblastine, and cisplatin doxorubicin (MVAC protocol). When cisplatin is contra-indicated, another platinum Salt, carboplatin, is used in combination with gemcitabine. Vinflunine is the only molecule to have obtained a marketing approval for patients who failed first-line chemotherapy including a platinum salt. The overall prognosis of patients remains dismal, since the median overall survival is 12 to 14 months for patients being treated with cisplatin, whereas it is less than 1 year for patients receiving carboplatin. The identification of new effective drugs is a major challenge for the coming years. PMID:25668832

  4. Differentiating bladder carcinoma from bladder wall using 3D textural features: an initial study

    NASA Astrophysics Data System (ADS)

    Xu, Xiaopan; Zhang, Xi; Liu, Yang; Tian, Qiang; Zhang, Guopeng; Lu, Hongbing

    2016-03-01

    Differentiating bladder tumors from wall tissues is of critical importance for the detection of invasion depth and cancer staging. The textural features embedded in bladder images have demonstrated their potentials in carcinomas detection and classification. The purpose of this study was to investigate the feasibility of differentiating bladder carcinoma from bladder wall using three-dimensional (3D) textural features extracted from MR bladder images. The widely used 2D Tamura features were firstly wholly extended to 3D, and then different types of 3D textural features including 3D features derived from gray level co-occurrence matrices (GLCM) and grey level-gradient co-occurrence matrix (GLGCM), as well as 3D Tamura features, were extracted from 23 volumes of interest (VOIs) of bladder tumors and 23 VOIs of patients' bladder wall. Statistical results show that 30 out of 47 features are significantly different between cancer tissues and wall tissues. Using these features with significant differences between these two types of tissues, classification performance with a supported vector machine (SVM) classifier demonstrates that the combination of three types of selected 3D features outperform that of using only one type of features. All the observations demonstrate that significant textural differences exist between carcinomatous tissues and bladder wall, and 3D textural analysis may be an effective way for noninvasive staging of bladder cancer.

  5. Bladder filling variation during radiation treatment of prostate cancer: Can the use of a bladder ultrasound scanner and biofeedback optimize bladder filling?

    SciTech Connect

    Stam, Marcel R. . E-mail: m.stam@rther.umcn.nl; Lin, Emile N.J. Th. van; Vight, Lisette P. van der; Kaanders, Johannes; Visser, Andries G.

    2006-06-01

    Purpose: To investigate the use of a bladder ultrasound scanner in achieving a better reproducible bladder filling during irradiation of pelvic tumors, specifically prostate cancer. Methods and Materials: First, the accuracy of the bladder ultrasound scanner relative to computed tomography was validated in a group of 26 patients. Next, daily bladder volume variation was evaluated in a group of 18 patients. Another 16 patients participated in a biofeedback protocol, aiming at a more constant bladder volume. The last objective was to study correlations between prostate motion and bladder filling, by using electronic portal imaging device data on implanted gold markers. Results: A strong correlation between bladder scanner volume and computed tomography volume (r = 0.95) was found. Daily bladder volume variation was very high (1 Sd = 47.2%). Bladder filling and daily variation did not significantly differ between the control and the feedback group (47.2% and 40.1%, respectively). Furthermore, no linear correlations between bladder volume variation and prostate motion were found. Conclusions: This study shows large variations in daily bladder volume. The use of a biofeedback protocol yields little reduction in bladder volume variation. Even so, the bladder scanner is an easy to use and accurate tool to register these variations.

  6. [Intradiverticular bladder tumors. Three case reports].

    PubMed

    Fekak, H; Rabu, R; Joual, A; Bennani, S; Moufid, K; Sarf, S; Debragh, A; el Mimu, M; Benjelloun, S

    2002-01-01

    The bladder tumours in vesical diverticula is rare, and the poor prognosis, because it was often with early invasion. We reported three cases of bladder tumours in vesical diverticula, with delay of diagnosis two, eight and twelve months respectively. The radiology exploration suspected the diagnosis and the histology biopsy confirmed a diagnosis of primary transitional cell carcinoma in two cases: PTa GI and T2 GII, and in an other case it was a invasive epidermoid carcinoma. The first patient was dead by urethral resection of the bladder tumour. The second required a cytoprototectomy and the last patient. The treatment consisted of radiotherapy and chemotherapy. We insisted of the particularity diagnosis, histology and therapeutic for bladder tumour in vesical diverticula and the early diagnosis in order to have a good prognosis.

  7. Aging changes in the kidneys and bladder

    MedlinePlus

    ... and urethra. Muscle changes and changes in the reproductive system can affect bladder control. Aging Changes and Their ... the bones, muscles, and joints In the male reproductive system In the female reproductive system In organs, tissues, ...

  8. A new technique for bladder washing.

    PubMed

    Miller, D C; Fitkin, D L; Kropp, K A; Selman, S H

    1992-01-01

    We describe a simple adaptation of the Water Pik (Teledyne Water Pik, Fort Collins, Colorado) irrigating device which allows vigorous, direct-vision agitation of the bladder wall. Three groups of mongrel dogs were subjected to cystoscopy and either syringe barbotage, half-speed Water Pik irrigation, or full-speed Water Pik irrigation of the bladder wall. Transitional cell counts were then done on centrifuged aliquots of each bladder wash specimen. The average number of transitional cells per high-power field were similar between the control group and the syringe barbotage group (2.5 and 1.5 respectively). However, both the half-speed and the full-speed Water Pik groups demonstrated statistically higher cell counts (5.7 and 13.7) when compared to both the controls and syringe barbotage groups. We conclude that Water Pik irrigation is an effective method to increase cell yield in bladder wash specimens. PMID:1729530

  9. Recovery After Stroke: Bladder and Bowel Function

    MedlinePlus

    ... urination.  Urinary retention – trouble urinating or not completely emptying your bladder.  Constipation – being unable to have a ... or a specialist in medical problems of the stomach, intestines and associated organs.  Many nurses are trained ...

  10. [Modern approaches to the treatment of patients with overactive bladder and urge urinary incontinence].

    PubMed

    Razdorskaia, M V; Neĭmark, A I; Aliev, R T

    2013-01-01

    Overactive bladder (OAB) is found in 20% of patients with various disorders of urination, and the imperative urinary incontinence diagnosed in one third of these patients. The study was aimed to improvement the treatment outcomes in OAB women with imperative incontinence and obstructive urination disorders by using a combination of alpha1-adrenoblockers and PDE-5 inhibitors, and to evaluation of relationship between clinical and urodynamic manifestations of the disease. The state of the microcirculation of the bladder mucosa before and after treatment was also evaluated. We have examined and treated 40 women aged 17 to 69 years with disease duration ranged from 1 to 20 years. Patients received combination of al-adrenoblocker alfuzosin (dalfaz) 5 mg at night and reversible selective PDE5 inhibitor tadalafil (Cialis) 5 mg daily in the morning for a month. After treatment, according to the uroflowmetry and cystometry data, the time of urination was reduced, urinary volume and maximum urinary flow rate, as well as cystometric capacity have increased; involuntary detrusor contractions in the bladder filling phase (spontaneous or provoked) became less, or absent. According to the results of ultrasound examination, residual urine volume has decreased. Laser Doppler flowmetry showed an increase of neurogenic tone in precapillary, bypass coefficient and microcirculation effectiveness index, increase in microcirculation index and the coefficient of variation, indicating an improvement of microcirculation in the bladder mucosa. As a result of treatment, the clinical effect was seen in 29 (73%) patients, urinary incontinence was noted only in 6 (15%) patients. PMID:23662495

  11. Holmium laser lithotripsy of bladder calculi

    NASA Astrophysics Data System (ADS)

    Beaghler, Marc A.; Poon, Michael W.

    1998-07-01

    Although the overall incidence of bladder calculi has been decreasing, it is still a significant disease affecting adults and children. Prior treatment options have included open cystolitholapaxy, blind lithotripsy, extracorporeal shock wave lithotripsy, and visual lithotripsy with ultrasonic or electrohydraulic probes. The holmium laser has been found to be extremely effective in the treatment of upper tract calculi. This technology has also been applied to the treatment of bladder calculi. We report our experience with the holmium laser in the treatment of bladder calculi. Twenty- five patients over a year and a half had their bladder calculi treated with the Holmium laser. This study was retrospective in nature. Patient demographics, stone burden, and intraoperative and post-operative complications were noted. The mean stone burden was 31 mm with a range of 10 to 60 mm. Preoperative diagnosis was made with either an ultrasound, plain film of the abdomen or intravenous pyelogram. Cystoscopy was then performed to confirm the presence and determine the size of the stone. The patients were then taken to the operating room and given a regional or general anesthetic. A rigid cystoscope was placed into the bladder and the bladder stone was then vaporized using the holmium laser. Remaining fragments were washed out. Adjunctive procedures were performed on 10 patients. These included transurethral resection of the prostate, transurethral incision of the prostate, optic internal urethrotomy, and incision of ureteroceles. No major complications occurred and all patients were rendered stone free. We conclude that the Holmium laser is an effective and safe modality for the treatment of bladder calculi. It was able to vaporize all bladder calculi and provides a single modality of treating other associated genitourinary pathology.

  12. The "bends" and neurogenic bladder dysfunction.

    PubMed

    Elliott, D S; Mutchnik, S; Boone, T B

    2001-02-01

    Decompression sickness (the "bends") is a well-known risk of scuba diving. The pathophysiology and treatment is well documented. In the urologic data, no reference to the development of a neurogenic bladder as a result of an episode of the bends was found. We present the evaluation and management of a previously asymptomatic man who developed detrusor hyperreflexia after an episode of decompression sickness. Urologists in coastal communities should be aware of the potential risk of the development of neurogenic bladder.

  13. Laparoscopic Hernia Repair and Bladder Injury

    PubMed Central

    Bhoyrul, Sunil; Mulvihill, Sean J.

    2001-01-01

    Background: Bladder injury is a complication of laparoscopic surgery with a reported incidence in the general surgery literature of 0.5% and in the gynecology literature of 2%. We describe how to recognize and treat the injury and how to avoid the problem. Case Reports: We report two cases of bladder injury repaired with a General Surgical Interventions (GSI) trocar and a balloon device used for laparoscopic extraperitoneal inguinal hernia repair. One patient had a prior appendectomy; the other had a prior midline incision from a suprapubic prostatectomy. We repaired the bladder injury, and the patients made a good recovery. Conclusion: When using the obturator and balloon device, it is important to stay anterior to the preperitoneal space and bladder. Prior lower abdominal surgery can be considered a relative contraindication to extraperitoneal laparoscopic hernia repair. Signs of gas in the Foley bag or hematuria should alert the surgeon to a bladder injury. A one- or two-layer repair of the bladder injury can be performed either laparoscopically or openly and is recommended for a visible injury. Mesh repair of the hernia can be completed provided no evidence exists of urinary tract infection. A Foley catheter is placed until healing occurs. PMID:11394432

  14. Urodynamic outcome of parasacral transcutaneous electrical neural stimulation for overactive bladder in children

    PubMed Central

    Barroso, Ubirajara; Carvalho, Marcelo Tomás; Veiga, Maria Luisa; Moraes, Marília Magalhães; Cunha, Carolina Coelho; Lordêlo, Patrícia

    2015-01-01

    ABSTRACT Objective: To evaluate the urodynamic changes immediately after the first session (acute effect) and after the last session of parasacral TENS in children with idiopathic OAB. Materials and methods: We performed urodynamic evaluation immediately before and after the first session of parasacral TENS and immediately after the last session (7 weeks later). Only children with idiopathic isolated OAB were included. Patients with dysfunctional voiding were not included. Results: 18 children (4 boys and 14 girls, mean age of 8.7) were included in the first analysis (urodynamic study before and immediately after the first session) and 12 agreed to undergo the third urodynamic study. Urodynamic before and immediately after the first session: There was no change in the urodynamic parameters, namely low MCC, low bladder compliance, presence of IDC, the average number of IDC, or in the maximum detrusor pressure after the first exam. Urodynamic after the last session: The bladder capacity improved in most patients with low capacity (58% vs. 8%). Detrusor overactivity was observed in 11 (92%) before treatment and 8 (76%) after. There was not a significant reduction in the average number of inhibited contractions after TENS (p=0.560) or in the detrusor pressure during the inhibited contraction (p=0.205). Conclusion: There was no change in the urodynamic parameters immediately after the first session of stimulation. After the last session, the only urodynamic finding that showed improvement was bladder capacity. PMID:26401867

  15. Near infrared spectroscopy evaluation of bladder function: the impact of skin pigmentation on detection of physiologic change during voiding

    NASA Astrophysics Data System (ADS)

    Shadgan, Babak; Stothers, Lynn; Molavi, Behnam; Mutabazi, Sharif; Mukisa, Ronald; Macnab, Andrew

    2015-02-01

    Background: Prior research indicates the epidermal pigment layer of human skin (Melanin) has a significant absorption coefficient in the near infra-red (NIR) region; hence attenuation of light in vivo is a potential confounder for NIR spectroscopy (NIRS). A NIRS method developed for transcutaneous evaluation of bladder function is being investigated as a means of improving the burden of bladder disease in sub-Saharan Africa. This required development of a simple wireless NIRS device suitable for use as a screening tool in patients with pigmented skin where the NIR light emitted would penetrate through the epidermal pigment layer and return in sufficient quantity to provide effective monitoring. Methods: Two healthy subjects, one with pigmented skin and one with fair skin, were monitored as they voided spontaneously using the prototype transcutaneous NIRS device positioned over the bladder. The device was a self-contained wireless unit with light emitting diodes (wavelengths 760 and 850 nanometres) and interoptode distance of 4cm. The raw optical data were transmitted to a laptop where graphs of chromophore change were generated with proprietary software and compared between the subjects and with prior data from asymptomatic subjects. Results: Serial monitoring was successful in both subjects. Voiding volumes varied between 350 and 380 cc. In each subject the patterns of chromophore change, trend and magnitude of change were similar and matched the physiologic increase in total and oxygenated hemoglobin recognized to occur in normal bladder contraction during voiding. Conclusions: Skin pigmentation does not compromise the ability of transcutaneous NIRS to interrogate physiologic change in the bladder during bladder contraction in healthy subjects.

  16. Contracting and Higher Education.

    ERIC Educational Resources Information Center

    Ferris, James M.

    1991-01-01

    The potential gains in efficiency of three types of contracts in college administration are contrasted. Contract types include explicit contracts in the budgeting process between the state and higher education institutions; institutional contracting for inputs; and interinstitutional contracting. The tradeoff between production cost savings and…

  17. Reproducibility of the bladder shape and bladder shape changes during filling

    SciTech Connect

    Lotz, Heidi T.; Herk, Marcel van; Betgen, Anja; Pos, Floris; Lebesque, Joos V.; Remeijer, Peter

    2005-08-15

    The feasibility of high precision radiotherapy to the bladder region is limited by bladder motion and volume changes. In the near future, we plan to begin treatment delivery of bladder cancer patients with the acquisition of a cone beam CT image on which the complete bladder will be semi-automatically localized. Subsequently, a bladder shape model that was developed in a previous study will be used for bladder localization and for the prediction of shape changes in the time interval between acquisition and beam delivery. For such predictions, knowledge about urinary inflow rate is required. Therefore, a series of MR images was acquired over 1 h with time intervals of 10 min for 18 healthy volunteers. To gain insight in the reproducibility of the bladder shape over longer periods of time, two additional MRI series were recorded for 10 of the volunteers. To a good approximation, the bladder volume increased linearly in time for all individuals. Despite receiving drinking instructions, we found a large variation in the inflow rate between individuals, ranging from 2.1 to 15 cc/min (mean value: 9{+-}3 cc/min). In contrast, the intravolunteer variation was much smaller, with a mean standard deviation (SD) of 0.4 cc/min. The inflow rate was linearly correlated with age (negative slope). To study the reproducibility of the bladder shape, we compared bladder shapes of equal volume. For all individuals, the caudal part of the bladder was the most reproducible (variations<0.3 cm in all cases). The cranial and posterior parts of the bladder was much less reproducible, with local SD values up to {approx}1.2 cm for bladders with a volume of 200 cc. These large long-term variations were primarily caused by changes in position and filling of the small bowel and rectum. However, for short time intervals, the rectal filling was (nearly) constant. Therefore, the reproducibility of urinary inflow, combined with the previously developed shape model gives us an excellent tool to

  18. Work Capacity of the Bladder During Voiding: A Novel Method to Evaluate Bladder Contractile Function and Bladder Outlet Obstruction

    PubMed Central

    Liu, Ning; Man, Li-Bo; He, Feng; Huang, Guang-Lin; Zhou, Ning; Zhu, Xiao-Fei

    2015-01-01

    Background: Work in voiding (WIV) of the bladder may be used to evaluate bladder status throughout urination rather than at a single time point. Few studies, however, have assessed WIV owing to the complexity of its calculations. We have developed a method of calculating work capacity of the bladder while voiding and analyzed the associations of bladder work parameters with bladder contractile function and bladder outlet obstruction (BOO). Methods: The study retrospectively evaluated 160 men and 23 women, aged >40 years and with a detrusor pressure at maximal flow rate (Pdet Qmax) of ≥40 cmH2O in men, who underwent urodynamic testing. The bladder power integration method was used to calculate WIV; WIV per second (WIV/t) and WIV per liter of urine voided (WIV/v) were also calculated. In men, the relationships between these work capacity parameters and Pdet Qmax and Abrams-Griffiths (AG) number were determined using linear-by-linear association tests, and relationships between work capacity parameters and BOO grade were investigated using Spearman's association test. Results: The mean WIV was 1.15 ± 0.78 J and 1.30 ± 0.88 J, mean WIV/t was 22.95 ± 14.45 mW and 23.78 ± 17.02 mW, and mean WIV/v was 5.59 ± 2.32 J/L and 2.83 ± 1.87 J/L in men and women, respectively. In men, WIV/v showed significant positive associations with Pdet Qmax (r = 0.845, P = 0.000), AG number (r = 0.814, P = 0.000), and Schafer class (r = 0.726, P = 0.000). Conversely, WIV and WIV/t showed no associations with Pdet Qmax or AG number. In patients with BOO (Schafer class > II), WIV/v correlated positively with increasing BOO grade. Conclusions: WIV can be calculated from simple urodynamic parameters using the bladder power integration method. WIV/v may be a marker of BOO grade, and the bladder contractile function can be evaluated by WIV and WIV/t. PMID:26668148

  19. Cone Beam CT Imaging Analysis of Interfractional Variations in Bladder Volume and Position During Radiotherapy for Bladder Cancer

    SciTech Connect

    Yee, Don; Parliament, Matthew; Rathee, Satyapal; Ghosh, Sunita; Ko, Lawrence; Murray, Brad

    2010-03-15

    Purpose: To quantify daily bladder size and position variations during bladder cancer radiotherapy. Methods and Materials: Ten bladder cancer patients underwent daily cone beam CT (CBCT) imaging of the bladder during radiotherapy. Bladder and planning target volumes (bladder/PTV) from CBCT and planning CT scans were compared with respect to bladder center-of-mass shifts in the x (lateral), y (anterior-posterior), and z (superior-inferior) coordinates, bladder/PTV size, bladder/PTV margin positions, overlapping areas, and mutually exclusive regions. Results: A total of 262 CBCT images were obtained from 10 bladder cancer patients. Bladder center of mass shifted most in the y coordinate (mean, -0.32 cm). The anterior bladder wall shifted the most (mean, -0.58 cm). Mean ratios of CBCT-derived bladder and PTV volumes to planning CT-derived counterparts were 0.83 and 0.88. The mean CBCT-derived bladder volume (+- standard deviation [SD]) outside the planning CT counterpart was 29.24 cm{sup 3} (SD, 29.71 cm{sup 3}). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm{sup 3} (SD, 21.64 cm{sup 3}). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm{sup 3} (SD, 36.51 cm{sup 3}). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm{sup 3} (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm{sup 3} (SD, 3.97 cm{sup 3}). CBCT bladder/ PTV volumes significantly differed from planning CT counterparts (p = 0.047). Conclusions: Significant variations in bladder and PTV volume and position occurred in patients in this trial.

  20. Lightweight bladder lined pressure vessels

    DOEpatents

    Mitlitsky, Fred; Myers, Blake; Magnotta, Frank

    1998-01-01

    A lightweight, low permeability liner for graphite epoxy composite compressed gas storage vessels. The liner is composed of polymers that may or may not be coated with a thin layer of a low permeability material, such as silver, gold, or aluminum, deposited on a thin polymeric layer or substrate which is formed into a closed bladder using torispherical or near torispherical end caps, with or without bosses therein, about which a high strength to weight material, such as graphite epoxy composite shell, is formed to withstand the storage pressure forces. The polymeric substrate may be laminated on one or both sides with additional layers of polymeric film. The liner may be formed to a desired configuration using a dissolvable mandrel or by inflation techniques and the edges of the film seamed by heat sealing. The liner may be utilized in most any type of gas storage system, and is particularly applicable for hydrogen, gas mixtures, and oxygen used for vehicles, fuel cells or regenerative fuel cell applications, high altitude solar powered aircraft, hybrid energy storage/propulsion systems, and lunar/Mars space applications, and other applications requiring high cycle life.

  1. Lightweight bladder lined pressure vessels

    DOEpatents

    Mitlitsky, F.; Myers, B.; Magnotta, F.

    1998-08-25

    A lightweight, low permeability liner is described for graphite epoxy composite compressed gas storage vessels. The liner is composed of polymers that may or may not be coated with a thin layer of a low permeability material, such as silver, gold, or aluminum, deposited on a thin polymeric layer or substrate which is formed into a closed bladder using tori spherical or near tori spherical end caps, with or without bosses therein, about which a high strength to weight material, such as graphite epoxy composite shell, is formed to withstand the storage pressure forces. The polymeric substrate may be laminated on one or both sides with additional layers of polymeric film. The liner may be formed to a desired configuration using a dissolvable mandrel or by inflation techniques and the edges of the film sealed by heat sealing. The liner may be utilized in most any type of gas storage system, and is particularly applicable for hydrogen, gas mixtures, and oxygen used for vehicles, fuel cells or regenerative fuel cell applications, high altitude solar powered aircraft, hybrid energy storage/propulsion systems, and lunar/Mars space applications, and other applications requiring high cycle life. 19 figs.

  2. Effects of Lateral Funiculus Sparing, Spinal Lesion Level, and Gender on Recovery of Bladder Voiding Reflexes and Hematuria in Rats

    PubMed Central

    Ferrero, Sunny L.; Brady, Tiffany D.; Dugan, Victoria P.; Armstrong, James E.; Hubscher, Charles H.

    2015-01-01

    Abstract Deficits in bladder function are complications following spinal cord injury (SCI), severely affecting quality of life. Normal voiding function requires coordinated contraction of bladder and urethral sphincter muscles dependent upon intact lumbosacral reflex arcs and integration of descending and ascending spinal pathways. We previously reported, in electrophysiological recordings, that segmental reflex circuit neurons in anesthetized male rats were modulated by a bilateral spino-bulbo-spinal pathway in the mid-thoracic lateral funiculus. In the present study, behavioral measures of bladder voiding reflexes and hematuria (hemorrhagic cystitis) were obtained to assess the correlation of plasticity-dependent recovery to the degree of lateral funiculus sparing and mid-thoracic lesion level. Adult rats received mid-thoracic-level lesions at one of the following severities: complete spinal transection; bilateral dorsal column lesion; unilateral hemisection; bilateral dorsal hemisection; a bilateral lesion of the lateral funiculi and dorsal columns; or a severe contusion. Voiding function and hematuria were evaluated by determining whether the bladder was areflexic (requiring manual expression, i.e., “crede maneuver”), reflexive (voiding initiated by perineal stroking), or “automatic” (spontaneous voiding without caretaker assistance). Rats with one or both lateral funiculi spared (i.e., bilateral dorsal column lesion or unilateral hemisection) recovered significantly faster than animals with bilateral lateral funiculus lesions, severe contusion, or complete transection. Bladder reflex recovery time was significantly slower the closer a transection lesion was to T10, suggesting that proximity to the segmental sensory and sympathetic innervation of the upper urinary tract (kidney, ureter) should be avoided in the choice of lesion level for SCI studies of micturition pathways. In addition, hematuria duration was significantly longer in males, compared to

  3. Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence.

    PubMed

    Wyman, J F; Burgio, K L; Newman, D K

    2009-08-01

    Behavioural interventions are effective treatments for overactive bladder (OAB) and urgency urinary incontinence (UUI). They are in part aimed at improving symptoms with patient education on healthy bladder habits and lifestyle modifications, including the establishment of normal voiding intervals, elimination of bladder irritants from the diet, management of fluid intake, weight control, management of bowel regularity and smoking cessation. Behavioural interventions also include specific training techniques aimed at re-establishing normal voiding intervals and continence. Training techniques include bladder training, which includes a progressive voiding schedule together with relaxation and distraction for urgency suppression, and multicomponent behavioural training, which, in conjunction with pelvic floor muscle (PFM) exercises, includes PFM contraction to control urgency and increase the interval between voids. Guidelines for the conservative treatment of OAB and UUI have been published by several organisations and the physiological basis and evidence for the effectiveness of behavioural interventions, including lifestyle modifications, in the treatment of OAB and UUI have been described. However, many primary care clinicians may have a limited awareness of the evidence supporting the often straight-forward treatment recommendations and guidance for incorporating behavioural interventions into busy primary care practices, because most of this information has appeared in the specialty literature. The purpose of this review is to provide an overview of behavioural interventions for OAB and UUI that can be incorporated with minimal time and effort into the treatment armamentarium of all clinicians that care for patients with bladder problems. Practical supporting materials that will facilitate the use of these interventions in the clinic are included; these can be used to help patients understand lifestyle choices and voiding behaviours that may improve function in

  4. Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

    PubMed

    Alberti, C

    2016-01-01

    To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

  5. Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

    PubMed Central

    ALBERTI, C.

    2016-01-01

    To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering. Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either “unseeded” (cell free) or autologous “cell seeded” tissue engineering scaffolds. Different categories of cell sources – from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells – have been taken into consideration to reach the construction of suitable “cell seeded” templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications. PMID:27142819

  6. The role of TRPM8 in the Guinea-pig bladder-cooling reflex investigated using a novel TRPM8 antagonist.

    PubMed

    Gardiner, Jennifer C; Kirkup, Anthony J; Curry, John; Humphreys, Sian; O'Regan, Paul; Postlethwaite, Michael; Young, Kimberley C; Kitching, Linda; Ethell, Brian T; Winpenny, David; McMurray, Gordon

    2014-10-01

    Patients with overactive bladder often exhibit abnormal bladder contractions in response to intravesical cold saline (positive ice-water test). The molecular entity involved in cold sensation within the urinary bladder is unknown, but a potential candidate is the ion channel, transient receptor potential (melastatin)-8 (TRPM8). The objective of the present study was to investigate the role of TRPM8 in a bladder-cooling reflex evoked in anaesthetised guinea-pigs that is comparable to the positive ice-water test seen in patients. Guinea-pig TRPM8 was cloned from L6 dorsal root ganglia (DRG) and expressed in HEK293 cells. Functional agonist- and cold-induced Ca2+ influx and electrophysiology assays were performed in these cells, and for comparison in HEK293 cells expressing human TRPM8, using a novel TRPM8 antagonist, the S-enantiomer of 1-phenylethyl 4-(benzyloxy)-3-methoxybenzyl (2-aminoethyl) carbamate hydrochloride (PBMC). Potency data from these assays was used to calculate intravenous infusion protocols for targeted plasma concentrations of PBMC in studies on micturition reflexes evoked by intravesical infusion of menthol or cold saline in anaesthetised guinea-pigs. Tissue expression of TRPM8 in guinea-pig bladder, urethra and in dorsal root ganglia neurones traced from the bladder was also investigated. TRPM8 mRNA and protein were detected in L6 dorsal root ganglia, bladder urothelium and smooth muscle. PBMC antagonised in vitro activation of human and guinea-pig TRPM8 and reversed menthol and cold-induced facilitation of the micturition reflex at plasma concentrations consistent with in vitro potencies. The present data suggest that the bladder-cooling reflex in the guinea-pig involves TRPM8. The potential significance of TRPM8 in bladder disease states deserves future investigation. PMID:25058909

  7. The role of TRPM8 in the Guinea-pig bladder-cooling reflex investigated using a novel TRPM8 antagonist.

    PubMed

    Gardiner, Jennifer C; Kirkup, Anthony J; Curry, John; Humphreys, Sian; O'Regan, Paul; Postlethwaite, Michael; Young, Kimberley C; Kitching, Linda; Ethell, Brian T; Winpenny, David; McMurray, Gordon

    2014-10-01

    Patients with overactive bladder often exhibit abnormal bladder contractions in response to intravesical cold saline (positive ice-water test). The molecular entity involved in cold sensation within the urinary bladder is unknown, but a potential candidate is the ion channel, transient receptor potential (melastatin)-8 (TRPM8). The objective of the present study was to investigate the role of TRPM8 in a bladder-cooling reflex evoked in anaesthetised guinea-pigs that is comparable to the positive ice-water test seen in patients. Guinea-pig TRPM8 was cloned from L6 dorsal root ganglia (DRG) and expressed in HEK293 cells. Functional agonist- and cold-induced Ca2+ influx and electrophysiology assays were performed in these cells, and for comparison in HEK293 cells expressing human TRPM8, using a novel TRPM8 antagonist, the S-enantiomer of 1-phenylethyl 4-(benzyloxy)-3-methoxybenzyl (2-aminoethyl) carbamate hydrochloride (PBMC). Potency data from these assays was used to calculate intravenous infusion protocols for targeted plasma concentrations of PBMC in studies on micturition reflexes evoked by intravesical infusion of menthol or cold saline in anaesthetised guinea-pigs. Tissue expression of TRPM8 in guinea-pig bladder, urethra and in dorsal root ganglia neurones traced from the bladder was also investigated. TRPM8 mRNA and protein were detected in L6 dorsal root ganglia, bladder urothelium and smooth muscle. PBMC antagonised in vitro activation of human and guinea-pig TRPM8 and reversed menthol and cold-induced facilitation of the micturition reflex at plasma concentrations consistent with in vitro potencies. The present data suggest that the bladder-cooling reflex in the guinea-pig involves TRPM8. The potential significance of TRPM8 in bladder disease states deserves future investigation.

  8. Glucocorticoid therapy and risk of bladder cancer

    PubMed Central

    Dietrich, K; Schned, A; Fortuny, J; Heaney, J; Marsit, C; Kelsey, K T; Karagas, M R

    2009-01-01

    Background: Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk. Methods: In a population-based case–control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use. Results: In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR=1.85, 95% CI=1.24–2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR=2.12, 95% CI=1.17–3.85) and tumours with high (3+) p53 staining intensity (OR=2.35, 95% CI=1.26–4.36). Conclusion: Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology. PMID:19773763

  9. Noninvasive Electromagnetic Detection of Bladder Cancer

    PubMed Central

    Cormio, Luigi; Vedruccio, Clarbruno; Leucci, Giorgio; Massenio, Paolo; Di Fino, Giuseppe; Cavaliere, Vincenzo; Carrieri, Giuseppe

    2014-01-01

    Objectives. Normal and neoplastic human tissues have different electromagnetic properties. This study aimed to determine the diagnostic accuracy of noninvasive electromagnetic detection of bladder cancer (BC) by the tissue-resonance interaction method (TRIM-prob). Patients and Methods. Consecutive patients were referred for cystoscopy because of (i) microscopic or gross hematuria and/or irritative voiding symptoms and (ii) bladder ultrasounds and urinary cytology findings negative or just suspicious of malignancy. Patients were first submitted to TRIM-prob bladder scanning by a single investigator and then to cystoscopy by another investigator blind to TRIM-prob data. Results. In 125 evaluated patients cystoscopy was positive for BC in 47 and negative in the remaining 78; conversely, TRIM-prob bladder scanning was positive for BC in 53 and negative in 72. In particular, TRIM-prob scanning yielded 7 false positives and only one false negative; therefore, its overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.9%, 89.9%, 86.8%, 98.6%, and 93.6%, respectively. Conclusions. TRIM-prob bladder scanning was a simple and quite accurate method for non-invasive electromagnetic detection of BC. If the elevated positive and negative predictive values will be replicated in further well-designed studies, it could be used to screen asymptomatic patients at high risk of BC. PMID:24563795

  10. [Epidemiological investigation on bladder cancer and occupations].

    PubMed

    Obata, K; Ohno, Y; Aoki, K

    1989-12-01

    A population-based case-control study was conducted in Boston, U.S.A., Manchester, U.K., and Nagoya, Japan to assess the associations of occupations with bladder cancer in men. In Nagoya, cancer cases were identified through Nagoya Bladder Cancer Registry, and controls were randomly selected from the general population using electoral registers. Study subjects, all males, analyzed were 430 cases and 397 controls in Boston; 339 and 493 in Manchester, and 220 and 443 in Nagoya, respectively. Occupations significantly related to an increased bladder cancer risk were those manufacturing or handling dyes, leather, paint or organic chemicals in Boston, and leather or medical workers in Manchester. Occupations significantly associated with bladder cancer development were not found in Nagoya. In general, risk related to occupations was relatively higher in the younger age group (less than 65 years old) than in the older age group (greater than or equal to 65 yrs old). Statistically significant differences in bladder cancer risk were not demonstrated between manufacturing workers and service workers.

  11. Expression profiles of variation integration genes in bladder urothelial carcinoma.

    PubMed

    Wang, J M; Wang, Y Q; Gao, Z L; Wu, J T; Shi, B K; Yu, C C

    2014-01-01

    Bladder cancer is a common cancer worldwide and its incidence continues to increase. There are approximately 261,000 cases of bladder cancer resulting in 115,000 deaths annually. This study aimed to integrate bladder cancer genome copy number variation information and bladder cancer gene transcription level expression data to construct a causal-target module network of the range of bladder cancer-related genomes. Here, we explored the control mechanism underlying bladder cancer phenotype expression regulation by the major bladder cancer genes. We selected 22 modules as the initial module network to expand the search to screen more networks. After bootstrapping 100 times, we obtained 16 key regulators. These 16 key candidate regulatory genes were further expanded to identify the expression changes of 11,676 genes in 275 modules, which may all have the same regulation. In conclusion, a series of modules associated with the terms 'cancer' or 'bladder' were considered to constitute a potential network.

  12. Complete duplication of bladder and urethra: a case report.

    PubMed

    Esham, W; Holt, H A

    1980-05-01

    A case of complete duplication of the bladder and urethra in a girl is reported, demonstrating outlet obstruction in the bladder on the left side. Associated anomalies and pertinent literature are reviewed.

  13. Autophagy and urothelial carcinoma of the bladder: A review

    PubMed Central

    Chandrasekar, Thenappan

    2016-01-01

    The incidence of urothelial carcinoma of the urinary bladder (bladder cancer) remains high. While other solid organ malignancies have seen significant improvement in morbidity and mortality, there has been little change in bladder cancer mortality in the past few decades. The mortality is mainly driven by muscle invasive bladder cancer, but the cancer burden remains high even in nonmuscle invasive bladder cancer due to high recurrence rates and risk of progression. While apoptosis deregulation has long been an established pathway for cancer progression, nonapoptotic pathways have gained prominence of late. Recent research in the role of autophagy in other malignancies, including its role in treatment resistance, has led to greater interest in the role of autophagy in bladder cancer. Herein, we summarize the literature regarding the role of autophagy in bladder cancer progression and treatment resistance. We address it by systematically reviewing treatment modalities for nonmuscle invasive and muscle invasive bladder cancer. PMID:27326411

  14. [Bladder stone surrounding a foreign body: a case report].

    PubMed

    Fekak, H; Rabii, R; Moufid, K; Guessous, H; Joual, A; Bennani, S; Elmrini, M; Benjeloun, S

    2003-04-01

    The bladder can be the site of various foreign bodies. We report one case of bladder stone including a foreign body in a 24 years old man with a psychomotor deficiency who was admitted for pyuria, block miction and bladder symptoms. The pelvic X-Ray film showed a bladder stone including a sewing needle. We analysed the diagnosis, aspect and therapeutic management of this case. PMID:12741198

  15. Delayed Diagnosis of Iatrogenic Bladder Perforation in a Neonate

    PubMed Central

    Perez, Jose A.; Rich, Mark A.; Swana, Hubert S.

    2016-01-01

    Iatrogenic bladder injuries have been reported in the neonate during umbilical artery/vein catheterization, voiding cystourethrogram, urinary catheterizations, and overwhelming hypoxic conditions. Patients with iatrogenic bladder perforations can present with acute abdomen indicating urinary peritonitis, septic-uremic shock, or subtle symptoms like abdominal distension, pain, hematuria, uremia, electrolyte imbalances, and/or difficulty urinating. The following neonatal case report of perforated bladder includes a review of the signs, symptoms, diagnostic tools, and management of bladder injury in neonates. PMID:27747129

  16. The various types of neurogenic bladder dysfunction: an update of current therapeutic concepts.

    PubMed

    Madersbacher, H

    1990-05-01

    weak reflex detrusor contractions are present. (3) With the combination of an areflexive or hyporeflexive detrusor and a flaccid pelvic floor, passive voiding by abdominal straining or by the Credé manoeuvre is usually recommended, but should be replaced by CIC if this mechanism of bladder emptying creates unphysiological high and dangerous intravesical pressures, or if vesico-uretero-renal reflux is present. Neurogenic urinary stress incontinence is usually associated with this type of lesion and can be successfully treated by the implantation of an artificial urinary sphincter (Scott). However in two thirds of the patients with neurogenic bladder dysfunction, additional, usually operative treatment is necessary to meet the criteria for implantation. Moreover, a 30% rate of repair operations must be accepted by patients, but is becoming less frequently required with an improved design of the device.(ABSTRACT TRUNCATED AT 400 WORDS)

  17. Gall bladder Adenocarcinoma in a Young Girl.

    PubMed

    Date, Shivprasad V; Rizvi, S J

    2015-04-01

    A 16-year-old girl presented with abdominal discomfort, weakness, and jaundice. General examination revealed deep icterus with hard lymph nodes in left supraclavicular region. On gastrointestinal examination, we appreciated a hard intra-abdominal lump in the right hypochondrium. Biochemical evaluation showed features of obstructive jaundice. Imaging confirmed the presence of gall bladder lump with multiple intra-abdominal lymph nodes. Fine needle aspiration cytology of neck nodes demonstrated metastatic adenocarcinoma. Fine needle aspiration cytology of the gall bladder lump (done under sonographic guidance) confirmed poorly differentiated adenocarcinoma. To the best of our knowledge, malignancy of the gall bladder has not been reported in individuals less than 18 years in India, and only three cases have been reported worldwide in English literature. PMID:26139973

  18. A flowgraph model for bladder carcinoma

    PubMed Central

    2014-01-01

    Background Superficial bladder cancer has been the subject of numerous studies for many years, but the evolution of the disease still remains not well understood. After the tumor has been surgically removed, it may reappear at a similar level of malignancy or progress to a higher level. The process may be reasonably modeled by means of a Markov process. However, in order to more completely model the evolution of the disease, this approach is insufficient. The semi-Markov framework allows a more realistic approach, but calculations become frequently intractable. In this context, flowgraph models provide an efficient approach to successfully manage the evolution of superficial bladder carcinoma. Our aim is to test this methodology in this particular case. Results We have built a successful model for a simple but representative case. Conclusion The flowgraph approach is suitable for modeling of superficial bladder cancer. PMID:25080066

  19. Gall bladder Adenocarcinoma in a Young Girl.

    PubMed

    Date, Shivprasad V; Rizvi, S J

    2015-04-01

    A 16-year-old girl presented with abdominal discomfort, weakness, and jaundice. General examination revealed deep icterus with hard lymph nodes in left supraclavicular region. On gastrointestinal examination, we appreciated a hard intra-abdominal lump in the right hypochondrium. Biochemical evaluation showed features of obstructive jaundice. Imaging confirmed the presence of gall bladder lump with multiple intra-abdominal lymph nodes. Fine needle aspiration cytology of neck nodes demonstrated metastatic adenocarcinoma. Fine needle aspiration cytology of the gall bladder lump (done under sonographic guidance) confirmed poorly differentiated adenocarcinoma. To the best of our knowledge, malignancy of the gall bladder has not been reported in individuals less than 18 years in India, and only three cases have been reported worldwide in English literature.

  20. Botulinum Toxin to Treat Neurogenic Bladder.

    PubMed

    Smith, Christopher P; Chancellor, Michael B

    2016-02-01

    Alteration in neural control from suprapontine areas to the nerves innervating the bladder can lead to bladder dysfunction and the development of a neurogenic bladder (NGB). Patients with NGB often suffer from urinary incontinence, which can lead to adverse events such as urinary tract infections and decubiti, in addition to creating a large care burden for family members or healthcare providers and significantly impairing patient quality of life. The common failure of anticholinergic medications has spurned the development of second-line treatments, including the use of botulinum toxin. OnabotulinumtoxinA (onaBoNT-A; BOTOX, Allergan, Inc.) was approved by the U.S. Food and Drug Administration (FDA) in 2011 to treat neurogenic detrusor overactivity in patients with urinary incontinence resulting from a NGB. In this review the authors summarize pertinent results from key trials leading to FDA approval of onaBoNT-A as well as more recent long-term data.

  1. Optimizing systemic therapy for bladder cancer.

    PubMed

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  2. Urothelial bladder cancer with cavitary lung metastases.

    PubMed

    Kurian, Anil; Lee, Jason; Born, Abraham

    2011-01-01

    Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Longterm survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis. PMID:21766082

  3. Neural reconstruction methods of restoring bladder function

    PubMed Central

    Gomez-Amaya, Sandra M.; Barbe, Mary F.; de Groat, William C.; Brown, Justin M.; Tuite, Gerald F.; Corcos, Jacques; Fecho, Susan B.; Braverman, Alan S.; Ruggieri, Michael R.

    2015-01-01

    During the past century, diverse studies have focused on the development of surgical strategies to restore function of a decentralized bladder after spinal cord or spinal root injury via repair of the original roots or by transferring new axonal sources. The techniques included end-to-end sacral root repairs, transfer of roots from other spinal segments to sacral roots, transfer of intercostal nerves to sacral roots, transfer of various somatic nerves to the pelvic or pudendal nerve, direct reinnervation of the detrusor muscle, or creation of an artificial reflex pathway between the skin and the bladder via the central nervous system. All of these surgical techniques have demonstrated specific strengths and limitations. The findings made to date already indicate appropriate patient populations for each procedure, but a comprehensive assessment of the effectiveness of each technique to restore urinary function after bladder decentralization is required to guide future research and potential clinical application. PMID:25666987

  4. Bladder Leiomyoma Presenting With LUTS and Coexisting Bladder and Uterine Leiomyomata: A Review of Two Cases

    PubMed Central

    Jain, Sudhir Kumar; Tanwar, Raman; Mitra, Aparajita

    2014-01-01

    Mesenchymal tumors of the urinary bladder are a rare occurrence, the most common among them being leiomyoma of the bladder. These tumors commonly present with irritative urinary symptoms progressing gradually to obstructive symptoms as the size increases. We report on two patients who presented with lower urinary tract symptoms (LUTS). One of the patients also had concomitant bladder and uterine leiomyomata, which is the first such case to be reported in the literature. It is essential to differentiate leiomyoma from other common causes of LUTS. Cold cup biopsy has a significant false-negative rate and, in such cases, a wide local excision provides an optimal cure with excellent results. PMID:24791156

  5. Calcifying nanoparticles associated encrusted urinary bladder cystitis

    PubMed Central

    Jelic, Tomislav M; Roque, Rod; Yasar, Uzay; Tomchin, Shayna B; Serrato, Jose M; Deem, Samuel G; Tierney, James P; Chang, Ho-Huang

    2008-01-01

    Encrusted cystitis is a subtype of chronic cystitis characterized by multiple calcifications in the form of plaques located in the interstitium of the urinary bladder mucosa and frequently associated with mucosal ulcers. It is a very rare disease of controversial etiology. Our transmission electron microscopy of the calcified plaques of encrusted cystitis has revealed that the smallest formed particles (elementary units) of these calcifications are electron-dense shells surrounding an electron lucent core, diagnostic of calcifying nanoparticles (previously called nanobacteria). We pioneer the notion that calcifying nanoparticles are the causative agents of encrusted urinary bladder cystitis. PMID:18990947

  6. Urinary Tract Infection and Neurogenic Bladder.

    PubMed

    McKibben, Maxim J; Seed, Patrick; Ross, Sherry S; Borawski, Kristy M

    2015-11-01

    Urinary tract infections (UTIs) are frequent, recurrent, and lifelong for patients with neurogenic bladder and present challenges in diagnosis and treatment. Patients often present without classic symptoms of UTI but with abdominal or back pain, increased spasticity, and urinary incontinence. Failure to recognize and treat infections can quickly lead to life-threatening autonomic dysreflexia or sepsis, whereas overtreatment contributes to antibiotic resistance, thus limiting future treatment options. Multiple prevention methods are used but evidence-based practices are few. Prevention and treatment of symptomatic UTI requires a multimodal approach that focuses on bladder management as well as accurate diagnosis and appropriate antibiotic treatment. PMID:26475949

  7. Calcifying nanoparticles associated encrusted urinary bladder cystitis.

    PubMed

    Jelic, Tomislav M; Roque, Rod; Yasar, Uzay; Tomchin, Shayna B; Serrato, Jose M; Deem, Samuel G; Tierney, James P; Chang, Ho-Huang

    2008-01-01

    Encrusted cystitis is a subtype of chronic cystitis characterized by multiple calcifications in the form of plaques located in the interstitium of the urinary bladder mucosa and frequently associated with mucosal ulcers. It is a very rare disease of controversial etiology. Our transmission electron microscopy of the calcified plaques of encrusted cystitis has revealed that the smallest formed particles (elementary units) of these calcifications are electron-dense shells surrounding an electron lucent core, diagnostic of calcifying nanoparticles (previously called nanobacteria). We pioneer the notion that calcifying nanoparticles are the causative agents of encrusted urinary bladder cystitis. PMID:18990947

  8. Small cell carcinoma of the bladder

    PubMed Central

    Calado, Bruno Nagel; Maron, Paulo Eduardo Goulart; Vedovato, Bruno César; Barrese, Tomas Zecchini; Fernandes, Roni de Carvalho; Perez, Marjo Deninson Cardenuto

    2015-01-01

    Small cell carcinoma of the urinary bladder is an extremely aggressive and rare tumor. Even though small cell carcinoma most commonly arises from the lungs there are several reports of small cell carcinoma in extrapulmonary sites. Due to its low frequency there is no well-established management for this disease. We report the case of a 61 year-old man with small cell carcinoma of the bladder who underwent radical cystectomy following neoadjuvant chemotherapy. We also reviewed the literature for the optimal treatment strategy. PMID:25517085

  9. Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis

    PubMed Central

    Osterberg, E. Charles; Elliott, Sean P.; Hittelman, Adam B.

    2016-01-01

    We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting.

  10. Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis

    PubMed Central

    Osterberg, E. Charles; Elliott, Sean P.; Hittelman, Adam B.

    2016-01-01

    We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting. PMID:27656309

  11. Fgfr2 is integral for bladder mesenchyme patterning and function

    PubMed Central

    Walker, K. A.; Ikeda, Y.; Zabbarova, I.; Schaefer, C. M.; Bushnell, D.; De Groat, W. C.; Kanai, A.

    2015-01-01

    While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor (Fgfr)2 is necessary for kidney and ureter mesenchymal development. The objective of the present study was to determine the role of Fgfr2 in the bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in the bladder mesenchyme (Fgfr2BM−/−). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblot analysis, void stain on paper, ex vivo bladder sheet assays, and in vivo decerebrated cystometry. Compared with control bladders, embryonic day 16.5 (E16.5) Fgfr2BM−/− bladders had thin muscle layers with less α-smooth muscle actin and thickened lamina propria with increased collagen type Ia and IIIa that intruded into the muscle. The reciprocal changes in mutant layer thicknesses appeared partly due to a cell fate switch. From postnatal days 1 to 30, Fgfr2BM−/− bladders demonstrated progressive muscle loss and increased collagen expression. Postnatal Fgfr2BM−/− bladder sheets exhibited decreased agonist-mediated contractility and increased passive stretch tension versus control bladder sheets. Cystometry revealed high baseline and threshold pressures and shortened intercontractile intervals in Fgfr2BM−/− versus control bladders. Mechanistically, whereas Shh expression appeared normal, mRNA and protein readouts of hedgehog activity were increased in E16.5 Fgfr2BM−/− versus control bladders. Moreover, E16.5 Fgfr2BM−/− bladders exhibited higher levels of Cdo and Boc, hedgehog coreceptors that enhance sensitivity to Shh, compared with control bladders. In conclusion, loss of Fgfr2 in the bladder mesenchyme leads to abnormal bladder morphology and decreased compliance and contractility. PMID:25656370

  12. Assessment of antiseptic bladder washout procedures using a physical model of the catheterised bladder.

    PubMed

    Stickler, D J; Clayton, C L; Chawla, J C

    1987-11-01

    A simple physical model of the catheterised bladder has been used to assess the activities of antiseptic agents that have been recommended as bladder instillations in the treatment of urinary tract infections in patients with indwelling catheters. The activities of povidone-iodine, phenoxyethanol, chlorhexidine, chlorhexidine supplemented with EDTA + Tris, noxythiolin and neomycin were examined against selected species of uropathogens. Except for phenoxyethanol against Pv. stuartii and possibly Ps. aeruginosa, single applications of these antibacterials for 30 min were not effective in sterilising urine in the artificial bladder. However, a second application 1 h later of phenoxyethanol but not chlorhexidine or povidone-iodine did eradicate Ps. aeruginosa. It is suggested that bacteria growing as a film on the bladder wall are particularly resistant to antimicrobials.

  13. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells.

    PubMed

    Mahajan, Pradeep V; Subramanian, Swetha; Danke, Amit; Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted. PMID:27656308

  14. Solitary Fibrous Tumor in a Female Urinary Bladder.

    PubMed

    Mustafa, Hiba J; Menon, Sharifa

    2016-07-01

    Solitary fibrous tumors of the bladder are extremely rare especially in the females. This is the third case of SFT in a female urinary bladder. We are presenting a case of 36-years-old female who underwent a procedure for what thought to be cervical myoma. Cystectomy and bilateral ureteral re-implantation were performed. Mass showed to be solitary fibrous tumor of the urinary bladder. These tumors are rarely occur in extrapleural spaces. Only few cases had been reported in the urinary bladder including 2 in the female and 10 in the male bladder.

  15. Solitary Fibrous Tumor in a Female Urinary Bladder.

    PubMed

    Mustafa, Hiba J; Menon, Sharifa

    2016-07-01

    Solitary fibrous tumors of the bladder are extremely rare especially in the females. This is the third case of SFT in a female urinary bladder. We are presenting a case of 36-years-old female who underwent a procedure for what thought to be cervical myoma. Cystectomy and bilateral ureteral re-implantation were performed. Mass showed to be solitary fibrous tumor of the urinary bladder. These tumors are rarely occur in extrapleural spaces. Only few cases had been reported in the urinary bladder including 2 in the female and 10 in the male bladder. PMID:27335777

  16. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells

    PubMed Central

    Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted.

  17. Novel therapeutic approaches for recurrent nonmuscle invasive bladder cancer.

    PubMed

    Boehm, Brock E; Svatek, Robert S

    2015-05-01

    This article summarizes strategies being investigated in patients with nonmuscle invasive bladder cancer. Progress has been made toward improving the delivery method of intravesical agents. Intravesical therapy is limited by the amount of time that the agent remains in contact with the bladder. Bladder cancer is considered to be responsive to immune therapy. Thus, many novel approaches are immune-based therapies and include cancer vaccines, use of Bacillus Calmette-Guérin (BCG) subcomponents, and checkpoint inhibitors. Finally, access to bladder mucosa via direct catheterization into the bladder via the urethra has enabled unique strategies for delivery of cancer therapy including viral- or plasmid-based gene therapy.

  18. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells

    PubMed Central

    Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted. PMID:27656308

  19. BCG Induced Necrosis of the Entire Bladder Urothelium.

    PubMed

    Krönig, Malte; Jilg, Cordula; Burger, Dieter; Langer, Mathias; Timme-Bronsert, Sylvia; Werner, Martin; Wetterauer, Ulrich; Seemann, Wolfgang-Schultze

    2015-09-01

    Instillation therapy with attenuated tuberculosis bacteria (BCG) can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  20. BCG Induced Necrosis of the Entire Bladder Urothelium.

    PubMed

    Krönig, Malte; Jilg, Cordula; Burger, Dieter; Langer, Mathias; Timme-Bronsert, Sylvia; Werner, Martin; Wetterauer, Ulrich; Seemann, Wolfgang-Schultze

    2015-09-01

    Instillation therapy with attenuated tuberculosis bacteria (BCG) can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence. PMID:26793538

  1. Activation of bitter taste receptors (tas2rs) relaxes detrusor smooth muscle and suppresses overactive bladder symptoms

    PubMed Central

    Nyirimigabo, Eric; Mi, Yue; Wang, Yan; Liu, Qinghua; Man, Libo; Wu, Shiliang; Jin, Jie; Ji, Guangju

    2016-01-01

    Bitter taste receptors (TAS2Rs) are traditionally thought to be expressed exclusively on the taste buds of the tongue. However, accumulating evidence has indicated that this receptor family performs non-gustatory functions outside the mouth in addition to taste. Here, we examined the role of TAS2Rs in human and mouse detrusor smooth muscle (DSM). We showed that mRNA for various TAS2R subtypes was expressed in both human and mouse detrusor smooth muscle (DSM) at distinct levels. Chloroquine (CLQ), an agonist for TAS2Rs, concentration-dependently relaxed carbachol- and KCl-induced contractions of human DSM strips. Moreover, 100 μM of CLQ significantly inhibited spontaneous and electrical field stimulation (EFS)-induced contractions of human DSM strips. After a slight contraction, CLQ (1 mM) entirely relaxed carbachol-induced contraction of mouse DSM strips. Furthermore, denatonium and quinine concentration-dependently decreased carbachol-induced contractions of mouse DSM strips. Finally, we demonstrated that CLQ treatment significantly suppressed the overactive bladder (OAB) symptoms of mice with partial bladder outlet obstruction (PBOO). In conclusion, we for the first time provide evidence of the existence of TAS2Rs in the urinary DSM and demonstrate that TAS2Rs may represent a potential target for OAB. These findings open a new approach to develop drugs for OAB in the future. PMID:27056888

  2. Noninvasive Evaluation of Bladder Wall Mechanical Properties as a Function of Filling Volume: Potential Application in Bladder Compliance Assessment

    PubMed Central

    Mynderse, Lance; Husmann, Douglas; Urban, Matthew; Alizad, Azra

    2016-01-01

    Purpose We propose a novel method to monitor bladder wall mechanical properties as a function of filling volume, with the potential application to bladder compliance assessment. The proposed ultrasound bladder vibrometry (UBV) method uses ultrasound to excite and track Lamb waves on the bladder wall from which its mechanical properties are derived by fitting measurements to an analytical model. Of particular interest is the shear modulus of bladder wall at different volumes, which we hypothesize, is similar to measuring the compliance characteristics of the bladder. Materials and Methods Three experimental models were used: 1) an ex vivo porcine model where normal and aberrant (stiffened by formalin) bladders underwent evaluation by UBV; 2) an in vivo study to evaluate the performance of UBV on patients with clinically documented compliant and noncompliant bladders undergoing UDS; and 3) a noninvasive UBV protocol to assess bladder compliance using oral hydration and fractionated voiding on three healthy volunteers. Results The ex vivo studies showed a high correlation between the UBV parameters and direct pressure measurement (R2 = 0.84–0.99). A similar correlation was observed for 2 patients with compliant and noncompliant bladders (R2 = 0.89–0.99) undergoing UDS detrusor pressure-volume measurements. The results of UBV on healthy volunteers, performed without catheterization, were comparable to a compliant bladder patient. Conclusion The utility of UBV as a method to monitor changes in bladder wall mechanical properties is validated by the high correlation with pressure measurements in ex vivo and in vivo patient studies. High correlation UBV and UDS in vivo studies demonstrated the potential of UBV as a bladder compliance assessment tool. Results of studies on healthy volunteers with normal bladders demonstrated that UBV could be performed noninvasively. Further studies on a larger cohort are needed to fully validate the use of UBV as a clinical tool for

  3. Bladder leiomyoma: Presentation, evaluation and treatment

    PubMed Central

    Khater, Nazih; Sakr, Ghazi

    2012-01-01

    Background Bladder leiomyomas are benign mesenchymal neoplasms and very rare urinary tumours that represent <0.5% of all bladder tumours, with only 250 cases reported worldwide to date. The importance of recognising their characteristic features, leading to their correct treatment, is fundamental. Therefore, we reviewed reports of leiomyomas of the urinary bladder, their causes, clinical presentations, imaging methods and surgical management, updated to 2012. Methods We retrospectively reviewed articles published in the USA, Europe and Asia, from 1953 to date, using PubMed, Medscape, Medline and the several major journals. We report areas of controversies and well-established guidelines. Results We reviewed 36 articles that confirmed, with a high level of evidence-based medicine, that the male to female ratio is equal, the cause of bladder leiomyomas remains unknown, and their most common presentation is obstructive uropathy; endovesical tumours are the most common. Their radiological diagnosis can be made by ultrasonography, computed tomography or magnetic resonance imaging. Complete surgical resection is a very effective treatment, associated with almost no recurrence. Conclusion In symptomatic patients a complete surgical resection can give a very good outcome, with almost no recurrence. PMID:26579246

  4. Bladder cancer: molecular determinants of personalized therapy.

    PubMed

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  5. Small cell carcinoma of the urinary bladder.

    PubMed

    Pant-Purohit, Mukta; Lopez-Beltran, Antonio; Montironi, Rodolfo; MacLennan, Gregory T; Cheng, Liang

    2010-02-01

    Small cell carcinoma of the urinary bladder (SCCUB) is a rare and aggressive cancer of the bladder. SCCUB is part of neuroendocrine family of tumors that affect several organ systems including respiratory, gastrointestinal and male and female genitourinary tract. SCCUB affect males predominantly with common risk factors include smoking, bladder calculi, bladder manipulation, and chronic cystitis. Prognosis of SCCUB remains poor due to high metastatic potential and lack of symptoms in earlier stages of the disease. Pathogenesis of the disease is linked to loss of genetic material, hypermethylation of tumor suppressors and at times amplification of the chromosomal regions carrying oncogenes. Majority of cases are treated with local resection of the tumor with neoadjuvant or adjuvant platinum-based chemotherapy regimen. Radiation therapy is used as alternative to radical cystectomy or as palliative measure. This article provides epidemiology, molecular pathogenesis, histochemistry, and current management options for SCCUB. Furthermore we reviewed all recent studies involving advancement in targeted molecular therapy for neuroendocrine tumors. PMID:20017108

  6. Arsenic and bladder cancer: observations and suggestions.

    PubMed

    Radosavljević, Vladan; Jakovljević, Branko

    2008-10-01

    Arsenic from drinking water is a well-known risk factor for bladder cancer. The purpose of this paper is to systematize some important yet often overlooked facts considering the relationship between arsenic exposure and the occurrence of bladder cancer. Since the exposure to inorganic arsenic from food, inhaled air, and skin absorption as well as arsenic methylation ability are not fully investigated, our assumption is that the exposure of arsenic only from drinking water is underestimated and its role as a risk factor is highly overestimated. This paper proposes some qualitative and quantitative parameters of arsenic as a risk factor for bladder cancer. The recommended qualitative parameters of arsenic intake are first, pathways of exposure, and second, toxicity and metabolism. The suggested quantitative parameters of arsenic intake include amounts of arsenic absorbed in the body, duration of arsenic exposure, and duration of arsenic presence in the urinary bladder. This approach can be implemented in a systematic classification and explanation of various risk factors and their mutual interactions for other types of cancer or diseases in general.

  7. Somatic mutation of PTEN in bladder carcinoma

    PubMed Central

    Aveyard, J S; Skilleter, A; Habuchi, T; Knowles, M A

    1999-01-01

    The tumour suppressor gene PTEN/MMAC1, which is mutated or homozygously deleted in glioma, breast and prostate cancer, is mapped to a region of 10q which shows loss of heterozygosity (LOH) in bladder cancer. We screened 123 bladder tumours for LOH in the region of PTEN. In 53 informative muscle invasive tumours (≥ pT2), allele loss was detected in 13 (24.5%) and allelic imbalance in four tumours (overall frequency 32%). LOH was found in four of 60 (6.6%) informative, non-invasive tumours (pTa/pT1). We screened 63 muscle invasive tumours for PTEN mutations by single-strand conformation polymorphism (SSCP) analysis and for homozygous deletion by duplex quantitative polymerase chain reaction (PCR). Two homozygous deletions were identified but no mutations. Of 15 bladder tumour cell lines analysed, three showed homozygous deletion of all or part of the PTEN gene, but none had mutations detectable by SSCP analysis. Our results indicate that PTEN is involved in the development of some bladder tumours. The low frequency of mutation of the retained allele in tumours with 10q23 LOH suggests that there may be another predominant mechanism of inactivation of the second allele, for example small intragenic deletions, that hemizygosity may be sufficient for phenotypic effect, or that there is another target gene at 10q23. © 1999 Cancer Research Campaign PMID:10360673

  8. How frequent are overactive bladder symptoms in women with urodynamic verification of an overactive bladder?

    PubMed Central

    Yeniel, Ahmet Özgür; Ergenoğlu, Mete Ahmet; Meseri, Reci; Aşkar, Niyazi; İtil, İsmail Mete

    2012-01-01

    Objective To determine the relationship between overactive bladder symptoms and urodynamic verification of overactive bladder. Material and Methods Between June 2011 and November 2011, 159 patients underwent urodynamics (UDS) at our urogynecology unit in the Ege University Hospital. Of these, 95 patients who complained of urgency, did not have any overt neurological diseases, bladder outlet obstruction and did not take any medication affecting the lower urinary tract function were evaluated. SPSS (ver. 15.0) was used to evaluate the data and the chi-square test and t test for independent samples were used for analysis. Results The mean age was found to be 54.5±12. Frequency was the most frequent symptom in women with overactive bladder (OAB) (82.1%), nocturia (57.8%) and (57.8%) urgency urinary incontinence followed in frequency. Detrusor over activity incidence was found to be 38.9%. There was no significant relationship between the presence of detrusor over activity (DOA) and OAB symptoms. Leak at urodynamics was found in 46.3% and there is no significant association with detrusor overactivity. Total bladder capacity was found to be significantly lower in women who had DOA (p=0.000). Conclusion It appears that overactive bladder symptoms do not predict detrusor over activity. Urodynamic investigation is not mandatory in the initial management of women with only OAB symptoms. PMID:24592016

  9. Management options for sphincteric deficiency in adults with neurogenic bladder

    PubMed Central

    Mayer, Erik N.; Lenherr, Sara

    2016-01-01

    Neurogenic bladder is a very broad disease definition that encompasses varied disease and injury states affecting the bladder. The majority of patients with neurogenic bladder dysfunction do not have concomitant intrinsic sphincteric deficiency (ISD), but when this occurs the challenges of management of urinary incontinence from neurogenic bladder are compounded. There are no guidelines for surgical correction of ISD in adults and most of the literature on treatment of the problem comes from treatment of children with congenital diseases, such as myelomeningocele. Our goal, in this review, is to present some of the common surgical options for ISD [including artificial urinary sphincters, bladder slings, bladder neck reconstruction (BNR) and urethral bulking agents] and the evidence underlying these treatments in adults with neurogenic bladder. PMID:26904420

  10. Genetics of Bladder Malignant Tumors in Childhood.

    PubMed

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-02-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  11. Bladder perforation in a peritoneal dialysis patient.

    PubMed

    Ounissi, M; Sfaxi, M; Fayala, H; Abderrahim, E; Ben Abdallah, T; Chebil, M; Ben Maiz, H; Kheder, A

    2012-05-01

    The dysfunction of the catheter in peritoneal dialysis (PD) is a frequent complication. However, perforation of organs are rare, particularly that of the urinary bladder. This requires an early diagnosis and prompt treatment of patients. We report here the case of a 38-year-old woman having end-stage renal disease due to autosomal-dominant polycystic kidney disease treated by PD since November 2000. Three years later, she was treated for Staphylococcal peritonitis. Four months later, she presented with a severe urge to urinate at the time of the fluid exchanges. The biochemical analysis of the fluid from the bladder showed that it was dialysis fluid. Injection of contrast through the catheter demonstrated the presence of a fistula between the bladder and the peritoneal cavity. She underwent cystoscopic closure of the fistulous tract and the PD catheter was removed. Subsequently, the patient was treated by hemodialysis. One month later, a second catheter was implanted surgically after confirming the closure of the fistula. Ten days later, she presented with pain at the catheter site and along the tunnel, which was found to be swollen along its track. The injection of contrast produced swelling of the subcutaneous tunnel but without extravasation of the dye. PD was withdrawn and the patient was put back on hemodialysis. Bladder fistula is a rare complication in PD and diagnosis should be suspected when patient complains of an urge to pass urine during the exchanges, which can be confirmed by contrast study showing presence of dye in the bladder. PD may be possible after the closure of the fistula, but recurrence may occur. PMID:22569443

  12. Bladder cancer: clinical and pathological profile.

    PubMed

    Lopez-Beltran, Antonio

    2008-09-01

    Bladder tumours represent a heterogeneous group of cancers. The natural history of these bladder cancers is that of recurrence of disease and progression to higher grade and stage disease. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumour characteristics, mainly tumour grade and stage. The most recent World Health Organization (WHO) classification of tumours of the urinary system includes urothelial flat lesions: flat hyperplasia, dysplasia and carcinoma in situ. The papillary lesions are broadly subdivided into benign (papilloma and inverted papilloma), papillary urothelial neoplasia of low malignant potential (PUNLMP) and non-invasive papillary carcinoma (low or high grade). The initial proposal of the 2004 WHO has been achieved, with most reports supporting that categories are better defined than in previous classifications. An additional important issue is that PUNLMP, the most controversial proposal of the WHO in 2004, has lower malignant behaviour than low-grade carcinoma. Whether PUNLMP remains a clinically useful category, or whether this category should be expanded to include all low-grade, stage Ta lesions (PUNLMP and low-grade papillary carcinoma) as a wider category of less aggressive tumours not labelled as cancer, needs to be discussed in the near future. This article summarizes the recent literature concerning important issues in the pathology and the clinical management of patients with bladder urothelial carcinoma. Emphasis is placed on clinical presentation, the significance of haematuria, macroscopic appearance (papillary, solid or mixed, single or multiple) and synchronous or metachronous presentation (field disease vs monoclonal disease with seeding), classification and microscopic variations of bladder cancer with clinical significance, TNM distribution and the pathological grading according to the 2004 WHO proposal.

  13. Genetics of Bladder Malignant Tumors in Childhood

    PubMed Central

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-01-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  14. Probiotics, dendritic cells and bladder cancer.

    PubMed

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette-Guérin).

  15. Probiotics, dendritic cells and bladder cancer.

    PubMed

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  16. Reviving Ulysses contracts.

    PubMed

    Spellecy, Ryan

    2003-12-01

    Ulysses contracts have faced paternalism objections since they first were proposed. Since the contracts are designed to override a present request from a legally competent patient in favor of a past request made by that patient, enforcement of these contracts was argued to be unjustifiable strong paternalism. Recent legal developments and new theories of practical reasoning suggest that the discussion of Ulysses contracts should be revived. This paper argues that with a proper understanding of the future-directed planning embodied in Ulysses contracts, the charge of strong paternalism can be answered, and the enforcement of some Ulysses contracts may be justified under the rubric of weak paternalism.

  17. In vivo and in vitro pharmacological characterization of SVT-40776, a novel M3 muscarinic receptor antagonist, for the treatment of overactive bladder

    PubMed Central

    Salcedo, C; Davalillo, S; Cabellos, J; Lagunas, C; Balsa, D; Pérez-del-Pulgar, S; Ballarín, M; Fernández, AG

    2009-01-01

    Background and purpose: Highly selective M3 muscarinic receptor antagonists may represent a better treatment for overactive bladder syndrome, diminishing side effects. Cardiac side effects of non-selective antimuscarinics have been associated with activity at M2 receptors as these receptors are mainly responsible for muscarinic receptor-dependent bradycardia. We have investigated a novel antimuscarinic, SVT-40776, highly selective for M3 over M2 receptors (Ki = 0.19 nmol·L−1 for M3 receptor affinity). This study reports the functional activity of SVT-40776 in the bladder, relative to its activity in atria. Experimental approach: In vitro and ex vivo (oral dosing) inhibition of mouse detrusor and atrial contractile responses to carbachol were used to study the functional activity of SVT-40776. The in vivo efficacy of SVT-40776 was characterized by suppression of isovolumetric spontaneous bladder contractions in anaesthetized guinea pigs after intravenous administration. Key results: SVT-40776 was the most potent in inhibiting carbachol-induced bladder contractions of the anti-cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT-40776 exhibited the highest urinary versus cardiac selectivity (199-fold). In the guinea pig in vivo model, SVT-40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 µg·kg−1 i.v), without affecting arterial blood pressure. Conclusions and implications: SVT-40776 is a potent inhibitor of M3 receptor-related detrusor contractile activity. The absence of effects on isolated atria preparations represents an interesting characteristic and suggests that SVT-40776 may lack unwanted cardiac effects; a feature especially relevant in a compound intended to treat mainly elderly patients. British Journal of Pharmacology (2009) doi:10.1111/j.1476-5381.2008.00082.x PMID:19222482

  18. Activation of soluble guanylyl cyclase by BAY 58-2667 improves bladder function in cyclophosphamide-induced cystitis in mice.

    PubMed

    de Oliveira, Mariana G; Calmasini, Fabiano B; Alexandre, Eduardo C; De Nucci, Gilberto; Mónica, Fabíola Z; Antunes, Edson

    2016-07-01

    Activators of soluble guanylyl cyclase (sGC) interact directly with its prosthetic heme group, enhancing the enzyme responsiveness in pathological conditions. This study aimed to evaluate the effects of the sGC activator BAY 58-2667 on voiding dysfunction, protein expressions of α1 and β1 sGC subunits and cGMP levels in the bladder tissues after cyclophosphamide (CYP) exposure. Female C57BL/6 mice (20-25 g) were injected with CYP (300 mg/kg ip) to induce cystitis. Mice were pretreated or not with BAY 58-2667 (1 mg/kg, gavage), given 1 h before CYP injection. The micturition patterns and in vitro bladder contractions were evaluated at 24 h. In freely moving mice, the CYP injection produced reduced the micturition volume and increased the number of urine spots. Cystometric recordings in CYP-injected mice revealed significant increases in basal pressure, voiding frequency, and nonvoiding contractions (NVCs), along with decreases in bladder capacity, intercontraction interval, and compliance. BAY 58-2667 significantly prevented the micturition alterations observed in both freely moving mice and cystometry and normalized the reduced in vitro carbachol-induced contractions in the CYP group. Reduced protein expressions of α1 and β1 sGC subunits and of cGMP levels were observed in the CYP group, all of which were prevented by BAY 58-2667. CYP exposure significantly increased reactive-oxygen species (ROS) generation in both detrusor and urothelium, and this was normalized by BAY 58-2667. The increased myeloperoxidase and cyclooxygenase-2 activities in the bladders of the CYP group remained unchanged by BAY 58-2667. Activators of sGC may constitute a novel and promising therapeutic approach for management of interstitial cystitis. PMID:27122537

  19. Magnetic Fluid Hyperthermia for Bladder Cancer: A Preclinical Dosimetry Study

    PubMed Central

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea D.; Etienne, Wiguins; Ashcraft, Kathleen A.; McNerny, Katie L.; Mashal, Alireza; Nouls, John; Maccarini, Paolo F.; Beyer, Wayne F.; Inman, Brant; Dewhirst, Mark W.

    2014-01-01

    Purpose This paper describes a preclinical investigation of the feasibility of thermotherapy treatment of bladder cancer with Magnetic Fluid Hyperthermia (MFH), performed by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Materials and Methods The bladders of twenty-five female rats were instilled with magnetite-based nanoparticles, and hyperthermia was induced using a novel small animal magnetic field applicator (Actium Biosystems, Boulder, CO). We aimed to increase the bladder lumen temperature to 42°C in <10 min and maintain that temperature for 60 min. Temperatures were measured within the bladder lumen and throughout the rat with seven fiberoptic probes (OpSens Technologies, Quebec, Canada). An MRI analysis was used to confirm the effectiveness of the catheterization method to deliver and maintain various nanoparticle volumes within the bladder. Thermal dosimetry measurements recorded the temperature rise of rat tissues for a variety of nanoparticle exposure conditions. Results Thermal dosimetry data demonstrated our ability to raise and control the temperature of rat bladder lumen ≥1°C/min to a steady-state of 42°C with minimal heating of surrounding normal tissues. MRI scans confirmed the homogenous nanoparticle distribution throughout the bladder. Conclusion These data demonstrate that our MFH system with magnetite-based nanoparticles provide well-localized heating of rat bladder lumen with effective control of temperature in the bladder and minimal heating of surrounding tissues. PMID:24050253

  20. The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder.

    PubMed

    Persyn, Sara; De Wachter, Stefan; Wyndaele, Jean-Jacques; Eastham, Jane; Gillespie, James

    2016-07-01

    β3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the β3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro-contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro-contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by β1/β2-adrenoceptor mechanisms. No evidence was obtained for any β3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of β3-adrenergic agonists remains unknown.

  1. Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

    ClinicalTrials.gov

    2015-06-19

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  2. Bladder Cancer: A Simple Model Becomes Complex

    PubMed Central

    Pierro, Giovanni Battista Di; Gulia, Caterina; Cristini, Cristiano; Fraietta, Giorgio; Marini, Lorenzo; Grande, Pietro; Gentile, Vincenzo; Piergentili, Roberto

    2012-01-01

    Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small non-coding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using “bladder cancer” as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up- or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genome-wide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up- or down-regulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non

  3. β-Adrenoceptor-mediated Relaxation of Urinary Bladder Muscle in β2-Adrenoceptor Knockout Mice

    PubMed Central

    Propping, Stefan; Lorenz, Kristina; Michel, Martin C.; Wirth, Manfred P.; Ravens, Ursula

    2016-01-01

    Background and Objective: In order to characterize the β-adrenoceptor (AR) subtypes involved in agonist-stimulated relaxation of murine urinary bladder we studied the effects of (-)-isoprenaline and CL 316,243 on tonic contraction and spontaneous contractions in detrusor strips of wild-type (WT) and β2-AR knockout (β2-AR KO) mice. Materials and Methods: Urinary bladders were isolated from male WT and β2-AR KO mice. β-AR subtype expression was determined with quantitative real-time PCR. Intact muscle strips pre-contracted with KCl (40 mM) were exposed to cumulatively increasing concentrations of (-)-isoprenaline or β3-AR agonist CL 316,243 in the presence and absence of the subtype-selective β-AR blockers CGP 20712A (β1-ARs), ICI 118,551 (β2-ARs), and L748,337 (β3-ARs). Results: Quantitative real-time PCR confirmed lack of β2-AR expression in bladder tissue from β2-AR KO mice. In isolated detrusor strips, pre-contraction with KCl increased basal tone and enhanced spontaneous activity significantly more in β2-AR KO than in WT. (-)-Isoprenaline relaxed tonic tension and attenuated spontaneous activity with similar potency, but the concentrations required were two orders of magnitude higher in β2-AR KO than WT. The concentration-response curves (CRCs) for relaxation were not affected by CGP 20712A (300 nM), but were shifted to the right by ICI 118,551 (50 nM) and L748,337 (10 μM). The -logEC50 values for (-)-isoprenaline in WT and β2-AR KO tissue were 7.98 and 6.00, respectively, suggesting a large receptor reserve of β2-AR. (-)-CL 316,243 relaxed detrusor and attenuated spontaneous contractions from WT and β2-AR KO mice with a potency corresponding to the drug’s affinity for β3-AR. L743,337 shifted the CRCs to the right. Conclusion: Our findings in β2-AR KO mice suggest that there is a large receptor reserve for β2-AR in WT mice so that this β-AR subtype will mediate relaxation of tone and attenuation of spontaneous activity under physiological

  4. Teaching about Contracts.

    ERIC Educational Resources Information Center

    Froman, Michael; Kosnoff, Kathy

    1978-01-01

    Presents teaching strategies for introducing high school students to contract law. Offers as a case study a contract agreement between pro football players and team owners. Stresses basic elements of contracts (offer, acceptance, consideration, and understanding the bargaining process). Journal available from the American Bar Association, 1155…

  5. The Joy of Contracts.

    ERIC Educational Resources Information Center

    Hegarty, Kevin

    This paper is a practical guide that explains and illustrates contracts between libraries and vendors for computerized circulation systems. It describes the elements of a typical contract to include the equipment and services that should be specified in the contract and establishes scheduling and acceptance testing needs. Included in a contract…

  6. Contracting for Services.

    ERIC Educational Resources Information Center

    Jenkins, Robin E.; Nord, Roy

    1982-01-01

    The major steps a college should undertake in contracting for services, including the initial determination as to whether or not contracting is the best way to provide a particular service, are described. Three general activities that apply to decisions about contracting in most circumstances are: investigating service characteristics; identifying…

  7. Russian Teaching Contracts.

    ERIC Educational Resources Information Center

    Stevens, Betsy

    2000-01-01

    Analyzes two Russian teaching contracts, rhetorically comparing purpose and audience, culture, gender, and the role of the individual versus the state. Uses anecdotal episodes as a framework for examining Russian culture and analyzing university teaching contracts, concluding that the contracts are not only brief and factual but also reflect a…

  8. Desensitization of the guinea-pig urinary bladder by the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate and by substance P.

    PubMed Central

    Hourani, S. M.

    1984-01-01

    Adenosine 5'-triphosphate (ATP), substance P (SP) and non-cholinergic nerve stimulation contracted the guinea-pig urinary bladder. SP and two poorly-degradable analogues of ATP, the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP and L-AMP-PCP), were used to desensitize the guinea-pig bladder. Desensitization of the bladder by AMP-PCP (50 microM) or by L-AMP-PCP (50 microM) abolished the responses to ATP, and inhibited the responses to non-cholinergic nerve stimulation and to SP. The responses to histamine were unaffected. Desensitization by SP (1 microM) inhibited the responses to SP itself, but not the responses to ATP, L-AMP-PCP or non-cholinergic nerve stimulation. These results suggest that SP may act partly by releasing ATP, and support the suggestion that ATP rather than SP is the non-cholinergic stimulatory transmitter. PMID:6203588

  9. Paraneoplastic retinopathy associated with occult bladder cancer

    PubMed Central

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia; Berman, Dalia C

    2016-01-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool. PMID:27146943

  10. Paraneoplastic retinopathy associated with occult bladder cancer.

    PubMed

    Nivean, M; Muttuvelu, Danson V; Afzelius, Pia; Berman, Dalia C

    2016-03-01

    The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool. PMID:27146943

  11. Hyperthermia as a treatment for bladder cancer.

    PubMed

    Rampersaud, Edward N; Vujaskovic, Zeljko; Inman, Brant A

    2010-11-15

    Modern cancer care is characterized by a focus on organ-sparing multi-modal treatments. In the case of non-muscle-invasive bladder cancer this is particularly true; treatment is focused on reducing the frequency of low-risk recurrences and preventing high-risk progression. Deep regional hyperthermia is an oncologic therapeutic modality that can help achieve these two goals. The combination of hyperthermia with chemotherapy and radiotherapy has improved patient outcomes in several tumor types. In this review, we highlight the biology of therapeutic fever-range hyperthermia, discuss how hyperthermia is administered and dosed, demonstrate how heat can be added to other treatment regimens, and summarize the data supporting the role of hyperthermia in the management of bladder cancer.

  12. HLA class I expression in bladder carcinomas.

    PubMed

    Cabrera, T; Pedrajas, G; Cozar, J M; Garrido, A; Vicente, J; Tallada, M; Garrido, F

    2003-10-01

    HLA class I molecules are frequently lost in a large variety of human carcinomas, possibly because of T-cell immune selection of major histocompatibility complex class I deficient tumor variants. We report that this phenomenon is also a frequent event in bladder carcinomas. Of a total of 72 bladder carcinomas, 72% of the tumors had at least one alteration in HLA class I expression. These altered HLA class I phenotypes were classified as total HLA class I loss (25%; phenotype I); HLA-A or/and HLA-B locus-specific loss (12%; phenotype III); and HLA class I allelic loss (35%; phenotype II or IV). Comparison of histopathological parameters with HLA class I expression showed a statistically significant relationship with the degree of differentiation and tumor recurrence.

  13. Bladder cancer: approaches to prevention and control.

    PubMed

    Koroltchouk, V; Stanley, K; Stjernswärd, J; Mott, K

    1987-01-01

    Bladder cancer is the twelfth most common cancer globally, with approximately 170 000 new cases each year; a third of these cases are in the developing countries. There are two major etiological types. The first is more common in the industrialized countries and is associated with exposure to certain occupational and environmental carcinogens, but most importantly with tobacco smoking. The second type is associated with Schistosoma haematobium infection of the urinary tract and is one of the most frequent tumours in eastern Mediterranean and African countries. Both types of bladder cancer are largely preventable. Comprehensive education and legislative approaches are recommended to reduce tobacco consumption and exposure to industrial carcinogens. Safe and effective drugs are available to treat schistosomiasis within integrated control programmes in endemic areas.

  14. [Phytoperfusion of the bladder after adenomectomy].

    PubMed

    Davidov, M I; Goriunov, V G; Kubarikov, P G

    1995-01-01

    For continuous irrigation of the bladder after prostatic adenomectomy herb infusion (Urtica dioica L. 12-15 g/l, Hypericum perforatum L. 8-12 g/l. Marticaria recutita L. 8-10 g/l, folia Plantaginis majoris 7-10 g/l, Herba Millefolii 4-6 g/l, folia Betula 3-5 g/l. Artemisia vulgaris L. 1-2 g/l, folia Fragaria vesca 3-4 g/l, water 11 maximum) was dripped through a thin suprapubic and urethral drainages. Such phytoperfusion of the urinary bladder used in 22 patients reduced postoperative blood loss, bacteriuria, prevented hemorrhagic and purulent inflammation following adenomectomy. Side systemic effects were not reported. PMID:8571476

  15. Improving Systemic Chemotherapy for Bladder Cancer.

    PubMed

    Rose, Tracy L; Milowsky, Matthew I

    2016-05-01

    Systemic chemotherapy is integral to the management of muscle-invasive and metastatic bladder cancer (BCa). Neoadjuvant chemotherapy has been increasingly utilized for muscle-invasive BCa over the past several years, and several options for cisplatin-based regimens have emerged. Adjuvant chemotherapy may be considered for select patients who did not receive neoadjuvant therapy. Systemic chemotherapy added to radiotherapy is a critical component of a bladder-preserving approach and superior to radiotherapy alone. Cisplatin-based chemotherapy has been the mainstay for metastatic BCa for more than three decades. Novel targeted agents are in development fueled by the recent molecular characterization of BCa. Recent trials of immunotherapy have demonstrated the possibility of a less toxic and potentially more effective treatment for metastatic disease. It is an extremely exciting time for BCa research, and much needed improvements in systemic treatment are most certainly on the horizon. PMID:26984414

  16. [Inflammatory myofibroblastic tumours of the bladder].

    PubMed

    Dakir, Mohamed; Taha, Abdellatif; Attar, Hicham; Sarf, Ismail; Aboutaib, Rachid; Moussaoui, Ali; Meziane, Fathi

    2004-12-01

    The inflammatory myofibroblastic tumour of the bladder is a rare benign affection that interests mainly young adults. Its etiopathogeny remains unknown, but its tumoral origin was evocated recently by Griffin (1999), incriminating a chromosomic abnormality involving the ALK gene. We will discuss the etiopathogenic, anatopathological and therapeutical aspects of this lesion for which the diagnosis is histological and the treatment remains conservative with a good prognosis.

  17. Iatrogenic foreign body in the urinary bladder.

    PubMed

    Shah, Safdar; Qureshi, Farhan; Rakhio, Sain

    2015-04-01

    A 60 years old man presented with a history of suprapubic pain, painful micturition, perineal pain, and acute retention of urine followed by catheterization. On abdominal ultrasound, there was a metallic needle found in the urinary bladder which was confirmed on pelvis X-ray. The needle was found to be a metallic piece of a resectoscope cutting loop which was removed through cystourethroscopy. PMID:25899202

  18. New method of postprostatectomy bladder irrigation.

    PubMed

    MacDermott, J P; Ewing, R; Gray, B K

    1989-01-01

    Bacterial filters have been used to sterilise the hospital water supply in order to provide irrigant for postprostatectomy irrigation. This method was compared retrospectively to bladder irrigation derived from a still on the ward. Postoperative bacteriuria was similar in both groups of 75 patients, occurring in 23.7% of patients irrigated from the still and in 20% of patients irrigated via the filters. The bacterial filter proved reliable and as safe as using water from the still. PMID:2714320

  19. Interstitial cystitis/painful bladder syndrome.

    PubMed

    Panzera, Alis Kolter

    2007-02-01

    Interstitial cystitis (IC) is a chronic, painful bladder syndrome primarily found in women. Although the direct cause(s) of IC are unknown, several theories exist. Common symptoms include urinary urgency, frequency, and pain. Treatment options include behavioral therapies, use of pharmacologic agents, and surgery. Patients benefit from prompt diagnosis and initiation of treatments. Important clinical features of IC in women including the pathology, common symptoms, and recommended evaluation and management strategies are reviewed.

  20. Persistent neurogenic bladder dysfunction due to infantile botulism.

    PubMed

    Breinbjerg, Anders; Rittig, Søren; Kamperis, Konstantinos

    2014-01-13

    We present a child, 5 months of age, diagnosed with infantile botulism, showing the signs of neurogenic bladder dysfunction. The patient presented with progressive muscle weakness, hypotonia, suckling and swallowing problems and absent peripheral reflexes at clinical examination. Botulinum neurotoxin type A was detected in her serum, confirming the diagnosis. Starting at day 6, the girl presented with a urinary retention initially necessitating free bladder drainage and subsequently intermittent catheterisation. After 6 weeks in intensive care, the patient recovered but the bladder underactivity persisted. Four months following recovery, a urodynamic evaluation was performed, showing a near normal detrusor activity and normal bladder emptying, and the catheterisation was ceased. At 6 months, the girl was diagnosed with a urinary tract infection and bladder emptying problems, which persisted, and clean intermittent catheterisation was started. The final urodynamic evaluation, a year and a half after her initial presentation, revealed a normal detrusor activity and an adequate bladder emptying.

  1. [The biochemical carcinogenesis of selected heavy metals in bladder cancer].

    PubMed

    Rorbach-Dolata, Anna; Marchewka, Zofia; Piwowar, Agnieszka

    2015-01-01

    Bladder cancer takes the second place in the classification of morbidity of urinary system cancers. Many chemical factors take part in cancerogenesis. It is suggested that exposure to heavy metals such as arsenic, chromium, nickel and cadmium as well as its metabolites may trigger the bladder cancer through inducing excessive reactive oxygen species production and oxidative stress formation which are responsible for DNA damage. In patients with bladder cancer is observed the disorder of processes regulated by p-53, including apoptosis. There are many patients with bladder cancer with confirmed absence of retinoblastoma protein, which is responsible of holding on the process of coming up the cells with mutation into synthesis, where the replication process undergoes. It is mentioned that excessive expression of proto-oncogenes may also cause the bladder cancer. The article concerns biochemical effects of exposure to chosen heavy metals and their potential role in bladder cancer progression. PMID:26689010

  2. Anatomic Variant of Liver, Gall Bladder and Inferior Vena Cava.

    PubMed

    Sontakke, Yogesh Ashok; Gladwin, V; Chand, Parkash

    2016-07-01

    The morphology and relations of liver, gall bladder and inferior vena cava are cardinal. Their anatomical variations may be a reason for the adverse surgical outcome. During routine anatomy dissection of an abdomen, we noticed a variant liver, gall bladder and inferior vena cava in a 63-year-old male cadaver. In the specimen, a retrohepatic segment of inferior vena cava was found to be intrahepatic. On dissection, it was observed that inferior vena cava was covered entirely by a liver tissue on its dorsal aspect. In the same specimen, the gall bladder had undulated inferior surface. On dissection of the gall bladder, numerous mucosal folds were present in the interior. A band of fibrous tissue was found, which was extending from the right side of the gall bladder to the falciform ligament. Hence, preoperative scanning of congenital variations of the liver, gall bladder and inferior vena cava may be compassionate in planning safe surgeries and interventional abdominal procedures. PMID:27630832

  3. Anatomic Variant of Liver, Gall Bladder and Inferior Vena Cava

    PubMed Central

    Gladwin, V.; Chand, Parkash

    2016-01-01

    The morphology and relations of liver, gall bladder and inferior vena cava are cardinal. Their anatomical variations may be a reason for the adverse surgical outcome. During routine anatomy dissection of an abdomen, we noticed a variant liver, gall bladder and inferior vena cava in a 63-year-old male cadaver. In the specimen, a retrohepatic segment of inferior vena cava was found to be intrahepatic. On dissection, it was observed that inferior vena cava was covered entirely by a liver tissue on its dorsal aspect. In the same specimen, the gall bladder had undulated inferior surface. On dissection of the gall bladder, numerous mucosal folds were present in the interior. A band of fibrous tissue was found, which was extending from the right side of the gall bladder to the falciform ligament. Hence, preoperative scanning of congenital variations of the liver, gall bladder and inferior vena cava may be compassionate in planning safe surgeries and interventional abdominal procedures. PMID:27630832

  4. Adenocarcinoma of the urinary bladder, mesonephroid type: a rare case

    PubMed Central

    Abbas, Mahmoud; Kramer, Mario W.; Wolters, Mathias; Herrman, Thomas R.W.; Becker, Jan U.; Kreipe, Hans-Heinrich

    2013-01-01

    Primary adenocarcinoma of the urinary bladder is a rare disease. It occurs in 0.5–2% of all bladder cancers and is discussed as the malignant counterpart of nephrogenic adenomas. We report a 46-year-old white female presented with gross hematuria for clinical examination. Histopathology revealed pT2, Pn1, L1, G2 adenocarcinoma of the bladder and carcinoma in situ according to the TNM classification. Computed tomography scan diagnostic was unremarkable. Patients with adenocarcinoma of the urinary bladder should be treated vigorously and without time delay. Only 7 cases of adenocarcinoma in the urinary bladder (mesonephroid) have been described until now. We present a case of clear cell adenocarcinoma of the urinary bladder, mesonephroid type that early diagnosed and till now 3 months after the cystectomy without symptoms and without complications. PMID:23772302

  5. Targeting glycogen metabolism in bladder cancer

    PubMed Central

    Lew, Carolyn Ritterson; Guin, Sunny; Theodorescu, Dan

    2015-01-01

    Metabolism has been a heavily investigated topic in cancer research for the past decade. Although the role of aerobic glycolysis (the Warburg effect) in cancer has been extensively studied, abnormalities in other metabolic pathways are only just being understood in cancer. One such pathway is glycogen metabolism; its involvement in cancer development, particularly in urothelial malignancies, and possible ways of exploiting aberrations in this process for treatment are currently being studied. New research shows that the glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) is a novel tumour suppressor in bladder cancer. Loss of AGL leads to rapid proliferation of bladder cancer cells. Another enzyme involved in glycogen debranching, glycogen phosphorylase, has been shown to be a tumour promoter in cancer, including in prostate cancer. Studies demonstrate that bladder cancer cells in which AGL expression is lost are more metabolically active than cells with intact AGL expression, and these cells are more sensitive to inhibition of both glycolysis and glycine synthesis—two targetable pathways. As a tumour promoter and enzyme, glycogen phosphorylase can be directly targeted, and preclinical inhibitor studies are promising. However, few of these glycogen phosphorylase inhibitors have been tested for cancer treatment in the clinical setting. Several possible limitations to the targeting of AGL and glycogen phosphorylase might also exist. PMID:26032551

  6. Bladder management after total joint arthroplasty.

    PubMed

    Knight, R M; Pellegrini, V D

    1996-12-01

    This study was undertaken to determine the impact of an indwelling Foley catheter on bladder dysfunction and incidence of urinary tract infections after total joint arthroplasty. A prospective randomized controlled trial was conducted assigning use of an indwelling Foley catheter (group 1) or intermittent catheterization (group 2) for 48 hours following operation. Postoperative cultures were obtained on days 2 and 5, and the number of intermittent catheterization events and void and catheterization volumes were recorded. Concurrent cost-effectiveness analysis was conducted. One hundred nineteen of 174 consecutive patients having elective primary total joint arthroplasty completed the study. Five of 62 patients (8%) in group 1 and 7 of 57 patients (12%) in group 2 developed urinary tract infections (NS, P = 45). Twenty patients (35%) in group 2 and 12 (19%) in group 1 required straight catheterization for inability to void 48 hours after surgery (P = .05). Seventeen patients (35%) in group 2 and eight patients (16%) in group 1 required straight catheterization after epidural analgesia was discontinued (P = .024). Bladder management by indwelling Foley catheter saved more than 150 minutes of direct nursing contact per patient and $3,000 in total hospital costs. Indwelling Foley catheters reduced the frequency of postoperative urinary retention, were less labor intensive than intermittent straight catheterization, and were not associated with an increased risk of urinary infection. In the setting of epidural anesthesia and postoperative analgesia for total joint arthroplasty, management by indwelling catheter is a cost-effective strategy to facilitate postoperative return of normal bladder function.

  7. Hypercompliant Apical Membranes of Bladder Umbrella Cells

    PubMed Central

    Mathai, John C.; Zhou, Enhua H.; Yu, Weiqun; Kim, Jae Hun; Zhou, Ge; Liao, Yi; Sun, Tung-Tien; Fredberg, Jeffrey J.; Zeidel, Mark L.

    2014-01-01

    Urinary bladder undergoes dramatic volume changes during filling and voiding cycles. In the bladder the luminal surface of terminally differentiated urothelial umbrella cells is almost completely covered by plaques. These plaques (500 to 1000 nm) are made of a family of proteins called uroplakins that are known to form a tight barrier to prevent leakage of water and solutes. Electron micrographs from previous studies show these plaques to be interconnected by hinge regions to form structures that appear rigid, but these same structures must accommodate large changes in cell shape during voiding and filling cycles. To resolve this paradox, we measured the stiffness of the intact, living urothelial apical membrane and found it to be highly deformable, even more so than the red blood cell membrane. The intermediate cells underlying the umbrella cells do not have uroplakins but their membranes are an order of magnitude stiffer. Using uroplakin knockout mouse models we show that cell compliance is conferred by uroplakins. This hypercompliance may be essential for the maintenance of barrier function under dramatic cell deformation during filling and voiding of the bladder. PMID:25229135

  8. Dietary factors associated with bladder cancer

    PubMed Central

    2016-01-01

    It is biologically plausible for dietary factors to influence bladder cancer risk considering that beneficial as well as harmful components of a diet are excreted through the urinary tract and in direct contact with the epithelium of the bladder. However, studies that investigated the association between dietary factors and bladder cancer (BC) risk have largely reported inconsistent results. The macronutrient intake and risk of BC could have yield inconsistent results across studies because of lack of details on the type, source and the quantities of different dietary fatty acids consumed. There is evidence to suggest that consumption of processed meat may increase BC risk. Dietary carbohydrate intake does not appear to be directly associated with BC risk. Even though a large number of studies have investigated the association between fruit/vegetable consumption/micronutrients in those and BC risk, they have yielded inconsistent results. Gender-specific subgroup analysis, details of how fruits and vegetables are consumed (raw vs. cooked), adequate control for smoking status/aggressiveness of the cancer and consideration of genetic make-up may clarify these inconsistent results. There is no strong evidence to suggest that supplementation with any common micronutrient is effective in reducing BC risk. These limitations in published research however do not totally eclipse the observation that a diet rich in fruits and vegetables and low in processed meat along with especially smoking cessation may convey some protective effects against BC risk. PMID:27326403

  9. Diagnostics techniques in nonmuscle invasive bladder cancer

    PubMed Central

    Soubra, Ayman; Risk, Michael C.

    2015-01-01

    Introduction: Nonmuscle invasive bladder cancer (NMIBC) is the most common presentation of bladder cancer and is often treatable with endoscopic resection and intravesical therapies. Cystoscopy and urine cytology are the gold standard in diagnosis and surveillance but are limited by their sensitivity in some situations. We seek to provide an overview of recent additions to the diagnostic armamentarium for urologists treating this disease. Methods: Articles were identified through a literature review of articles obtained through PubMed searches including the terms “bladder cancer” and various diagnostic techniques described in the article. Results: A variety of urinary biomarkers are available to assist the diagnosis and management of patients with NMIBC. Many have improved sensitivity over urine cytology, but less specificity. There are certain situations in which this has proved valuable, but as yet these are not part of the standard guidelines for NMIBC. Fluorescence cystoscopy has level 1 evidence demonstrating increased rates of tumor detection and prolonged recurrence-free survival when utilized for transurethral resection. Other technologies seeking to enhance cystoscopy, such as narrow band imaging, confocal laser endomicroscopy, and optical coherence tomography are still under evaluation. Conclusions: A variety of urine biomarker and adjunctive endoscopic technologies have been developed to assist the management of NMIBC. While some, such as fluorescence cystoscopy, have demonstrated a definite benefit in this disease, others are still finding their place in the diagnosis and treatment of this disease. Future studies should shed light on how these can be incorporated to improve outcomes in NMIBC. PMID:26604438

  10. Targeting glycogen metabolism in bladder cancer.

    PubMed

    Ritterson Lew, Carolyn; Guin, Sunny; Theodorescu, Dan

    2015-07-01

    Metabolism has been a heavily investigated topic in cancer research for the past decade. Although the role of aerobic glycolysis (the Warburg effect) in cancer has been extensively studied, abnormalities in other metabolic pathways are only just being understood in cancer. One such pathway is glycogen metabolism; its involvement in cancer development, particularly in urothelial malignancies, and possible ways of exploiting aberrations in this process for treatment are currently being studied. New research shows that the glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) is a novel tumour suppressor in bladder cancer. Loss of AGL leads to rapid proliferation of bladder cancer cells. Another enzyme involved in glycogen debranching, glycogen phosphorylase, has been shown to be a tumour promoter in cancer, including in prostate cancer. Studies demonstrate that bladder cancer cells in which AGL expression is lost are more metabolically active than cells with intact AGL expression, and these cells are more sensitive to inhibition of both glycolysis and glycine synthesis--two targetable pathways. As a tumour promoter and enzyme, glycogen phosphorylase can be directly targeted, and preclinical inhibitor studies are promising. However, few of these glycogen phosphorylase inhibitors have been tested for cancer treatment in the clinical setting. Several possible limitations to the targeting of AGL and glycogen phosphorylase might also exist.

  11. Bladder Cancer Screening in Aluminum Smelter Workers

    PubMed Central

    Taiwo, Oyebode A.; Slade, Martin D.; Cantley, Linda F.; Tessier-Sherman, Baylah; Galusha, Deron; Kirsche, Sharon R.; Donoghue, A. Michael

    2015-01-01

    Objective: To present results of a bladder cancer screening program conducted in 18 aluminum smelters in the United States from January 2000 to December 2010. Methods: Data were collected on a cohort of workers with a history of working in coal tar pitch volatile exposed areas including urine analysis for conventional cytology and ImmunoCyt/uCyt+ assay. Results: ImmunoCyt/uCyt+ and cytology in combination showed a sensitivity of 62.30%, a specificity of 92.60%, a negative predictive value of 99.90%, and a positive predictive value of 2.96%. Fourteen cases of bladder cancer were detected, and the standardized incidence ratio of bladder cancer was 1.18 (95% confidence interval, 0.65 to 1.99). Individuals who tested positive on either test who were later determined to be cancer free had undergone expensive and invasive tests. Conclusions: Evidence to support continued surveillance of this cohort has not been demonstrated. PMID:25525927

  12. Bladder cancer and occupational exposure to leather.

    PubMed Central

    Marrett, L D; Hartge, P; Meigs, J W

    1986-01-01

    A large case-control study of bladder cancer (2982 cases; 5782 controls) included information about occupational exposure to leather. Occupational histories of exposed white study subjects were reviewed and 150 were determined to have had "true" on the job exposure to leather. The odds ratio estimate (OR) of bladder cancer associated with such exposure in white subjects (n = 8063) was 1.4 (95% confidence limits = 1.0, 1.9) after adjustment for sex, age, and cigarette smoking. The risk was highest in those first employed in a leather job before 1945, although no dose-response relation with duration of leather employment was found. Subjects employed in "dusty" leather jobs had a slightly higher risk than those with other types of leather jobs. Our results are consistent with reports of an increased risk of bladder cancer associated with exposure to leather. Although the agents responsible have not been identified, our findings of an increased risk associated with exposure in the earlier years of this century and in dusty jobs suggest that leather dusts may be important. PMID:3947575

  13. Bladder neck sparing in radical prostatectomy

    PubMed Central

    Smolski, Michal; Esler, Rachel C.; Turo, Rafal; Collins, Gerald N.; Oakley, Neil; Brough, Richard

    2013-01-01

    The role of a bladder neck sparing (BNS) technique in radical prostatectomy (RP) remains controversial. The potential advantages of improved functional recovery must be weighed against oncological outcomes. We performed a literature review to evaluate the current knowledge regarding oncological and functional outcomes of BNS and bladder neck reconstruction (BNr) in RP. A systematic literature review using on-line medical databases was performed. A total of 33 papers were identified evaluating the use of BNS in open, laparoscopic and robotic-assisted RP. The majority were retrospective case series, with only one prospective, randomised, blinded study identified. The majority of papers reported no significant difference in oncological outcomes using a BNS or BNr technique, regardless of the surgical technique employed. Quoted positive surgical margin rates ranged from 6% to 32%. Early urinary continence (UC) rates were ranged from 36% to 100% at 1 month, with long-term UC rate reported at 84-100% at 12 months if the bladder neck (BN) was spared. BNS has been shown to improve early return of UC and long-term UC without compromising oncological outcomes. Anastomotic stricture rate is also lower when using a BNS technique. PMID:24235797

  14. [Tissue engineering in urology, new approaches for urinary bladder reconstruction].

    PubMed

    Murav'ev, A N; Orlova, N V; Blinova, M I; Iudintseva, N M

    2015-01-01

    Tissue engineering as applied to urologic pathology is covered extremely poor in the literature despite recently gaining popularity of regenerative medicine. The review reflects the current problems associated with reconstructive surgery of the urinary bladder, experience of the researchers from the United States in implementing cellular technologies for bladder replacement, the problems and prospects of this direction in case of such a severe pathology, as fibrous transformated bladder.

  15. Robotic repair of scrotal bladder hernia during robotic prostatectomy.

    PubMed

    Sung, Ee-Rah; Park, Sung Yul; Ham, Won Sik; Jeong, Wooju; Lee, Woo Jung; Rha, Koon Ho

    2008-09-01

    We report a case of scrotal bladder hernia in a 68-year-old man who was also diagnosed with prostate cancer. We fixed the herniated portion of the bladder using robotics after having successfully accomplished robotic prostatectomy. To the best of our knowledge, this is the first case report on simultaneous repair of scrotal bladder hernia and prostate cancer where both pathological findings have been treated with the assistance of robotics at a single operation. PMID:27628264

  16. Complete transurethral bladder eversion 3 months after hemipelvectomy.

    PubMed

    Lowe, Gregory; Mandalapu, Subbarao; Gilleran, Jason

    2010-02-01

    A 46-year-old white female underwent a left hemipelvectomy for chondrosarcoma. She presented with total incontinence and a bulging vaginal mass. Exam confirmed complete transurethral bladder eversion that was addressed with transvaginal multilayer bladder neck closure and suprapubic tube placement. Eventually she underwent abdominal hysterectomy, mesh sacral colpopexy, and catheterizable stoma creation. Patient is continent of urine 3 months postoperatively. We present the first reported case of bladder eversion after hemipelvectomy and propose possible pathophysiologic mechanisms. PMID:19629370

  17. Hair dye use and risk of bladder cancer in the New England bladder cancer study.

    PubMed

    Koutros, Stella; Silverman, Debra T; Baris, Dalsu; Zahm, Shelia Hoar; Morton, Lindsay M; Colt, Joanne S; Hein, David W; Moore, Lee E; Johnson, Alison; Schwenn, Molly; Cherala, Sai; Schned, Alan; Doll, Mark A; Rothman, Nathaniel; Karagas, Margaret R

    2011-12-15

    Aromatic amine components in hair dyes and polymorphisms in genes that encode enzymes responsible for hair dye metabolism may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by N-acetyltransferase-1 (NAT1), NAT2, glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) genotypes in a population-based case-control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer-assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration or number of applications of hair dyes and bladder cancer among women or men was apparent, but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer [odds ratio (OR) = 3.3, 95% confidence interval (CI): 1.2-8.9]. Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR = 7.3, 95% CI: 1.6-32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. Although we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene-environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies. PMID:21678399

  18. Diagnosis and treatment of bladder cancer: how can we improve?

    PubMed

    Gorin, Michael A; Ayyathurai, Rajinikanth; Soloway, Mark S

    2012-05-01

    The majority of patients with bladder cancer will be diagnosed following an episode of hematuria. With few exceptions, these patients should be referred for a complete urologic evaluation, including a history and physical examination, flexible cystoscopy, imaging of the upper urinary tract, and optional urine cytology. Those found to have a bladder tumor should undergo transurethral resection for the combined purposes of initial staging and treatment. Delays in diagnosing invasive bladder cancer are associated with adverse outcomes. In this review, we cover the diagnosis and management of bladder cancer. In addition, we discuss ways to improve outcomes through increased public awareness, improvements in tumor detection, accurate staging, and regimented patient surveillance.

  19. Biomarkers for bladder cancer management: present and future

    PubMed Central

    Ye, Fei; Wang, Li; Castillo-Martin, Mireia; McBride, Russell; Galsky, Matthew D; Zhu, Jun; Boffetta, Paolo; Zhang, David Y; Cordon-Cardo, Carlos

    2014-01-01

    Accurate and sensitive detection of bladder cancer is critical to diagnose this deadly disease at an early stage, estimate prognosis, predict response to treatment, and monitor recurrence. In past years, laboratory diagnosis and surveillance of urinary bladder cancer have improved significantly. Although urine cytology remains the gold standard test, many new urinary biomarkers have been identified. Furthermore, recent advances in genomic studies of bladder cancer have helped to refine our understanding of the pathogenesis of the disease, the biological basis for outcome disparities, and to inform more efficient treatment and surveillance strategies. In this article, the established diagnostic tests, newly identified biomarkers and genomic landscape of bladder cancer will be reviewed. PMID:25374904

  20. Initial evaluation of whole bladder wall photodynamic therapy after intravesical ALA sensitization for carcinoma in situ of the bladder

    NASA Astrophysics Data System (ADS)

    D'Hallewin, Marie-Ange; Star, Willem M.; Baert, Luc

    1997-12-01

    Carcinoma in situ (CIS) of the bladder is a treacherous entity, that will develop into invasive cancer. Early treatment is mandatory in order to prevent progression. When conservative measures, such as Bacillus Calmette Querin (BCG) instillations have failed, radical cystectomy and urinary diversion is recommended. Whole bladder wall photodynamic therapy (PDT) with Photofrin II has been shown to be effective in eradicating carcinoma in situ, but often resulted in bladder shrinking. We wanted to evaluate the effects of PDT after aminolevulinic acid (ALA) sensitization. Six patients with refractory carcinoma in situ of the bladder were treated with whole bladder wall photodynamic therapy, after intravesical sensitization with aminolevulinic acid. The total light dose (scattered plus non scattered) was 75 J/cm2. No skin sensitization occurred, nor loss of bladder capacity. One patient did not respond and was successfully treated with BCG. Another patient developed distant metastases. Carcinoma in situ was completely absent after 3 months in four patients (66%).

  1. Proteomics Analysis of Bladder Cancer Exosomes*

    PubMed Central

    Welton, Joanne L.; Khanna, Sanjay; Giles, Peter J.; Brennan, Paul; Brewis, Ian A.; Staffurth, John; Mason, Malcolm D.; Clayton, Aled

    2010-01-01

    Exosomes are nanometer-sized vesicles, secreted by various cell types, present in biological fluids that are particularly rich in membrane proteins. Ex vivo analysis of exosomes may provide biomarker discovery platforms and form non-invasive tools for disease diagnosis and monitoring. These vesicles have never before been studied in the context of bladder cancer, a major malignancy of the urological tract. We present the first proteomics analysis of bladder cancer cell exosomes. Using ultracentrifugation on a sucrose cushion, exosomes were highly purified from cultured HT1376 bladder cancer cells and verified as low in contaminants by Western blotting and flow cytometry of exosome-coated beads. Solubilization in a buffer containing SDS and DTT was essential for achieving proteomics analysis using an LC-MALDI-TOF/TOF MS approach. We report 353 high quality identifications with 72 proteins not previously identified by other human exosome proteomics studies. Overrepresentation analysis to compare this data set with previous exosome proteomics studies (using the ExoCarta database) revealed that the proteome was consistent with that of various exosomes with particular overlap with exosomes of carcinoma origin. Interrogating the Gene Ontology database highlighted a strong association of this proteome with carcinoma of bladder and other sites. The data also highlighted how homology among human leukocyte antigen haplotypes may confound MASCOT designation of major histocompatability complex Class I nomenclature, requiring data from PCR-based human leukocyte antigen haplotyping to clarify anomalous identifications. Validation of 18 MS protein identifications (including basigin, galectin-3, trophoblast glycoprotein (5T4), and others) was performed by a combination of Western blotting, flotation on linear sucrose gradients, and flow cytometry, confirming their exosomal expression. Some were confirmed positive on urinary exosomes from a bladder cancer patient. In summary, the

  2. Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

    SciTech Connect

    Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg; He, Jiwei; Guzzo, Thomas; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; Malkowicz, S. Bruce; Christodouleas, John

    2013-03-01

    Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” if a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder

  3. Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome.

    PubMed

    Morelli, Annamaria; Comeglio, Paolo; Filippi, Sandra; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Yehiely-Cohen, Ravit; Maneschi, Elena; Gacci, Mauro; Carini, Marco; Adorini, Luciano; Vannelli, Gabriella B; Maggi, Mario

    2012-10-01

    In the male, metabolic syndrome (MetS) is associated to an increased risk of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). A recently established rabbit model of high fat diet (HFD)-induced MetS showed hypogonadism and the presence of prostate gland alterations, including inflammation, hypoxia and fibrosis. The present study investigated whether HFD-induced MetS might also alter bladder structure and function. Testosterone and the farnesoid X receptor (FXR) agonist INT-747, were evaluated for possible effects on HFD bladder. MetS rabbits develop bladder alterations, including fibrosis (reduced muscle/fiber ratio), hypoxia [2-fold increase as compared to regular diet (RD) group], low-grade inflammation (increased leukocyte infiltration and inflammatory markers) and RhoA/ROCK hyperactivity. Bladder strips from HFD rabbits, pre-contracted with carbachol, showed an overactive response to the selective ROCK inhibitor Y-27632. All these HFD-induced bladder alterations were partially blunted by testosterone and almost completely reverted by INT-747. Both treatments prevented some MetS features (glucose intolerance and visceral fat increase), thus suggesting that their effects on bladder could be ascribed to an improvement of the metabolic and/or hypogonadal state. However, a pathogenetic role for hypogonadism has been ruled out as GnRH analog-induced hypogonadal rabbits, fed a regular diet, did not show any detectable bladder alterations. In addition, INT-747 did not revert the MetS-induced hypogonadal state. FXR mRNA was highly expressed in rabbit bladder and positively associated with visceral fat increase. A direct effect of INT-747 on bladder smooth muscle was further suggested by inhibition of RhoA/ROCK-mediated activity by in vitro experiments on isolated cells. In conclusion, HFD-related MetS features are associated to bladder derangements, which are ameliorated by testosterone or INT-747 administration. INT-747 showed the most marked

  4. Urothelium muscarinic activation phosphorylates CBSSer227 via cGMP/PKG pathway causing human bladder relaxation through H2S production

    PubMed Central

    d’Emmanuele di Villa Bianca, Roberta; Mitidieri, Emma; Fusco, Ferdinando; Russo, Annapina; Pagliara, Valentina; Tramontano, Teresa; Donnarumma, Erminia; Mirone, Vincenzo; Cirino, Giuseppe; Russo, Giulia; Sorrentino, Raffaella

    2016-01-01

    The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser227 following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders. PMID:27509878

  5. Urothelium muscarinic activation phosphorylates CBS(Ser227) via cGMP/PKG pathway causing human bladder relaxation through H2S production.

    PubMed

    d'Emmanuele di Villa Bianca, Roberta; Mitidieri, Emma; Fusco, Ferdinando; Russo, Annapina; Pagliara, Valentina; Tramontano, Teresa; Donnarumma, Erminia; Mirone, Vincenzo; Cirino, Giuseppe; Russo, Giulia; Sorrentino, Raffaella

    2016-01-01

    The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders. PMID:27509878

  6. Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder.

    PubMed

    Silva-Ramos, M; Silva, I; Faria, M; Magalhães-Cardoso, M T; Correia, J; Ferreirinha, F; Correia-de-Sá, P

    2015-12-01

    This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [(3)H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [(3)H]ACh was higher (P < 0.05) in detrusor strips from BPH patients. The extracellular hydrolysis of ATP and, subsequent, adenosine formation was slower (t (1/2) 73 vs. 36 min, P < 0.05) in BPH detrusor strips. The A(1) receptor-mediated inhibition of evoked [(3)H]ACh release by adenosine (100 μM), NECA (1 μM), and R-PIA (0.3 μM) was enhanced in BPH bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A(1) immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A1 inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL(-1)) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A(1) receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A(1) receptor activation might be useful to control bladder overactivity in BPH patients.

  7. Time-dependent bladder tissue regeneration using bilayer bladder acellular matrix graft-silk fibroin scaffolds in a rat bladder augmentation model.

    PubMed

    Zhao, Yang; He, Yi; Zhou, Zhe; Guo, Jian-hua; Wu, Jia-sheng; Zhang, Ming; Li, Wei; Zhou, Juan; Xiao, Dong-dong; Wang, Zhong; Sun, Kang; Zhu, Ying-jian; Lu, Mu-jun

    2015-09-01

    With advances in tissue engineering, various synthetic and natural biomaterials have been widely used in tissue regeneration of the urinary bladder in rat models. However, reconstructive procedures remain insufficient due to the lack of appropriate scaffolding, which should provide a waterproof barrier function and support the needs of various cell types. To address these problems, we have developed a bilayer scaffold comprising a porous network (silk fibroin [SF]) and an underlying natural acellular matrix (bladder acellular matrix graft [BAMG]) and evaluated its feasibility and potential for bladder regeneration in a rat bladder augmentation model. Histological (hematoxylin and eosin and Masson's trichrome staining) and immunohistochemical analyses demonstrated that the bilayer BAMG-SF scaffold promoted smooth muscle, blood vessel, and nerve regeneration in a time-dependent manner. At 12weeks after implantation, bladders reconstructed with the BAMG-SF matrix displayed superior structural and functional properties without significant local tissue responses or systemic toxicity. These results demonstrated that the bilayer BAMG-SF scaffold may be a promising scaffold with good biocompatibility for bladder regeneration in the rat bladder augmentation model.

  8. Time-dependent bladder tissue regeneration using bilayer bladder acellular matrix graft-silk fibroin scaffolds in a rat bladder augmentation model.

    PubMed

    Zhao, Yang; He, Yi; Zhou, Zhe; Guo, Jian-hua; Wu, Jia-sheng; Zhang, Ming; Li, Wei; Zhou, Juan; Xiao, Dong-dong; Wang, Zhong; Sun, Kang; Zhu, Ying-jian; Lu, Mu-jun

    2015-09-01

    With advances in tissue engineering, various synthetic and natural biomaterials have been widely used in tissue regeneration of the urinary bladder in rat models. However, reconstructive procedures remain insufficient due to the lack of appropriate scaffolding, which should provide a waterproof barrier function and support the needs of various cell types. To address these problems, we have developed a bilayer scaffold comprising a porous network (silk fibroin [SF]) and an underlying natural acellular matrix (bladder acellular matrix graft [BAMG]) and evaluated its feasibility and potential for bladder regeneration in a rat bladder augmentation model. Histological (hematoxylin and eosin and Masson's trichrome staining) and immunohistochemical analyses demonstrated that the bilayer BAMG-SF scaffold promoted smooth muscle, blood vessel, and nerve regeneration in a time-dependent manner. At 12weeks after implantation, bladders reconstructed with the BAMG-SF matrix displayed superior structural and functional properties without significant local tissue responses or systemic toxicity. These results demonstrated that the bilayer BAMG-SF scaffold may be a promising scaffold with good biocompatibility for bladder regeneration in the rat bladder augmentation model. PMID:26049152

  9. Overactive bladder – 18 years – Part II

    PubMed Central

    Truzzi, Jose Carlos; Gomes, Cristiano Mendes; Bezerra, Carlos A.; Plata, Ivan Mauricio; Campos, Jose; Garrido, Gustavo Luis; Almeida, Fernando G.; Averbeck, Marcio Augusto; Fornari, Alexandre; Salazar, Anibal; Dell’Oro, Arturo; Cintra, Caio; Sacomani, Carlos Alberto Ricetto; Tapia, Juan Pablo; Brambila, Eduardo; Longo, Emilio Miguel; Rocha, Flavio Trigo; Coutinho, Francisco; Favre, Gabriel; Garcia, José Antonio; Castaño, Juan; Reyes, Miguel; Leyton, Rodrigo Eugenio; Ferreira, Ruiter Silva; Duran, Sergio; López, Vanda; Reges, Ricardo

    2016-01-01

    ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder. PMID:27176185

  10. Issues in physician contracting.

    PubMed

    Fanburg, John D; Leone, Alyson M

    2005-09-01

    Dermatologists will enter into a number of different contracts during their professional careers. It is important that in each agreement they enter, dermatologists reap the benefits that they aspire for and understand the consequences of each provision. This article addresses just a few of the different issues that arise in physician contracting, such as choosing the appropriate form of business entity; the importance of a writing; term and termination of the contract; compensation models; benefits, vacation and other time off included in the contract; malpractice insurance; and restrictive covenants. Each provision should be carefully analyzed to ensure that it will protect the best interests of the dermatologist in that situation. PMID:16202950

  11. Bladder wall thickness in the assessment of neurogenic bladder: a translational discussion of current clinical applications

    PubMed Central

    Sturm, Renea M.

    2016-01-01

    The prospective trial by Kim et al. “Can Bladder Wall Thickness Predict Videourodynamic Findings in Children with Spina Bifida?” published in Journal of Urology investigated the measurement of bladder wall thickness (BWT) as a non-invasive assessment tool for lower urinary tract changes in neurogenic bladder (NGB). In this study, no significant association was observed between BWT and high-risk urodynamic parameters. This editorial discusses the basic science of bladder wall thickening as well as prior studies relating wall thickness to clinical parameters. Although Kim et al. provide a unique literature contribution in terms of assessment of BWT at defined percent cystometric capacity, specific aspects of study methodology and population may have contributed to a lack of correlation with high-risk urodynamic findings. The application of non-invasive modalities to lower urinary tract assessment of NGB remains a promising and relevant area of future research to prevent progression to end stage lower urinary tract changes for all individuals with spina bifida. PMID:26889485

  12. Bladder Neck Urothelial Carcinoma: A Urinary Bladder Subsite Carcinoma With Distinct Clinicopathology.

    PubMed

    Xiao, Guang-Qian; Rashid, Hani

    2015-10-01

    To evaluate the clinicopathology of carcinomas originating in the urinary bladder neck, 316 cystectomies for urinary bladder carcinoma performed between January 1, 2008, and December 31, 2013, were analyzed. Clinicopathological parameters were compared between bladder neck carcinomas (BNCs) and non-BNCs. Among the 316 cystectomies were 19 BNCs and 297 non-BNCs. BNCs accounted for 19/316 (6%) of all the cases, with a male-to-female ratio 18:1. Bladder neck location was significantly associated with advanced tumor stage. Ninety percent and 58% BNCs presented at stage ≥T2 and ≥T3, respectively, versus 62% and 38% non-BNCs at ≥T2 and ≥T3, respectively. Significantly higher percentage of lymphovascular invasion and lymph node metastasis were also seen in BNCs (68% and 47%, respectively) than in non-BNCs (29% and 17%, respectively). In conclusion, BNCs present with a significantly higher frequency of muscle invasion and advanced tumor stage, lymphovascular invasion, as well as local and distant metastasis at diagnosis compared with the non-BNCs group. Recognition of these unique clinicopathologic features with early detection and possibly more aggressive management of BNC can potentially have a significant impact on the patient's outcome.

  13. Not all neurogenic bladders are the same: a proposal for a new neurogenic bladder classification system

    PubMed Central

    2016-01-01

    Neurogenic bladder (NGB) has long been defined as a clinical entity that describes a heterogeneous collection of syndromes. The common theme is a bladder disorder concomitant with a neurologic disorder. This definition does not give the clinician much information about the bladder disorder, nor how to treat it, or even what the natural history of the disorder is likely to be. It may be time for a new classification scheme to better define the bladder defect and prognosis, as well as inform treatment. We propose a classification system based on seven categories, each having a neurologic defect in a distinct anatomic location. This is termed SALE (Stratify by Anatomic Location and Etiology). In addition, the presence or absence of bowel dysfunction and autonomic dysreflexia will be reported. In the future, as more definite prognostic information can be gleaned from biomarkers, we anticipate adding urinary nerve growth factor (NGF) and urinary brain-derived neurotrophic factor (BDNF) levels to the definition. We expect the SALE system to efficiently describe a patient suffering from NGB and simultaneously inform the most appropriate treatment, follow-up regimen, and long-term prognosis. PMID:26904408

  14. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method

    PubMed Central

    Yang, Ganglong; Xu, Zhipeng; Lu, Wei; Li, Xiang; Sun, Chengwen; Guo, Jia; Xue, Peng; Guan, Feng

    2015-01-01

    The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia), KK47 (low grade nonmuscle invasive bladder cancer, NMIBC), and YTS1 (metastatic bladder cancer) have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC) progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO) term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer. PMID:26230496

  15. Effects of Spinal and Peripheral Injection of α1A or α1D Adrenoceptor Antagonists on Bladder Activity in Rat Models with or without Bladder Outlet Obstruction

    PubMed Central

    Kim, Jae Heon; Shim, Ji Sung; Kang, Seung Chul; Shim, Kang Soo; Park, Jae Young; Moon, Du Geon; Lee, Jeong Gu

    2011-01-01

    Purpose Antagonists of α1-adrenergic receptors (α1ARs) relax prostate smooth muscle and relieve voiding and storage symptoms. Recently, increased expression of α1ARs with change of its subtype expression has been proved in bladder outlet obstruction (BOO). To search for the evidence of changes in α1ARs subtype expression and activity in the peripheral and spinal routes, the effects of spinal and peripheral administration of tamsulosin (an α1A/D-selective AR), naftopidil (an α1A/D-selective AR), and doxazosin (non-selective AR) on bladder activity were investigated in a rat model with or without BOO. Methods A total of 65 female Sprague-Dawley rats were divided into the BOO surgery group (n=47) and the sham surgery group (n=18). After 6 weeks, cystometry was assessed before and after intrathecal and intra-arterial administrations of tamsulosin, naftopidil, and doxazosin. Results After intra-arterial administrations of all three drugs, bladder capacity (BC) was increased and maximal intravesical pressure (Pmax) was decreased in both BOO and the sham rat models (P<0.05). After intrathecal administration of all three drugs, BC was increased and Pmax was decreased in only the BOO group. The episodes of involuntary contraction in the BOO rat models were decreased by intra-arterial administration (P=0.031). The increase of BC after intrathercal and intra-arterial administrations of α1ARs was significantly greater in the BOO group than in the sham group (P=0.023, P=0.041). In the BOO group, the increase of BC and decrease in Pmax were greater by intra-arterial administration than by intrathecal administration (P=0.035). There were no significant differences of the degrees of changes in the cystometric parameters among the three different α1ARs. Conclusions Up-regulations of the α1ARs in BOO were observed by the greater increases of BC after α1AR antagonist administrations in the BOO group than in the sham group. However, there were no subtype differences of the

  16. [Immunotherapy of Urothelial Carcinoma of the Bladder -  from BCG Vaccines to Targeted Therapy].

    PubMed

    Matoušková, M

    2015-01-01

    Bladder cancer has high prevalence in men and women. Bladder cancer usually originates from urothelium. More than 75% of cases are classified as nonmuscle invasive bladder cancer. Urothelial bladder carcinoma is usually managed by transurethral resection of the bladder tumor. Role of transurethral resection of the bladder tumor is also essential in bladder cancer staging. Local prophylaxis is used in nonmuscle invasive bladder cancer to reduce risk of recurrence. While local chemoprophylaxis is sufficient in low and middle risk patients, intravesical instillation of Mycobacterium bovis bacillus CalmetteGuerin (BCG) is preferred in high risk bladder cancer. Chemotherapy alone or in combination with locoregional treatment is used in advanced bladder cancer. New immunotherapy modalities have proven their efficacy in several clinical studies in advanced bladder cancer.

  17. Treatment of bladder cancer with Ho:YAG laser

    NASA Astrophysics Data System (ADS)

    Shi, Hong-Min; Zhu, Jing; Zhang, Hui-Guo; Zhang, Mei-Jue; Xu, Jian; Dai, Shen-guo; Wu, Jia-Jun; Jiang, Yu

    1998-11-01

    Among tumors of urinary system, the morbidity of bladder cancer is the first one. It is multiple, also has high risk of regeneration. The paper reports that 679 bladder tumors in 108 patients had treated for 284 times by pulsed HO:YAG laser from July 1994-June 1997.

  18. Recent advances in the diagnosis and treatment of bladder cancer

    PubMed Central

    2013-01-01

    Bladder cancer is the commonest malignancy of the urinary tract. In this review, we look at the latest developments in the diagnosis and management of this condition. Cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer. Various alternatives have been investigated, either to reduce the frequency of cystoscopy, or improve its sensitivity for detection of tumors. These include urine-based markers and point-of-care tests. Narrow-band imaging and photodynamic diagnosis/blue-light cystoscopy have shown promise in improving detection and reducing recurrence of bladder tumors, by improving the completion of bladder resection when compared with standard resection in white light. The majority of patients with a new diagnosis of bladder cancer have non-muscle-invasive bladder cancer, which requires adjuvant intravesical chemotherapy and/or immunotherapy. Recent developments in post-resection intravesical regimens are discussed. For patients with muscle-invasive bladder cancer, both laparoscopic radical cystectomy and robot-assisted radical cystectomy have been shown to reduce peri-operative morbidity, while being oncologically equivalent to open radical cystectomy in the medium term. Bladder-preserving strategies entail resection and chemoradiation, and in selected patients give equivalent results to surgery. The development, advantages, and disadvantages of these newer approaches are also discussed. PMID:23327481

  19. Radiation Dose-Volume Effects of the Urinary Bladder

    SciTech Connect

    Viswanathan, Akila N.; Marks, Lawrence B.; Eifel, Patricia J.; Shipley, William U.

    2010-03-01

    An in-depth overview of the normal-tissue radiation tolerance of the urinary bladder is presented. The most informative studies consider whole-organ irradiation. The data on partial-organ/nonuniform irradiation are suspect because the bladder motion is not accounted for, and many studies lack long enough follow-up data. Future studies are needed.

  20. A Methylation Panel for Bladder Cancer — EDRN Public Portal

    Cancer.gov

    Participate in a prevalidation study for methylation based detection of bladder cancer. In addition, a panel of three markers identified will be evaluated for their ability to a) identify bladder cancer patients from those with benign urologic disease; b) identify patients with superficial (papillary) cancers from those with high grade invasive cancers

  1. Fish gall bladder consumption presenting as acute renal failure.

    PubMed

    Gupta, A; Karnik, N D; Gupta, V A; Hase, N K

    2015-01-01

    A forty two year old male was admitted with history of anuria and breathlessness following consumption of raw rohu fish gall bladder. He had azotemia and required hemodialysis. His renal failure improved over a period of about four weeks. Incidences have been reported from South East Asian countries associating consumption of raw rohu fish gall bladder with acute renal failure.

  2. High Frequency Sacral Root Nerve Block Allows Bladder Voiding

    PubMed Central

    Boger, Adam S.; Bhadra, Narendra; Gustafson, Kenneth J

    2013-01-01

    1) Aims Dyssynergic reflexive external urethral sphincter (EUS) activity following spinal cord injury can prevent bladder voiding, resulting in significant medical complications. Irreversible sphincterotomies or neurotomies can prevent EUS activation and allow bladder voiding, but may cause incontinence or loss of sacral reflexes. We investigated whether kilohertz frequency (KF) electrical conduction block of the sacral roots could prevent EUS activation and allow bladder voiding. 2) Methods The S2 sacral nerve roots were stimulated bilaterally to generate bladder pressure in 6 cats. One S1 nerve root was stimulated proximally (20 Hz biphasic pulse trains) to evoke EUS pressure, simulating worst-case dyssynergic EUS reflexes. KF waveforms (12.5 kHz biphasic square wave) applied to an electrode implanted distally on the S1 nerve root blocked nerve conduction, preventing the increase in EUS pressure and allowing voiding. 3) Results Applying KF waveforms increased bladder voiding in single, limited-duration trials from 3 ± 6% to 59 ± 12%. Voiding could be increased to 82 ± 9% of the initial bladder volume by repeating or increasing the duration of the trials. 4) Conclusions Sacral nerve block can prevent EUS activation and allow complete bladder voiding, potentially eliminating the need for a neurotomy. Eliminating neurotomy requirements could increase patient acceptance of bladder voiding neuroprostheses, increasing patient quality of life and reducing the cost of patient care. PMID:22473837

  3. Uterine inversion with massive uterovaginal prolapse and multiple bladder stones.

    PubMed

    Naidu, Aruku; Nusee, Zalina; Tayib, Shahila

    2011-06-01

    A non-puerperal uterine inversion in advanced uterovaginal prolapse is a rare occurrence. Even more unusual is the presence of bladder calculi in these two conditions, which has not been documented before. We report a case of acute urinary retention secondary to severe uterovaginal prolapse associated with uterine inversion and multiple bladder calculi.

  4. Fish gall bladder consumption presenting as acute renal failure.

    PubMed

    Gupta, A; Karnik, N D; Gupta, V A; Hase, N K

    2015-01-01

    A forty two year old male was admitted with history of anuria and breathlessness following consumption of raw rohu fish gall bladder. He had azotemia and required hemodialysis. His renal failure improved over a period of about four weeks. Incidences have been reported from South East Asian countries associating consumption of raw rohu fish gall bladder with acute renal failure. PMID:26440398

  5. Morphology of the gas bladder in bumblebee catfishes (Siluriformes, Pseudopimelodidae).

    PubMed

    Birindelli, José L O; Shibatta, Oscar A

    2011-07-01

    The gross morphology of the gas bladder is described and compared for representatives of all valid genera of Pseudopimelodidae (Siluriformes). Cephalosilurus albomarginatus and species of Batrochoglanis, and Microglanis have the most basic form: a large, cordiform gas bladder with a simple internal T-shaped septum. Cephalosilurus apurensis, C. fowleri, and C. nigricauda also have a large, cordiform gas bladder, but they have well-developed trabeculae associated with the internal T-shaped septum, and a pair of well-developed constrictor muscles inserted on the external wall; the latter feature is present in most species of Pimelodidae, but absent in all other catfishes. The monotypic Lophiosilurus alexandri also has well-developed constrictor muscles, and its gas bladder is moderately sized. The species of Pseudopimelodus and Cruciglanis have a diminutive gas bladder partially divided into two lateral sacs without internal communication, and lack constrictor muscles. The parapophysis of the fourth vertebra is a wide and long shelf connected to the dorsal surface of the gas bladder in most pseudopimelodid genera. However, in the species of Pseudopimelodus and Cruciglanis the parapophysis of the fourth vertebra is shorter and has its anterior ramus folded back, partially covering the gas bladder anteroventrally; and the tympanic opening is smaller than in species of the other genera. Five phylogenetic characters are proposed based on the morphology of the gas bladder and associated structures in species of Pseudopimelodidae, and the evolution of those characters in the family is discussed. J. Morphol., 2011. © 2011 Wiley-Liss, Inc. PMID:21538478

  6. MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

    EPA Science Inventory

    MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

    Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydrox...

  7. Inguinal bladder hernia associated with vesico-ureteric reflux.

    PubMed

    Noble, J G; Christmas, T J; Chapple, C R; Rickards, D

    1992-04-01

    The urinary bladder is frequently found as a component of inguinal herniae. This report describes a case of 'bladder hernia' associated with vesico-ureteric reflux. The current methods of investigation and subsequent treatment for this condition are reviewed along with the possible underlying cause of vesico-ureteric reflux in this case.

  8. Ingested arsenic, keratoses, and bladder cancer.

    PubMed

    Cuzick, J; Sasieni, P; Evans, S

    1992-08-15

    A cohort of 478 patients treated with Fowler's solution (potassium arsenite) in Lancashire, England, during the period 1945-1969 and previously followed until January 1, 1980, was followed for an additional 11 years. A significant excess of bladder cancer mortality occurred (observed/expected ratio = 5/1.6; p = 0.05). No excess was found for other causes of death. In a subcohort of 142 patients examined for signs of arsenicism around 1970, all 11 subsequent cancer deaths occurred in those with signs of arsenicism (p = 0.0009).

  9. Carcinoma of gall bladder presenting as dermatomyositis

    PubMed Central

    Narasimhaiah, Deepti Akkihebbal; Premkumar, Jennifer Anne; Moses, Viju; Chacko, Geeta

    2011-01-01

    Cancer-related muscle diseases are usually paraneoplastic disorders. Dermatomyositis (DM) is a type of inflammatory myopathy that is strongly associated with a broad range of malignant disorders. The malignancy can occur before, concomitantly or after the onset of myositis. The malignancies most commonly associated with DM are carcinomas of ovary, lung, stomach, colorectal and pancreas, as well as non-Hodgkin’s lymphoma. An association of DM with carcinoma of the gall bladder (GB) is extremely rare with only two previously reported cases in the literature. We report a case of carcinoma of GB with DM as the paraneoplastic manifestation. PMID:21655205

  10. Ten genetic polymorphisms in bladder cancer.

    PubMed Central

    Cartwright, R A; Adib, R; Appleyard, I; Coxon, J G; Glashan, R W; Richards, B; Robinson, M R; Sunderland, E; Barham-Hall, D

    1983-01-01

    Data are presented on a group of cases of primary carcinoma of the bladder, detailing red cell surface blood group antigenic phenotypes, serum haptoglobin phenotypes, and some red cell isoenzyme phenotypes. Account is taken of the stage of the disease at presentation. The results are compared with corresponding phenotype frequencies in groups of presumed healthy persons originating either in Yorkshire or County Durham. Differences in relative incidences were found in the haptoglobin, phosphoglucomutase (PGM), and some other systems. These are both differences between all cases and controls and between particular stages at presentation and controls. PMID:6221102

  11. Pathophysiology and animal modeling of underactive bladder.

    PubMed

    Tyagi, Pradeep; Smith, Phillip P; Kuchel, George A; de Groat, William C; Birder, Lori A; Chermansky, Christopher J; Adam, Rosalyn M; Tse, Vincent; Chancellor, Michael B; Yoshimura, Naoki

    2014-09-01

    While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB.

  12. Emerging neural stimulation technologies for bladder dysfunctions.

    PubMed

    Lee, Jee Woong; Kim, Daejeong; Yoo, Sangjin; Lee, Hyungsup; Lee, Gu-Haeng; Nam, Yoonkey

    2015-03-01

    In the neural engineering field, physiological dysfunctions are approached by identifying the target nerves and providing artificial stimulation to restore the function. Neural stimulation and recording technologies play a central role in this approach, and various engineering devices and stimulation techniques have become available to the medical community. For bladder control problems, electrical stimulation has been used as one of the treatments, while only a few emerging neurotechnologies have been used to tackle these problems. In this review, we introduce some recent developments in neural stimulation technologies including microelectrode array, closed-loop neural stimulation, optical stimulation, and ultrasound stimulation.

  13. Bladder cancer: innovative approaches beyond the diagnosis.

    PubMed

    Piergentili, R; Carradori, S; Gulia, C; De Monte, C; Cristini, C; Grande, P; Santini, E; Gentile, V; Di Pierro, G B

    2014-01-01

    Bladder carcinoma (BC) is the most common urinary malignant tumor. In the light of the unsuccessful current therapies and their side effects, new pharmacological strategies are needed. In addition to the well known therapeutic possibilities described in the first section, we focused our attention on very recent and innovative tools to approach this target (new drug candidates from epigenetic modulators to endothelin receptor inhibitors, improved technological formulations, active principles from plants, and dietary components). Then, in the last paragraph, we analyzed the etiology of recurrent BC, with particular attention to cellular microenvironment. In fact, the incidence of recurrence is up to 90%, and 25% of tumours show progression towards invasiveness.

  14. Solitary fibrous tumor in bladder: a case report.

    PubMed

    Wang, Tao; Chen, Ruibao; Qiao, Jiankun; Hu, Tao; Liu, Jihong; Yang, Weiming; Ye, Zhangqun

    2010-06-01

    Solitary fibrous tumor (SFT) in bladder is extremely rare. In this study, we reported one case of bladder SFT and reviewed the only ten cases of the disease that had been reported so far. The patient suffered from residual urine sensation and urethral pain. Cystoscopy revealed a 7-cm protruding mass at the dome of the bladder, and bladder mucosa biopsy showed normal differentiation of the bladder mucosa with a small amount of inflammatory cells. Radical resection of the tumor was performed in this patient. Pathological examination found uniform, haphazardly arranged spindle cells, the majority of which were CD34-positive and Vimentin-positive and proved that the mass was a solitary fibrous tumor. Within a period of 9 months of follow-up, no reoccurrence was found.

  15. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

    PubMed Central

    Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

    2016-01-01

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer.

  16. Anticholinergic therapy for overactive bladder: a nicotinic modality?

    PubMed

    Toler, Steven M; Yohannes, Daniel; Lippiello, Patrick M; Chancellor, Michael B

    2013-09-01

    Until recently the treatment of Overactive Bladder (OAB) has primarily been aimed at mitigating hypercholinergic activity in the bladder via antagonism of muscarinic acetylcholine receptors. However, antimuscarinic therapies have limited efficacy and significant side effects. It is now known that nicotinic acetylcholine receptor (nAChR) subtypes are expressed in the urothelium and on afferent nerve fibers in the bladder, and it is believed that these receptors serve to communicate urgency and facilitate voiding function. This presents the opportunity for an alternative to the antimuscarinic approach, one which involves inhibition of nAChRs in the bladder that are chronically overstimulated by acetylcholine. Specifically, we hypothesize that an orally administered nAChR-selective inhibitor with extensive renal elimination will result in higher local concentrations in the bladder and lower systemic exposure than current therapies, representing a novel targeted approach to the treatment of OAB with a more favorable side effect profile.

  17. Radical Cystectomy and Orthotopic Bladder Substitution Using Ileum

    PubMed Central

    Park, Jinsung

    2011-01-01

    Over the past decade, continent urinary diversion, especially orthotopic bladder substitutions, has become increasingly popular following radical cystectomy for bladder cancer. The ultimate goal of orthotopic bladder substitution is to offer patients the best quality of life, similar to that of patients with native bladders. To achieve that purpose, surgeons should be familiar with the characteristics of good candidates for neobladders, the possible intraoperative and postoperative problems related to the surgery, and the solutions to these problems. Postoperative surveillance and instructions given to the patients also contribute to successful, functional results. Here, we reviewed the indications, pitfalls, and solutions for orthotopic bladder substitutions and the patients' quality of life after surgery. When performed properly, orthotopic continent diversion offers good quality of life with few long-term complications. Therefore, we believe it is the best option for the majority of patients requiring cystectomy. PMID:21556208

  18. Bladder Cancer Patient Advocacy: A Global Perspective

    PubMed Central

    Quale, Diane Zipursky; Bangs, Rick; Smith, Monica; Guttman, David; Northam, Tammy; Winterbottom, Andrew; Necchi, Andrea; Fiorini, Edoardo; Demkiw, Stephanie

    2015-01-01

    Abstract Over the past 20 years, cancer patient advocacy groups have demonstrated that patient engagement in cancer care is essential to improving patient quality of life and outcomes. Bladder cancer patient advocacy only began 10 years ago in the United States, but is now expanding around the globe with non-profit organizations established in Canada, the United Kingdom and Italy, and efforts underway in Australia. These organizations, at different levels of maturity, are raising awareness of bladder cancer and providing essential information and resources to bladder cancer patients and their families. The patient advocacy organizations are also helping to advance research efforts by funding research proposals and facilitating research collaborations. Strong partnerships between these patient advocates and the bladder cancer medical community are essential to ensuringsustainability for these advocacy organizations, increasing funding to support advances in bladder cancer treatment, and improving patient outcomes. PMID:27398397

  19. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

    PubMed Central

    Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

    2016-01-01

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. PMID:27660445

  20. Gall bladder sludge and stones in multitransfused Egyptian thalassaemic patients.

    PubMed

    el-Nawawy, A; Kassem, A S; Eissa, M; Abdel-Fattah, M; Safwat, M

    2001-01-01

    One hundred Egyptian beta-thalassaemic patients on a long-term transfusion/chelation programme were evaluated for the prevalence of gall bladder sludge and stones and the associated risk factors. Fifty healthy individuals served as controls. Abdominal ultrasonography revealed that 14% of the thalassaemic patients had gall bladder sludge or stones (6% stones and 8% sludge). The thalassaemic patients with this complication were older, had a higher prevalence of gall bladder symptoms, higher levels of pretransfusion haemoglobin, larger amounts of transfused red cells, and more were regularly transfused. Multiple logistic regression analysis revealed that the presence that gall bladder symptoms and the amount of transfused red cells were the only significant predictors of the occurrence of gall bladder sludge or stones.

  1. 48 CFR 235.006 - Contracting methods and contract type.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... contract type. 235.006 Section 235.006 Federal Acquisition Regulations System DEFENSE ACQUISITION... CONTRACTING 235.006 Contracting methods and contract type. (b)(i) For major defense acquisition programs as... award a fixed-price type contract for a development program effort unless— (1) The level of program...

  2. Performance Contracting Overview.

    ERIC Educational Resources Information Center

    Wohlferd, Gerald H.

    Conclusions reached after three years of performance contracting experience and materials with which to judge the validity of the conclusions are presented in this overview of performance contracting. The conclusions are: (1) commercial firms are no better at teaching children than are public schools; (2) commercial firms expend as much or more…

  3. The New Employment Contract?

    ERIC Educational Resources Information Center

    Levine, David I.

    2002-01-01

    In the classic employment contract, especially at large companies, wages were not strongly responsive to the labor market. Instead, individual companies had distinctive company wage levels and patterns. An exhaustive study of employers and employees in the United States and Japan examined whether the "old employment contract" has been replaced.…

  4. Contracting for Telecommunications Systems.

    ERIC Educational Resources Information Center

    Brautigam, Arthur W.

    1984-01-01

    Reasons for changing telephone systems at colleges and universities and the preparation and evaluation of requests for proposals (RFP) are discussed. The negotiation and monitoring of the contract are also addressed. It is noted that contracting for a new telecommunications system is extremely complex. Reasons for changing systems include cost…

  5. Whither Performance Contracting?

    ERIC Educational Resources Information Center

    Green, Norman S.

    This report describes briefly performance contracts; discusses their shortcomings, pitfalls, and advantages; and gives some insight into the future development of this new concept. Two shortcomings of performance contracting include (1) teaching to the test and (2) board abdication of its responsibility for making final decisions about educational…

  6. Novel non invasive diagnostic strategies in bladder cancer

    PubMed Central

    TRUTA, ANAMARIA; POPON, TUDOR ADRIAN HODOR; SARACI, GEORGE; GHERVAN, LIVIU; POP, IOAN VICTOR

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, −145, −222, −210, −10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population. PMID:27152066

  7. Computer-aided detection of bladder tumors based on the thickness mapping of bladder wall in MR images

    NASA Astrophysics Data System (ADS)

    Zhu, Hongbin; Duan, Chaijie; Jiang, Ruirui; Li, Lihong; Fan, Yi; Yu, Xiaokang; Zeng, Wei; Gu, Xianfeng; Liang, Zhengrong

    2010-03-01

    Bladder cancer is reported to be the fifth leading cause of cancer deaths in the United States. Recent advances in medical imaging technologies, such as magnetic resonance (MR) imaging, make virtual cystoscopy a potential alternative with advantages as being a safe and non-invasive method for evaluation of the entire bladder and detection of abnormalities. To help reducing the interpretation time and reading fatigue of the readers or radiologists, we introduce a computer-aided detection scheme based on the thickness mapping of the bladder wall since locally-thickened bladder wall often appears around tumors. In the thickness mapping method, the path used to measure the thickness can be determined without any ambiguity by tracing the gradient direction of the potential field between the inner and outer borders of the bladder wall. The thickness mapping of the three-dimensional inner border surface of the bladder is then flattened to a twodimensional (2D) gray image with conformal mapping method. In the 2D flattened image, a blob detector is applied to detect the abnormalities, which are actually the thickened bladder wall indicating bladder lesions. Such scheme was tested on two MR datasets, one from a healthy volunteer and the other from a patient with a tumor. The result is preliminary, but very promising with 100% detection sensitivity at 7 FPs per case.

  8. Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels.

    PubMed

    Magari, Tomohiro; Shibata, Yasuhiro; Arai, Seiji; Kashiwagi, Bunzo; Suzuki, Keiji; Suzuki, Kazuhiro

    2014-01-01

    We examined the effect of androgens on bladder blood flow (BBF), bladder function and histological changes in castrated male rats. Male Wistar rats were classified into unoperated group (control group), groups castrated at the age of 8 weeks (group 8wPC) and groups castrated at the age of 4 weeks (group 4wPC). Each rat was used at the age of 20 weeks. BBF was measured using fluorescent microspheres. Bladder cystometry was performed without anesthesia or restraint; the bladder was first irrigated with saline and then with 0.25% acetic acid (AA) solution. Maximum voiding pressure and voiding interval were measured. The bladder and iliac artery were histologically examined for differences in smooth muscle and quantity of collagen fiber to analyze the effect of castration on the smooth muscle content. No differences were noted in BBF following castration. The voiding intervals for all groups were shortened (P < 0.001) following AA irrigation. No significant difference was noted in the maximum voiding pressure. Histological changes were observed in bladder and iliac artery. Smooth muscle/collagen ratio at the bladder was lower in groups 8wPC and 4wPC compared to the control group (P< 0.01), while that at the iliac artery was decreased in group 4wPC compared to the control group (P< 0.001). In conclusion, our findings indicate that castration does not alter BBF, but leads to histological changes in the bladder as well as its associated blood vessels.

  9. Signaling in muscle contraction.

    PubMed

    Kuo, Ivana Y; Ehrlich, Barbara E

    2015-02-02

    Signaling pathways regulate contraction of striated (skeletal and cardiac) and smooth muscle. Although these are similar, there are striking differences in the pathways that can be attributed to the distinct functional roles of the different muscle types. Muscles contract in response to depolarization, activation of G-protein-coupled receptors and other stimuli. The actomyosin fibers responsible for contraction require an increase in the cytosolic levels of calcium, which signaling pathways induce by promoting influx from extracellular sources or release from intracellular stores. Rises in cytosolic calcium stimulate numerous downstream calcium-dependent signaling pathways, which can also regulate contraction. Alterations to the signaling pathways that initiate and sustain contraction and relaxation occur as a consequence of exercise and pathophysiological conditions.

  10. Bladder neck incompetence at posterior urethroplasty.

    PubMed

    Koraitim, Mamdouh M

    2015-03-01

    The finding of an incompetent bladder neck (BN) at the time of posterior urethroplasty will necessarily exacerbate the already difficult situation. In such cases the aim of the treatment is not only to restore urethral continuity by end-to-end urethral anastomosis, but also to restore the function of the BN to maintain urinary continence. Fortunately, the incidence of incompetence of the BN at posterior urethroplasty is uncommon, usually ≈4.5%. It seems that pelvic fracture-related BN injuries, in contrast to urethral injuries which result from a shearing force, are due to direct injury by the sharp edge of the fractured and displaced pubic bone. The risk of injuries to the BN is greater in children, in patients with a fracture involving both superior and inferior pubic rami on the same side, and in those managed initially by primary realignment. An incompetent BN is suspected by finding an open rectangular BN on cystography, and a fixedly open BN on suprapubic cystoscopy. An incompetent BN can be treated either subsequent to or concomitant with the urethral repair, according to whether a perineal or a perineo-abdominal urethroplasty is used, respectively. Several options have been reported to treat pelvic fracture-related BN incompetence, including reconstructing the BN, forming a new sphincter by tubularisation of a rectangular flap of the anterior bladder wall, and mechanical occlusion by an artificial sphincter or collagen injection. Reconstruction of the BN by the Young-Dees-Leadbetter∗∗ procedure probably provides the most successful results.

  11. Solitary fibrous tumor of the urinary bladder.

    PubMed

    Kim, Se Hoon; Cha, Kyung Bin; Choi, Young Deuk; Cho, Nam Hoon

    2004-06-30

    Solitary fibrous tumor (SFT) is a distinct spindle cell tumor arising mainly in the pleura, however, SFT of extra-pleural sites had been reported. To our knowledge, five cases of the urinary bladder SFT had been reported. We have recently experienced a case of SFT of the urinary bladder in a 56-year- old man who was admitted to the hospital with a 4-month history of voiding difficulty, frequency, and residual urine sensation. A computerized tomography scan revealed a 12cm sized intravesical mass. The mass was marginally excised under the impression of it being a benign spindle cell tumor by pre-operative needle biopsy. On gross examination, the mass was multinodular, creamy white, and the cut surface was fibrotic with a rubbery consistency. Microscopic examination revealed haphazardly arranged spindle cells with a lace-like deposition of inter- and pericellular collagen. Areas of increased cellularity show nuclear atypia and occasional mitoses (2-3/10HPF). The immunohistochemical staining revealed an intense CD34 and bcl-2 immunoreactivity. Although the exact biologic behavior of these tumors has not been clarified, most of the reported cases have undergone a benign clinical course.

  12. Polymeric Bladder for Storing Liquid Oxygen

    NASA Technical Reports Server (NTRS)

    Walker, David H.; Harvey, Andrew C.; Leary, William

    2009-01-01

    A proposed system for storing oxygen in liquid form and dispensing it in gaseous form is based on (1) initial subcooling of the liquid oxygen; (2) containing the liquid oxygen in a flexible vessel; (3) applying a gas spring to the flexible vessel to keep the oxygen compressed above the saturation pressure and, thus, in the liquid state; and (4) using heat leakage into the system for vaporizing the oxygen to be dispensed. In a typical prior system based on these principles, the flexible vessel is a metal bellows housed in a rigid tank, and the gas spring consists of pressurized helium in the tank volume surrounding the bellows. Unfortunately, the welds in the bellows corrugations are subject to fatigue, and, because bellows have large ullage, a correspondingly large fraction of the oxygen content cannot be expelled. In the proposed system, the flexible vessel would be a bladder made of a liquid- crystal polymer (LCP). (LCPs are strong and compatible with liquid oxygen.) In comparison with a metal bellows, a polymeric bladder would have less ullage and would weigh less. In experiments involving fatigue cycling at liquid-nitrogen temperatures, two LCPs were found to be suitable for this application.

  13. Active surveillance for nonmuscle invasive bladder cancer.

    PubMed

    Miyake, Makito; Fujimoto, Kiyohide; Hirao, Yoshihiko

    2016-06-01

    Nonmuscle invasive bladder cancer (NMIBC) is known to be a heterogeneous malignancy that requires varying treatment modalities and follow-up schedules. Low-grade Ta papillary tumors are categorized as low-risk NMIBC because of their favorable prognosis. There is an expanding movement that overdiagnosis and overtreatment should be avoided considering the economic impact and the patients' quality of life. It has been over 10 years since the initial assessment of active surveillance for low-risk NMIBC suggested its feasibility and safety. However, urologists are still unfamiliar with this treatment option, which can be ideal in appropriately selected patients. In this review article, we focus on active surveillance for low-risk NMIBC and discuss the evidence and rationale for this treatment option. There are several issues to resolve in order to advocate active surveillance as a standard option in selected patients. A specific follow-up protocol including intervals of cystoscopy, urine cytology, urine markers, and other radiographic examinations need to be optimized and validated. Finally, we integrate the available data into the follow-up strategy and propose a new surveillance protocol for active surveillance of recurrent low-risk bladder cancer. PMID:27326406

  14. Bladder Endometriosis Mimicking TCC - A Case Report.

    PubMed

    Gupta, Asish; Bhatnagar, Atul; Seth, B N; Dang, Arbinder; Gupta, Vineeta

    2016-02-01

    Endometriosis is the ectopic presence of endometrial tissue outside the uterus. Though on its own endometriosis is not a rare lesion, the involvement of the urinary tract is rare but with the bladder being the most commonly affected organ. Endometriosis is usually seen in females between the ages of 30-40 years and may occur due to fluctuating levels of oestrogen and progesterone. Clinically the patient maybe asymptomatic or show symptoms of dysmenorrhea, irregular or heavy periods, pain in the pelvic area, lower abdomen or in the back. It has been suggested that ultrasonography should be done either before or during menstruation as the lesion becomes more evident and a biopsy taken during this period is a strong aid in reaching a final diagnosis. We report here an unusual case of bladder endometriosis where the patient came with severe pelvic pain and an endoluminal mass seen on the ultrasonographic report. Based on these findings a differential of transitional cell carcinoma was given which was ruled out based on the cystoscopic findings.

  15. Bladder Endometriosis Mimicking TCC - A Case Report.

    PubMed

    Gupta, Asish; Bhatnagar, Atul; Seth, B N; Dang, Arbinder; Gupta, Vineeta

    2016-02-01

    Endometriosis is the ectopic presence of endometrial tissue outside the uterus. Though on its own endometriosis is not a rare lesion, the involvement of the urinary tract is rare but with the bladder being the most commonly affected organ. Endometriosis is usually seen in females between the ages of 30-40 years and may occur due to fluctuating levels of oestrogen and progesterone. Clinically the patient maybe asymptomatic or show symptoms of dysmenorrhea, irregular or heavy periods, pain in the pelvic area, lower abdomen or in the back. It has been suggested that ultrasonography should be done either before or during menstruation as the lesion becomes more evident and a biopsy taken during this period is a strong aid in reaching a final diagnosis. We report here an unusual case of bladder endometriosis where the patient came with severe pelvic pain and an endoluminal mass seen on the ultrasonographic report. Based on these findings a differential of transitional cell carcinoma was given which was ruled out based on the cystoscopic findings. PMID:27042525

  16. Application of Bladder Acellular Matrix in Urinary Bladder Regeneration: The State of the Art and Future Directions

    PubMed Central

    Pokrywczynska, Marta; Drewa, Gerard; Drewa, Tomasz

    2015-01-01

    Construction of the urinary bladder de novo using tissue engineering technologies is the “holy grail” of reconstructive urology. The search for the ideal biomaterial for urinary bladder reconstruction has been ongoing for decades. One of the most promising biomaterials for this purpose seems to be bladder acellular matrix (BAM). In this review we determine the most important factors, which may affect biological and physical properties of BAM and its regeneration potential in tissue engineered urinary bladder. We also point out the directions in modification of BAM, which include incorporation of exogenous growth factors into the BAM structure. Finally, we discuss the results of the urinary bladder regeneration with cell seeded BAM. PMID:25793199

  17. Dose to the gall bladder from a /sup 99m/Tc labeled gall bladder scanning agent

    SciTech Connect

    Bernard, S.R.; Chen, S.M.

    1981-06-01

    A mathematical gall bladder was added to the mathematical phantom and the specific absorbed fractions (PHI) were calculated for the 22 target organs (for the source in the gall bladder) by the Monte Carlo code. From these data and the /sup 99m/Tc decay scheme data, the S factors (rads per ..mu..Ci-day residence) for the organs when the source is in the gall bladder were estimated. From the reciprocity relationship for PHI, the S factors for the gall bladder when the source is located in any of the 22 source organs of the phantom were also estimated. The dose to the gall bladder wall from a single injection of the /sup 99m/Tc labeled scanning agent into man is estimated to be approx. 0.52 rads/mCi plus or minus about 1/2 this value depending on the assumptions in the estimation of this value.

  18. Whole-Pelvis or Bladder-Only Chemoradiation for Lymph Node-Negative Invasive Bladder Cancer: Single-Institution Experience

    SciTech Connect

    Tunio, Mutahir A.; Hashmi, Altaf; Qayyum, Abdul; Mohsin, Rehan; Zaeem, Ahmed

    2012-03-01

    Purpose: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard bladder preserving option for patients with invasive bladder cancer. The standard practice is to treat elective pelvic lymph nodes, so our aim was to evaluate whether bladder-only (BO) CCRT leads to results similar to those obtained by standard WP-CCRT. Methods and Materials: Patient eligibility included histopathologically proven muscle-invasive bladder cancer, lymph nodes negative (T2-T4, N-) by radiology, and maximal transurethral resection of bladder tumor with normal hematologic, renal, and liver functions. Between March 2005 and May 2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120 patients) and BO-CCRT (110 patients). Data regarding the toxicity profile, compliance, initial complete response rates at 3 months, and occurrence of locoregional or distant failure were recorded. Results: With a median follow-up time of 5 years (range, 3-6), WP-CCRT was associated with a 5-year disease-free survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5). The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT, respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP-CCRT and 51% for BO-CCRT (p = 0.8). Conclusion: BO-CCRT showed similar rates of bladder preservation, disease-free survival, and overall survival rates as those of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node-negative bladder cancer to minimize the side effects of CCRT.

  19. Differential effects of intravesical resiniferatoxin on excitability of bladder spinal neurons upon colon–bladder cross-sensitization

    PubMed Central

    Malykhina, Anna P.; Qin, Chao; Lei, Qi; Pan, Xiao-Qing; Meerveld, Beverley Greenwood-Van; Foreman, Robert D.

    2013-01-01

    Cross-sensitization in the pelvis may contribute to etiology of functional pelvic pain disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS). Increasing evidence suggests the involvement of transient receptor potential vanilloid 1 (TRPV1) receptors in the development of neurogenic inflammation in the pelvis and pelvic organ cross-sensitization. The objective of this study was to test the hypothesis that desensitization of TRPV1 receptors in the urinary bladder can minimize the effects of cross-sensitization induced by experimental colitis on excitability of bladder spinal neurons. Extracellular activity of bladder neurons was recorded in response to graded urinary bladder distension (UBD) in rats pretreated with intravesical resiniferatoxin (RTX, 10−7 M). Colonic inflammation was induced by intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The duration of excitatory responses to noxious UBD during acute colonic inflammation (3 days post-TNBS) was significantly shortened in the group with RTX pretreatment (25.37±.5 s, n=49) when compared to the control group (35.1±4.2 s, n=43, p≤0.05). The duration of long-lasting excitatory responses, but not short-lasting responses of bladder spinal neurons during acute colitis was significantly reduced by RTX from 52.9±6.6 s (n=21, vehicle group) to 34.4±2.1 s (RTX group, n=21, p≤0.05). However, activation of TRPV1 receptors in the urinary bladder prior to acute colitis increased the number of bladder neurons receiving input from large somatic fields from 22.7% to 58.2% (p≤0.01). The results of our study provide evidence that intravesical RTX reduces the effects of viscerovisceral cross-talk induced by colonic inflammation on bladder spinal neurons. However, RTX enhances the responses of bladder neurons to somatic stimulation, thereby limiting its therapeutic potential. PMID:23146715

  20. A microangiographic study of the effect of hyperthermia on the rabbit bladder

    NASA Technical Reports Server (NTRS)

    Hietala, S. O.; Howells, R.; Hazra, I. A.

    1978-01-01

    A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

  1. Assessment of Bladder Motion for Clinical Radiotherapy Practice Using Cine-Magnetic Resonance Imaging

    SciTech Connect

    McBain, Catherine A.; Khoo, Vincent S.; Buckley, David L.; Sykes, Jonathan S.; Green, Melanie M.; Cowan, Richard A.; Hutchinson, Charles E.; Moore, Christopher J.; Price, Patricia M.

    2009-11-01

    Purpose: Organ motion is recognized as the principal source of inaccuracy in bladder radiotherapy (RT), but there is currently little information on intrafraction bladder motion. Methods and Materials: We used cine-magnetic resonance imaging (cine-MRI) to study bladder motion relevant to intrafraction RT delivery. On two occasions, a 28 minute cine-MRI sequence was acquired from 10 bladder cancer patients and 5 control participants immediately after bladder emptying, after abstinence from drinking for the preceding hour. From the resulting cine sequences, bladder motion was subjectively assessed. To quantify bladder motion, the bladder was contoured in imaging volume sets at 0, 14, and 28 min to measure changes to bladder volumes, wall displacements, and center of gravity (COG) over time. Results: The dominant source of bladder motion during imaging was bladder filling (up to 101% volume increase); rectal and small bowel movements were transient, with minimal impact. Bladder volume changes were similar for all participants. However for bladder cancer patients, wall displacements were larger (up to 58 mm), less symmetrical, and more variable compared with nondiseased control bladders. Conclusions: Significant and individualized intrafraction bladder wall displacements may occur during bladder RT delivery. This important source of inaccuracy should be incorporated into treatment planning and verification.

  2. 48 CFR 916.307 - Contract clauses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTRACT TYPES TYPES OF CONTRACTS Cost-Reimbursement Contracts 916.307 Contract clauses. (g) Insert the... solicitations and contracts when a cost-reimbursement research and development contract with a State or...

  3. Overview of bladder heating technology: matching capabilities with clinical requirements.

    PubMed

    Stauffer, Paul R; van Rhoon, Gerard C

    2016-06-01

    Moderate temperature hyperthermia (40-45°C for 1 h) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle-invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle-invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for heating bladder cancer. Systems are described for thermal conduction heating of the bladder wall via circulation of hot fluid, intravesical microwave antenna heating, capacitively coupled radio-frequency current heating, and radiofrequency phased array deep regional heating of the pelvis. Relative heating characteristics of the available technologies are compared based on published feasibility studies, and the systems correlated with clinical requirements for effective treatment of MIBC and NMIBC. PMID:26939993

  4. HPLC assisted Raman spectroscopic studies on bladder cancer

    NASA Astrophysics Data System (ADS)

    Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

    2015-04-01

    We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

  5. The Case for Performance Contracting.

    ERIC Educational Resources Information Center

    Miller, Sutherland; Wilson, Nancy

    1981-01-01

    Discussed the State of Colorado's introduction of performance contracting into its relationships with community mental health centers. Describes the nature of the contract and its implementation. Particular emphasis is placed on the implications of the contract for program evaluation. (Author)

  6. Subclassification of muscarinic receptors in the heart, urinary bladder and sympathetic ganglia in the pithed rat. Selectivity of some classical agonists.

    PubMed

    van Charldorp, K J; de Jonge, A; Thoolen, M J; van Zwieten, P A

    1985-12-01

    In pithed normotensive rats muscarinic receptors were characterized in heart, urinary bladder and sympathetic ganglia; the selectivity of some classical muscarinic agents for these subtypes was investigated. The potencies in decreasing heart rate, increasing bladder pressure and increasing diastolic blood pressure were measured for the following, intraarterially administered cholinergic agonists: McN-A-343 ([4-m-chlorophenylcarbamoyloxy]-2-butynyltrimethylammonium), pilocarpine, carbachol, oxotremorine, arecoline, acetyl-beta-methylcholine and acetylcholine. The selective M1-antagonist pirenzepine, the mixed M1/M2-antagonist dexetimide and the cardioselective M2-antagonist gallamine were used as tools for identification of the receptors. All data were obtained after intravenous pretreatment with a high dose of atenolol to eliminate tachycardia induced by stimulating sympathetic ganglionic muscarinic receptors. Dexetimide strongly antagonized the bradycardia as well as the increase in bladder pressure induced by pilocarpine, carbachol, oxotremorine, arecoline, acetyl-beta-methylcholine and acetylcholine, whereas pirenzepine was much less effective. Gallamine antagonized the bradycardia, whereas no influence was found on the bladder contraction. Pilocarpine acted as a partial agonist in reducing heart rate as well as in increasing bladder pressure, whereas McN-A-343 was almost ineffective in doses up to 1 mg/kg. The hypertensive response to pilocarpine and carbachol was less pronounced than that produced by McN-A-343. Pirenzepine and dexetimide significantly antagonized the hypertensive response to McN-A-343 and pilocarpine, whereas gallamine was much less effective. The hypertensive response induced by carbachol was totally blocked by hexamethonium. The other agonists used in this study did not produce a significant increase in diastolic blood pressure in doses that produced a maximal effect on heart rate and urinary bladder pressure.(ABSTRACT TRUNCATED AT 250 WORDS

  7. Endoscopic Gold Fiducial Marker Placement into the Bladder Wall to Optimize Radiotherapy Targeting for Bladder-Preserving Management of Muscle-Invasive Bladder Cancer: Feasibility and Initial Outcomes

    PubMed Central

    Garcia, Maurice M.; Gottschalk, Alexander R.; Brajtbord, Jonathan; Konety, Badrinath R.; Meng, Maxwell V.; Roach, Mack; Carroll, Peter R.

    2014-01-01

    Background and Purpose Bladder radiotherapy is a management option for carefully selected patients with muscle-invasive bladder cancer. However, the inability to visualize the tumor site during treatment and normal bladder movement limits targeting accuracy and increases collateral radiation. A means to accurately and reliably target the bladder during radiotherapy is needed. Materials and Methods Eighteen consecutive patients with muscle-invasive bladder cancer (T1–T4) elected bladder-preserving treatment with maximal transurethral resection (TUR), radiation and concurrent chemotherapy. All underwent endoscopic placement of 24-K gold fiducial markers modified with micro-tines (70 [2.9×0.9 mm.]; 19 [2.1×0.7 mm.) into healthy submucosa 5-10 mm. from the resection margin, using custom-made coaxial needles. Marker migration was assessed for with intra-op bladder-filling cystogram and measurement of distance between markers. Set-up error and marker retention through completion of radiotherapy was confirmed by on-table portal imaging. Results Between 1/2007 and 7/2012, a total of 89 markers (3–5 per tumor site) were placed into 18 patients of mean age 73.6 years. Two patients elected cystectomy before starting treatment; 16/18 completed chemo-radiotherapy. All (100%) markers were visible with all on-table (portal, cone-beam CT), fluoroscopy, plain-film, and CT-scan imaging. In two patients, 1 of 4 markers placed at the tumor site fell-out (voided) during the second half of radiotherapy. All other markers (80/82, 98%) were present through the end of radio-therapy. No intraoperative (e.g. uncontrolled bleeding, collateral injury) or post-operative complications (e.g. stone formation, urinary tract infection, post-TUR hematuria >48 hours) occurred. Use of micro-tined fiducial tumor-site markers afforded a 2 to 6-fold reduction in bladder-area targeted with high-dose radiation. Discussion Placement of the micro-tined fiducial markers into the bladder was feasible and

  8. On the mechanical role of de novo synthesized elastin in the urinary bladder wall.

    PubMed

    Wognum, Silvia; Schmidt, David E; Sacks, Michael S

    2009-10-01

    The urinary bladder wall (UBW), which is composed of smooth muscle, collagen, and elastin, undergoes profound remodeling in response to changes in mechanical loading resulting from various pathologies. In our laboratory, we have observed the production of fibrillar elastin in the extracellular matrix (ECM), which makes the UBW a particularly attractive tissue to investigate smooth muscle tissue remodeling. In the present study, we explored the mechanical role that de novo elastin fibers play in altering UBW ECM mechanical behavior using a structural constitutive modeling approach. The mechanical behavior of the collagen fiber component of the UBW ECM was determined from the biaxial stress-stretch response of normal UBW ECM, based on bimodal fiber recruitment that was motivated by the UBW's unique collagen fiber structure. The resulting fiber ensemble model was then combined with an experimentally derived fiber angular distribution to predict the biaxial mechanical behavior of normal and the elastin-rich UBW ECM to elucidate the underlying mechanisms of elastin production. Results indicated that UBW ECM exhibited a distinct structure with highly coiled collagen fiber bundles and visible elastic fibers in the pathological situation. Elastin-rich UBW ECM had a distinct mechanical behavior with higher compliance, attributable to the indirect effect of elastin fibers contracting the collagen fiber network, resulting in a retracted unloaded reference state of the tissue. In conclusion, our results suggest that the urinary bladder responds to prolonged periods of high strain by increasing its effective compliance through the interaction between collagen and de novo synthesized elastic fibers.

  9. Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation.

    PubMed

    Hughes, Francis M; Vivar, Nivardo P; Kennis, James G; Pratt-Thomas, Jeffery D; Lowe, Danielle W; Shaner, Brooke E; Nietert, Paul J; Spruill, Laura S; Purves, J Todd

    2014-02-01

    Bladder inflammation (cystitis) underlies numerous bladder pathologies and is elicited by a plethora of agents such as urinary tract infections, bladder outlet obstruction, chemotherapies, and catheters. Pattern recognition receptors [Toll-like receptors (TLRs) and Nod-like receptors (NLRs)] that recognize pathogen- and/or damage-associated molecular patterns (PAMPs and/or DAMPs, respectively) are key components of the innate immune system that coordinates the production (TLRs) and maturation (NLRs) of proinflammatory IL-1β. Despite multiple studies of TLRs in the bladder, none have investigated NLRs beyond one small survey. We now demonstrate that NLRP3 and NLRC4, and their binding partners apoptosis-associated speck-like protein containing a COOH-terminal caspase recruitment domain (ASC) and NLR family apoptosis inhibitory protein (NAIP), are expressed in the bladder and localized predominantly to the urothelia. Activated NLRs form inflammasomes that activate caspase-1. Placement of a NLRP3- or NLRC4-activating PAMP or NLRP3-activating DAMPs into the lumen of the bladder stimulated caspase-1 activity. To investigate inflammasomes in vivo, we induced cystitis with cyclophosphamide (CP, 150 mg/kg ip) in the presence or absence of the inflammasome inhibitor glyburide. Glyburide completely blocked CP-induced activation of caspase-1 and the production of IL-1β at 4 h. At 24 h, glyburide reduced two markers of inflammation by 30-50% and reversed much of the inflammatory morphology. Furthermore, glyburide reversed changes in bladder physiology (cystometry) induced by CP. In conclusion, NLRs/inflammasomes are present in the bladder urothelia and respond to DAMPs and PAMPs, whereas NLRP3 inhibition blocks bladder dysfunction in the CP model. The coordinated response of NLRs and TLRs in the urothelia represents a first-line innate defense that may provide an important target for pharmacological intervention.

  10. Structure and function in urinary bladder of foetal sheep.

    PubMed

    France, V M; Stanier, M W; Wooding, F B

    1974-06-01

    1. The structure and function of the epithelial lining of the urinary bladder of sheep foetuses was investigated by electron microscopic studies made in conjunction with a series of experiments in which the permeability of the bladder to sodium and water was measured in vitro. Measurements were made at gestational ages ranging from 50 to 141 days (term = 147 days) Osmolarity and electrolyte concentrations of urine found in the foetal bladder were also measured.2. The development of tight junctions between the bladder epithelial cells was investigated by incubating the tissue with solutions containing 1 mM-LaCl(3) on the mucosal surface. No penetration of the junctions by lanthanum was observed in foetuses of 90 days or older. In younger bladders, the epithelial layer was stripped by treatment with lanthanum, but tight junctions appeared to be fully developed in early bladders incubated without lanthanum.3. The surface structure of the luminal (mucosal) plasmalemma was fully developed at 50 days.4. Unidirectional fluxes of labelled sodium and water were measured with identical solutions bathing the two surfaces of the bladder wall. No net water movement occurred; the mean ratio of efflux to influx in nine bladders was 1.002 +/- 0.039 (S.E. of mean). Under these conditions, the flux ratio for sodium was 1.735 +/- 0.143 (S.E. of mean) in twelve bladders.5. Antidiuretic hormone (ADH) had no effect on net water movement but reduced the net efflux of sodium so that the flux ratio became 1.285 +/- 0.255 (S.E. of mean) n = 8. ADH also had a striking effect on the structure of the epithelium, causing marked swelling of the intercellular spaces. The tight junctions remained an effective barrier to lanthanum penetration under these conditions; lanthanum was not observed in the enlarged spaces.

  11. Clinicopathologic features and treatment outcome of urinary bladder neoplasm.

    PubMed

    Hooda, M N; Siddique, F H; Nabi, S; Islam, M W; Ara, K; Bhuiyan, Z I

    2014-04-01

    More than ninety percent of bladder neoplasm is Transitional Cell Carcinoma (TCC). About 85% of patients present with symptom of painless haematuria. However haematuria is quite often intermittent so that a negative result has little meaning in ruling out the presence of bladder cancer. The present study was conducted to observe the natural history of different clinicopathologic stages of bladder cancer after transurethral resection bladder tumor (TURBT), either intravescical chemotherapy (IVC) or immunotherapy with BCG and of other forms of therapy like radio-chemotherapy (RCT) and radical surgery in few cases. A consecutive series of 52 cases with different grades and stages of bladder cancer patients were studied. Those who were noncompliant with surgery were sent for RCT. The age range of the patients was 34 to 75 with mean 53 year. Macroscopic haematuria, flank pain, microscopic haematuria, bladder irritability was found in 43(82.7%), 06(11.5%), 03(5.8%), 32(61.5%) cases respectively and coincidental ureteral TCC with hydronephrosis was found in 04(7.7%) cases for whom radical nephreureterectomy and cystectomy with ileal conduit was done. Amongst the other muscle invasive tumor only three cases were compliant to do radical surgery; rest were advised to consult with oncologist for possible RCT. Superficial bladder cancer was 19(36.5%) and invasive bladder cancer was 33(63.5%). TURBT and IVT were offered for all superficial bladder tumors. Of them 06(31.5%) patients showed recurrence during the study period. More recurrences occur in IVC group (35.7%) than immunotherapy with BCG group (20%) Re-TURBT and stage wise treatment was offered to them. All recurrent cases were G-3 tumor and were multifocal. Recurrence rate is about 30%. Screening program and structured referral system should be developed to have early diagnosis for prompt treatment and best prognosis.

  12. Preclinical Dosimetry of Magnetic Fluid Hyperthermia for Bladder Cancer

    PubMed Central

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea; Etienne, Wiguins; Maccarini, Paolo F.; Inman, Brant; Dewhirst, Mark W.

    2013-01-01

    Background Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Methods The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. Results The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder ≥1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues. PMID:23837123

  13. Best practice in the assessment of bladder function in infants

    PubMed Central

    Leonard, Michael; Castagnetti, Marco

    2014-01-01

    The purpose of this article is to review normal developmental bladder physiology in infants and bladder dysfunction in conditions such as neurogenic bladder, posterior urethral valves and high grade vesicoureteric reflux. We contrast the classical concept that bladder function in nontoilet-trained children is thought to be ‘reflexive’ or ‘uninhibited’, with the results of more recent research showing that infants most commonly have a stable detrusor. The infant bladder is physiologically distinct from the state seen in older children or adults. The voiding pattern of the infant is characterized by an interrupted voiding stream due to lack of proper urinary sphincter relaxation during voiding. This is called physiologic detrusor sphincter dyscoordination and is different from the pathologic ‘detrusor sphincter dyssynergy’ seen in patients with neurogenic bladder. Urodynamic abnormalities in neonates born with spina bifida are common and depend on the level and severity of the spinal cord malformation. Upper neuron lesions most commonly lead to an overactive bladder with or without detrusor sphincter dyssynergy while a lower neuron lesion is associated with an acontractile detrusor with possible denervation of the external urinary sphincter. In infants with neurogenic bladder, the role of ‘early prophylactic treatment (clean intermittent catheterization and anticholinergics)’ versus initial ‘watchful waiting and treatment as needed’ is still controversial and needs more research. Many urodynamic-based interventions have been suggested in patients with posterior urethral valves and are currently under scrutiny, but their impact on the long-term outcome of the upper and lower urinary tract is still unknown. Cumulative data suggest that there is no benefit to early intervention regarding bladder function in infants with high-grade vesicoureteric reflux. PMID:25083164

  14. Preclinical dosimetry of magnetic fluid hyperthermia for bladder cancer

    NASA Astrophysics Data System (ADS)

    Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea; Etienne, Wiguins; Maccarini, Paolo F.; Inman, Brant; Dewhirst, Mark W.

    2013-02-01

    Background Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Methods The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. Results The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder >1°C/min to a steady-state of 42°C. Conclusion Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

  15. Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation.

    PubMed

    Hughes, Francis M; Vivar, Nivardo P; Kennis, James G; Pratt-Thomas, Jeffery D; Lowe, Danielle W; Shaner, Brooke E; Nietert, Paul J; Spruill, Laura S; Purves, J Todd

    2014-02-01

    Bladder inflammation (cystitis) underlies numerous bladder pathologies and is elicited by a plethora of agents such as urinary tract infections, bladder outlet obstruction, chemotherapies, and catheters. Pattern recognition receptors [Toll-like receptors (TLRs) and Nod-like receptors (NLRs)] that recognize pathogen- and/or damage-associated molecular patterns (PAMPs and/or DAMPs, respectively) are key components of the innate immune system that coordinates the production (TLRs) and maturation (NLRs) of proinflammatory IL-1β. Despite multiple studies of TLRs in the bladder, none have investigated NLRs beyond one small survey. We now demonstrate that NLRP3 and NLRC4, and their binding partners apoptosis-associated speck-like protein containing a COOH-terminal caspase recruitment domain (ASC) and NLR family apoptosis inhibitory protein (NAIP), are expressed in the bladder and localized predominantly to the urothelia. Activated NLRs form inflammasomes that activate caspase-1. Placement of a NLRP3- or NLRC4-activating PAMP or NLRP3-activating DAMPs into the lumen of the bladder stimulated caspase-1 activity. To investigate inflammasomes in vivo, we induced cystitis with cyclophosphamide (CP, 150 mg/kg ip) in the presence or absence of the inflammasome inhibitor glyburide. Glyburide completely blocked CP-induced activation of caspase-1 and the production of IL-1β at 4 h. At 24 h, glyburide reduced two markers of inflammation by 30-50% and reversed much of the inflammatory morphology. Furthermore, glyburide reversed changes in bladder physiology (cystometry) induced by CP. In conclusion, NLRs/inflammasomes are present in the bladder urothelia and respond to DAMPs and PAMPs, whereas NLRP3 inhibition blocks bladder dysfunction in the CP model. The coordinated response of NLRs and TLRs in the urothelia represents a first-line innate defense that may provide an important target for pharmacological intervention. PMID:24285499

  16. 48 CFR 232.617 - Contract clause.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Contract Debts 232.617 Contract clause... personnel at civilian schools, colleges, and universities; (B) Basic agreements with telephone companies...

  17. A Mouse Model of Furosemide-Induced Overactive Bladder.

    PubMed

    Saporito, Michael S; Zuvich, Eva; DiCamillo, Amy

    2016-01-01

    Detailed in this unit is a mouse model of overactive bladder and urinary incontinence based on diuretic stress-induced urination. The procedure involves the use of a unique, highly sensitive, and automated urine capturing method to measure urinary latency, frequency, and void volume. Although this method was first described and validated using an anti-muscarinic drug used for treating overactive bladder, subsequent work has shown that effective non-cholinergic agents can be detected. These findings indicate good predictive value for this model regarding the possible clinical utility of test agents as treatments for overactive bladder, regardless of their site of action. © 2016 by John Wiley & Sons, Inc. PMID:27636110

  18. Urethral duplication with unusual cause of bladder outlet obstruction

    PubMed Central

    Venkatramani, Vivek; George, Arun Jacob Philip; Chandrasingh, J.; Panda, Arabind; Devasia, Antony

    2016-01-01

    A 12-year-old boy presented with poor flow and recurrent urinary tract infections following hypospadias repair at the age of 3 years. The evaluation revealed urethral duplication with a hypoplastic dorsal urethra and patent ventral urethra. He also had duplication of the bladder neck, and on voiding cystourethrogram the ventral bladder neck appeared hypoplastic and compressed by the dorsal bladder neck during voiding. The possibility of functional obstruction of the ventral urethra by the occluded dorsal urethra was suspected, and he underwent a successful urethro-urethrostomy. PMID:27127361

  19. Transitional cell bladder carcinoma with presentation mimicking ovarian carcinoma.

    PubMed

    Erickson, D R; Dabbs, D J; Olt, G J

    1996-05-01

    In the case described here, the patient's initial presentation suggested ovarian carcinoma. She had recurrent ascites, a pelvic mass, elevated CA-125, and extensive peritoneal carcinomatosis with transitional cell histology. The presence of hematuria prompted a cystoscopy, which revealed the true site of origin to be the urinary bladder rather than ovaries. This presentation is extremely rare for bladder cancer. Since transitional cell tumors from the bladder have a much worse prognosis than those of ovarian origin, it is important to identify the primary site correctly. Therefore, cystoscopy is essential for patients with hematuria, and should be considered in cases of apparent primary peritoneal carcinoma with transitional cell histology.

  20. Photoacoustic imaging of the bladder: a pilot study.

    PubMed

    Kamaya, Aya; Vaithilingam, Srikant; Chung, Benjamin I; Oralkan, Omer; Khuri-Yakub, Butrus T

    2013-07-01

    Photoacoustic imaging is a promising new technology that combines tissue optical characteristics with ultrasound transmission and can potentially visualize tumor depth in bladder cancer. We imaged simulated tumors in 5 fresh porcine bladders with conventional pulse-echo sonography and photoacoustic imaging. Isoechoic biomaterials of different optical qualities were used. In all 5 of the bladder specimens, photoacoustic imaging showed injected biomaterials, containing varying degrees of pigment, better than control pulse-echo sonography. Photoacoustic imaging may be complementary to diagnostic information obtained by cystoscopy and urine cytologic analysis and could potentially obviate the need for biopsy in some tumors before definitive treatment.

  1. Role of autologous bladder-neck slings: a urogynecology perspective.

    PubMed

    Zoorob, Dani; Karram, Mickey

    2012-08-01

    The concept of the autologous pubovaginal sling involves supporting the proximal urethra and bladder neck with a piece of graft material, achieving continence either by providing a direct compressive force on the urethra/bladder outlet or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during transmission of increased abdominal pressure. Pubovaginal slings using a biological sling material (whether autologous, allograft, or xenograft) can be used successfully to manage primary or recurrent stress incontinence. This article addresses the indications for the use of an autologous bladder-neck sling, describes the surgical techniques, and discusses outcomes and technical considerations. PMID:22877713

  2. Long-term complications following bladder augmentations in patients with spina bifida: bladder calculi, perforation of the augmented bladder and upper tract deterioration

    PubMed Central

    2016-01-01

    Background We desire to review our experience with bladder augmentation in spina bifida patients followed in a transitional and adult urologic practice. This paper will specifically focus on three major complications: bladder calculi, the most frequent complication found following bladder augmentation, perforation of the augmentation, its most lethal complication and finally we will address loss of renal function as a direct result of our surgical reconstructive procedures. Methods We reviewed a prospective data base maintained on patients with spina bifida followed in our transitional and adult urology clinic from 1986 to date. Specific attention was given to patients who had developed bladder calculi, sustained a spontaneous perforation of the augmented bladder or had developed new onset of renal scarring or renal insufficiency (≥ stage 3 renal failure) during prolonged follow-up. Results The development of renal stones (P<0.05) and symptomatic urinary tract infections (P<0.0001) were found to be significantly reduced by the use of high volume (≥240 mL) daily bladder wash outs. Individuals who still developed bladder calculi recalcitrant to high volume wash outs were not benefited by the correction of underlying metabolic abnormalities or mucolytic agents. Spontaneous bladder perforations in the adult patient population with spina bifida were found to be directly correlated to substance abuse and noncompliance with intermittent catheterization, P<0.005. Deterioration of the upper tracts as defined by the new onset of renal scars occurred in 40% (32/80) of the patients managed by a ileocystoplasty and simultaneous bladder neck outlet procedure during a median follow-up interval 14 years (range, 8–45 years). Development of ≥ stage 3 chronic renal failure occurred within 38% (12/32) of the patients with scarring i.e., 15% (12/80) of the total patient population. Prior to the development of the renal scarring, 69% (22/32) of the patients had been noncompliant

  3. Changes in Aquaporin 1 Expression in Rat Urinary Bladder after Partial Bladder Outlet Obstruction: Preliminary Report

    PubMed Central

    Kim, Sun-Ouck; Song, Seung Hee; Ahn, Kuyoun; Kwon, Dongdeuk; Ryu, Soo Bang

    2010-01-01

    Purpose Aquaporins (AQPs) are membrane proteins that facilitate water movement across biological membranes. AQPs are also called water channels, and they have recently been reported to be expressed in rat and human urothelium. The purposes of this study were to investigate the effect of bladder outlet obstruction (BOO) on the rat urothelium and AQP1 expression in rat urothelium. Materials and Methods Female Sprague-Dawley rats (230-240 g each, n=20) were divided into 2 groups: the sham group (the Con group, n=10) and the partial BOO group (the BOO group, n=10). The BOO group underwent a partial BOO. The expression and cellular localization of AQP1 were determined by performing Western blotting and immunohistochemistry on the rat urinary bladder. Results AQP1 immunoreactivity in both the control and the BOO groups was localized in the capillaries, arterioles, and venules of the lamina propria of the urinary bladder. The protein expression of AQP1 was significantly increased in the BOO group. Conclusions This study showed that BOO causes a significant increase in the expression of AQP1. This may imply that AQP1 has a functional role in the detrusor instability that occurs in association with BOO. PMID:20428433

  4. Checking software contracts

    SciTech Connect

    Mitchell, R.; Maung, I.; Howse, J.; Heathcote, T.

    1995-12-31

    In object-oriented software, contracts between classes can be expressed in terms of preconditions, postconditions and invariants. In the programming language Eiffel, contracts can be checked at run-time. Within inheritance hierarchies, contracts can be used to control the redefinition of services. In Eiffel, the rules ensure that redefinition is safe in the presence of polymorphism and dynamic binding. This paper shows that Eiffel`s support for contracts can be extended, both to cover the polymorphic case more fully, and to cover other uses of inheritance, including its use for selectively reusing code from a parent class. The paper proposes that software designers should state what properties they claim for any uses of inheritance, in order that extra checks on consistency can be applied, and shows that some extra debugging power could be obtained easily, by changing only the run-time system for Eiffel, rather than the language itself.

  5. Mechanics of Vorticella Contraction

    PubMed Central

    Misra, Gaurav; Dickinson, Richard B.; Ladd, Anthony J.C.

    2010-01-01

    Abstract Vorticella convallaria is one of a class of fast-moving organisms that can traverse its body size in less than a millisecond by rapidly coiling a slender stalk anchoring it to a nearby surface. The stalk houses a fiber called the spasmoneme, which winds helically within the stalk and rapidly contracts in response to calcium signaling. We have developed a coupled mechanical-chemical model of the coiling process, accounting for the coiling of the elastic stalk and the binding of calcium to the protein spasmin. Simulations of the model describe the contraction and recovery processes quantitatively. The stalk-spasmoneme system is shown to satisfy geometric constraints, which explains why the cell body sometimes rotates during contraction. The shape of the collapsing and recovering stalk bounds its effective bending stiffness. Simulations suggest that recovery from the contracted state is driven by the stalk at a rate controlled by dissociation of calcium from spasmin. PMID:20550905

  6. 3 CFR - Government Contracting

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... contract oversight could reduce such sums significantly. Government outsourcing for services also raises... governmental functions. Agencies and departments must operate under clear rules prescribing when outsourcing is... oversee acquisitions appropriately; and (4) clarify when governmental outsourcing for services is and...

  7. Use of cone-beam computed tomography to characterize daily urinary bladder variations during fractionated radiotherapy for canine bladder cancer.

    PubMed

    Nieset, Jessica R; Harmon, Joseph F; Larue, Susan M

    2011-01-01

    Urinary bladder cancer is difficult to treat accurately with fractionated radiation therapy (RT) due to daily positional changes of the bladder and surrounding soft-tissue structures. We quantified the daily motion experienced by the canine bladder with patients in dorsal vs. sternal vs. lateral recumbency. We also described the dose distribution for three different planning target volume expansions (5, 10, and 15 mm) for each of the three positions to ensure adequate bladder dose and minimize irradiation of nearby healthy tissues. Analysis was based on data from retrospective daily cone-beam computed tomography (CT) (CBCT) images obtained for positioning of canine patients undergoing routine RT. Organs of interest were contoured on each CBCT data set and the images, along with the contours, were registered to the original planning CT. All measurements were made relative to the planning CT and dosimetric data for the organs of interest was determined using a dose volume histogram generated from sample parallel-opposed beam configuration. There was a wide range in bladder position throughout treatment. The least amount of bladder variation and the lowest rectal dose was with dogs in lateral recumbency. It was also determined that a margin of 10 mm would allow for sufficient dose to be delivered to the bladder while minimizing rectal dose.

  8. CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration

    PubMed Central

    Gong, Yanqing; Qiu, Wei; Ning, Xianghui; Yang, Xinyu; Liu, Libo; Wang, Zicheng; Lin, Jian; Li, Xuesong; Guo, Yinglu

    2015-01-01

    The coiled coil is a superhelical structural protein motif involved in a diverse array of biological functions, and the abnormal expression of the coiled-coil domain containing proteins has a direct link with the phenotype of tumor cell migration, invasion and metastasis. The aim of this study was to investigate the critical role of Coiled-coil domain-containing protein 34 (CCDC34) in bladder carcinogenesis, which has never been reported to date. Here, we found CCDC34 expression was elevated in bladder cancer tissues and cell lines. The knockdown of CCDC34 via lentivirus-mediated siRNA significantly suppressed bladder cancer cells proliferation and migration, and induced cell cycle arrest at G2/M phase and increased apoptosis in vitro. In addition, CCDC34 knockdown suppressed bladder tumor growth in nude mice. Moreover, CCDC34 silencing decreased the phosphorylation of MEK, ERK1/2, JNK, p38 and Akt, and the expressions of c-Raf and c-Jun, indicating MAPK and AKT pathways (ERK/MAPK, p38/MAPK, JNK/MAPK and PI3K/Akt) might be involved in CCDC34 regulation of bladder cancer cell proliferation and migration. Our findings revealed for the first time a potential oncogenic role for CCDC34 in bladder carcinoma pathogenesis and it may serve as a biomarker or even a therapeutic target for bladder cancer. PMID:26312564

  9. Pseudocarcinomatous hyperplasia of the urinary bladder.

    PubMed

    Wu, Angela

    2014-10-01

    We review the morphology and differential diagnoses of pseudocarcinomatous hyperplasia of the bladder, using a study case to illustrate the discussion. Pseudocarcinomatous hyperplasia is a rare, reactive response to an ischemic insult, classically to radiation therapy, and consists of proliferative, pseudoinfiltrative urothelial nests within the stroma. The presence of background radiation therapy-related changes, such as numerous dilated thrombosed vessels, reactive-appearing endothelial and stromal cells, edema, and hemorrhage, can provide clues to the diagnosis. The main differential diagnoses include invasive urothelial carcinoma and the nested variant of urothelial carcinoma; morphologic features, such as the presence or absence of background therapy-related changes and the architecture and the cytologic atypia of the nests, can help distinguish between pseudocarcinomatous hyperplasia and urothelial carcinoma.

  10. Review of the epidemiology of overactive bladder

    PubMed Central

    Eapen, Renu S; Radomski, Sidney B

    2016-01-01

    Overactive bladder (OAB) is common in both men and women. It is a symptom complex that causes significant detriment to quality of life in patients. Although the prevalence of OAB is similar in both sexes, there are sex-specific differences in individual symptoms and the impact on quality of life. The coexistence of benign prostatic hyperplasia with OAB can worsen quality of life in men. This review examines the major studies that looked at the epidemiology of OAB as it relates to both sexes. It focuses on both the overall prevalence rates and the incidence of individual symptoms. This paper also addresses the level of bother and quality of life in men and women with OAB. In addition, the relationship between OAB and benign prostatic hyperplasia is reviewed. PMID:27350947

  11. Protein Profiling of Bladder Urothelial Cell Carcinoma

    PubMed Central

    Hu, Jinghai; Ye, Fei; Cui, Miao; Lee, Peng; Wei, Chengguo; Hao, Yuanyuan; Wang, Xiaoqing; Wang, Yanbo; Lu, Zhihua; Galsky, Matthew; McBride, Russell; Wang, Li; Wang, Dongwen; Cordon-Cardo, Carlos; Wang, Chunxi; Zhang, David Y.

    2016-01-01

    This study aimed to detect protein changes that can assist to understand the underlying biology of bladder cancer. The data showed forty five proteins were found to be differentially expressed comparing tumors vs non-tumor tissues, of which EGFR and cdc2p34 were correlated with muscle invasion and histological grade. Ten proteins (ß-catenin, HSP70, autotaxin, Notch4, PSTPIP1, DPYD, ODC, cyclinB1, calretinin and EPO) were able to classify muscle invasive BCa (MIBC) into 2 distinct groups, with group 2 associated with poorer survival. Finally, 3 proteins (P2X7, cdc25B and TFIIH p89) were independent factors for favorable overall survival. PMID:27626805

  12. Protein Profiling of Bladder Urothelial Cell Carcinoma.

    PubMed

    Hu, Jinghai; Ye, Fei; Cui, Miao; Lee, Peng; Wei, Chengguo; Hao, Yuanyuan; Wang, Xiaoqing; Wang, Yanbo; Lu, Zhihua; Galsky, Matthew; McBride, Russell; Wang, Li; Wang, Dongwen; Cordon-Cardo, Carlos; Wang, Chunxi; Zhang, David Y

    2016-01-01

    This study aimed to detect protein changes that can assist to understand the underlying biology of bladder cancer. The data showed forty five proteins were found to be differentially expressed comparing tumors vs non-tumor tissues, of which EGFR and cdc2p34 were correlated with muscle invasion and histological grade. Ten proteins (ß-catenin, HSP70, autotaxin, Notch4, PSTPIP1, DPYD, ODC, cyclinB1, calretinin and EPO) were able to classify muscle invasive BCa (MIBC) into 2 distinct groups, with group 2 associated with poorer survival. Finally, 3 proteins (P2X7, cdc25B and TFIIH p89) were independent factors for favorable overall survival. PMID:27626805

  13. Small Cell Carcinoma of the Gall Bladder.

    PubMed

    Haid, Max; Gahju, Badri; Schulz, Craig; Sterner, David; Falconer, Steven

    2016-04-01

    Small cell carcinoma of the gall bladder (SCCGB) is a rare condition, with only 53 prior cases reported in the world literature when our case was first diagnosed. Our patient was found to have limited stage disease and was treated with sequential laparoscopic cholecystectomy, etoposide/carboplatin chemotherapy followed by consolidating loco-regional radiation therapy. She is alive and well without evidence of disease more than 132 months since diagnosis. We describe here our experience in the diagnosis, staging workup, treatment, and surveillance of a case of SCCGB and review the published literature. Treated aggressively with currently available methods, patients with limited stage SCCGB can have an excellent prognosis. The authors' intent is to provide a reasonable plan of treatment for other physicians facing such an unusual patient. PMID:27197345

  14. Surgical treatment of gall-bladder cancer.

    PubMed

    Masior, Łukasz; Krasnodębski, Maciej; Kobryń, Konrad; Grąt, Michał; Krawczyk, Marek

    2015-06-01

    Despite the aggressive nature and poor prognosis of gall-bladder cancer there is a group of patients who can achieve significant benefits from a radical surgical treatment. The possibility of obtaining long-term survival, even in case of patients with locally advanced cancer and metastases to regional lymph nodes, prompts to verify nihilistic approach to the treatment of this disease. Obviously such therapy can and should be performed only in centers specializing in hepatobiliary surgery. Due to the high recurrence rate, most of which are systemic, the hope of improving treatment outcomes should be sought in the use of combination therapy, based on a new chemotherapy and chemoradiotherapy regimens with the addition of targeted therapy. Unfortunately, the current application of these methods did not bring the expected benefits. PMID:26247506

  15. Laser ablation of gall bladder stones

    NASA Astrophysics Data System (ADS)

    Marafi, M.; Makdisi, Y.; Bhatia, K. S.; Abdulah, A. H.; Kokaj, Y.; Mathew, K.; Quinn, F.; Qabazard, A.

    1999-06-01

    Study of laser interaction with calculi is presented. A system of Nd-Yag and Ho-Yag pulsed lasers were used to produce fluorescence and plasma signals at the stone surface surrounded by saline and bile fluids. Fourth harmonic from Nd-Yag laser was transmitted to the samples by graded UV optical fibres. Gall bladder stones of various compositions were subjected to the high power Ho-Yag laser. Temporal transients and spectral evolution of plasma and fluorescence signals were monitored by a streak camera. A profile of acoustic pressures generated by shock waves was recorded with sensitive hydrophones placed in the surrounding fluids. Ablation threshold, cavitation process and fluorescence dependence on the laser parameters were studied in detail. Potential of stone identification by fluorescence and possible hydrodynamic model for ablation of biological samples is discussed.

  16. Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

    SciTech Connect

    Coen, John J.; Paly, Jonathan J.; Niemierko, Andrzej; Kaufman, Donald S.; Heney, Niall M.; Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U.

    2013-06-01

    Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

  17. Urinary tract infection in the neurogenic bladder

    PubMed Central

    Vigil, Humberto R.

    2016-01-01

    There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥103 CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5–14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required. PMID:26904414

  18. Bladder neck incompetence at posterior urethroplasty

    PubMed Central

    Koraitim, Mamdouh M.

    2015-01-01

    The finding of an incompetent bladder neck (BN) at the time of posterior urethroplasty will necessarily exacerbate the already difficult situation. In such cases the aim of the treatment is not only to restore urethral continuity by end-to-end urethral anastomosis, but also to restore the function of the BN to maintain urinary continence. Fortunately, the incidence of incompetence of the BN at posterior urethroplasty is uncommon, usually ≈4.5%. It seems that pelvic fracture-related BN injuries, in contrast to urethral injuries which result from a shearing force, are due to direct injury by the sharp edge of the fractured and displaced pubic bone. The risk of injuries to the BN is greater in children, in patients with a fracture involving both superior and inferior pubic rami on the same side, and in those managed initially by primary realignment. An incompetent BN is suspected by finding an open rectangular BN on cystography, and a fixedly open BN on suprapubic cystoscopy. An incompetent BN can be treated either subsequent to or concomitant with the urethral repair, according to whether a perineal or a perineo-abdominal urethroplasty is used, respectively. Several options have been reported to treat pelvic fracture-related BN incompetence, including reconstructing the BN, forming a new sphincter by tubularisation of a rectangular flap of the anterior bladder wall, and mechanical occlusion by an artificial sphincter or collagen injection. Reconstruction of the BN by the Young-Dees-Leadbetter∗∗ procedure probably provides the most successful results. PMID:26019982

  19. Transurethral resection of the bladder tumour (TURBT) for non-muscle invasive bladder cancer: basic skills.

    PubMed

    Furuse, Hiroshi; Ozono, Seiichiro

    2010-08-01

    Transurethral resection of the bladder tumour (TURBT) is the standard surgical procedure for non-muscle invasive bladder cancer. We believe that all urologists should be trained in this procedure. This DVD provides an overview of TURBT with particular focus on basic skills, including basic surgical techniques such as the obturator nerve block. Important basic surgical skills required for complete TURBT in non-muscle invasive bladder cancer are: (i) resection of all visible tumors; (ii) resection of apparently normal mucosa on the border of the tumor; (iii) resection of the muscle layer at the base of the tumor until normal muscle fibers are visible; (iv) in applicable cases, random biopsy of apparently normal urothelium of the bladder wall and transurethral resection (TUR) biopsy of both sides of the prostatic urethra; and (v) when possible, after these procedures are completed, a different operating surgeon should inspect the bladder lumen to confirm that there are no remaining tumors. In particular, sampling resection should be implemented in apparently normal mucosa for approximately 1 cm around the tumor, and at the base of the tumor down to the superficial muscle layer. Resected specimens should be examined histopathologically in order to confirm the absence of malignant findings. Fundamental procedures for TURBT include both one-stage and two-stage resection. One-stage resection is used for relatively small tumors and involves a single procedure with simultaneous resection of both the tumor and the tissue at the tumor base down to the superficial muscle layer. In the two-stage resection, the first resection exposes the lower level of the mucosa and the second resection removes that lower mucosal layer in order to sample the superficial muscle layer for cancer staging. At the start of the resection, the loop is electrified before it makes contact with the mucosa. Delicate movements of the sheath should be used, along with delicate movement of the loop itself

  20. Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function

    SciTech Connect

    Shipley, W.U.; Kaufman, S.D.; Prout, G.R. Jr.

    1987-10-01

    Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial. 13 references.

  1. A RARE CASE OF SQUAMOUS CELL CARCINOMA IN URINARY BLADDER DIVERTICULUM SUCCESSFULLY TREATED BY BLADDER-SPARING SURGERY.

    PubMed

    Štimac, Goran; Knežević, Matej; Grubišić, Igor; Soipi, Soip; Tomas, Davor; Krušlin, Božo

    2015-09-01

    The aim is to report a rare case of squamous cell carcinoma arising in a urinary bladder diverticulum and present recent literature overview of treatment options. A 56-year-old man presented with intermittent hematuria. Ultrasound examination indicated primary carcinoma in the urinary bladder diverticulum. Diagnosis was confirmed with cystoscopy and computed tomography. Transvesical diverticulectomy with regional lymphadenectomy was undertaken. Two years after initial treatment, the patient was well without evidence of tumor relapse. This report implicates that although aggressive surgical approach is recommended in the majority of bladder diverticulum tumors, simple diverticulectomy may be indicated in selected, confined cases.

  2. Generic method for automatic bladder segmentation on cone beam CT using a patient-specific bladder shape model

    SciTech Connect

    Schoot, A. J. A. J. van de Schooneveldt, G.; Wognum, S.; Stalpers, L. J. A.; Rasch, C. R. N.; Bel, A.; Hoogeman, M. S.; Chai, X.

    2014-03-15

    Purpose: The aim of this study is to develop and validate a generic method for automatic bladder segmentation on cone beam computed tomography (CBCT), independent of gender and treatment position (prone or supine), using only pretreatment imaging data. Methods: Data of 20 patients, treated for tumors in the pelvic region with the entire bladder visible on CT and CBCT, were divided into four equally sized groups based on gender and treatment position. The full and empty bladder contour, that can be acquired with pretreatment CT imaging, were used to generate a patient-specific bladder shape model. This model was used to guide the segmentation process on CBCT. To obtain the bladder segmentation, the reference bladder contour was deformed iteratively by maximizing the cross-correlation between directional grey value gradients over the reference and CBCT bladder edge. To overcome incorrect segmentations caused by CBCT image artifacts, automatic adaptations were implemented. Moreover, locally incorrect segmentations could be adapted manually. After each adapted segmentation, the bladder shape model was expanded and new shape patterns were calculated for following segmentations. All available CBCTs were used to validate the segmentation algorithm. The bladder segmentations were validated by comparison with the manual delineations and the segmentation performance was quantified using the Dice similarity coefficient (DSC), surface distance error (SDE) and SD of contour-to-contour distances. Also, bladder volumes obtained by manual delineations and segmentations were compared using a Bland-Altman error analysis. Results: The mean DSC, mean SDE, and mean SD of contour-to-contour distances between segmentations and manual delineations were 0.87, 0.27 cm and 0.22 cm (female, prone), 0.85, 0.28 cm and 0.22 cm (female, supine), 0.89, 0.21 cm and 0.17 cm (male, supine) and 0.88, 0.23 cm and 0.17 cm (male, prone), respectively. Manual local adaptations improved the segmentation

  3. Alum irrigation in massive bladder hemorrhage in severe renal failure.

    PubMed

    Modi, K B; Paterson, P J

    1988-09-01

    We report a patient with severe renal failure in whom massive bladder hemorrhage was successfully treated with alum irrigation. There was no substantial potassium or aluminum absorption with alum irrigation.

  4. Profile of Lesions in Cystoscopic Bladder Biopsies: A Histopathological Study

    PubMed Central

    Srikousthubha; Sukesh; C.V, Raghuveer; Hingle, Sanjay

    2013-01-01

    Aim and Introduction: Urinary bladder lesions, non-neoplastic and neoplastic, are collectively responsible for significant morbidity and mortality throughout the world. The present study aimed to study the histopathology of various lesions of the bladder through cystoscopic biopsies. Material and Methods: The present prospective study aimed to study the histopathology of various lesions of the urinary bladder through cystoscopic biopsies. All patients who visited Urology Outpatients Department for haematuria and dysuria were subjected to cystoscopy. Results: Histopathological examinations revealed an equal share of non neoplastic lesions and neoplastic lesions. Amongst the non neoplastic lesions, 84% were inflammatory lesions. Urothelial tumours (96%) formed the bulk amongst neoplastic lesions. Conclusion: This article has stressed upon the importance of histopathological examinations in evaluating bladder pathologies. PMID:24086853

  5. TCGA Bladder Cancer Study Reveals Potential Drug Targets - TCGA

    Cancer.gov

    Investigators with the TCGA Research Network have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease.

  6. [Leiomyoma of the bladder causing the destruction of a kidney].

    PubMed

    Kehila, Mehdi; Mekni, Karima; Abouda, Hassine Saber; Chtourou, Maher; Zeghal, Dorra; Chanoufi, Mohamed Badis

    2016-01-01

    Leiomyoma of the bladder is a rare benign tumor deemed to have a good prognosis after surgical treatment. This is unfortunately not always true. We report the case of a 33 year-old patient who consulted for lumbar pain on right side. Exploration of patient revealed bladder floor solid tumor with non-functioning right kidney and left urinary tract dilation. Cystoscopy objectified solid tumor of the right perimeatal bladder. Tumor biopsies were performed together with the insertion of a left double J stent. Anatomo-pathologic study showed leiomyoma of the bladder. The patient underwent laparoscopic myomectomy. The postoperative course was uneventful. Pathological effect and sequelae was complete distruction of kidney. PMID:27583074

  7. Genetic variant as a marker for bladder cancer therapy

    Cancer.gov

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  8. TCGA bladder cancer study reveals potential drug targets

    Cancer.gov

    Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

  9. Immune Response Following Photodynamic Therapy For Bladder Cancer

    NASA Astrophysics Data System (ADS)

    Raymond K.

    1989-06-01

    This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

  10. Segmental irradiation of the bladder with neodymium YAG laser irradiation

    SciTech Connect

    McPhee, M.S.; Mador, D.R.; Tulip, J.; Ritchie, B.; Moore, R.; Lakey, W.H.

    1982-11-01

    The Neodymium YAG laser energy source can be readily adapted for cystoscopic use by some simple modifications of existing urologic equipment. Both the fiberoptic resectoscope and a deflecting cystourethroscope have been adapted for this purpose. Fixation of the fiber tip 1 cm. from the target and use of a divergent beam of 36 degrees allows the delivery of standardized dosage to a relatively large bladder tissue volume. Animal experiments involving 35 mongrel dogs established that repetitive overlapping doses of 200 joules ech can successfully treat a large area of bladder resulting in a full thickness bladder wall injury. This technique has been used in 4 high risk patients with infiltrating bladder cancer without adverse sequelae. The ability to reliably produce a full thickness lesion may give this modality a therapeutic advantage over conventional cautery techniques especially for the treatment of residual infiltrative carcinoma.

  11. Inflatable bladder to facilitate handling of heavy objects - A concept

    NASA Technical Reports Server (NTRS)

    Mc Goldrick, G. J.

    1969-01-01

    Inflatable bladder facilitates the removal of heavy, highly finished metal parts from tote boxes or shipping containers. The proposed concept permits removal without danger of damage to the parts or injury to handling personnel.

  12. Rationale for an early detection program for bladder cancer

    PubMed Central

    Khochikar, Makarand V.

    2011-01-01

    Introduction: A total of 356,557 new cases were diagnosed annually worldwide in 2009, it was estimated that 52,810 new patients were to be diagnosed with bladder cancer and there were 10,180 projected deaths from the disease in the USA. Despite being the fourth commonest cancer in men, we do not have an early detection/screening program for bladder cancer. The review was aimed at looking at the evidence for the rationale for an early detection program for bladder cancer. Materials and Methods: A detailed search on bladder cancer epidemiology, diagnosis, pathology, tumor markers, treatment outcomes, screening, morbidity and mortality of bladder cancer was carried out on Pubmed central/Medline. Original articles, review articles, monograms, book chapters on bladder cancer, text books on urological oncology, oncology and urology were reviewed. The latest information for new articles before publication was last accessed in June 2010. Discussion and Conclusions: Bladder cancer is the fourth commonest cancer in men, the annual death rate from this disease is significant and every year there is an increase in its incidence globally. The prognosis of bladder cancer is stage and grade dependent; the lower the stage (T2 or less) the better is the survival. Delay in the diagnosis and treatment does alter the overall outcome. Therefore, there is a clear need for early detection of bladder cancer and screening program. Although we do not have an ideal marker for bladder cancer, it is time we maximize the potential of markers such as UroVysion, NMP22 along with cytology to start such a program. May be as a first step the early detection and screening program could be started in high-risk population. It is not worth waiting till we find the best marker as it would be unfair to our patients. The fear of unnecessary tests and treatment in bladder cancer after its detection in screening program is without any substance. The cost-effectiveness of such a program is certainly

  13. Na+ transport by rabbit urinary bladder, a tight epithelium.

    PubMed

    Lewis, S A; Diamond, J M

    1976-08-27

    By in vitro experiments on rabbit bladder, we reassessed the traditional view that mammalian urinary bladder lacks ion transport mechanisms. Since the ratio of actual-to-nominal membrane area in folded epithelia is variable and hard to estimate, we normalized membrane properties to apical membrane capacitance rather than to nominal area (probably 1 muF approximately 1 cm2 actual area). A new mounting technique that virtually eliminates edge damage yielded resistances up to 78,000 omega muF for rabbit bladder, and resistances for amphibian skin and bladder much higher than those usually reported. This technique made it possible to observe a transport-related conductance pathway, and a close correlation between transepithelial conductance (G) and short-circuit current (Isc) in these tight epithelia. G and Isc were increased by mucosal (Na+) [Isc approximately 0 when (Na+) approximately 0], aldosterone, serosal (HCO-3) and high mucosal (H+); were decreased by amiloride, mucosal (Ca++), ouabain, metabolic inhibitors and serosal (H+); and were unaffected by (Cl-) and little affected by antidiuretic hormone (ADH). Physiological variation in the rabbits' dietary Na+ intake caused variations in bladder G and Isc similar to those caused by the expected in vivo changes in aldosterone levels. The relation between G and Isc was the same whether defined by diet changes, natural variation among individual rabbits, or most of the above agents. A method was developed for separately resolving conductances of junctions, basolateral cell membrane, and apical cell membrane from this G--Isc relation. Net Na+ flux equalled Isc. Net Cl- flux was zero on short circuit and equalled only 25% of net Na+ flux in open circuit. Bladder membrane fragments contained a Na+-K+-activated, ouabain-inhibited ATPase. The physiological significance of Na+ absorption against steep gradients in rabbit bladder may be to maintain kidney-generated ion gradients during bladder storage of urine, especially

  14. Vitamin B12 deficiency after irradiation for bladder carcinoma

    SciTech Connect

    Kinn, A.C.; Lantz, B.

    1984-05-01

    Vitamin B12 deficiency was found in 10 of 41 patients who underwent radiotherapy before cystectomy with Bricker urinary diversion for carcinoma of the bladder. Of 13 patients given full irradiation because of inoperable bladder cancer 5 had malabsorption of vitamin B12. Serum folic acid was normal in these patients, indicating predominantly ileal irradiation sequelae. Routine evaluation of serum vitamin B12 after radiotherapy is recommended so that appropriate medication can be given, if possible before neurological symptoms appear.

  15. Overactive bladder: strategies to ensure treatment compliance and adherence

    PubMed Central

    Dhaliwal, Prabhpreet; Wagg, Adrian

    2016-01-01

    Overactive bladder is a common, debilitating condition for many patients who may benefit from pharmacological management of their condition. However, adherence to medication in this condition is markedly worse than other chronic medical conditions. This review explores what is known about persistence and the factors which influence medication adherence for overactive bladder, those factors that might be modifiable to improve adherence, and the measures the health care provider can take to optimize adherence to therapy and thereby improve treatment outcomes. PMID:27350744

  16. Association between interleukin-22 genetic polymorphisms and bladder cancer risk

    PubMed Central

    Zhao, Tao; Wu, XiaoHou; Liu, JiaJi

    2015-01-01

    OBJECTIVE: The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated. MATERIALS AND METHODS: A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays. RESULTS: Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer. CONCLUSION: To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding. PMID:26598081

  17. Medical management of neurogenic bladder with oral therapy

    PubMed Central

    2016-01-01

    This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series. PMID:26904412

  18. Medical management of neurogenic bladder with oral therapy.

    PubMed

    Cameron, Anne P

    2016-02-01

    This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series.

  19. Androgen activates β-catenin signaling in bladder cancer cells.

    PubMed

    Li, Yi; Zheng, Yichun; Izumi, Koji; Ishiguro, Hitoshi; Ye, Bo; Li, Faqian; Miyamoto, Hiroshi

    2013-06-01

    Androgen receptor (AR) signals have been implicated in bladder carcinogenesis and tumor progression. Activation of Wnt/β-catenin signaling has also been reported to correlate with bladder cancer progression and poor patients' outcomes. However, cross talk between AR and β-catenin pathways in bladder cancer remains uncharacterized. In radical cystectomy specimens, we immunohistochemically confirmed aberrant expression of β-catenin especially in aggressive tumors. There was a strong association between nuclear expressions of AR and β-catenin in bladder tumors (P=0.0215). Kaplan-Meier and log-rank tests further revealed that reduced membranous β-catenin expression (P=0.0276), nuclear β-catenin expression (P=0.0802), and co-expression of nuclear AR and β-catenin (P=0.0043) correlated with tumor progression after cystectomy. We then assessed the effects of androgen on β-catenin in AR-positive and AR-negative bladder cancer cell lines. A synthetic androgen R1881 increased the expression of an active form of β-catenin and its downstream target c-myc only in AR-positive lines. R1881 also enhanced the activity of β-catenin-mediated transcription, which was abolished by an AR antagonist hydroxyflutamide. Using western blotting and immunofluorescence, R1881 was found to induce nuclear translocation of β-catenin when co-localized with AR. Finally, co-immunoprecipitation revealed androgen-induced associations of AR with β-catenin or T-cell factor (TCF) in bladder cancer cells. Thus, it was likely that androgen was able to activate β-catenin signaling through the AR pathway in bladder cancer cells. Our results also suggest that activation of β-catenin signaling possibly via formation of AR/β-catenin/TCF complex contributes to the progression of bladder cancer, which may enhance the feasibility of androgen deprivation as a potential therapeutic approach. PMID:23447569

  20. Studies on the nucleic acid of human bladder carcinoma

    SciTech Connect

    Nabih, I.; Mantawy, M.M.; Abdel-Hamid, A.Z. )

    1990-01-01

    DNA was isolated from different histopathologic types and grades of human bladder carcinoma. The isolated DNA was submitted to quantitative determination and base composition analysis. A pilot study was done on the effect of gamma irradiation as a physical mutagen on characteristics of DNA in the examined tissues. Identity in the genetic components in the urinary bilharziasis snails and the human bladder cancer was observed. The same was observed in both intestinal bilharziasis snails and the cancerous intestinal tissues.

  1. Inflammatory Myofibroblastic Tumor in the Bladder: A Case Report

    PubMed Central

    Kondo, Takuya; Kawahara, Takashi; Chiba, Sawako; Ohtaka, Mari; Kumano, Yohei; Saitoh, Yoko; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-ichi; Miyoshi, Yasuhide; Yumura, Yasushi; Yao, Masahiro; Inayama, Yoshiaki; Uemura, Hiroji

    2016-01-01

    A 36-year-old male was referred to our department for further examination of asymptomatic gross hematuria emanating from a bladder tumor. Cystoscopy revealed a broad-based tumor 40 mm in diameter. Urinary cytology was negative. Preoperative magnetic resonance imaging suggested a muscle invasive tumor. Transurethral resection was performed, and the pathological findings revealed an inflammatory myofibroblastic tumor. We herein report a rare case of bladder inflammatory myofibroblastic tumor.

  2. Alterations in phenotypic biochemical markers in bladder epithelium during tumorigenesis.

    PubMed

    Rao, J Y; Hemstreet, G P; Hurst, R E; Bonner, R B; Jones, P L; Min, K W; Fradet, Y

    1993-09-01

    Phenotypic biochemical markers of oncogenesis and differentiation were mapped in bladder biopsies to investigate changes that occur in bladder tumorigenesis and to identify markers for increased bladder cancer risk. Touch preparations from biopsy specimens from 30 patients were obtained from tumors, the adjacent bladder epithelium, and random distant bladder epithelium. Markers, including DNA ploidy, epidermal growth factor receptor (EGFR), and oncoproteins, were quantified in individual cells by using quantitative fluorescence image analysis. Cluster analysis revealed the markers fell into three independent groups: (i) G-actin and EGFR; (ii) ploidy, cytology, and p185 (HER-2/neu oncoprotein) (ERBB2); and (iii) p300, a low-grade tumor antigen. Each marker displayed a gradient of abnormality from distant field to adjacent field to tumor. Different patterns for each marker suggested a developmental sequence of bladder cancer oncogenesis; G-actin was altered in 58% of distant biopsies (vs. 0/6 normals, P < 0.001), ploidy and cytology were altered in < 20% of distant fields and approximately 80% of tumors, and the other markers were intermediate. Patterns of EGFR and p185 suggest low-and high-grade tracks diverge early (P < 0.05 by Mann-Whitney U test for EGFR and ANOVA for p185). In conclusion, this study shows that a sequence of phenotypic changes accompanies development and progression of bladder cancers. Biochemical alterations in cells of the bladder field are often detectable before abnormal pathology, and markers previously thought to be limited to tumors were found in the field. The hierarchy of expression may be useful in identifying high-risk patients, assessing completeness of response to therapy, and monitoring and predicting recurrence. PMID:8367495

  3. A rare cyclic recurrent hematuria case; bladder endometriosis

    PubMed Central

    Akpınar, Süha; Çelebioğlu, Emre

    2015-01-01

    Endometriosis is a benign gynecological disease that is characterized by the presence of functional endometrial tissue outside the uterus. Although the ovaries and uterine ligaments are the most common locations, urinary tract involvement especially the bladder endometriosis is a rare entity in women of reproductive age with clinical symptoms of cyclical urgency, hematuria and suprapubic pain. We herein present magnetic resonance imaging (MRI) findings of spontaneous bladder endometriosis case with cyclical hematuria symptoms. PMID:26029655

  4. A rare cyclic recurrent hematuria case; bladder endometriosis.

    PubMed

    Akpınar, Süha; Yılmaz, Güliz; Çelebioğlu, Emre

    2015-06-01

    Endometriosis is a benign gynecological disease that is characterized by the presence of functional endometrial tissue outside the uterus. Although the ovaries and uterine ligaments are the most common locations, urinary tract involvement especially the bladder endometriosis is a rare entity in women of reproductive age with clinical symptoms of cyclical urgency, hematuria and suprapubic pain. We herein present magnetic resonance imaging (MRI) findings of spontaneous bladder endometriosis case with cyclical hematuria symptoms. PMID:26029655

  5. Syncope in a patient with giant bladder diverticulum.

    PubMed

    Kaneko, Nozomu; Kawasaki, Tatsuya; Boku, Hidehisa; Kamitani, Tadaaki

    2012-01-01

    Syncope is common in clinical practice, but the cause is often difficult to diagnose. We report a 75-year-old man who was referred to the emergency department because of syncope after an urgent sensation of urinating during jogging. He was finally diagnosed as having a giant bladder diverticulum due to prostatic hyperplasia accompanied by neurally mediated syncope. Excessive urinary retention is a possible cause of not only giant bladder diverticula but also syncope due to vagal enhancement. PMID:22821117

  6. Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

    PubMed

    Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

    2012-06-01

    The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

  7. Affine Contractions on the Plane

    ERIC Educational Resources Information Center

    Celik, D.; Ozdemir, Y.; Ureyen, M.

    2007-01-01

    Contractions play a considerable role in the theory of fractals. However, it is not easy to find contractions which are not similitudes. In this study, it is shown by counter examples that an affine transformation of the plane carrying a given triangle onto another triangle may not be a contraction even if it contracts edges, heights or medians.…

  8. Educational Performance Contracting. PREP-28.

    ERIC Educational Resources Information Center

    National Center for Educational Communication (DHEW/OE), Washington, DC. Div. of Practice Improvement.

    This document explicates what is involved in educational performance contracting. Four basic types of contracts can be used to procure goods and services: fixed and performance contracts for resources and fixed and performance contracts for results. The basic considerations in choice of type are risk, relative technologies, management skills…

  9. Service contract management and negotiation.

    PubMed

    Wickesser, T A

    1994-04-01

    Service contract management can have a profound impact on the life cycle cost and general performance of serviced equipment. Negotiating service contracts from the client's perspective can help to ensure that the facility is receiving the best possible service and terms during the contract period. This document shows examples of contract considerations.

  10. Involvement of the Androgen and Glucocorticoid Receptors in Bladder Cancer.

    PubMed

    McBeth, Lucien; Grabnar, Maria; Selman, Steven; Hinds, Terry D

    2015-01-01

    Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-) α isoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer. PMID:26347776

  11. Reduced Glucocorticoid Receptor Expression Predicts Bladder Tumor Recurrence and Progression

    PubMed Central

    Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J.; Miyamoto, Hiroshi

    2015-01-01

    Objectives To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. Methods We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Results Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P = .026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (P < .001) and 61 (73%) of 84 non–muscle-invasive (NMI) tumors vs 26 (40%) of 65 muscle-invasive (MI) carcinomas (P < .001) were moderately to strongly immunoreactive for GR. Kaplan-Meier and log-rank tests revealed that loss or weak positivity of GR significantly or marginally correlated with recurrence of NMI tumors (P = .025), progression of MI tumors (P = .082), and cancer-specific survival of MI tumors (P = .067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P = .034). Conclusions GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. PMID:25015855

  12. Stem cell applications for pathologies of the urinary bladder.

    PubMed

    Mousa, Noha A; Abou-Taleb, Hisham A; Orabi, Hazem

    2015-06-26

    New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient's quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context.

  13. Tumor motion and deformation during external radiotherapy of bladder cancer

    SciTech Connect

    Lotz, Heidi T.; Pos, Floris J.; Hulshof, Maarten C.C.M.; Herk, Marcel van; Lebesque, Joos V.; Duppen, Joop C.; Remeijer, Peter . E-mail: prem@nki.nl

    2006-04-01

    Purpose: First, to quantify bladder-tumor motion in 3 dimensions during a 4-week to 5-week course of external radiotherapy. Second, to relate the motion to the tumor location on the bladder wall. Third, to extensively evaluate gross tumor volume (GTV) shape and volume changes during the course of the treatment. Methods and Materials: Multiple repeat computed tomography (CT) images were obtained for 21 bladder cancer patients. These scans were matched to the rigid bony anatomy. For each patient, the main direction and magnitude of the tumor movement was determined by use of principle-component analysis. To study GTV shape changes, all GTVs were registered to the GTV in the planning CT scan, and the residual shape errors were determined by measurement of edge variations perpendicular to the median surface. Results: Gross tumor volume translations were largest in cranial-caudal and anterior-posterior direction (SD, 0.1 to {approx}0.9 cm). The translations were strongly correlated with the tumor location on the bladder wall. The average value of the local standard deviations of the GTV shape ranged from 0.1 to approximately 0.35 cm. Conclusions: Despite large differences in bladder filling, variations in GTV shape were small compared with variations in GTV position. Geometric uncertainties in the GTV position depended strongly on the tumor location on the bladder wall.

  14. Bladder rupture associated with uterine rupture at delivery.

    PubMed

    Yang, Bo

    2011-05-01

    This paper seeks to study the clinical presentation and emergency treatment of bladder rupture associated with uterine rupture at delivery. From June to December 2009, three cases of rupture of the uterus involving maternal bladder during labor at Revolutionary Hospital at Hodeidah, Yemen were reviewed. Intraoperatively, it appeared that the posterior wall of the bladder and the anterior wall of the uterus had ruptured; the laceration of the posterior bladder wall was closed in two layers. Of the patients who underwent the operations, one patient developed vesicovaginal fistula, which was repaired vaginally after 6 months, and the patient had a successful outcome. The others got uneventful recovery and there was no vesicovaginal fistula or hydronephrosis during follow-up. Uterine rupture and associated injury to the maternal bladder was rarely reported. It would be life threatening or would lead to long-term complications. Both urologists and obstetrician should keep bladder injuries in mind, as serious outcomes might occur during labor. Surgical treatment could be the preferred approach for this situation.

  15. Novel targeted bladder drug-delivery systems: a review

    PubMed Central

    Zacchè, Martino Maria; Srikrishna, Sushma; Cardozo, Linda

    2015-01-01

    The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy. PMID:26649286

  16. Botulinum Toxin A for Bladder Pain Syndrome/Interstitial Cystitis

    PubMed Central

    Chiu, Bin; Tai, Huai-Ching; Chung, Shiu-Dong; Birder, Lori A.

    2016-01-01

    Botulinum neurotoxin A (BoNT-A), derived from Clostridium botulinum, has been used clinically for several diseases or syndrome including chronic migraine, spasticity, focal dystonia and other neuropathic pain. Chronic pelvic or bladder pain is the one of the core symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC). However, in the field of urology, chronic bladder or pelvic pain is often difficult to eradicate by oral medications or bladder instillation therapy. We are looking for new treatment modality to improve bladder pain or associated urinary symptoms such as frequency and urgency for patients with BPS/IC. Recent studies investigating the mechanism of the antinociceptive effects of BoNT A suggest that it can inhibit the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. In this review, we will examine the evidence supporting the use of BoNTs in bladder pain from basic science models and review the clinical studies on therapeutic applications of BoNT for BPS/IC. PMID:27376330

  17. Involvement of the Androgen and Glucocorticoid Receptors in Bladder Cancer

    PubMed Central

    McBeth, Lucien; Grabnar, Maria; Selman, Steven; Hinds, Terry D.

    2015-01-01

    Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-) α isoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer. PMID:26347776

  18. Nested and Dynamic Contract Boundaries

    NASA Astrophysics Data System (ADS)

    Strickland, T. Stephen; Felleisen, Matthias

    Previous work on software contracts assumes fixed and statically known boundaries between the parties to a contract. Implementations of contract monitoring systems rely on this assumption to explain the nature of contract violations and to assign blame to violators. In this paper, we explain how to implement arbitrary, nested, and dynamic contract boundaries with two examples. First, we add nestable contract regions to a static, first-order module system. Second, we show that even a dynamic, higher-order, and hierarchical module system can be equipped with software contracts that support precise blame assignment.

  19. A simple technique for evacuating air bubbles with scum from the bladder dome during transurethral resection of bladder tumor.

    PubMed

    Takeshita, Hideki; Moriyama, Shingo; Chiba, Koji; Noro, Akira

    2014-12-01

    Air bubbles floating in the bladder dome during transurethral resection of a bladder tumor can interfere with the resection, causing intravesical explosion and increasing the potential risk of tumor cell reimplantation. We describe a simple and effective technique for evacuating air bubbles from the bladder dome using routine resectoscopes. First, the beak of the resectoscope is positioned near the air bubble in the bladder dome. Second, the drainage channel of the resectoscope is closed. Third, the irrigation tube is detached from the irrigation channel, and then the channel is opened. Subsequently, the air bubble with entangled scum will be retrogradely aspirated from the beak of the resectoscope to the irrigation channel. Reversing the direction of the water stream enables evacuation of the air bubble with the scum under direct vision. This simple and effective technique may assist surgeons and ensure the safety of patients during a transurethral procedure. PMID:25562002

  20. Safety of three sequential whole bladder photodynamic therapy (WBPDT) treatments in the management of resistant bladder cancer

    NASA Astrophysics Data System (ADS)

    Mejia, Maria C.; Nseyo, Unyime O.

    2009-02-01

    INTRODUCTION: WBPDT has been used to treat resistant superficial bladder cancer, with clinical benefits and associated dose-dependent side effects. OBJECTIVE: The objective of this study was to assess the safety of three sequential WBPDT treatments in patients with resistant non-muscle invasive (NMI) bladder cancer. MATERIALS AND METHODS: 12 males and one female provided written informed consent in this Phase II study. Each patient received intravenous injection of Photofrin® (AXCAN Parma Inc, Canada) at 1.5 mg/kg two days prior to whole bladder laser (630nm) treatment. Assessment of safety and efficacy included weekly urinary symptoms; cystoscopy, biopsy and cytology; and measurement of bladder volume quarterly after each treatment at baseline, six and 12 months. Treatment #2 and/or #3 occurred only in the absence of bladder contracture, and/or disease progression. RESULTS: 13 patients: 12 males and one female have been enrolled and average age of enrollees is 67.1(52 - 87) years. Four patients had Ta-T1/Grade I-III tumors; two patients had CIS associated with T1/GI-III; and seven patients had carcinoma in situ (CIS) only. Three patients received 3/3 treatments, and are evaluable for toxicity; three patients received two treatments only; and seven patients received one treatment only. There was no bladder contracture; transient mild to moderate bladder irritative voiding symptoms of dysuria, urinary frequency, nocturia and urgency occurred in all patients. The three evaluable patients were without evidence of disease at average of 13.1 (7-20) months. CONCLUSION: Three sequential WBPDT treatments might have a favorable toxicity profile in the management of recurrent/ refractory non-muscle invasive bladder cancer.

  1. Lectin histochemical examination of rabbit bladder glycoproteins and characterization of a mucin isolated from the bladder mucosa.

    PubMed

    Buckley, M; Xin, P; Washington, S; Herb, N; Erickson, D; Bhavanandan, V P

    2000-03-15

    The glycocalyx of the mucosal surface of urinary bladder acts as an effective barrier against invasion by pathogenic microorganisms and injury from toxic substances in the urine. Defects in these bladder mucosal components could thus be important factors in the development of diseases such as interstitial cystitis and lower urinary tract infections. However, information on the nature of glycoconjugates of mammalian bladder mucosa is very limited. In this study, the glycoconjugates of rabbit bladder were examined histochemically using biotinylated lectins with specificities for a variety of carbohydrate moieties. Three [Artocarpus integrifolia (Jacalin), Datura stramonium (DSL), and Maackia amurensis II (MAL-II)] of the lectins bound predominantly to the luminal cell layer, with decreased binding to the basal layers of the epithelium. In contrast, Ricinus communis I and Sambucus nigra lectins did not bind to the cells in the epithelium but strongly interacted with the subepithelial layers, especially the lamina propria. The intensity of the staining by Jacalin and MAL-II was significantly reduced by prior treatment of the bladder sections with O-sialoglycoprotein endopeptidase, indicating that the ligands of these lectins are primarily mucin glycoproteins. In parallel biochemical studies, a high-molecular-weight glycoprotein with characteristics typical of epithelial mucins was purified from the mucosa of rabbit bladder explant cultures metabolically labeled with [(3)H]glucosamine. Quantitative analysis of the sialic acid, uronic acid, and hexosamine contents of delipidated rabbit bladder mucosa revealed a larger proportion of sialoglycoproteins compared with glycosaminoglycans. Taken together, the results of histochemical and biochemical analyses indicate that glycoproteins rather than glycosaminoglycans are the major components of the bladder epithelium, and that the former include a mucin.

  2. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

    PubMed

    Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

    2016-07-01

    Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. PMID:27080594

  3. Weakness of the Pelvic Floor Muscle and Bladder Neck Is Predicted by a Slight Rise in Abdominal Pressure During Bladder Filling: A Video Urodynamic Study in Children

    PubMed Central

    2016-01-01

    Purpose: To investigate the significance of slowly rising abdominal pressure (SRAP), which is often observed in nonneurogenic children during bladder filling in video urodynamic studies (VUDSs). Methods: The records of patients who underwent VUDS from July 2011 to June 2013 were reviewed. SRAP was defined as a rising curve over 5 cm H2O from the baseline abdominal pressure during the filling phase in VUDS. Bladder descent was defined when the base of the bladder was below the upper line of the pubic symphysis. An open bladder neck was defined as the opening of the bladder neck during the filling phase. Results: Of the 488 patients, 285 were male patients. The mean age at VUDS was 3.7 years (range, 0.2–17.6 years). The VUDS findings were as follows: SRAP, 20.7% (101 of 488); descending bladder, 14.8% (72 of 488); and bladder neck opening, 4.3% (21 of 488). Of the 72 patients with a descending bladder, 84.7% had SRAP. A significant difference in the presence of SRAP was found between the descending bladder and the normal bladder (P<0.001). Of the 101 patients with SRAP, 40 (39.6%) did not have a descending bladder. Of the 40 patients, 14 (35.0%) had a bladder neck opening, which was a high incidence compared with the 4.3% in all subjects (P<0.001). Conclusions: SRAP was associated with a descending bladder or a bladder neck opening, suggesting that SRAP is a compensatory response to urinary incontinence. SRAP may also predict decreased function of the bladder neck or pelvic floor muscle. PMID:27032558

  4. Consensus, contracts, and committees.

    PubMed

    Moreno, J D

    1991-08-01

    Following a brief account of the puzzle that ethics committees present for the Western Philosophical tradition, I will examine the possibility that social contract theory can contribute to a philosophical account of these committees. Passing through classical as well as contemporary theories, particularly Rawls' recent constructivist approach, I will argue that social contract theory places severe constraints on the authority that may legitimately be granted to ethics committees. This, I conclude, speaks more about the suitability of the theory to this level of analysis than about the ethics committee phenomenon itself.

  5. Bladder neck closure and suprapubic catheter placement as definitive management of neurogenic bladder

    PubMed Central

    Colli, Janet; Lloyd, L. Keith

    2011-01-01

    Objective Surgical management for neurogenic bladder may require abandonment of the native urethra due to intractable urinary incontinence, irreparable urethral erosion, severe scarring from previous transurethral procedures, or urethrocutaneous fistula. In these patients, bladder neck closure (BNC) excludes the native urethra and provides continence while preserving the antireflux mechanism of the native ureters. This procedure is commonly combined with ileovesicostomy or continent catheterizable stoma, with or without augmentation enterocystoplasty. Alternatively, BNC can be paired with suprapubic catheter diversion. This strategy does not require a bowel segment, resulting in shorter operative times and less opportunity for bowel-related morbidity. The study purpose is to examine preoperative characteristics, indications, complications, and long-term maintenance of renal function of BNC patients. Methods A retrospective review of medical records of 35 patients who underwent BNC with suprapubic catheter placement from 1998 to 2007 by a single surgeon (LKL) was completed. Results Neurogenic bladder was attributable to spinal cord injury in 71%, 23% had multiple sclerosis, and 9% had cerebrovascular accident. Indications for BNC included severe urethral erosion in 80%, decubitus ulcer exacerbated by urinary incontinence in 34%, urethrocutaneous fistula in 11%, and other indications in 9%. The overall complication rate was 17%. All but two patients were continent at follow-up. Forty-nine per cent of patients had imaging available for review, none of which showed deterioration of the upper tracts. Conclusions Our results suggest that BNC in conjunction with suprapubic catheter diversion provides an excellent chance at urethral continence with a reasonable complication rate. PMID:21756565

  6. Refractory overactive bladder: Beyond oral anticholinergic therapy

    PubMed Central

    Glinski, Ronald W.; Siegel, Steven

    2007-01-01

    Objectives: In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments. Materials and Methods: A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options. Results: In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted. Conclusion: The vast majority of OAB patients can be managed successfully by behavioral options with or without

  7. [Bladder dysfunction and surgery in the small pelvis. Therapeutic possibilities].

    PubMed

    Schönberger, B

    2003-12-01

    The more extensive a surgical procedure in a small pelvis, the higher the risk for the lower urinary tract with its nerve supply and nerve plexus. This concerns mainly the sympathetic chains, the parasympathetic structures and, rarely, the visceral supply of the pelvic floor. Direct trauma to the bladder and its vascular supply as well as indirect injury by displacement of the bladder need to be seriously considered. Problems with micturition and impaired storage capacity of the bladder are the result. Complete urodynamic examination and follow-up can help in differentiating between temporary and persisting disturbances and in taking therapeutical decisions. The most evident postoperative complication is disturbed micturition, managed initially by suprapubic urinary diversion, followed as soon as possible by intermittent self-catheterisation. This is the only way to avoid overstretching of the bladder, recurring urinary tract infection and damage to the upper urinary tract. Restoration of spontaneous micturition can be supported by drug treatment with parasympatholytics and/or alpha-blockers if the measured bladder pressure and residual urine are within tolerable limits. For electrostimulation of micturition, intravesical therapy, although timeconsuming, is best suited because it can easily be done on an outpatient basis. More promising seems bilateral sacral neuromodulation, which, however, is a rather complicated and expensive procedure. Surgical procedures to reduce the voiding resistance of the bladder involve the risk of postoperative incontinence because the sphincter function in those patients is often disturbed too. Persisting problems with bladder storage capacity as a result of tumor surgery in the small pelvis are frequently secondary to retention of urine (overflow incontinence). In these cases, regular evacuation of the bladder by intermittent self-catheterisation can lead to social acceptance. Reduced bladder compliance and lowering of the urethral

  8. 48 CFR 417.204 - Contracts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 417.204 Contracts. The head of the contracting activity is authorized to approve contracts which exceed the 5 year limitation in FAR 17.204(e)....

  9. Management of Urinary Incontinence in Complete Bladder Duplication by Injection of Bulking Agent at Bladder Neck Level into the Proximal Urethra

    PubMed Central

    Khorramirouz, Reza; Ladi Seyedian, Seyedeh Sanam; Keihani, Sorena; Kajbafzadeh, Abdol-Mohammad

    2016-01-01

    Bladder duplication is a rare entity in children. The term encompasses a wide spectrum of anomalies from isolated bladder duplication in coronal or sagittal planes to duplicated bladder exstrophy and associated musculoskeletal and visceral anomalies. Given this wide variability, the treatment of these patients is not standardized. We hereby present a female patient with chief complaint of long-standing urinary incontinence who had complete bladder and urethral duplication and pubic diastasis. The patient was treated with bulking agent injection at the incompetent bladder neck and proximal urethra with resolution of incontinence, obviating the need for extensive surgeries. PMID:26904349

  10. Management of Urinary Incontinence in Complete Bladder Duplication by Injection of Bulking Agent at Bladder Neck Level into the Proximal Urethra.

    PubMed

    Khorramirouz, Reza; Ladi Seyedian, Seyedeh Sanam; Keihani, Sorena; Kajbafzadeh, Abdol-Mohammad

    2016-01-01

    Bladder duplication is a rare entity in children. The term encompasses a wide spectrum of anomalies from isolated bladder duplication in coronal or sagittal planes to duplicated bladder exstrophy and associated musculoskeletal and visceral anomalies. Given this wide variability, the treatment of these patients is not standardized. We hereby present a female patient with chief complaint of long-standing urinary incontinence who had complete bladder and urethral duplication and pubic diastasis. The patient was treated with bulking agent injection at the incompetent bladder neck and proximal urethra with resolution of incontinence, obviating the need for extensive surgeries. PMID:26904349

  11. Semiautomatic bladder segmentation on CBCT using a population-based model for multiple-plan ART of bladder cancer

    NASA Astrophysics Data System (ADS)

    Chai, Xiangfei; van Herk, Marcel; Betgen, Anja; Hulshof, Maarten; Bel, Arjan

    2012-12-01

    The aim of this study is to develop a novel semiautomatic bladder segmentation approach for selecting the appropriate plan from the library of plans for a multiple-plan adaptive radiotherapy (ART) procedure. A population-based statistical bladder model was first built from a training data set (95 bladder contours from 8 patients). This model was then used as constraint to segment the bladder in an independent validation data set (233 CBCT scans from the remaining 22 patients). All 3D bladder contours were converted into parametric surface representations using spherical harmonic expansion. Principal component analysis (PCA) was applied in the spherical harmonic-based shape parameter space to calculate the major variation of bladder shapes. The number of dominating PCA modes was chosen such that 95% of the total shape variation of the training data set was described. The automatic segmentation started from the bladder contour of the planning CT of each patient, which was modified by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to best fit the bladder boundary in the localization CBCT image. A cost function was defined to measure the goodness of fit of the segmentation on the localization CBCT image. The segmentation was obtained by minimizing this cost function using a simplex optimizer. After automatic segmentation, a fast manual correction method was provided to correct those bladders (parts) that were poorly segmented. Volume- and distance-based metrics and the accuracy of plan selection from multiple plans were evaluated to quantify the performance of the automatic and semiautomatic segmentation methods. For the training data set, only seven PCA modes were needed to represent 95% of the bladder shape variation. The mean CI overlap and residual error (SD) of automatic bladder segmentation over all of the validation data were 70.5% and 0.39 cm, respectively. The agreement of plan

  12. Excitatory cholinergic and purinergic signaling in bladder are equally susceptible to botulinum neurotoxin a consistent with co-release of transmitters from efferent fibers.

    PubMed

    Lawrence, Gary W; Aoki, K Roger; Dolly, J Oliver

    2010-09-01

    Mediators of neuromuscular transmission in rat bladder strips were dissected pharmacologically to examine their susceptibilities to inhibition by botulinum neurotoxins (BoNTs) and elucidate a basis for the clinical effectiveness of BoNT/A in alleviating smooth muscle spasms associated with overactive bladder. BoNT/A, BoNT/C1, or BoNT/E reduced peak and average force of muscle contractions induced by electric field stimulation (EFS) in dose-dependent manners by acting only on neurogenic, tetrodotoxin-sensitive responses. BoNTs that cleaved vesicle-associated membrane protein proved to be much less effective. Acetylcholine (ACh) and ATP were found to provide virtually all excitatory input, because EFS-evoked contractions were abolished by the muscarinic receptor antagonist, atropine, combined with either a desensitizing agonist of P2X(1) and P2X(3) or a nonselective ATP receptor antagonist. Both transmitters were released in the innervated muscle layer and, thus, persisted after removal of urothelium. Atropine or a desensitizer of the P2X(1) or P2X(3) receptors did not alter the rate at which muscle contractions were weakened by BoNT/A. Moreover, although cholinergic and purinergic signaling could be partially delineated by using high-frequency EFS (which intensified a transient, largely atropine-resistant spike in muscle contractions that was reduced after P2X receptor desensitization), they proved equally susceptible to BoNT/A. Thus, equi-potent blockade of ATP co-released with ACh from muscle efferents probably contributes to the effectiveness of BoNT/A in treating bladder overactivity, including nonresponders to anticholinergic drugs. Because purinergic receptors are known mediators of sensory afferent excitation, inhibition of efferent ATP release by BoNT/A could also help to ameliorate acute pain and urgency sensation reported by some recipients.

  13. Isolated Epithelial Cells of the Toad Bladder

    PubMed Central

    Gatzy, J. T.; Berndt, W. O.

    1968-01-01

    Epithelial cells of the toad bladder were disaggregated with EDTA, trypsin, hyaluronidase, or collagenase and were then scraped free of the underlying connective tissue. In most experiments EDTA was complexed with a divalent cation before the tissue was scraped. QOO2, sucrose and inulin spaces, and electrolytes of the isolated cells were measured. Cells disaggregated by collagenase or hyaluronidase consumed O2 at a rate of 4 µl hr-1 dry wt-1. QOO2 was increased 50% by ADH (100 U/liter) or by cyclic 3',5'-AMP (10 mM/liter). Na+-free Ringer's depressed the QOO2 by 40%. The QOO2 of cells prepared by trypsin treatment or by two EDTA methods was depressed by Na+-free Ringer's but was stimulated relatively little by ADH. Two other EDTA protocols produced cells that did not respond to Na+ lack or ADH. The intracellular Na+ and K+ concentrations of collagenase-disaggregated cells were 32 and 117 mEq/kg cell H2O, respectively. Cation concentrations of hyaluronidase cells were similar, but cells that did not respond to ADH had higher intracellular Na+ concentrations. Cells unresponsive to ADH and Na+ lack had high sucrose spaces and low transcellular membrane gradients of Na+, K+, and Cl-. The results suggest that trypsin and EDTA disaggregation damage the active Na+ transport system of the isolated cell. Certain EDTA techniques may also produce a general increase in permeability. Collagenase and hyaluronidase cells appear to function normally. PMID:4300150

  14. [Benzidine dyes and risk of bladder cancer].

    PubMed

    Miyakawa, M; Yoshida, O

    1989-12-01

    Until the early 1970's there was little concern about dyes which contain benzidine as an integral part of their chemical structure. Furthermore, use of the finished dyes was not considered dangerous. To ascertain whether azo dyes are associated with risk of development of bladder tumors in workers who handpaint Yuzen-type silk kimonos in Kyoto, we investigated the disintegration of dyes to benzidine. In these studies, we found that in rats and mice benzidine-based dyes are metabolized to benzidine and that the azo linkage of benzidine dyes is reduced by Escherichia coli and soil bacteria. These experimental findings were reported previously. In this report, we outline an approach to these studies. Many of the dyes used to color paper, textiles, lipstick, bait used by fishermen, as well as hair dyes, and dyes used in research, for pharmaceutical products, and by defence personnel for the detection of liquid chemical warfare agents, have been shown to be potentially mutagenic or carcinogenic. We review the literature on these dyes. PMID:2618904

  15. Treatment of bladder cancer in the elderly

    PubMed Central

    Erlich, Annette

    2016-01-01

    As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes. PMID:27326404

  16. Comprehensive Molecular Characterization of Urothelial Bladder Carcinoma

    PubMed Central

    2014-01-01

    Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. To date, no molecularly targeted agents have been approved for the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell cycle regulation, chromatin regulation, and kinase signaling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in miRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the PI3K/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any common cancer studied to date, suggesting the future possibility of targeted therapy for chromatin abnormalities. PMID:24476821

  17. Cannabinoids: potential targets for bladder dysfunction.

    PubMed

    Ruggieri, Michael R

    2011-01-01

    Cannabinoids are the active chemical components of Cannabis sativa (marijuana). The medical use of cannabis goes back over 5,000 years. Cannabinoids produce a very wide array of central and peripheral effects, some of which may have beneficial clinical applications. The discovery of cannabinoid receptors has spawned great interest within the pharmaceutical industry with the hopes of capitalizing on the beneficial effects of cannabis without the unwanted psychotropic effects on the central and peripheral nervous system. This chapter presents an overview of the pharmacology of cannabinoids and their derivatives. It reviews the current literature on central and peripheral cannabinoid receptors as related to effects on the lower urinary tract and the role of these receptors in normal and abnormal urinary tract function. An objective evaluation of the published results of clinical trials of cannabis extracts for the treatment of bladder dysfunction resulting from multiple sclerosis is also presented. It is clear that cannabinoid receptors are present in the lower urinary tract as well as spinal and higher centers involved in lower urinary tract control. Systemic cannabinoids have effects on the lower urinary tract that may be able to become clinically useful; however, a much greater understanding of the mechanisms of cannabinoid receptors in control of the human lower urinary tract is necessary to facilitate development of novel cannabinoid drugs for treatment of pelvic disorders.

  18. Treatment of bladder cancer in the elderly.

    PubMed

    Erlich, Annette; Zlotta, Alexandre R

    2016-06-01

    As the population ages and life expectancy increases in the human population, more individuals will be diagnosed with bladder cancer (BC). The definition of who is elderly is likely to change in the future from the commonly used cut-off of ≥75 years of age. Physiological rather than chronological age is key. BC care in the elderly is likely to become a very common problem in daily practice. Concerns have been raised that senior BC patients are not given treatments that could cure their disease. Clinicians lack quantitative and reliable estimates of competing mortality risks when considering treatments for BC. Majority of patients diagnosed with BC are elderly, making treatment decisions complex with their increasing number of comorbidities. A multidisciplinary approach to these patients may be a way to incorporate discussion from various disciplines regarding treatment options available. Here we review various treatment options for elderly patients with muscle invasive BC and nonmuscle invasive BC. We include differences in treatments from robotic versus open radical cystectomy, various urinary diversion techniques, chemotherapy, radiation therapy and combination treatments. In clinical practice, treatment decisions for elderly patients should be done on a case-by-case basis, tailored to each patient with their specific histories and comorbidities considered. Some healthy elderly patients may be better candidates for extensive curative treatments than their younger counterparts. This implies that these important, life-altering decisions cannot be solely based on age as many other factors can affect patient survival outcomes. PMID:27326404

  19. Squamous cell carcinoma of the bladder.

    PubMed

    Johnson, D E; Schoenwald, M B; Ayala, A G; Miller, L S

    1976-05-01

    Clinical and morphological features of 90 cases of squamous cell carcinoma of the bladder have been reviewed. The lesions were solitary in 90 per cent of the patients, developed without a history of vesical malignant disease in 82 per cent and were invasive at the time of diagnosis in all cases. Ureteral obstruction was demonstrated in 42 per cent of the group. The over-all survival rate at 5 years was only 10.6 per cent. There were 17 patients who received no therapy, all of whom were dead before 2 years. Unassisted supervoltage radiation therapy for patients with stages B2 and C lesions yielded a 5-year survival rate only 17.7 per cent. However, preoperative radiotherapy followed by simple total cystectomy and urinary diversion in a small number of patients with stages B2 and C lesions resulted in a 5-year survival rate in excess of 34 per cent. We are encouraged by this finding and believe that combination therapy warrants further clinical trial.

  20. [Benzidine dyes and risk of bladder cancer].

    PubMed

    Miyakawa, M; Yoshida, O

    1989-12-01

    Until the early 1970's there was little concern about dyes which contain benzidine as an integral part of their chemical structure. Furthermore, use of the finished dyes was not considered dangerous. To ascertain whether azo dyes are associated with risk of development of bladder tumors in workers who handpaint Yuzen-type silk kimonos in Kyoto, we investigated the disintegration of dyes to benzidine. In these studies, we found that in rats and mice benzidine-based dyes are metabolized to benzidine and that the azo linkage of benzidine dyes is reduced by Escherichia coli and soil bacteria. These experimental findings were reported previously. In this report, we outline an approach to these studies. Many of the dyes used to color paper, textiles, lipstick, bait used by fishermen, as well as hair dyes, and dyes used in research, for pharmaceutical products, and by defence personnel for the detection of liquid chemical warfare agents, have been shown to be potentially mutagenic or carcinogenic. We review the literature on these dyes.

  1. Roles of Polyuria and Hyperglycemia on Bladder Dysfunction in Diabetes

    PubMed Central

    Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

    2014-01-01

    Purpose Diabetes mellitus (DM) causes diabetic bladder dysfunction (DBD). We aimed to identify the pathogenic roles of polyuria and hyperglycemia on DBD in rats. Materials and Methods Seventy-two female Sprague-Dawley rats were divided: age-matched controls (control), sham urinary diversion (sham), urinary diversion (UD), streptozotocin-induced diabetes after sham UD (DM), streptozotocin-induced diabetes after UD (UD+DM), and 5% sucrose-induced diuresis after sham UD (DIU). UD was performed by ureterovaginostomy 10d before DM induction. Animals were evaluated 20 wks after DM or diuresis induction. We measured 24-hr drinking and voiding volumes and cystometry (CMG). Bladders were harvested for quantification of smooth muscle, urothelium, and collagen. We measured nitrotyrosine and manganese superoxide dismutase (MnSOD) in bladder. Results Diabetes and diuresis caused increases in drinking volume, voiding volume and bladder weight. Bladder weights decreased in the UD and UD+DM groups. Intercontractile intervals, voided volume, and compliance increased in the DIU and DM groups, decreased in the UD, and further decreased in the UD+DM group. The total cross-sectional tissue, smooth muscle and urothelium areas increased in the DIU and DM groups, and decreased in the UD and UD+DM groups. As percentages of total tissue area, collagen decreased in the DIU and DM groups, and increased in the UD and UD+DM groups, and smooth muscle and urothelium decreased in the UD and UD+DM groups. Nitrotyrosine and MnSOD increased in DM and UD+DM rats. Conclusions Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may play a pathogenic role in late stage DBD. PMID:22999997

  2. Hypertension, diuretics and antihypertensives in relation to bladder cancer

    PubMed Central

    Jiang, Xuejuan; Castelao, J.Esteban; Yuan, Jian-Min; Groshen, Susan; Stern, Mariana C.; Conti, David V.; Cortessis, Victoria K.; Coetzee, Gerhard A.; Pike, Malcolm C.; Gago-Dominguez, Manuela

    2010-01-01

    The aim of this study is to investigate the relationships between hypertension, hypertension medication and bladder cancer risk in a population-based case–control study conducted in Los Angeles. Non-Asians between the ages of 25 and 64 years with histologically confirmed bladder cancers diagnosed between 1987 and 1996 were identified through the Los Angeles County Cancer Surveillance Program. A total of 1585 cases and their age-, gender- and race-matched neighborhood controls were included in the analyses. Conditional logistic regression models were used to examine the relationship between history of hypertension, medication use and bladder cancer risk. A history of hypertension was not related to bladder cancer; however, among hypertensive individuals, there was a significant difference in bladder cancer risk related to the use of diuretics or antihypertensive drugs (P for heterogeneity = 0.004). Compared with individuals without hypertension, hypertensive individuals who regularly used diuretics/antihypertensives had a similar risk [odds ratio (OR) 1.06; 95% confidence interval (CI) 0.86–1.30], whereas untreated hypertensive subjects had a 35% reduction in risk (OR: 0.65; 95% CI: 0.48–0.88). A greater reduction in bladder cancer risk was observed among current-smokers (OR: 0.43; 95% CI: 0.27–0.71) and carriers of GSTM1-null (homozygous absence) genotypes (OR: 0.43; 95% CI: 0.22–0.85). Similarly, among smokers with GSTM1-null genotype, levels of 4-aminobiphenyl-hemoglobin adducts were significantly lower among untreated hypertensive individuals (45.7 pg/g Hb) compared with individuals without hypertension (79.8 pg/g Hb) (P = 0.009). In conclusion, untreated hypertension was associated with a reduced risk of bladder cancer. PMID:20732908

  3. Acting Out Muscle Contraction.

    ERIC Educational Resources Information Center

    Hudson, Margaret

    2003-01-01

    Describes a science activity that can be implemented into anatomy and physiology courses that demonstrates the interactions between action and myosin, the roles of sodium and calcium ions in the regulation of contraction, and the functions of the plasma membrane and the sarcoplasmic reticulum. (YDS)

  4. Contracting for Audit Services.

    ERIC Educational Resources Information Center

    Heifetz, Harry S.

    1987-01-01

    The Single Audit Act of 1984 requires most school districts receiving over $25,000 in federal funds to undergo financial audits. This article highlights requirements for selecting certified public accountants to perform the audit and suggests factors to be considered before drafting a contract or letter of engagement. A sample letter is included.…

  5. Paradental Training Contract.

    ERIC Educational Resources Information Center

    Lane Community Coll., Eugene, OR.

    This report describes institutional, faculty, and student activities and problems resulting from Lane Community College's acceptance of a federal contract to develop a paradental training program designed specifically to provide training/retraining required to quality military-trained dental corpsmen for examination by the Oregon State Board of…

  6. Copyright or Contract?

    ERIC Educational Resources Information Center

    Okerson, Ann

    1997-01-01

    Most authors and publishers of electronic information believe that current copyright law does not address technical capabilities or reader uses and have turned to contracts or licenses to define the rights of owners and users. Discusses copyrights, fair use, and licenses and highlights licensing's unresolved issues: use and users; archiving;…

  7. Contracting for Learning.

    ERIC Educational Resources Information Center

    Donald, Janet G.

    1976-01-01

    A learning contract is a document, drawn up by a student and his instructor or advisor that specifies what the student will learn, how this will be accomplished, within what period of time, and what the criteria of evaluation will be. The student and instructor agree upon specific objectives, resources to be used, and feedback sessions.…

  8. Contracting for Classroom Services.

    ERIC Educational Resources Information Center

    McLaughlin, John; Brown, Senn

    2000-01-01

    Like county governments, hospitals, and municipalities, superintendents must develop policies and protocols for requesting proposals, administering contracts, and ensuring desired results of private-sector services. Administrators should consider performance criteria, legal issues, cost and efficiency analysis, contractor evaluation criteria, and…

  9. The Factors That Affect Improvement of Neurogenic Bladder by Severe Lumbar Disc Herniation in Operation

    PubMed Central

    Jeon, Joon Bok; Kim, Do Keun; Kim, Ji-Yong

    2016-01-01

    Objective This study analyzed retrospectively the bladder function of patients after early surgery for cauda equina syndrome (CES) performed within 24 or 48 hours, or after 48 hours of the onset of autonomic symptoms. Methods We retrospectively reviewed the clinical data of 31 patients after decompression surgery for lumbar disc herniation (LDH) who had been diagnosed with CES between January 2001 and December 2014 at Inha University Hospital. The following factors were assessed to evaluate the influence of time to surgery: bladder function, rectal incontinence, sexual dysfunction, LDH level, and degree of spinal canal compression. Results After decompression, the outcome group was categorized into normal bladder function and abnormal bladder function. The patients operated on within 48 hours showed an improved postoperative outcome. Among 16 patients operated on within 48 hours, 13 (81%) recovered normal bladder function. In contrast, among 15 patients with decompression after 48 hours, 6 (40%) recovered normal bladder function. Among 21 patients with mild bladder dysfunction at admission, 16 (76%) recovered normal bladder function after decompression. Conclusion Our study suggests that patients who have decompression surgery within 48 hours of the onset of bladder dysfunction, improve their chances of recovering bladder function than those who have a late operation (>48 hours). Also, patients with mild bladder dysfunction are more likely to recover bladder function after decompression, than patients with severe bladder dysfunction. PMID:27799991

  10. Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study

    PubMed Central

    Vermeulen, S H; Hanum, N; Grotenhuis, A J; Castaño-Vinyals, G; van der Heijden, A G; Aben, K K; Mysorekar, I U; Kiemeney, L A

    2015-01-01

    Background: Controversy exists on whether urinary tract infection (UTI) is a risk factor for urinary bladder cancer (UBC). Here, the association is investigated using data from one of the largest bladder cancer case–control studies worldwide. Methods: Information on (i) history and age at onset of regular cystitis (‘regular low-UTI') and (ii) number and age at onset of UTI treated with antibiotics (‘UTI-ab') from 1809 UBC patients and 4370 controls was analysed. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, education, smoking, and use of aspirin/ibuprofen were generated, for men and women separately. Results: Regular low-UTI was associated with an increased UBC risk (men: OR (95% CI) 6.6 (4.2–11); women: 2.7 (2.0–3.5)), with stronger effects in muscle-invasive UBC. Statistically significant decreased risks (ORs ∼0.65) were observed for up to five UTI-ab, specifically in those who (had) smoked and experienced UTI-ab at a younger age. In women, UTI experienced after menopause was associated with a higher UBC risk, irrespective of the number of episodes. Conclusions: Regular cystitis is positively associated with UBC risk. In contrast, a limited number of episodes of UTI treated with antibiotics is associated with decreased UBC risk, but not in never-smokers and postmenopausal women. PMID:25429525

  11. Employee contract issues for dermatologists.

    PubMed

    Brown, Christopher E; Indest, George F

    2013-12-01

    Employees and employers routinely face negotiating and preparing physician employment contracts. It is important for both sides to know and understand the basic information on what a comprehensive employment contract for a dermatologist should contain. There are various employment contract provisions from both the employee's perspective and the employer's perspective that must be considered when preparing physician employment contracts. This article provides basic advice and recommendations on requirements that should be included in such contracts. It suggests legal pitfalls that can be avoided through various contract clauses.

  12. Employee contract issues for dermatologists.

    PubMed

    Brown, Christopher E; Indest, George F

    2013-12-01

    Employees and employers routinely face negotiating and preparing physician employment contracts. It is important for both sides to know and understand the basic information on what a comprehensive employment contract for a dermatologist should contain. There are various employment contract provisions from both the employee's perspective and the employer's perspective that must be considered when preparing physician employment contracts. This article provides basic advice and recommendations on requirements that should be included in such contracts. It suggests legal pitfalls that can be avoided through various contract clauses. PMID:24800433

  13. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype

    PubMed Central

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D.; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G.

    2013-01-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited down-regulation and mislocalization of α3- and α5-integrins by immunohistochemistry but, surprisingly, had normal morphology, permeability, and transepithelial resistance when compared with Cre-negative littermate controls. β1-cKO mice were incontinent, as judged by random urine leakage on filter paper (4-fold higher spotting, P<0.01; 2.5-fold higher urine area percentage, P<0.05). Urodynamic function assessed by cystometry revealed bladder overfilling with 80% longer intercontractile intervals (P<0.05) and detrusor hyperactivity (3-fold more prevoid contractions, P<0.05), but smooth muscle contractility remained intact. ATP secretion into the lumen was elevated (49 vs. 22 nM, P<0.05), indicating abnormal filling-induced purinergic signaling, and short-circuit currents (measured in Ussing chambers) revealed 2-fold higher stretch-activated ion channel conductances in response to hydrostatic pressure of 1 cmH2O (P<0.05). We conclude that loss of integrin signaling from urothelium results in incontinence and overactive bladder due to abnormal mechanotransduction; more broadly, our findings indicate that urothelium itself directly modulates voiding.—Kanasaki, K., Yu, W., von Bodungen, M., Larigakis, J. D., Kanasaki, M., Ayala de la Pena, F., Kalluri, R., Hill, W.G. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype. PMID:23395910

  14. Bladder selectivity of the novel β₃-agonist ritobegron (KUC-7483) explored by in vitro and in vivo studies in the rat.

    PubMed

    Maruyama, Itaru; Goi, Yoshiaki; Tatemichi, Satoshi; Maruyama, Kazuyasu; Hoyano, Yuji; Yamazaki, Yoshinobu; Kusama, Hiroshi

    2012-08-01

    We performed in vitro and in vivo experiments to evaluate the pharmacological profile of ritobegron and its effects on the bladder in rats. β(3)-AR selectivity was assessed using CHO cells expressing various subtypes of the human β-adrenoceptor (AR). Effects on isolated organs were evaluated using the organ-bath method. Effects on intravesical pressure, heart rate, and mean blood pressure were evaluated in urethane-anesthetized rats. Ritobegron increased cAMP accumulation in a concentration-dependent manner in CHO cells expressing any one of three human β-AR, its selectivity for β(3)-AR being 301-fold and 32-fold higher versus β(1)-AR and β(2)-AR, respectively. Ritobegron decreased the resting tension of the isolated bladder in a concentration-dependent manner (EC(50), 7.7 × 10(-8) mol/L; maximal relaxation, 97.0 %), and the β(3)-AR antagonist SR58894A produced a parallel rightward-shift of this concentration-response curve without altering the maximal response [pK(B) value, 6.43]. Ritobegron concentration-dependently increased atrial rate and decreased myometrial contractions in vitro, and its selectivity for the bladder was 2,078-fold higher versus the atria and 14-fold higher versus the uterus. In vivo, ritobegron induced a dose-dependent decrease in intravesical pressure (ED(50) 0.4 mg/kg), without affecting heart rate and only slightly lowering mean blood pressure. Thus, ritobegron displayed potent and selective β(3)-AR agonistic activity toward transfected human β-AR and exhibited a high selectivity for the bladder versus other organs in rats. Moreover, it decreased intravesical pressure with minimal effects on the cardiovascular system in anesthetized rats. These results suggest that ritobegron shows promise as a potential agent for the treatment of overactive bladder. PMID:22552730

  15. Cyclophosphamide-Induced Bladder Inflammation Sensitizes and Enhances P2X Receptor Function in Rat Bladder Sensory Neurons

    PubMed Central

    Dang, Khoa; Lamb, Kenneth; Cohen, Michael; Bielefeldt, Klaus; Gebhart, G. F.

    2009-01-01

    We studied sensitization of retrogradely labeled bladder sensory neurons and plasticity of P2X receptor function in a model of cystitis using patch-clamp techniques. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally to rats on days 0, 2, and 4. On day 5, lumbosacral (LS, L6–S2) or thoracolumbar (TL, T12–L2) dorsal root ganglia were removed and dissociated. Bladders from CYP-treated rats showed partial loss of the urothelium and greater myeloperoxidase activity compared with controls. Bladder neurons from CYP-treated rats were increased in size (based on whole cell capacitance) compared with controls and exhibited lower activation threshold, increased action potential width, and greater number of action potentials in response to current injection or application of purinergic agonists. Most control LS bladder neurons (>85%) responded to ATP or α,β-metATP with a slowly desensitizing current; these agonists affected only half of TL neurons, producing predominantly fast/mixed desensitizing currents. CYP treatment increased the fraction of TL bladder neurons sensitive to purinergic agonists (>80%) and significantly increased current density in both LS and TL bladder neurons compared with control. Importantly, LS and TL neurons from CYP-treated rats showed a selective increase in the functional expression of heteromeric P2X2/3 and homomeric P2X3 receptors, respectively. Although desensitizing kinetics were slower in LS neurons from CYP-treated compared with control rats, recovery kinetics were similar. The present results demonstrate that bladder inflammation sensitizes and increases P2X receptor expression and/or function for both pelvic and lumbar splanchnic pathways, which contribute, in part, to the hypersensitivity associated with cystitis. PMID:17959738

  16. Glucocorticoid receptor beta increases migration of human bladder cancer cells.

    PubMed

    McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

    2016-05-10

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GRβ compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GRβ in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3' untranslated region (UTR) of human GRβ revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GRβ by 3.8 fold. In addition, miR144 and GRβ were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3'UTR of GRβ. Sweet-P effectively prevented miR144 actions and decreased GRβ expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease. PMID:27036026

  17. The actions of neurotensin in rat bladder detrusor contractility

    PubMed Central

    Dong, Xingyou; Bai, Xinyu; Zhao, Jiang; Wang, Liang; Wang, Qingqing; Li, Longkun

    2015-01-01

    This study assessed the expression, distribution and function of neurotensin (NTs) and two main neurotensin receptors (NTSR), NTSR1 and NTSR2 in normal rat urinary bladders. NTs is primarily located in the suburothelium and the interstitium of smooth muscle bundles. The NTSR1 and NTSR2 receptor subtypes are found to co-localize with smooth muscle cells (SMCs). NTs not only can directly act on bladder SMCs to induce intracellular calcium mobilization by activating the phospholipase C/inositol triphosphate (PLC/IP3) pathway, promoting extracellular calcium influx through a non-selective cation channels, but may be also involved in the modulation of the cholinergic system. Nowadays, the selective antimuscarinic drugs (solifenacin) and the selective beta 3-adrenergic agonist (mirabegron) are used as the first-line pharmacotherapy for overactive bladder (OAB), but without satisfactory treatment benefits in some patients. This study provided evidence suggesting that bladder NTs may play an important role in the regulation of micturition. Further research is needed to investigate the effects of NTs on bladder contractility and the underlying mechanism, which might reveal that the administration of NTSR antagonists can potentially relieve the symptoms of OAB by coordination with antimuscarinic pharmacotherapy. PMID:26053252

  18. An essential role for decorin in bladder cancer invasiveness

    PubMed Central

    El Behi, Mohamed; Krumeich, Sophie; Lodillinsky, Catalina; Kamoun, Aurélie; Tibaldi, Lorenzo; Sugano, Gaël; De Reynies, Aurélien; Chapeaublanc, Elodie; Laplanche, Agnès; Lebret, Thierry; Allory, Yves; Radvanyi, François; Lantz, Olivier; Eiján, Ana María; Bernard-Pierrot, Isabelle; Théry, Clotilde

    2013-01-01

    Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murine bladder tumour cell line MB49 and its more aggressive variant MB49-I, we demonstrate that the adaptive immune system efficiently limits progression of MB49, whereas MB49-I has lost tumour antigens and is insensitive to adaptive immune responses. Furthermore, we unravel a parallel mechanism developed by MB49-I to subvert its environment: de novo secretion of the proteoglycan decorin. We show that decorin overexpression in the MB49/MB49-I model is required for efficient progression, by promoting angiogenesis and tumour cell invasiveness. Finally, we show that these results are relevant to muscle-invasive human bladder carcinomas, which overexpress decorin together with angiogenesis- and adhesion/migration-related genes, and that decorin overexpression in the human bladder carcinoma cell line TCCSUP is required for efficient invasiveness in vitro. We thus propose decorin as a new therapeutic target for these aggressive tumours. PMID:24142880

  19. Adaptive radiotherapy for invasive bladder cancer: A feasibility study

    SciTech Connect

    Pos, Floris J. . E-mail: f.pos@nki.nl; Hulshof, Maarten; Lebesque, Joos; Lotz, Heidi; Tienhoven, Geertjan van; Moonen, Luc; Remeijer, Peter

    2006-03-01

    Purpose: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation. Methods and Materials: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV{sub CONV}). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV{sub ART}). The GTV{sub ART} was expanded with a 1 cm margin for the construction of a PTV{sub ART}. Starting in the third week, patients were treated to PTV{sub ART}. Repeat CT scans were used to evaluate treatment accuracy. Results: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV{sub ART}. On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV{sub ART} with PTV{sub CONV} (p < 0.0001). Conclusion: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes.

  20. Overactive bladder – 18 years – part I

    PubMed Central

    Truzzi, Jose Carlos; Gomes, Cristiano Mendes; Bezerra, Carlos A.; Plata, Ivan Mauricio; Campos, Jose; Garrido, Gustavo Luis; Almeida, Fernando G.; Averbeck, Marcio Augusto; Fornari, Alexandre; Salazar, Anibal; Dell'Oro, Arturo; Cintra, Caio; Sacomani, Carlos Alberto Ricetto; Tapia, Juan Pablo; Brambila, Eduardo; Longo, Emilio Miguel; Rocha, Flavio Trigo; Coutinho, Francisco; Favre, Gabriel; Garcia, José Antonio; Castaño, Juan; Reyes, Miguel; Leyton, Rodrigo Eugenio; Ferreira, Ruiter Silva; Duran, Sergio; López, Vanda; Reges, Ricardo

    2016-01-01

    ABSTRACT Abstract: Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals – including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years. PMID:27176184