A new problem in inflammatory bladder diseases: use of mobile phones!

PubMed

Koca, Orhan; Gokce, Ali Murat; Akyuz, Mehmet; Ercan, Feriha; Yurdakul, Necati; Karaman, Muhammet Ihsan

2014-01-01

Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor.

Women's experiences of living with neurogenic bladder and bowel after spinal cord injury: life controlled by bladder and bowel.

PubMed

Nevedal, Andrea; Kratz, Anna L; Tate, Denise G

2016-01-01

Neurogenic bladder and bowel (NBB) is a chronic condition hindering the functioning and quality of life (QOL) of people with spinal cord injury (SCI). NBB research has focused on men with SCI leaving unanswered questions about women's experiences of living with NBB. The purpose of this study was to identify and describe women's experiences of living with SCI and NBB. Secondary analysis of semi-structured interviews from a larger qualitative study of women with SCI (N = 50) was carried out. Transcripts were coded for bowel and bladder content. Pile-sorting techniques were used to identify emergent themes related to NBB. Meta-themes were categorized under the International Classification of Functioning, Disability and Health. Bladder and bowel topics were spontaneously discussed by 46 out of 50 study participants suggesting the salience of this issue for women with SCI. We identified 6 meta-themes: life controlled by bladder and bowel, bladder and bowel accidents, women's specific challenges, life course disruption, bladder and bowel medical management, and finding independence. Findings describe concerns, strategies, and the detrimental impact of NBB in the lives of women with SCI. Findings inform policy makers, health care and rehabilitation professionals to improve accessibility and quality of life for women with NBB. Women with spinal cord injury (SCI) reported gender specific challenges to living with neurogenic bladder and bowel (NBB). Interventions designed for women with SCI can address these problems and provide recommendations for prevention and treatment. Women described the detrimental impact of NBB on life course expectations, emotional, social, physical health, and quality of life domains. Psychosocial and educational programs can be developed to address these challenges and improve overall quality of life. Recommendations for special treatment and policy considerations are needed to maximize women's independence and health while living with NBB after SCI.

The morphological regeneration and functional restoration of bladder defects by a novel scaffold and adipose-derived stem cells in a rat augmentation model.

PubMed

Wang, Qiong; Xiao, Dong-Dong; Yan, Hao; Zhao, Yang; Fu, Shi; Zhou, Juan; Wang, Zhong; Zhou, Zhe; Zhang, Ming; Lu, Mu-Jun

2017-06-24

Due to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs) for bladder defect repair, various scaffolds have been applied in combination with ASCs to promote bladder regeneration and restore bladder function. However, the low survival rate of ASCs and the difficulty of promoting bladder functional recovery are still unsolved. To explore these problems, we investigated the feasibility of a novel scaffold seeded with ASCs in a rat model of bladder augmentation. A novel autologous myofibroblast (AM)-silk fibroin (SF) scaffold was harvested after subcutaneously prefabricating the bladder acellular matrix grafts (BAMG) and SF by removing the BAMG. The AM-SF scaffolds were then seeded with ASCs (AM-SF-ASCs). Fifty percent supratrigonal cystectomies were performed followed by augmenting the cystectomized defects with AM-SF scaffolds or AM-SF-ASCs. The histological and functional assessments of bladders were performed 2, 4, and 12 weeks after surgery while the ASCs were tracked in vivo. For bladder tissue regeneration, immunofluorescence analysis revealed that AM-SF-ASCs (the experimental group) promoted better morphological regeneration of the urothelium, vessels, bladder smooth muscle, and nerve than AM-SF scaffolds (the control group). Regarding functional restoration, the AM-SF-ASC group exhibited higher bladder compliance and relatively normal micturition pattern compared to the AM-SF group. In addition, a certain number of surviving ASCs could be found in vivo 12 weeks after implantation, and some of them had differentiated into smooth muscle cells. The AM-SF scaffolds with ASCs could rapidly promote bladder morphological regeneration and improved bladder urinary function. In addition, the bag-shaped structure of the AM-SF scaffold can improve the survival of ASCs for at least 12 weeks. This strategy of AM-SF-ASCs has a potential to repair large-scale bladder defects in the clinic in the future.

The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder.

PubMed

Greenland, J E; Hvistendahl, J J; Andersen, H; Jörgensen, T M; McMurray, G; Cortina-Borja, M; Brading, A F; Frøkiaer, J

2000-06-01

To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs. Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

Sacral root neuromodulation in the treatment of various voiding and storage problems.

PubMed

Shaker, H; Hassouna, M M

1999-01-01

This paper reviews the use of sacral neuromodulation as a treatment modality for patients with bladder dysfunction. The dual functions of the urinary bladder are to act as a reservoir and to evacuate under voluntary control. Bladder dysfunction is a descriptive term describing the loss or the impairment of one or both of these functions. In the first part of the manuscript we describe the different components of sacral neuromodulation: the screening test known as percutaneous nerve evaluation (PNE), which involves screening patients who could potentially benefit from the therapy. Those who show a satisfactory response will have a permanent neuroprosthesis implanted. The technical aspects of both components of neuromodulation are described in detail, as well as the technical difficulties encountered. In the second part we present our long-term results in patients with sacral neuromodulation. Sacral neuromodulation is a safe and efficient therapeutic modality that helps patients with refractory voiding dysfunction restore their bladder function.

Bladder welding in rats using controlled temperature CO2 laser system.

PubMed

Lobik, L; Ravid, A; Nissenkorn, I; Kariv, N; Bernheim, J; Katzir, A

1999-05-01

Laser tissue welding has potential advantages over conventional suture closure of surgical wounds. It is a noncontact technique that introduces no foreign body and limits the possibility of infections and complications. The closure could be immediately watertight and the procedure may be less traumatic, faster and easier. In spite of these positives laser welding has not yet been approved for wide use. The problem in the clinical implementation of this technique arises from the difficulty in defining the conditions under which a highly reliable weld is formed. We have assumed that the successful welding of tissues depends on the ability to monitor and control the surface temperature during the procedure, thereby avoiding underheating or overheating. The purpose of this work was to develop a laser system for reliable welding of urinary tract tissues under good temperature control. We have developed a "smart" laser system that is capable of a dual role: transmitting CO2 laser power for tissue heating, and noncontact (radiometric) temperature monitoring and control. Bladder opening (cystotomy) was performed in 38 rats. Thirty-three animals underwent laser welding. In 5 rats (control group) the bladder wound was closed with one layer of continuous 6-0 dexon sutures. Reliable welding was obtained when the surface temperature was kept at 71 + 5C. Quality of weld was controlled immediately after operation. The rats were sacrificed on days 2, 10 and 30 for histological study. Bladder closure using the laser welding system was successful in 31/33 (94%) animals. Histological examination revealed an excellent welding and healing of the tissue. Efficiency of laser welding of urinary bladder in rats was confirmed by high survival rate and quality of scar that was demonstrated by clinical and histological examinations. In the future, optimal laser welding conditions will be studied in larger animals, using CO2 lasers and other lasers, with deeper radiation penetration into tissues.

A case-control study on the association between bladder cancer and prior bladder calculus.

PubMed

Chung, Shiu-Dong; Tsai, Ming-Chieh; Lin, Ching-Chun; Lin, Herng-Ching

2013-03-15

Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. This case-control study included 2,086 cases who had received their first-time diagnosis of BC between 2001 and 2009 and 10,430 randomly selected controls without BC. Conditional logistic regressions were employed to explore the association between BC and having been previously diagnosed with bladder calculus. Of the sampled subjects, bladder calculus was found in 71 (3.4%) cases and 105 (1.1%) controls. Conditional logistic regression analysis revealed that the odds ratio (OR) of having been diagnosed with bladder calculus before the index date for cases was 3.42 (95% CI = 2.48-4.72) when compared with controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and renal disease, tobacco use disorder, obesity, alcohol abuse, and schistosomiasis, bladder outlet obstruction, and urinary tract infection. We further analyzed according to sex and found that among males, the OR of having been previously diagnosed with bladder calculus for cases was 3.45 (95% CI = 2.39-4.99) that of controls. Among females, the OR was 3.05 (95% CI = 1.53-6.08) that of controls. These results add to the evidence surrounding the conflicting reports regarding the association between BC and prior bladder calculus and highlight a potential target population for bladder cancer screening.

Structural and vascular response of normal and obstructed rabbit whole bladders to distension.

PubMed

Matsumoto, Seiji; Chichester, Paul; Kogan, Barry A; Levin, Robert M

2003-12-01

To investigate the structural and morphologic effect of distension after partial outlet obstruction in rabbits. Thirty male New Zealand white rabbits were separated into two groups: control (sham) and partial outlet obstruction (3 weeks). Three rabbits from each group were distended to 5%, 25%, 50%, 100%, and 125% of capacity. Each bladder was fixed at the volume in buffered formalin for 6 to 8 hours. Sections of dorsal and ventral bladder were blocked, and cross sections were evaluated. Quantitative morphometry was performed, and CD31 immunohistochemistry was used to characterize the vascularity. Partial outlet obstruction resulted in increased bladder weight and capacity and increased thickness of the mucosa, submucosa, detrusor, and serosa. In the control bladder, the greatest thinning was seen between 5% and 25% capacity, and in the obstructed group, the greatest thinning occurred between 25% and 50%. The level of vascular collapse was significantly greater for the control bladders than for the obstructed bladders at all levels of distension. Finally, the obstructed bladders showed a significantly greater level of vascularity in the submucosa than the control bladders. Normal bladder distension resulted in significant morphologic changes when the bladder was distended to 25% of capacity but changed relatively little between 25% and 125%. However, distension of the obstructed bladder resulted in significant morphologic changes when the bladder was distended from 25% to 50% of capacity but changed relatively little between 50% and 125%.

Cerebral control of the bladder in normal and urge-incontinent women

PubMed Central

Griffiths, Derek; Tadic, Stasa D.; Schaefer, Werner; Resnick, Neil M.

2007-01-01

Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 – 85 years): 11 “cases” with urge incontinence and DO (proven previously) and 10 normal “controls”. Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In “controls”, increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger “cases”, ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly “cases” showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase. Conclusion: Among normal “controls”, increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent “cases” and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older “cases” reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO). PMID:17574871

Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

PubMed Central

Peterson, Abbey; Erickson, Cuixia Shi; Nelson, Mark T.; Vizzard, Margaret A.

2014-01-01

Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for 2 wk. Stressed FVB mice exhibited nonvoiding bladder contractions and a decrease in both micturition interval (increased voiding frequency) and bladder capacity compared with control animals. ELISAs demonstrated a significant increase in histamine protein expression with no change in nerve growth factor protein expression in the urinary bladder compared with controls. Unlike stressed mice, mice exposed to an increased stress paradigm exhibited increased bladder capacities and intermicturition intervals (decreased voiding frequency). Both histamine and nerve growth factor protein expression were significantly increased with increased stress compared with control bladders. The change in bladder function from increased voiding frequency to decreased voiding frequency with increased stress intensity suggests that changes in social stress-induced urinary bladder dysfunction are context and duration dependent. In addition, changes in the bladder inflammatory milieu with social stress may be important contributors to changes in urinary bladder function. PMID:25100077

Urgency in overactive bladder: translating experimental data into clinical practice.

PubMed

Wyndaele, Jean-Jacques; De Wachter, Stefan

2008-05-01

In overactive bladder (OAB) syndrome, urgency is considered to be the key symptom that generates or affects all other symptoms. Urgency has been defined by the latest International Continence Society (ICS) terminology report as "the complaint of a sudden compelling desire to pass urine, which is difficult to defer". This definition has caused some debate and a final terminology has not yet been agreed upon. However, many would agree that urgency is different from urge when describing bladder sensation, and "urgency" has become one of the leading topics in OAB diagnosis and a primary endpoint in evaluation of treatment. Despite the many potential targets for pharmacological treatment, few drugs other than antimuscarinic agents have passed the proof-of-concept stage. There are multiple mechanisms, some proven in concept but more theoretical, by which a pharmacological agent may facilitate lower urinary tract filling/urine storage, bladder sensation and bladder emptying, although organ selectivity is often a problem. Oxybutynin, tolterodine, darifenacin, solifenacin and trospium have shown superiority to placebo, with a different incidence of side effects among the different drugs. Larger randomized, controlled trials in clinical settings are required to further establish the role of these medications in the management of urgency and OAB syndrome. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

The use of computed tomography for assessment of the swim bladder in koi carp (Cyprinus carpio).

PubMed

Pees, Michael; Pees, Kathrin; Kiefer, Ingmar

2010-01-01

Seven normal koi (Cyprinus carpio) and seven koi with negative buoyancy were examined using computed tomography (CT) to assess the swim bladder. The volume of the swim bladder was calculated in all animals. In the healthy koi there was a statistical correlation (r = 0.996) between body mass and swim bladder volume with volume (ml) being related to body mass according to the formula 4.9 +/- 0.054 x BM (g). In all koi with buoyancy problems, the gas volume of the swim bladder was reduced. Additionally, fluid was found within the swim bladder in three of the abnormal koi. CT proved to be a quick noninvasive technique for the examination of the swim bladder in koi.

On the nature of bladder sensation: the concept of sensory modulation.

PubMed

De Wachter, S G; Heeringa, R; van Koeveringe, G A; Gillespie, J I

2011-09-01

Going to the toilet is an essential everyday event. Normally, we do not give much thought to the sensations and factors that trigger voiding behavior: we just go. For many people, this apparently simple task is complicated and dominates their life. They have strong sensations and sudden desires to void, often resulting in incontinence. It is therefore important that we understand the origins for this functional change and identify means to alleviate it. Literature survey. A considerable body of work has focused on this problem and ideas and concepts on the nature of bladder sensations are embedded in the literature. In this paper we argue the necessity to return to first principles and a re-examination of the problem. We explore the use of focus groups to identify relevant bladder sensation and what triggers 'bladder' behavior. We argue that there are differences in what can be described as 'introspective bladder sensations' and the sensations reported immediately before a void, 'void sensations'. Finally, we propose an alternative model describing how peripheral information generating 'introspective sensations' and 'void sensations' might be different but interrelated sensations. By exploring such ideas and identifying such complexity it is our intention to stimulate debate and generate further research in the field in order to understand better the physiology of bladder sensation and the pathology of increased urge, frequency and incontinence. Review of the literature on bladder sensation and the established ideas suggests that we might be missing something and the problem of normal and increased sensation and of urgency may be much more complex. Copyright © 2011 Wiley-Liss, Inc.

Vapor compression distillation module

NASA Technical Reports Server (NTRS)

Nuccio, P. P.

1975-01-01

A Vapor Compression Distillation (VCD) module was developed and evaluated as part of a Space Station Prototype (SSP) environmental control and life support system. The VCD module includes the waste tankage, pumps, post-treatment cells, automatic controls and fault detection instrumentation. Development problems were encountered with two components: the liquid pumps, and the waste tank and quantity gauge. Peristaltic pumps were selected instead of gear pumps, and a sub-program of materials and design optimization was undertaken leading to a projected life greater than 10,000 hours of continuous operation. A bladder tank was designed and built to contain the waste liquids and deliver it to the processor. A detrimental pressure pattern imposed upon the bladder by a force-operated quantity gauge was corrected by rearranging the force application, and design goals were achieved. System testing has demonstrated that all performance goals have been fulfilled.

Family history of cancer and the risk of bladder cancer: A case-control study from Italy.

PubMed

Turati, Federica; Bosetti, Cristina; Polesel, Jerry; Serraino, Diego; Montella, Maurizio; Libra, Massimo; Facchini, Gaetano; Ferraroni, Monica; Tavani, Alessandra; La Vecchia, Carlo; Negri, Eva

2017-06-01

A family history of bladder cancer has been associated with the risk of bladder cancer, but quantification of the excess risk in different populations is still a relevant issue. Further, the role of a family history of other cancers on the risk of bladder cancer remains unclear. We analyzed data from an Italian case-control study, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) were estimated through unconditional logistic regression models, adjusted for sex, age, study center, year of interview and further for education, smoking and sibling's number. The OR for family history of bladder cancer was 2.13 (95% confidence intervals (95%CIs) 1.02-4.49) from the model with partial adjustment, and 1.99 (95%CI 0.91-4.32) after additional adjustment for smoking and siblings' number, based on 23 cases (3.3%) and 11 controls (1.7%) with a family history of bladder cancer. The fully adjusted OR was 3.77 when the relative was diagnosed at age below 65years. Smokers with a family history of bladder cancer had a four-fold increased risk compared to non-smokers without a family history. Bladder cancer risk was significantly increased among subjects with a family history of hemolymphopoietic cancers (OR=2.97, 95%CI 1.35-6.55). Family history of cancer at other sites showed no significant association with bladder cancer risk. This study confirms an approximately two-fold increased risk of bladder cancer for family history of bladder cancer, and indicates a possible familial clustering of bladder cancer with cancers of the hemolymphopoietic system. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

NASA Astrophysics Data System (ADS)

Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

2017-02-01

Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (p<0.0001). The differential uptake of IRDye800CW-DG by the neoplastic urinary bladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet obstruction.

PubMed

Shiina, Kazuhiro; Hayashida, Ken-Ichiro; Ishikawa, Kazuo; Kawatani, Masahito

2016-01-01

Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.

Bowel and bladder-control anxiety: a preliminary description of a viscerally-centred phobic syndrome.

PubMed

Kamboj, Sunjeev K; Langhoff, Christine; Pajak, Rosanna; Zhu, Alex; Chevalier, Agnes; Watson, Sue

2015-03-01

People with anxiety disorders occasionally report fears about losing control of basic bodily functions in public. These anxieties often occur in the absence of physical disorder and have previously been recognized as "obsessive" anxieties reflecting a preoccupation with loss of bowel/bladder control. Motivated by our observations of the non-trivial occurrence of such anxieties in our clinical practice we sought to fill a gap in the current understanding of "bowel/bladder-control anxieties". Eligible participants completed an internet survey. Bowel/bladder-control anxieties (n = 140) tended to emerge in the mid to late 20s and were associated with high levels of avoidance and functional impairment. There was a high prevalence of panic attacks (78%); these were especially prevalent among those with bowel-control anxiety. Of those with panic attacks, 62% indicated that their main concern was being incontinent during a panic attack. Significantly, a proportion of respondents (~16%) reported actually being incontinent during a panic attack. Seventy percent of participants reported intrusive imagery related to loss of bowel/bladder control. Intrusion-related distress was correlated with agoraphobic avoidance and general role impairment. Some differences were noted between those with predominantly bowel-, predominantly bladder- and those with both bowel and bladder-control anxieties. This preliminary characterization indicates that even in a non-treatment seeking community sample, bowel/bladder-control anxieties are associated with high levels of distress and impairment. Further careful characterization of these anxieties will clarify their phenomenology and help us develop or modify treatment protocols in a way that takes account of any special characteristics of such viscerally-centred phobic syndromes.

Development of a Prosthesis for Urinary Control

NASA Technical Reports Server (NTRS)

Tenney, J. B.; Rabinowitz, R.; Tomkiewicz, Z.; Harrison, H. N.; Rogers, D. W.

1986-01-01

Report describes development and marketing of prosthetic sphincter for urinary control. With prosthetic device, patients void bladder every 3 to 4 hours. Periodic voiding keeps bladder muscles exercised and healthy and avoids bladder infections and kidney damage.

Quality of life in patients with muscle invasive and non-muscle invasive bladder cancer.

PubMed

Singer, S; Ziegler, C; Schwalenberg, T; Hinz, A; Götze, H; Schulte, T

2013-05-01

Compared to the literature on other malignancies, data on quality of life (QoL) in bladder cancer are sparse. This study sought answers to the following questions: In what QoL domains do patients with bladder cancer differ from the general population? Do patients with radical cystectomy differ in QoL compared to those who received conservative treatment? Do patients with neobladder generally have better QoL compared to patients with other diversion methods? At the beginning of inpatient rehabilitation, N = 823 patients with bladder cancer were assessed. Data of a representative community sample (N = 2037) were used for comparison. The questionnaire EORTC QLQ-C30 was used to measure QoL. Multivariate linear regression models were computed to investigate differences between groups. Patients with both non-muscle invasive and muscle invasive bladder cancer reported significantly more problems and worse functioning than the general population. Radiotherapy is associated with clinically relevant more pain, dyspnoea, constipation, appetite loss and decreased social functioning while chemotherapy is associated more with dyspnoea. Cystectomy patients reported more fatigue, appetite loss and decreased role functioning. Male patients ≥70 years with conduit experienced more sleep and emotional problems. These effects of urinary diversion were not observed in women and younger patients. Patients with bladder cancer experience various QoL concerns at the beginning of inpatient rehabilitation. These problems can partly be explained by the type of treatment the patients receive. Type of urinary diversion is relevant for QoL in subgroups of patients.

Sacral neuromodulations for female lower urinary tract, pelvic floor, and bowel disorders.

PubMed

Wehbe, Salim A; Whitmore, Kristene; Ho, Mat H

2010-10-01

In recent years, sacral neuromodulation (SNM) has been investigated for the treatment of various types of lower urinary tract and bowel dysfunctions. This review discusses recently published data related to the therapeutic applications of SNM in female lower urinary tract, pelvic floor, and bowel disorders. SNM has been employed initially in the treatment of refractory idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. Since then, several studies, including randomized and controlled trials, have confirmed the therapeutic effects of SNM in these disorders. The applications of SNM are now extended to the treatment of other female pelvic problems, such as fecal incontinence, chronic constipation, interstitial cystitis/painful bladder syndrome, sexual dysfunction, and neurogenic disorders, with similar promising results. SNM is approved by the Food and Drug Administration for the treatment of idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. SNM is not yet an approved method for the treatment of other pelvic disorders, but data supporting its benefit are emerging. The major advantage of SNM lies in its potential to treat the bladder, urethral sphincter, anal sphincters, and pelvic floor muscles simultaneously, which might result in better therapeutic effects.

Aging changes in the kidneys and bladder

MedlinePlus

... fluid from the body. The kidneys also help control the body's chemical balance. The kidneys are part of the urinary system, which also includes the ureters, bladder, and urethra. Muscle ... bladder control. AGING CHANGES AND THEIR EFFECTS ON THE KIDNEYS ...

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

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

PubMed

Lina, B A; Rutten, A A; Woutersen, R A

1993-12-01

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

In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats

PubMed Central

Van Gordon, Samuel; Tyler, Karl; Kropp, Bradley; Towner, Rheal; Lin, HsuehKung; Marentette, John O.; McHowat, Jane; Mohammedi, Ehsan; Greenwood-Van Meerveld, Beverley

2016-01-01

Loss of integrity of the protective impermeability barrier in the urothelium has been identified as significant in bladder dysfunction. In this study, we tested the theory that the luminal layer of glycosaminoglycans (GAG) serves as an important component of barrier function. The peptide polycation protamine sulfate (PS), 1 mg/ml, was instilled intravesically for 10 min into rat bladders. Chondroitinase ABC (ChABC), 63 IU/ml, was instilled into an additional six rats for 30 min to digest the GAG layer. Unmanipulated controls and sham-injected controls were also performed. After 24 h, the rats were euthanized, the bladders were removed, and permeability was assessed in the Ussing chamber and by diffusion of FITC-labeled dextran (4 kDa) to measure macromolecular permeability. The status of tight junctions was assessed by immunofluorescence and electron microscopy. In control and sham treated rat bladders, the transepithelial electrical resistance were means of 2.5 ± 1.1 vs. 2.6 ± 1.1 vs 1.2 ± 0.5 and 1.01 ± 0.7 kΩ·cm2 in the PS-treated and ChABC-treated rat bladders (P = 0.0016 and P = 0.0039, respectively). Similar differences were seen in dextran permeability. Histopathology showed a mild inflammation following PS treatment, but the ChABC-treated bladders were indistinguishable from controls. Tight junctions generally remained intact. ChABC digestion alone induced bladder permeability, confirming the importance of the GAG layer to bladder barrier function and supports that loss of the GAG layer seen in bladder biopsies of interstitial cystitis patients could be a significant factor producing symptoms for at least some interstitial cystitis/painful bladder syndrome patients. PMID:26911855

Evaluation of associations between lifetime exposure to drinking water disinfection by-products and bladder cancer in dogs.

PubMed

Backer, Lorraine C; Coss, Angela M; Wolkin, Amy F; Flanders, W Dana; Reif, John S

2008-06-01

To assess the risk of bladder cancer in dogs from exposure to drinking water disinfection by-products and determine whether dogs could serve as sentinels for human bladder cancer associated with such exposures. Case-control study. 100 dogs with cancer of the urinary bladder and 100 control dogs. Case and control dogs were frequency-matched by age (within 2 years) and sex. Owners of dogs enrolled provided verbal informed consent and were interviewed by telephone. The telephone questionnaire included a complete residence history for each dog. Each dog's total exposure history to trihalomethanes was reconstructed from its residence history and corresponding drinking water utility company data. No association was detected between increasing years of exposure to chlorinated drinking water and risk of bladder cancer. Dogs with bladder cancer were exposed to higher total trihalomethanes concentrations than control dogs; however, the difference was not significant. Although humans and their dogs live in the same household, the activity patterns of dogs may lead to lower exposures to household tap water. Thus, although exposure to disinfection by-products in tap water may be a risk factor for human bladder cancer, this may not be true for canine bladder cancer at the concentrations at which dogs are exposed.

Combination of Foot Stimulation and Tramadol Treatment Reverses Irritation Induced Bladder Overactivity in Cats

PubMed Central

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

2013-01-01

Purpose We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity. Materials and Methods Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition. Results Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment. Conclusions This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects. PMID:23088991

Urinary tract infections and reduced risk of bladder cancer in Los Angeles.

PubMed

Jiang, X; Castelao, J E; Groshen, S; Cortessis, V K; Shibata, D; Conti, D V; Yuan, J-M; Pike, M C; Gago-Dominguez, M

2009-03-10

We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case-control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46-0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18-0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation.

Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study.

PubMed

Mesich, M L L; Mayhew, P D; Paek, M; Holt, D E; Brown, D C

2009-12-01

To investigate the relationship between endocrinopathies and diagnosis of gall bladder mucocele in dogs via a retrospective case-control study. Records of 78 dogs with a surgical or ultrasonographic diagnosis of gall bladder mucocele were examined for the presence or absence of hyperadrenocorticism, hypothyroidism and diabetes mellitus. Two age- and breed-matched controls for each gall bladder mucocele dog (156 total control dogs) were examined for the same concurrent diseases. A matched case-control analysis was performed using conditional logistic regression. The odds of mucocele in dogs with hyperadrenocorticism were 29 times that of dogs without hyperadrenocorticism (P=0.001; 95 per cent CI 3.8, 219.9). No difference was found between dogs with and without diabetes mellitus. Although a significant association was found between gall bladder mucocele and hypothyroidism, potential observation bias was also identifi ed. Hyperadrenocorticoid dogs that were presented for acute illness with laboratory evidence of hepatobiliary disease should undergo evaluation for the presence of a biliary mucocele. Dogs diagnosed with a gall bladder mucocele should be screened for concurrent hyperadrenocorticism if clinical suspicion exists.

Hysterectomy - Series (image)

MedlinePlus

... hysterectomy. If the bladder was involved, then a catheter may remain in place for 3 to 4 days to help the bladder pass urine. Moving about as soon as possible helps to avoid blood clots in the legs and other problems. Walking to ...

Exposure to polycyclic aromatic hydrocarbons (PAHs) and bladder cancer: evaluation from a gene-environment perspective in a hospital-based case-control study in the Canary Islands (Spain)

PubMed Central

Boada, Luis D; Henríquez-Hernández, Luis A; Navarro, Patricio; Zumbado, Manuel; Almeida-González, Maira; Camacho, María; Álvarez-León, Eva E; Valencia-Santana, Jorge A; Luzardo, Octavio P

2015-01-01

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to bladder cancer. Objective: To evaluate the role of PAHs in bladder cancer, PAHs serum levels were measured in patients and controls from a case-control study. Methods: A total of 140 bladder cancer patients and 206 healthy controls were included in the study. Sixteen PAHs were analyzed from the serum of subjects by gas chromatography–mass spectrometry. Results: Serum PAHs did not appear to be related to bladder cancer risk, although the profile of contamination by PAHs was different between patients and controls: pyrene (Pyr) was solely detected in controls and chrysene (Chry) was exclusively detected in the cases. Phenanthrene (Phe) serum levels were inversely associated with bladder cancer (OR = 0·79, 95%CI = 0·64–0·99, P = 0·030), although this effect disappeared when the allelic distribution of glutathione-S-transferase polymorphisms of the population was introduced into the model (multinomial logistic regression test, P = 0·933). Smoking (OR = 3·62, 95%CI = 1·93–6·79, P<0·0001) and coffee consumption (OR = 1·73, 95%CI = 1·04–2·86, P = 0·033) were relevant risk factors for bladder cancer. Conclusions: Specific PAH mixtures may play a relevant role in bladder cancer, although such effect seems to be highly modulated by polymorphisms in genes encoding xenobiotic-metabolizing enzymes. PMID:25291984

Human urinary bladder regeneration through tissue engineering - an analysis of 131 clinical cases.

PubMed

Pokrywczynska, Marta; Adamowicz, Jan; Sharma, Arun K; Drewa, Tomasz

2014-03-01

Replacement of urinary bladder tissue with functional equivalents remains one of the most challenging problems of reconstructive urology over the last several decades. The gold standard treatment for urinary diversion after radical cystectomy is the ileal conduit or neobladder; however, this technique is associated with numerous complications including electrolyte imbalances, mucus production, and the potential for malignant transformation. Tissue engineering techniques provide the impetus to construct functional bladder substitutes de novo. Within this review, we have thoroughly perused the literature utilizing PubMed in order to identify clinical studies involving bladder reconstruction utilizing tissue engineering methodologies. The idea of urinary bladder regeneration through tissue engineering dates back to the 1950s. Many natural and synthetic biomaterials such as plastic mold, gelatin sponge, Japanese paper, preserved dog bladder, lyophilized human dura, bovine pericardium, small intestinal submucosa, bladder acellular matrix, or composite of collagen and polyglycolic acid were used for urinary bladder regeneration with a wide range of outcomes. Recent progress in the tissue engineering field suggest that in vitro engineered bladder wall substitutes may have expanded clinical applicability in near future but preclinical investigations on large animal models with defective bladders are necessary to optimize the methods of bladder reconstruction by tissue engineering in humans.

The inhibitory effect of sacral dorsal root ganglion stimulation on nociceptive and nonnociceptive bladder reflexes in cats.

PubMed

Wang, Zhaoxia; Liao, Limin; Deng, Han; Li, Xing; Chen, Guoqing

2018-05-01

To investigate the inhibitory effects of electrical stimulation of sacral dorsal root ganglion (DRG) on bladder activity under non-nociceptive and nociceptive bladder conditions in cats. 12 cats were divided into non-nociceptive and nociceptive groups. Saline was used to distend the bladder and induce non-nociceptive bladder activity, while acetic acid (AA, 0.25%) was used to induce nociceptive bladder overactivity, S1 or S2 DRG stimulation was applied via a pair of hook electrodes placed in the right S1 and S2 DRG. In both non-nociceptive and nociceptive groups, stimulation at 3 and 5 Hz significantly increased bladder capacity (BC) and no significantly different between the two frequencies. In non-nociceptive group, S1 DRG stimulation at 3 Hz was as effective (increasing BC to 139.7 ± 5.6 and 166.9 ± 12.21% of control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 129.2 ± 5.6 and 160.5 ± 13.3% of control). In nociceptive group, AA reduced the BC to 62.6 ± 11.7% of saline control. S1 DRG stimulation at 3 Hz was also as effective (increasing BC to 54.9 ± 5.5 and 61.9 ± 6.0% of saline control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 58.3 ± 3.7 and 65.6 ± 3.7% of control). This study showed the effective inhibition on bladder activity under both non-nociceptive and nociceptive conditions, suggesting the possibility of sacral DRG stimulation to treat bladder overactivity.

Effects of vitamin D analog on bladder function and sensory signaling in animal models of cystitis.

PubMed

Shapiro, Bennett; Redman, T Lawton; Zvara, Peter

2013-02-01

To measure the effects of nonhypercalcemic vitamin D receptor agonist elocalcitol on bladder function in rats with cyclophosphamide-induced cystitis and on bladder function and sensory nerve activity in a mouse with acetic acid-evoked bladder irritation. Female Wistar rats and male Balb/C mice were gavaged once daily with elocalcitol diluted in miglyol 812 (treatment group) or miglyol alone (control group). On experimental day 12, polyethylene tubing was implanted into the urinary bladder in all the animals. In the mice, a bipolar electrode was positioned under a single postganglionic bladder nerve. At 48 hours after surgery, bladder function was measured in awake, freely moving rats during bladder filling with 0.9% NaCl and both bladder function and sensory nerve activity was measured in awake, restrained mice during continuous intravesical infusion of 0.9% NaCl followed by 0.25% acetic acid. In rats, the treatment group showed a significant increase in bladder capacity and decrease in number of nonvoiding bladder contractions. In mice, the filling pressure during saline infusion was similar in both groups; however, during acetic acid infusion, the average filling pressure was significantly increased (47%) in the control group but not in the elocalcitol treatment group. The firing rate at filling pressure for the treatment group was 3.6-fold and 2.7-fold lower than that in the control group during the saline and acetic acid infusion, respectively. Oral treatment with elocalcitol suppressed signs of detrusor overactivity in both animal models and exerted strong suppressive effect on urinary bladder sensory signaling during filling in mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Cytokine expression in patients with bladder pain syndrome/interstitial cystitis ESSIC type 3C.

PubMed

Logadottir, Yr; Delbro, Dick; Fall, Magnus; Gjertsson, Inger; Jirholt, Pernilla; Lindholm, Catharina; Peeker, Ralph

2014-11-01

Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls. Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-α, TGF-β and IFN-γ was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count. IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-α, TGF-β and IFN-γ mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C. Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model.

PubMed

Sasaki, Noboru; Ishi, Kazuhiro; Kudo, Nobuki; Nakayama, Shouta M M; Nakamura, Kensuke; Morishita, Keitaro; Ohta, Hiroshi; Ishizuka, Mayumi; Takiguchi, Mitsuyoshi

2017-01-01

Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.

A case-control study of diesel exhaust exposure and bladder cancer.

PubMed

Wynder, E L; Dieck, G S; Hall, N E; Lahti, H

1985-08-01

The relationship between bladder cancer and employment in occupations involving exposure to diesel exhaust was examined using data from a hospital-based case-control study of men aged 20 to 80 years in 18 hospitals in six U.S. cities, from January 1981 to May 1983. In this analysis, 194 cases and 582 controls were compared according to occupation, smoking history, alcohol and coffee consumption, and various demographic variables. No difference was found in the proportion of bladder cancer cases employed in occupations with exposure to diesel exhaust compared to controls. This relationship did not change after taking smoking habits into account. Bladder cancer cases were significantly more likely to be current smokers of cigarettes than were controls.

Dysfunctional elimination symptoms in childhood and adulthood.

PubMed

Bower, W F; Yip, S K; Yeung, C K

2005-10-01

The dysfunctional elimination syndrome (DES) is rare in adulthood. We evaluate the natural history of DES to identify aspects of the disorder that may be carried into adulthood. A 2-part questionnaire was devised and self-administered to 191 consecutive women attending a urogynecological clinic (UG) and to 251 normal women. The first section asked for recall of childhood symptoms known to be associated with DES, while the lat-ter section explored current bladder and bowel problems. Data sets from the normal cohort (55) reporting current bladder problems were excluded. Descriptive statistics, chi-square and Mann-Whitney-U tests were used to compare variables. UG patients had significantly higher childhood DES scores than normal women. Overall 41.7% of UG patients could be labeled as having dysfunctional elimination as an adult. Symptoms reported significantly more often in childhood by UG patients than by control women were frequent urinary tract infection, vesicoureteral reflux, frequency, urge incontinence, slow and intermittent urine flow, small volume high urge voids, hospitalization for constipation, frequent fecal soiling and nocturnal enuresis. Higher DES scores correlated significantly with current adult urgency, urge leak, stress incontinence, incomplete emptying, post-void leak, hesitancy, nocturia and nocturnal enuresis. Constipation and fecal incontinence in adulthood also showed a significant association with high DES scores. Logistic regression revealed childhood urgency to be associated with adult DES. Childhood lower urinary tract dysfunction may have a negative impact on bladder and bowel function later life.

Cerebral control of the lower urinary tract: How age-related changes might predispose to urge incontinence

PubMed Central

Griffiths, D.; Tadic, S.D.; Schaefer, W.; Resnick, N.M.

2009-01-01

Loss of bladder control (urge incontinence) is common in elderly; the cause is usually unknown. Functional imaging has revealed the brain network controlling responses to bladder filling. Age-related changes in this network might predispose to urge incontinence. We sought such changes in 10 continent, healthy women aged 30 – 79 years who underwent fMRI while fluid (20 ml) was repeatedly infused into and withdrawn from the bladder. Data were collected in 4 measurement blocks with progressively increasing bladder volumes and were analyzed by SPM2, using the contrast infuse-withdraw to quantify response to bladder infusion. Effective connectivity was examined by physiophysiological interaction (PhPI; see interpretation in Supplementary Material), with right insula (RI) and dorsal anterior cingulate cortex (dACC) as seed regions. Dependence on age and bladder volume (=block number) was assessed. Bladder infusion evoked expected activations. Activation decreased with age in bilateral insula and dACC. PhPI revealed connectivity with RI and dACC in regions that included bilateral putamen and R pontine micturition center. Interaction (connectivity) tended to increase with age in regions including L insula, L paracentral lobule and PAG. Consistent with a special role in maintaining continence, medial prefrontal cortex (mPFC) showed a trend to deactivation on bladder infusion that became more prominent in old age, and a trend to negative interaction (connectivity) that weakened significantly with age. Thus, with increasing age, weaker signals in the bladder control network as a whole and/or changes in mPFC function or connecting pathways may be responsible for the development of urge incontinence. PMID:19427909

Guillain-Barré Syndrome: Prevalence and Long-Term Factors Impacting Bladder Function in an Australian Community Cohort

PubMed Central

Khan, Fary; Whishaw, Michael; Pallant, Julie F.

2013-01-01

Background and Purpose Urinary dysfunction is associated with significant morbidity in persons with Guillain-Barré Syndrome (GBS). The aim of this study was to describe prevalence and long-term impact of bladder dysfunction on daily activities and quality of life (QoL) in persons in chronic phase of GBS and to examine the relationships between commonly used continence measures in this cohort. Methods Prospective cohort (n=66) following GBS treatment (1996-2009) was recruited from a tertiary hospital and assessed using standardised measures for bladder dysfunction: American Urological Association (AUA) Symptom Index, Incontinence Impact Questionnaire, Urogenital Distress Inventory. Results Sixty-six participants (64% male, mean age 56 years, median disease duration of 6.1 years) completed the study. Of these more than half reported nocturia and one-third reported urinary urgency and frequency. Urinary problems impacted on participants' daily activities: physical recreation (21%), emotional health and mood (17%), entertainment (14%), participation and mobility (>30 min) (12%), and performance of household chores (8%). Since GBS, 49% reported interference of urinary symptoms with daily life to some extent; and adverse impact on QoL (10.6%). Significant relationship between bladder symptoms; and the level of urogenital distress (p<0.001) and the impact of urinary problems (p<0.001), was noted. Higher scores on the bladder scales showed significant correlations with psychological, functional and participation scales. The single QoL item (AUA scale) correlated significantly with all other bladder scales (rho=0.63-0.86). This can be a potential 'screening tool' to identify patients for further assessment. Conclusions Bladder dysfunction in chronic phase of GBS is not well studied. More research in longer-term screening and outcomes for bladder intervention are needed for integrated care and to guide treating clinicians. PMID:23894237

Therapeutic efficacy of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome.

PubMed

Kajiwara, Mitsuru; Inoue, Shougo; Kobayashi, Kanao; Ohara, Shinya; Teishima, Jun; Matsubara, Akio

2014-04-01

Narrow band imaging cystoscopy can increase the visualization and detection of Hunner's lesions. A single-center, prospective clinical trial was carried out aiming to show the effectiveness of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome. A total of 23 patients (19 women and 4 men) diagnosed as having ulcer-type interstitial cystitis/painful bladder syndrome were included. All typical Hunner's lesions and suspected areas identified by narrow band imaging were electrocoagulated endoscopically after the biopsy of those lesions. Therapeutic efficacy was assessed prospectively by using visual analog scale score of pain, O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score. The mean follow-up period was 22 months. All patients (100%) experienced a substantial improvement in pain. The average visual analog scale pain scores significantly decreased from 7.3 preoperatively to 1.2 1 month postoperatively. A total of 21 patients (91.3%) who reported improvement had at least a 50% reduction in bladder pain, and five reported complete resolution. Daytime frequency was significantly decreased postoperatively. O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score were significantly decreased postoperatively. However, during the follow-up period, a total of six patients had recurrence, and repeat narrow band imaging-assisted transurethral electrocoagulation of the recurrent lesions was carried out for five of the six patients, with good response in relieving bladder pain. Our results showed that narrow band imaging-assisted transurethral electrocoagulation could be a valuable therapeutic alternative in patients with ulcer-type interstitial cystitis/painful bladder syndrome, with good efficacy and reduction of recurrence rate. © 2014 The Japanese Urological Association.

Bladder control, urgency, and urge incontinence: evidence from functional brain imaging.

PubMed

Griffiths, Derek; Tadic, Stasa D

2008-01-01

To review brain imaging studies of bladder control in subjects with normal control and urge incontinence; to define a simple model of supraspinal bladder control; and to propose a neural correlate of urgency and possible origins of urge incontinence. Review of published reports of brain imaging relevant to urine storage, and secondary analyses of our own recent observations. In a simple model of normal urine storage, bladder and urethral afferents received in the periaqueductal gray (PAG) are mapped in the insula, forming the basis of sensation; the anterior cingulate gyrus (ACG) provides monitoring and control; the prefrontal cortex makes voiding decisions. The net result, as the bladder fills, is inhibition of the pontine micturition center (PMC) and of voiding, together with gradual increase in insular response, corresponding to increasing desire to void. In urge-incontinent subjects, brain responses differ. At large bladder volumes and strong sensation, but without detrusor overactivity (DO), most cortical responses become exaggerated, especially in ACG. This may be both a learned reaction to previous incontinence episodes and the neural correlate of urgency. The neural signature of DO itself seems to be prefrontal deactivation. Possible causes of urge incontinence include dysfunction of prefrontal cortex or limbic system, suggested by weak responses and/or deactivation, as well as abnormal afferent signals or re-emergence of infantile reflexes. Bladder control depends on an extensive network of brain regions. Dysfunction in various parts may contribute to urge incontinence, suggesting that there are different phenotypes requiring different treatments. (c) 2007 Wiley-Liss, Inc.

Artificial sweeteners and absence of bladder cancer risk in Copenhagen.

PubMed

Møller-Jensen, O; Knudsen, J B; Sørensen, B L; Clemmesen, J

1983-11-15

During the years 1979 to 1981 a population-based case-control study of bladder cancer including papillomas was performed in Greater Copenhagen. After exclusions some 388 patients (290 males; 98 females) and an age- and sex-matched group of 787 controls (592 males; 195 females) remained for analysis. Controls were selected at random from the general population of the study area. All persons were interviewed concerning use of artificial sweeteners in addition to their exposure to a number of other known or suspected risk factors for bladder cancer. Fifty-five male bladder cancer patients (19.4%) and 150 controls (25.7%) had at some time used artificial sweeteners regularly. Among females 27.1% of cases and 25.9% of controls regularly used sweeteners. In neither sex was the relative risk significantly increased in users compared with non-users of artificial sweeteners. The relative risk of 0.78 in the two sexes combined was not significantly different from 1.0 (95% C.I.: 0.58-1.05). There was no indication of a regular increase in risk with increasing daily consumption of table-top sweeteners nor was there any indication of an increase in risk with a duration of regular use of artificial sweeteners. Taking into account a possible latency period between first regular use and bladder cancer development did not change the finding of an absence of association between use of artificial sweeteners and the risk of bladder cancer. Neither saccharine nor cyclamate users had an increased risk of bladder cancer. This population-based case-control investigation provides further evidence that it is highly unlikely that the consumption of artificial sweeteners has contributed to current bladder cancer rates in man.

The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study.

PubMed

Coyne, Karin S; Sexton, Chris C; Irwin, Debra E; Kopp, Zoe S; Kelleher, Con J; Milsom, Ian

2008-06-01

To examine the effect overactive bladder (OAB) and other lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a population sample, as OAB often occurs in conjunction with many other LUTS. A nested case-control analysis was performed on men and women with (cases) and without (controls) OAB, from the EPIC study. OAB was assessed using 2002 International Continence Society definitions. Based on their responses to questions about LUTS, cases were classified into five groups; continent OAB, OAB with incontinence, OAB + postmicturition, OAB + voiding, and OAB + postmicturition + voiding. Both cases and controls were asked questions about symptom bother (OAB-q), generic QoL (EQ-5D), work productivity (Work Productivity and Activity Impairment, WPAI), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sexual satisfaction, and erectile dysfunction (men only) using the Massachusetts Male Aging Study. Cases answered additional condition-specific questions HRQoL (OAB-q short form), Patient Perception of Bladder Condition and work productivity related to a specific health problem (WPAI-SHP). General linear models were used to evaluate group differences. Of the EPIC participants, 1434 identified OAB cases were matched by age, gender and country, with 1434 participants designated as controls. Cases and controls were primarily Caucasian (96.2% and 96.7%, respectively), and most (65%) were female; the mean age was 53.8 and 53.7 years, respectively. Comorbid conditions differed significantly by case/control status, with cases reporting significantly greater rates of chronic constipation, asthma, diabetes, high blood pressure, bladder or prostate cancer, neurological conditions and depression. There were significant differences between the cases and controls in all reported LUTS. The OAB + postmicturition + voiding group reported significantly greater symptom bother, worse HRQoL, higher rates of depression and decreased enjoyment of sexual activity, than the other subgroups. OAB has a substantial, multidimensional impact on patients; OAB with additional LUTS has a greater impact. The diagnosis and treatment of OAB should be considered in conjunction with other LUTS, to maximize treatment options and optimize patient outcomes.

Fluorescent imaging of high-grade bladder cancer using a specific antagonist for chemokine receptor CXCR4.

PubMed

Nishizawa, Koji; Nishiyama, Hiroyuki; Oishi, Shinya; Tanahara, Noriko; Kotani, Hirokazu; Mikami, Yoshiki; Toda, Yoshinobu; Evans, Barry J; Peiper, Stephen C; Saito, Ryoichi; Watanabe, Jun; Fujii, Nobutaka; Ogawa, Osamu

2010-09-01

We previously reported that the expression of CXC chemokine receptor-4 (CXCR4) was upregulated in invasive bladder cancers and that the small peptide T140 was a highly sensitive antagonist for CXCR4. In this study, we identified that CXCR4 expression was induced in high-grade superficial bladder tumors, including carcinoma in situ and invasive bladder tumors. To visualize the bladder cancer cells using urinary sediments from the patients and chemically induced mouse bladder cancer model, a novel fluorescent CXCR4 antagonist TY14003 was developed, that is a T140 derivative. TY14003 could label bladder cancer cell lines expressing CXCR4, whereas negative-control fluorescent peptides did not label them. When labeling urinary sediments from patients with invasive bladder cancer, positive-stained cells were identified in all patients with bladder cancer and positive urine cytology but not in controls. Although white blood cells in urine were also labeled with TY14003, they could be easily discriminated from urothelial cells by their shape and size. Finally, intravesical instillation of TY14003 into mouse bladder, using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer model, demonstrated that fluorescent signals were detected in the focal areas of bladder of all mice examined at 12 weeks of BBN drinking by confocal microscopy and fluorescent endoscopy. On the contrary, all the normal bladders were found to be negative for TY14003 staining. In conclusion, these results indicate that TY14003 is a promising diagnostic tool to visualize small or flat high-grade superficial bladder cancer.

Detrusor underactivity and the underactive bladder: Symptoms, function, cause-what do we mean? ICI-RS think tank 2014.

PubMed

Smith, Phillip P; Birder, Lori A; Abrams, Paul; Wein, Alan J; Chapple, Chris R

2016-02-01

Impaired bladder emptying is a well-recognized cause of lower urinary tract symptoms. However, the symptoms produced do not always relate to voiding, and may include frequency, urgency and incontinence. Conversely, the etiology of symptoms of disturbed voiding is not necessarily dependent upon objectively impaired voiding. Terms including underactive bladder, detrusor underactivity, and impaired contractility describe aspects of these problems, and have been used somewhat interchangeably. It is possible that the present lack of effective therapy in many cases relates to both etiologic and diagnostic uncertainty stemming from terminologic imprecision. Detrusor underactivity has a standardized definition, unlike underactive bladder and impaired contractility. The relationships of symptoms, function, and cause were the focus of a 2014 ICI-RS Think Tank entitled Does Detrusor Underactivity Exist, and if so it is neurogenic, myogenic, or both? This review presents a summary of the problem and the Think Tank conclusions. A terminologic hierarchy and specific research goals are presented. © 2016 Wiley Periodicals, Inc.

The Curie–Da Vinci Connection: 5-Years' Experience With Laparoscopic (Robot-Assisted) Implantation for High-Dose-Rate Brachytherapy of Solitary T2 Bladder Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steen-Banasik, Elzbieta M. van der, E-mail: E.vanderSteen-Banasik@radiotherapiegroep.nl; Smits, Geert A.H.J.; Oosterveld, Bernard J.

Purpose: To report experience and early results of laparoscopic implantation for interstitial brachytherapy (BT) of solitary bladder tumors and the feasibility of a high-dose-rate (HDR) schedule. Methods and Materials: From December 2009 to April 2015, 57 patients with a T2 solitary bladder tumor were treated in Arnhem with transurethral bladder resection followed by external beam irradiation, applied to the bladder and regional iliac lymph nodes, 40 Gy in 20 fractions, 5 fractions per week, and within 1 week interstitial HDR BT, in selected cases combined with partial cystectomy and lymph node dissection. The BT catheters were placed via a transabdominal approach withmore » robotic assistance from a Da Vinci robot after a successful initial experience with a nonrobotic laparoscopic approach. The fraction schedule for HDR was 10 fractions of 2.5 Gy, 3 fractions per day. This was calculated to be equivalent to a reference low-dose-rate schedule of 30 Gy in 60 hours. Data for oncologic outcomes and toxicity (Common Toxicity Criteria version 4) were prospectively collected. Results: These modifications resulted in an average postoperative hospitalization of 6 days, minimal blood loss, and no wound healing problems. Two patients had severe acute toxicity: 1 pulmonary embolism grade 4 and 1 cardiac death. Late toxicity was mild (n=2 urogenital grade 3 toxicity). The median follow-up was 2 years. Using cumulative incidence competing risk analysis, the 2-year overall, disease-free, and disease-specific survival and local control rates were 59%, 71%, 87%, and 82%, respectively. Conclusions: The benefits of minimally invasive surgery for implantation of BT catheters and the feasibility of HDR BT in bladder cancer are documented. The patient outcome and adverse events are comparable to the best results published for a bladder-sparing approach.« less

Bladder function - neurological control

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... 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 ...

Barriers to physical activity and healthy eating in young breast cancer survivors: modifiable risk factors and associations with body mass index.

PubMed

Ventura, Emily E; Ganz, Patricia A; Bower, Julienne E; Abascal, Liana; Petersen, Laura; Stanton, Annette L; Crespi, Catherine M

2013-11-01

Physical activity (PA) and healthy eating (HE) are important behaviors to encourage in breast cancer survivors (BCS). We examined associations between various factors and barriers to PA (BPA) and barriers to HE (BHE), as well as relationships between barriers and body mass index (BMI) in younger BCS. Self-reported data from 162 BCS (mean age 48 years) were used. BPA were assessed with a 21-item scale and BHE with a 19-item scale. Participants were classified as high or low on each scale. Sociodemographic, medical, and psychosocial characteristics were compared by high/low barriers. Correlates of continuous BPA and BHE were assessed as were associations among BHE, BPA, and BMI. 61 % of participants were characterized as having low BHE and low BPA; 12 % were high for both. High BHE/high BPA participants had the least favorable scores for depression, perceived stress, social support, fatigue, bladder control, and weight problems. Factors associated with BHE were lower education, higher perceived stress, and more severe weight problems. Factors associated with BPA were more severe bladder control problems and lower physical well-being. Higher BHE and BPA were significantly and uniquely associated with higher BMI, controlling for covariates. Several biopsychosocial factors (e.g., depression, stress, and fatigue) characterize young BCS who experience barriers to both HE and PA. The correlates of BHE and BPA are distinct. Both BHE and BPA are associated with BMI. These results should be considered in designing interventions for younger women with breast cancer.

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

HAMLET treatment delays bladder cancer development.

PubMed

Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

2010-04-01

HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Total Fluid and Water Consumption and the Joint Effect of Exposure to Disinfection By-Products on Risk of Bladder Cancer

PubMed Central

Michaud, Dominique S.; Kogevinas, Manolis; Cantor, Kenneth P.; Villanueva, Cristina M.; Garcia-Closas, Monteserrat; Rothman, Nathaniel; Malats, Nuria; Real, Francisco X.; Serra, Consol; Garcia-Closas, Reina; Tardon, Adonina; Carrato, Alfredo; Dosemeci, Mustafa; Silverman, Debra T.

2007-01-01

Background Findings on water and total fluid intake and bladder cancer are inconsistent; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case–control studies observed a positive association between tap water and bladder cancer but none for nontap fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk. Objectives We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case–control study in Spain. Methods A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders. Results Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0.62; 95% confidence interval (CI), 0.40–0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47; 95% CI, 0.33–0.66; p for trend < 0.0001), but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure; we found no statistical interaction (p for interaction = 0.13). Conclusion Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level. PMID:18007986

Progressive vascular damage may lead to bladder underactivity in rats.

PubMed

Nomiya, Masanori; Yamaguchi, Osamu; Akaihata, Hidenori; Hata, Junya; Sawada, Norifumi; Kojima, Yoshiyuki; Andersson, Karl-Erik

2014-05-01

We assessed whether progressive vascular damage causes bladder underactivity in rats. Adult male Sprague Dawley® rats were divided into 4 groups. Controls received a regular diet and tap water. The L-NAME group received a 2% cholesterol diet and L-NAME (3 mg/ml) dissolved in drinking water. The arterial injury group underwent balloon endothelial injury of the common iliac arteries and received a 2% cholesterol diet and tap water after injury. The arterial injury/L-NAME group also received L-NAME dissolved in drinking water. At 8 weeks urodynamics were performed, bladder tissue was harvested for pharmacological studies, and the iliac arteries and bladders were histologically examined. Iliac arteries from the injury and injury/L-NAME groups showed neointimal formation and luminal occlusion but arteries from the L-NAME group did not. In the L-NAME and injury groups bladder capacity and voided volume were less than in controls. Conversely, in the injury/L-NAME group these cystometric parameters were significantly greater than in the other groups. Post-void residual volume in the injury/L-NAME group tended to increase compared with the other groups. Contractile responses of bladder strips to various stimuli in the L-NAME, injury and injury/L-NAME groups were significantly less than in controls and the lowest in the injury/L-NAME group. The injury and injury/L-NAME groups showed a significantly increased percent of collagen compared to controls. Pelvic arterial occlusive disease plus vascular endothelial dysfunction may cause progressive vascular damage resulting in bladder dysfunction that develops from bladder hyperactivity to bladder underactivity. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Mechanisms of Visceral Organ Crosstalk: Importance of Alterations in Permeability in Rodent Models

PubMed Central

Greenwood-Van Meerveld, B; Mohammadi, E; Tyler, K; Van Gordon, S; Parker, A; Towner, R; Hurst, R

2015-01-01

Purpose The pathophysiology of painful bladder syndrome (PBS) is poorly understood; however, there is evidence of female predominance and comorbidity with irritable bowel syndrome (IBS). Our hypothesis is that cross-sensitization between the bladder and colon is due to altered permeability in one organ affecting the other organ. Materials and methods Experiments were performed in anesthetized, ovariectomized (OVX) female rats. In separate groups, protamine sulfate was infused into the bladder or TNBS was infused into the colon, with untreated rats serving as controls. Both bladder and colonic tissue were harvested for all rats at 1, 3, and 5 days post-treatment. Permeability was assessed in vitro in Ussing chambers via measurements of transepithelial electrical resistance (TEER) and macromolecular flux of Fluorescein isothiocyanate (FITC)-4 dextran. Results Exposing the bladder to protamine sulfate induced a significant (p<0.05) decrease in bladder TEER and an increase in the translocation of FITC across the tissue compared to controls at 1 and 3 days. Colonic tissue from rats with enhanced bladder permeability exhibited a significant (p<0.05) decrease in TEER and increase in FITC when compared to untreated controls at all time points. Conversely, when colonic permeability was increased with TNBS, we observed an increase in bladder permeability in the absence of any changes to the bladder urothelium. Conclusions Changes in epithelial permeability may represent a novel mechanism for visceral organ crosstalk and may explain the overlapping symptomology of PBS and IBS. PMID:25776913

Repeated onabotulinumtoxin-a injections provide better results than single injection in treatment of painful bladder syndrome.

PubMed

Kuo, Hann-Chorng

2013-01-01

Onabotulinumtoxin-A (BoNT-A) is effective for the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS). However, long-term follow-up does not show successful outcome after a single injection. To evaluate the efficacy and safety of repeated intravesical BoNT-A injections for treatment of IC/PBS and compare the success rates among patient groups receiving different injection numbers. Prospective interventional study. Tertiary medical center. Intravesical injection of 100 U of BoNT-A was performed in 81 patients every 6 months for up to 4 times or until patients' symptoms significantly improved. Patients who received a single injection served as active controls. Measured parameters included O'Leary-Sant symptom indexes (ICSI) and problem indexes (ICPI), visual analogue score (VAS) for pain, voiding diary variables, urodynamic parameters, maximal bladder capacity under anesthesia, glomerulation grade, and global response assessment. Multiple measurements and Kaplan-Meier analysis were used for comparison of consecutive data and success rates among groups. Among 81 patients, 20 received single injections, 19 received 2 injections, 12 received 3 injections, and 30 received 4 injections. The mean (± standard deviation) of ICSI, ICPI, total scores, VAS, functional bladder capacity, and daytime frequency all showed significant improvement after repeated BoNT-A treatment with different injections. Significantly better success rates were noted in patients who received 4 repeated injections (P = 0.0242) and 3 injections (P = 0.050), compared to those who received a single injection. However, there was no significant difference of long-term success rates among patients who received 2, 3, and 4 injections. Lack of placebo control group is the main limitation. Repeated intravesical BoNT-A injections were safe and effective for pain relief and they increased bladder capacity and provided a better long-term success rate than a single injection did for treatment of IC/PBS.

Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy.

PubMed

Wognum, S; Bondar, L; Zolnay, A G; Chai, X; Hulshof, M C C M; Hoogeman, M S; Bel, A

2013-02-01

Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumor and the lack of visible anatomical landmarks for validation. The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight parameters were determined for the weighted S-TPS-RPM. The weighted S-TPS-RPM registration algorithm with optimal parameters significantly improved the anatomical accuracy as compared to S-TPS-RPM registration of the bladder alone and reduced the range of the anatomical errors by half as compared with the simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. The weighted algorithm reduced the RDE range of lipiodol markers from 0.9-14 mm after rigid bone match to 0.9-4.0 mm, compared to a range of 1.1-9.1 mm with S-TPS-RPM of bladder alone and 0.9-9.4 mm for simultaneous nonweighted registration. All registration methods resulted in good geometric accuracy on the bladder; average error values were all below 1.2 mm. The weighted S-TPS-RPM registration algorithm with additional weight parameter allowed indirect control over structure-specific flexibility in multistructure registrations of bladder and bladder tumor, enabling anatomically coherent registrations. The availability of an anatomically validated deformable registration method opens up the horizon for improvements in IGART for bladder cancer.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Occupational risk of bladder cancer among Iranian male workers

PubMed Central

Aminian, Omid; Saburi, Amin; Mohseni, Hossein; Akbari, Hamed; Chavoshi, Farzaneh; Akbari, Hesam

2014-01-01

Background: Approximately 5-10% of human cancers are thought to be caused by occupational exposure to carcinogens. Compare to other cancers, bladder cancer is most strongly linked to occupational exposure to chemical toxins. This study has been performed to understand which occupations and exposures are related to bladder cancer in Iran. Materials and Methods: This study is a case-control study which is conducted on cases with bladder cancer (160 cases) diagnosed in Baharlou hospital in 2007-2009. One hundred sixty cases without any occupational exposure were considered as controls matched for demographic characteristics. Demographic data and characteristics of occupation were compared. Results: Mean age of cases and controls were 63.7 and 64 years, respectively (P = 0.841). History of urinary tract stone had significantly difference in two groups (P = 0.039). Occupations such as bus and truck driving, road and asphalt making, mechanics, working in refinery and Petrochemical, plastic, metal manufactory, welding, and pipeline founded a higher risk for bladder cancer rather than controls. Conclusion: Our findings on Iranian workers are concurrent and compatible with findings of previous reports about occupational and environmental risk factors of bladder cancer. Although our study population was PMID:24833825

Plasticity in reflex pathways to the lower urinary tract following spinal cord injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2013-01-01

The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs. PMID:21596038

Nitrate in drinking water and risk of death from bladder cancer: an ecological case-control study in Taiwan.

PubMed

Chiu, Hui-Fen; Tsai, Shang-Shyue; Yang, Chun-Yuh

2007-06-01

The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41-2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer.

Development of upper tract stones in patients with congenital neurogenic bladder.

PubMed

Stephany, Heidi A; Clayton, Douglass B; Tanaka, Stacy T; Thomas, John C; Pope, John C; Brock, John W; Adams, Mark C

2014-02-01

Patients with neurogenic bladder are at increased risk of developing upper tract stones. We hypothesized that patients with lower urinary tract stone disease are at greater risk of developing upper tract stones. We performed a 10-year retrospective case-control study of patients with neurogenic bladder to determine the association between bladder and upper tract stones. Independent risk factors for upper tract stones were assessed. Cases and controls were matched 1:1. Univariable analysis was performed by Fisher's exact test and the Mann-Whitney U test. Multivariable logistic regression was performed. 52 cases and controls were identified. Cases were significantly more likely to be non-ambulatory, have bowel-urinary tract interposition, thoracic level dysraphism, and history of bladder stones. On multivariable analysis, independent predictors of stone formation were male sex (OR 2.82; p = 0.02), dysraphism involving the thoracic spine (OR 3.37; p = 0.014) bowel-urinary tract interposition (OR 2.611; p = 0.038), and a history of bladder stones (OR 3.57; p = 0.015). Patients with neurogenic bladder are at increased risk for upper tract stones. The presence of bladder stones may herald the development of upper tract stones. The predictors of stone disease identified should guide prospective studies to better understand the natural history of upper tract stone development in this population. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Common theme for drugs effective in overactive bladder treatment: Inhibition of afferent signaling from the bladder

PubMed Central

Hood, Brandy; Andersson, Karl-Erik

2013-01-01

The overactive bladder syndrome and detrusor overactivity are conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are still first-line treatment. These drugs often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium/suburothelium, the autonomous detrusor muscle activity during bladder filling and the diversity of nerve transmitters involved has sparked interest in both peripheral and central modulation of overactive bladder syndrome/detrusor overactivity pathophysiology. Three drugs recently approved for treatment of overactive bladder syndrome/detrusor overactivity (mirabegron, tadalafil and onabotulinum toxin A), representing different pharmacological mechanisms; that is, β-adrenoceptor agonism, phosphodiesterase type 5 inhibition, and inhibition of nerve release of efferent and afferent transmitters, all seem to have one effect in common: inhibition of the afferent nervous activity generated by the bladder during filling. In the present review, the different mechanisms forming the pharmacological basis for the use of these drugs are discussed. PMID:23072271

Hematuria and clot retention after transvaginal oocyte aspiration: a case report.

PubMed

Modder, Joshua; Kettel, L Michael; Sakamoto, Kyoko

2006-09-01

To report a case of bladder injury with hematuria and urinary retention after transvaginal oocyte aspiration. Case report. Emergency room in a university medical center. A 28-year-old woman presented with urinary retention and suprapubic pain 8 hours after oocyte aspiration. Foley catheter, intravenous fluid bolus, bladder irrigation, and computed tomography with postvoid films that showed a blood clot in the bladder. Patient was discharged home with antibiotics and catheter in place. Clinical follow-up. Patient passed voiding trial 4 days later and was artificially inseminated. No further hematuria or voiding problems were reported, and she had a successful pregnancy. Patients who elect to undergo oocyte aspiration should be warned about the possibility of bladder injury because of the close proximity of the ovaries to the bladder, and physicians should have an appropriate treatment plan.

Modulation of gene expression and cell-cycle signaling pathways by the EGFR inhibitor gefitinib (Iressa) in rat urinary bladder cancer.

PubMed

Lu, Yan; Liu, Pengyuan; Van den Bergh, Francoise; Zellmer, Victoria; James, Michael; Wen, Weidong; Grubbs, Clinton J; Lubet, Ronald A; You, Ming

2012-02-01

The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 × 10(-15) (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 × 10(-42) (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 × 10(-8) and r = 0.73, P = 1.50 × 10(-65), respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. ©2011 AACR.

[Post-operative course in tetraplegics after urological surgers (author's transl)].

PubMed

Vigreux, G; Vacant, J; Lepresle, E; Desalle De Hys, C; Debras, C

1976-06-01

The authors report their experience with 33 tetraplegics undergoing surgery. The operations were varied, endoscopic (resection of the bladder neck, of the prostate or striate sphincter, lithot-itiasis) or surgical (lombotomies, transintentinal cutaneous ureterostomies). The post-operative course may be dramatic or even fatal (acute hypertension with cerebral haemorrhage). Respiratory insufficiency poses no particular problem and can be controlled. Epidural anaesthesia maintained for several days makes it possible to avoid the more serious problems: -- autonomic hyperreflectivity, -- delayed resolution of ileus and digestive complication. The authors hence use epidural anaesthesia routinely and are satisfied with the technique.

Spine immobilization apparatus

NASA Technical Reports Server (NTRS)

Lambson, K. H.; Vykukal, H. C. (Inventor)

1981-01-01

The apparatus makes use of a normally flat, flexible bladder filled with beads or micro-balloons that form a rigid mass when the pressure within the bladder is decreased below ambient through the use of a suction pump so that the bladder can be conformed to the torso of the victim and provide the desired restraint. The bladder is strapped to the victim prior to being rigidified by an arrangement of straps which avoid the stomach area. The bladder is adapted to be secured to a rigid support, i.e., a rescue chair, so as to enable removal of a victim after the bladder has been made rigid. A double sealing connector is used to connect the bladder to the suction pump and a control valve is employed to vary the pressure within the bladder so as to soften and harden the bladder as desired.

Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wognum, S.; Chai, X.; Hulshof, M. C. C. M.

2013-02-15

Purpose: Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumormore » and the lack of visible anatomical landmarks for validation. Methods: The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight parameters were determined for the weighted S-TPS-RPM. Results: The weighted S-TPS-RPM registration algorithm with optimal parameters significantly improved the anatomical accuracy as compared to S-TPS-RPM registration of the bladder alone and reduced the range of the anatomical errors by half as compared with the simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. The weighted algorithm reduced the RDE range of lipiodol markers from 0.9-14 mm after rigid bone match to 0.9-4.0 mm, compared to a range of 1.1-9.1 mm with S-TPS-RPM of bladder alone and 0.9-9.4 mm for simultaneous nonweighted registration. All registration methods resulted in good geometric accuracy on the bladder; average error values were all below 1.2 mm. Conclusions: The weighted S-TPS-RPM registration algorithm with additional weight parameter allowed indirect control over structure-specific flexibility in multistructure registrations of bladder and bladder tumor, enabling anatomically coherent registrations. The availability of an anatomically validated deformable registration method opens up the horizon for improvements in IGART for bladder cancer.« less

Foods and risk of bladder cancer: a case-control study in Uruguay.

PubMed

Balbi, J C; Larrinaga, M T; De Stefani, E; Mendilaharsu, M; Ronco, A L; Boffetta, P; Brennan, P

2001-10-01

A case-control study on 144 cases of transitional cell bladder carcinoma and 576 hospitalized controls was conducted in Montevideo, Uruguay. Barbecued meat, salted meat and fried eggs were associated with significant increased risks of bladder cancer (odds ratio (OR) for high intake of salted meat 4.04, 95% confidence interval (CI) 2.24-7.27). On the other hand, all fruits, cooked vegetables, potatoes and cheese were associated with inverse associations (OR for high consumption of potatoes 0.38, 95% CI 0.23-0.64). The associations with salted and barbecued meat suggest that the way of preserving or cooking meat play a role in bladder carcinogenesis. More precisely, N-nitroso compounds and heterocyclic amines could be involved in this process.

Manipulating the extracellular matrix: an animal model of the bladder pain syndrome.

PubMed

Offiah, Ifeoma; Didangelos, Athanasios; OʼReilly, Barry A; McMahon, Stephen B

2017-01-01

Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.

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.

N-acetyltransferase 1*10 genotype in bladder cancer patients.

PubMed

Höhne, Svetlana; Gerullis, Holger; Blaszkewicz, Meinolf; Selinski, Silvia; Hengstler, Jan G; Otto, Thomas; Golka, Klaus

2017-01-01

In a large bladder cancer study in the greater Berlin area with 425 cases and 343 controls, the haplotype N-acetyltransferase 1*10 (NAT1*10) was associated with a decreased bladder cancer risk. In a recently published meta-analysis, results of the studies were found to be inconclusive. Therefore, the aim of this study was to investigate the frequency of NAT1*10 in bladder cancer patients and controls recruited in an area without industries reported to be associated with increased bladder cancer risk. Rs1057126 (1088 T > A) and rs15561 (1095 C > A) were determined in 412 bladder cancer patients and 415 controls without a known history of malignancies. With these two single-nucleotide polymorphisms (SNP), it was possible to distinguish between NAT1*4 (wild type), NAT1*3 (1095 C > A), and NAT1*10 (1088 T > A, 1095C > A). The frequencies of the determined NAT1 haplotypes did not differ markedly between cases and controls: NAT1*4: 74%, NAT1*3: 6%, NAT1*10: 20%. Bladder cancer risk was not significantly modulated by NAT1*10/*10 (OR 1.03, 95% CI 0.71-1.48) but was higher for NAT1*3/*3 genotypes (OR 2.05, 95% CI 1.32-3.21). In contrast to the Berlin study from 2001, data in present study demonstrated that NAT1*10 haplotype was not associated with a significantly decreased bladder cancer risk. This may be due to local effects in the greater Berlin area, particularly at the time of investigation. The findings of the present study are in agreement with observations of a recently published meta-analysis which also showed no relevant impact of NAT1*10 haplotype on bladder cancer risk. The impact of the rare NAT1*3/*3 genotype was significant but this may be attributed to rarity without major practical relevance.

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer

PubMed Central

Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Gerullis, Holger; Otto, Thomas; Roth, Emanuel; Volkert, Frank; Ovsiannikov, Daniel; Moormann, Oliver; Banfi, Gergely; Nyirady, Peter; Vermeulen, Sita H; Garcia-Closas, Montserrat; Figueroa, Jonine D; Johnson, Alison; Karagas, Margaret R; Kogevinas, Manolis; Malats, Nuria; Schwenn, Molly; Silverman, Debra T; Koutros, Stella; Rothman, Nathaniel; Kiemeney, Lambertus A; Hengstler, Jan G; Golka, Klaus

2017-01-01

Abstract Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case–control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case–control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93–3.47; P = 1.87 × 10−10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10–2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers. PMID:29028944

Local anaesthetic 5-aminolaeuvulinic acid photodynamic therapy in the treatment of superficial bladder cancer

NASA Astrophysics Data System (ADS)

Shackley, David C.

The aim of this thesis was to study aspects of the treatment of superficial bladder carcinoma using photodynamic therapy by combining the delivery of laser light energy with the photosensitiser 5-aminolaeuvulinic acid (ALA). ALA is a novel pro-drug, which can be absorbed intravesically where it is converted in diseased urothelium and tumour to the active photosensitiser, PpK. Following whole bladder light irradiation there is release of toxic radicals, which are scavenged by oxygen causing selective necrosis (PDT). Preliminary studies on animals suggest that ALA is superior to earlier bladder PDT sensitisers in that generalised photosensitivity and bladder contracture are avoided. These problems in conjunction with the complexity of PDT whereby a general anaesthetic with rigid cystoscopy under continuous irrigation are required, have previously limited the development of this modality as a practical therapy. (Abstract shortened by ProQuest.).

The Epigenetics of Kidney Cancer and Bladder Cancer

PubMed Central

Hoffman, Amanda M.; Cairns, Paul

2012-01-01

Summary This review focuses on the epigenetic alterations of aberrant promoter hypermethylation of genes, histone modifications or RNA interference in cancer cells. The current knowledge of hypermethylation of allele(s) in classical tumor suppressor genes in inherited and sporadic cancer, candidate tumor suppressor and other cancer genes is summarized gene by gene. Global and array-based studies of tumor cell hypermethylation are discussed. The importance of standardization of scoring of the methylation status of a gene is highlighted. The histone marks associated with hypermethylated genes, and the microRNAs with dysregulated expression, in kidney or bladder tumor cells are also discussed. Kidney cancer has the highest mortality rate of the genitourinary cancers. There are management issues with the high recurrence rate of superficial bladder cancer while muscle invasive bladder cancer has a poor prognosis. These clinical problems are the basis for translational application of gene hypermethylation to the diagnosis and prognosis of kidney and bladder cancer. PMID:22126150

Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection

PubMed Central

O’Brien, Valerie P.; Hannan, Thomas J.; Schaeffer, Anthony J.; Hultgren, Scott J.

2015-01-01

Purpose of review Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Recent findings Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. Summary The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact. PMID:25517222

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

PubMed Central

Hertting, Olof; Holm, Åsa; Lüthje, Petra; Brauner, Hanna; Dyrdak, Robert; Jonasson, Aino Fianu; Wiklund, Peter; Chromek, Milan; Brauner, Annelie

2010-01-01

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI. PMID:21179490

Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection.

PubMed

O'Brien, Valerie P; Hannan, Thomas J; Schaeffer, Anthony J; Hultgren, Scott J

2015-02-01

Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.

[Study on different responses of rats' small intestine mucous membrane and bladder transitional epithelium in the same carcinogenic urine environment].

PubMed

Wu, B; Pan, C; Song, G

2001-10-25

To preliminarily verify the tentative idea of replacement of bladder transitional epithelium with small intestine mucous membrane to prevent recurrence of carcinoma of bladder. A certain segment of small intestine was transplanted to the urinary bladder of the same body in 17 rats. Then N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) was used to induce carcinoma of bladder. BBN was used to 11 control rats that did not undergo operation. Bladder carcinoma failed to be found in the transplanted small intestine mucous membrane in all experimental rats except one. After stimulation of BBN, carcinoma of urinary bladder occurred in all rats' bladder transitional epithelium. 1) The carcinogenic substances in the urine of rats suffering from BBN-induced bladder carcinoma are carcinogenic only to bladder transitional epithelium and have no effect on small intestine epithelium. 2) Bladder transitional epithelium may be more sensitive to the urine carcinogenic substances and easier to be cancerized than small intestine epithelium. 3) The tentative idea of substitution of small intestine mucous membrane for bladder transitional epithelium to prevent the recurrence of bladder carcinoma is worth further studying.

Role of the brain stem in tibial inhibition of the micturition reflex in cats.

PubMed

Ferroni, Matthew C; Slater, Rick C; Shen, Bing; Xiao, Zhiying; Wang, Jicheng; Lee, Andy; Roppolo, James R; de Groat, William C; Tai, Changfeng

2015-08-01

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P < 0.05) increased bladder capacity to 30-60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300-900 μg) eliminated acute TNS inhibition and significantly (P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes. Copyright © 2015 the American Physiological Society.

Factors influencing bladder stone formation in patients with spinal cord injury.

PubMed

Favazza, Terry; Midha, Meena; Martin, Jessicca; Grob, B Mayer

2004-01-01

Bladder stones that form in patients with spinal cord injury (SCI) can cause significant morbidity. This study sought to analyze factors associated with bladder stone formation to determine which patients might be at increased risk to develop bladder stones. A review of 56 SCI patients treated for bladder calculi over a 10-year period at a single institution was performed. These patients were compared with a control population of general SCI patients known to be stone free. The factors compared were patient age, duration of injury, level of injury, completeness of injury, method of bladder management, and the presence of documented urinary tract infections with urease-producing organisms. All patients with stones were male and had a median age of 58.5 years. The median level of injury was C6, the median time since injury was 21 years, 66% had complete injuries, 68% managed their bladders with indwelling catheters or suprapubic tubes, and 83% had a history of infections with urease-producing organisms. When compared with the control group, patients forming bladder stones were older (P = 0.03), were more likely to have indwelling catheters (P < 0.0001), had a history of infections with urease-producing organisms (P = 0.04), and had complete injuries (P = 0.018). This information can be used to identify patients who have an increased risk of bladder stones and measures can be taken to reduce their incidence and morbidity.

Current management of overactive bladder.

PubMed

Cartwright, Rufus; Renganathan, Arasee; Cardozo, Linda

2008-10-01

The concept of overactive bladder has helped us address the problem of urgency and urge incontinence from a symptomatic perspective. In this review, we provide a critical summary of clinically relevant recent publications, focusing in particular on advances in our understanding of assessment methods and therapeutic interventions for overactive bladder in women. According to current definitions, the prevalence of overactive bladder in western nations is now estimated as 13.0%. Although the prevalence increases with age, the symptoms of overactive bladder may follow a relapsing and remitting course. There has been a proliferation of validated symptom and quality of life measures and increasing sophistication in the analysis of bladder diaries. The role of urodynamics in the evaluation of urgency remains uncertain, with many trials showing limited benefit as a preoperative investigation. Fluid restriction and bladder retraining remain important first-line interventions. Many new anticholinergic medications have been licensed, with limited benefits compared with existing preparations. Intravesical botulinum toxin has become a popular alternative for patients who fail oral therapies. Although there have been few important therapeutic innovations, recent publications have led to greater sophistication in assessment methods and a clearer understanding of the role of existing interventions.

Laparoscopic hernia repair and bladder injury.

PubMed

Dalessandri, K M; Bhoyrul, S; Mulvihill, S J

2001-01-01

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. 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. 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.

Effects of acute urinary bladder overdistension on bladder response during sacral neurostimulation.

PubMed

Bross, S; Schumacher, S; Scheepe, J R; Zendler, S; Braun, P M; Alken, P; Jünemann, K

1999-10-01

Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.

Control of gill ventilation and air-breathing in the bowfin amia calva

PubMed

Hedrick; Jones

1999-01-01

The purpose of this study was to investigate the roles of branchial and gas bladder reflex pathways in the control of gill ventilation and air-breathing in the bowfin Amia calva. We have previously determined that bowfin use two distinct air-breathing mechanisms to ventilate the gas bladder: type I air breaths are characterized by exhalation followed by inhalation, are stimulated by aquatic or aerial hypoxia and appear to regulate O2 gas exchange; type II air breaths are characterized by inhalation alone and possibly regulate gas bladder volume and buoyancy. In the present study, we test the hypotheses (1) that gill ventilation and type I air breaths are controlled by O2-sensitive chemoreceptors located in the branchial region, and (2) that type II air breaths are controlled by gas bladder mechanosensitive stretch receptors. Hypothesis 1 was tested by examining the effects of partial or complete branchial denervation of cranial nerves IX and X to the gill arches on gill ventilation frequency (fg) and the proportion of type I air breaths during normoxia and hypoxia; hypothesis II was tested by gas bladder inflation and deflation. Following complete bilateral branchial denervation, fg did not differ from that of sham-operated control fish; in addition, fg was not significantly affected by aquatic hypoxia in sham-operated or denervated fish. In sham-operated fish, aquatic hypoxia significantly increased overall air-breathing frequency (fab) and the percentage of type I breaths. In fish with complete IX-X branchial denervation, fab was also significantly increased during aquatic hypoxia, but there were equal percentages of type I and type II air breaths. Branchial denervation did not affect the frequency of type I air breaths during aquatic hypoxia. Gas bladder deflation via an indwelling catheter resulted in type II breaths almost exclusively; furthermore, fab was significantly correlated with the volume removed from the gas bladder, suggesting a volume-regulating function for type II air breaths. These results indicate that chronic (3-4 weeks) branchial denervation does not significantly affect fg or type I air-breathing responses to aquatic hypoxia. Because type I air-breathing responses to aquatic hypoxia persist after IX-X cranial nerve denervation, O2-sensitive chemoreceptors that regulate air-breathing may be carried in other afferent pathways, such as the pseudobranch. Gas bladder deflation reflexly stimulates type II breaths, suggesting that gas bladder volume-sensitive stretch receptors control this particular air-breathing mechanism. It is likely that type II air breaths function to regulate buoyancy when gas bladder volume declines during the inter-breath interval.

Molecular biology of bladder cancer.

PubMed

Martin-Doyle, William; Kwiatkowski, David J

2015-04-01

Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

Risk factors for bladder cancer in a cohort exposed to aromatic amines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulte, P.A.; Ringen, K.; Hemstreet, G.P.

1986-11-01

Occupational and nonoccupational risk factors for bladder cancer were analyzed in a cohort of 1385 workers with known exposure to a potent bladder carcinogen, beta-naphthylamine. Bladder cancer was approximately seven times (95% confidence interval (CI) = 3.9, 12.4) more likely in exposed rather than nonexposed individuals, yet, otherwise, the groups were generally similar in other exogenous or hereditary risk factors. A total of 13 cases of bladder cancer were identified. After the first year of a screening program involving 380 members of the cohort, 9 of the 13 cases of bladder cancer and 36 persons with atypical bladder cytology, histology,more » or pathology were compared with 335 noncases for distributions of different variables. Occupational variables were significant in a multivariate model that controlled for age, cigarette smoking history, and source of drinking water. The estimated odds ratio for the association for bladder cancer and the duration of employment, when controlling of these other variables, is 4.3 (95% CI = 1.8, 10.3). In addition to the occupational factors, age was significant in the multivariate analysis. Other potential risk factors, such as consumption of coffee or artificial sweeteners, use of phenacetin, or decreased use of vitamin A were not found to be significantly different in cases and noncases.« less

Receptors, channels, and signalling in the urothelial sensory system in the bladder

PubMed Central

Merrill, Liana; Gonzalez, Eric J.; Girard, Beatrice M.; Vizzard, Margaret A.

2017-01-01

The storage and periodic elimination of urine, termed micturition, requires a complex neural control system to coordinate the activities of the urinary bladder, urethra, and urethral sphincters. At the level of the lumbosacral spinal cord, lower urinary tract reflex mechanisms are modulated by supraspinal controls with mechanosensory input from the urothelium, resulting in regulation of bladder contractile activity. The specific identity of the mechanical sensor is not yet known, but considerable interest exists in the contribution of transient receptor potential (TRP) channels to the mechanosensory functions of the urothelium. The sensory, transduction, and signalling properties of the urothelium can influence adjacent urinary bladder tissues including the suburothelial nerve plexus, interstitial cells of Cajal, and detrusor smooth muscle cells. Diverse stimuli, including those that activate TRP channels expressed by the urothelium, can influence urothelial release of chemical mediators (such as ATP). Changes to the urothelium are associated with a number of bladder pathologies that underlie urinary bladder dysfunction. Urothelial receptor and/or ion channel expression and the release of signalling molecules (such as ATP and nitric oxide) can be altered with bladder disease, neural injury, target organ inflammation, or psychogenic stress. Urothelial receptors and channels represent novel targets for potential therapies that are intended to modulate micturition function or bladder sensation. PMID:26926246

The molecular genetic basis of mitochondrial malfunction in bladder tissue following outlet obstruction.

PubMed

Levin, Robert M; Hudson, Alan P

2004-08-01

Bladder dysfunction following partial outlet obstruction is a frequent consequence of benign prostatic hyperplasia and an increasingly common problem given the aging of the general population. Recent studies from this and other groups have begun to elucidate the molecular bases for the well described physiological malfunctions that characterize this clinical entity. We summarized and synthesized that information. Using modern methods of molecular genetics, including real-time polymerase chain reaction, real-time reverse transcriptase-polymerase chain reaction and others, as well as traditional experimental techniques such as electron microscopy we and others examined the transcriptional profile, morphology, etc of bladder smooth muscle mitochondria in experimental models of outlet obstruction. Data from many studies have demonstrated that aberrant gene expression in the mitochondrial and mitochondria related nuclear genetic systems underlies the loss of compliance and other attributes of bladder dysfunction following outlet obstruction. Such aberrant transcriptional characteristics engender loss of function in the electron transport and oxidative phosphorylation systems. Morphological studies of mitochondria in the animal model systems support this conclusion. In large part the loss of function in bladder smooth muscle following outlet obstruction results from the attenuation of mitochondrial energy production. In this article we reviewed and synthesized all available experimental observations relevant to this problem and we suggest future lines of inquiry that should prove fruitful in developing new strategies to treat the condition.

Current role of transcatheter arterial embolization for bladder and prostate hemorrhage.

PubMed

Loffroy, R; Pottecher, P; Cherblanc, V; Favelier, S; Estivalet, L; Koutlidis, N; Moulin, M; Cercueil, J P; Cormier, L; Krausé, D

2014-11-01

Intractable hematuria from the bladder or the prostate can be life-threatening and its management remains a difficult clinical problem. Severe bleeding can arise as a result of radiation cystitis, bladder carcinoma, cyclophosphamide-induced cystitis, severe infection, transurethral resection of the prostate and prostate cancer. When irrigation of the bladder through a three-way catheter and fulguration of the bleeding lesions fail to stop the hematuria, a life-threatening situation can develop, when blood transfusion fails to keep pace with the rate of blood loss. Patients with massive uncontrollable hematuria are often elderly and unfit for cystectomy as a treatment. Many urologists have had to manage this difficult problem, and several different treatments have been attempted and described, with varying degrees of success. Transcatheter arterial embolization of the vesical or prostatic arteries is occasionally indicated in these patients when all other measures have failed. There is limited published experience with this procedure, but success in 90% of patients is reported when the vesical or prostatic arteries can be identified. The aim of this review is to describe the current place of transcatheter arterial embolization in the management of severe bladder or prostate bleeding after failed conservative therapy, and to review its efficacy and morbidity. Copyright © 2014 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder dysfunction by increasing bladder capacity and decreasing voiding frequency in male rats

PubMed Central

Merrill, Liana

2014-01-01

Individuals with functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) often report symptom (e.g., urinary frequency) worsening due to stress. One member of the transient receptor potential ion channel vanilloid family, TRPV4, has recently been implicated in urinary bladder dysfunction disorders including OAB and IC/BPS. These studies address the role of TRPV4 in stress-induced bladder dysfunction using an animal model of stress in male rats. To induce stress, rats were exposed to 7 days of repeated variate stress (RVS). Quantitative PCR data demonstrated significant (P ≤ 0.01) increases in TRPV4 transcript levels in urothelium but not detrusor smooth muscle. Western blot analyses of split urinary bladders (i.e., urothelium and detrusor) showed significant (P ≤ 0.01) increases in TRPV4 protein expression levels in urothelial tissues but not detrusor smooth muscle. We previously showed that RVS produces bladder dysfunction characterized by decreased bladder capacity and increased voiding frequency. The functional role of TRPV4 in RVS-induced bladder dysfunction was evaluated using continuous, open outlet intravesical infusion of saline in conjunction with administration of a TRPV4 agonist, GSK1016790A (3 μM), a TRPV4 antagonist, HC067047 (1 μM), or vehicle (0.1% DMSO in saline) in control and RVS-treated rats. Bladder capacity, void volume, and intercontraction interval significantly decreased following intravesical instillation of GSK1016790A in control rats and significantly (P ≤ 0.01) increased following administration of HC067047 in RVS-treated rats. These results demonstrate increased TRPV4 expression in the urothelium following RVS and that TRPV4 blockade ameliorates RVS-induced bladder dysfunction consistent with the role of TRPV4 as a promising target for bladder function disorders. PMID:24965792

Simple prostatectomy

MedlinePlus

... if you have: Problems emptying your bladder (urinary retention) Frequent urinary tract infections Frequent bleeding from the ... to internal organs Erection problems (impotence) Loss of sperm fertility ( infertility ) Passing semen back up into the ...

The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder.

PubMed

Liu, Lu; Mansfield, Kylie J; Kristiana, Ika; Vaux, Kenneth J; Millard, Richard J; Burcher, Elizabeth

2007-01-01

Treatments targeting vanilloid receptor TRPV1 are effective in some bladder disorders. Our aim was to determine the expression profiles of TRPV1 in regions of human bladder and test the hypothesis that there would be an upregulation of TRPV1 in mucosa of patients with bladder hypersensitivity but not idiopathic detrusor overactivity (IDO). Women with sensory urgency (SU), interstitial cystitis (IC), and IDO were investigated by videourodynamics and cystoscopy. Control biopsies were used for comparison. Biopsies were dissected into mucosa and muscle, and evaluated for TRPV1 mRNA expression using quantitative competitive RT-PCR (QC-RT-PCR). TRPV1 mRNA from SU trigonal mucosa was significantly higher than control trigonal mucosa or SU bladder body mucosa. In contrast, in IDO patients, there was no difference between trigonal mucosa and body mucosa. In IC biopsies, RNA quality was substandard and unable to be used for analysis. The most striking finding was that TRPV1 mRNA expressed in SU trigonal mucosa was significantly inversely correlated with the bladder volume at first sensation of filling during cystometry. No such relationship was seen for IDO trigonal mucosa. No difference was seen in bladder body mucosa from any disease groups compared with age-matched control. The symptoms of SU were associated with the increased expression of TRPV1 mRNA in the trigonal mucosa. No upregulation or regional differences of TRPV1 mRNA were seen in IDO patients. TRPV1 may play a role in SU and premature first bladder sensation on filling.

Bladder function and falls in individuals with multiple sclerosis.

PubMed

Sung, JongHun; Shen, Sa; Motl, Robert W; Sosnoff, Jacob J

2016-11-01

To examine the association between bladder function and falls while controlling for mobility in individuals with multiple sclerosis (MS). A total of 92 ambulatory individuals with MS (mean age ± SD = 59.1 ± 7.3 years, female n = 69) were divided into two groups based on self-reported bladder function (none-mild n = 43 versus moderate-severe n = 49). The main outcome measure was a number of self-reported falls in the previous 3 months. Participants' demographic information (age, type of MS, gender, use of the assistive device) was also collected. The balance was quantified with the Berg balance scale, and walking speed was indexed with the timed 25-foot walk test. Negative binomial regression analysis was used to examine the association between bladder function and falls in individuals with MS while controlling for balance and walking. The median number of self-reported falls in the previous 3 months was 2 (interquartile range, 0-4). The severe bladder dysfunction group was more likely (incidence rate ratio = 1.84) to have a greater number of self-reported falls compared to mild bladder dysfunction group when balance and walking were taken into account. Bladder dysfunction is related to falls history independently of mobility in individuals with MS. Future research examining whether bladder management programmes have an impact on fall incidence in MS is warranted. Implications for rehabilitation Bladder dysfunction and falls are common health concerns in individuals with multiple sclerosis. Bladder dysfunction was associated with the number of falls in individuals with MS, and this association was independent of mobility. Bladder management should be included in fall prevention strategies in individuals with MS.

Urothelial Dysfunction and Chronic Inflammation are Associated With Increased Bladder Sensation in Patients With Chronic Renal Insufficiency.

PubMed

Cheng, Sheng-Fu; Jiang, Yuan-Hong; Kuo, Hann-Chorng

2018-01-01

Chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients usually have lower urinary tract symptoms, such as frequency and urgency. Additionally, they frequently suffer from urinary tract infections. This study investigated dysfunction and chronic inflammation of the bladder urothelium in ESRD/CKD patients. This study enrolled 27 patients with CKD (n=13) or ESRD (n=14) for urodynamic studies and bladder biopsies. Patients presented with detrusor underactivity (DU; n=8) or bladder oversensitivity (BO; n=19). Bladder biopsies were performed in these patients and in 20 controls. The bladder mucosa was examined for E-cadherin and zonula occludens-1 (ZO-1) expression, activated mast cell count (through tryptase staining), and urothelial apoptosis (through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling [TUNEL]). The urodynamic parameters were also compared with variables regarding urothelial dysfunction. The bladder mucosa samples of ESRD and CKD patients revealed significantly higher mast cell counts, more urothelial apoptosis, and lower levels of ZO-1 expression than the control samples. E-cadherin expression was significantly reduced in ESRD/CKD patients with DU, but not in ESRD/CKD patients with BO. Increased mast cell and apoptotic cell counts were also associated with ESRD/CKD with BO. Less expression of ZO-1 and E-cadherin was significantly associated with increased bladder sensation and a small bladder capacity. Bladder urothelial dysfunction and chronic inflammation were present to a noteworthy extent in patients with ESRD or CKD. Increased inflammation and defective barrier function were more notable in ESRD/CKD bladders with BO than in those with DU. The clinical characteristics of these patients may involve urothelial pathophysiology.

Pharmacologic evaluation of pressor and visceromotor reflex responses to bladder distension.

PubMed

Su, Xin; Riedel, Erin S; Leon, Lisa A; Laping, Nicholas J

2008-01-01

Several mechanisms that are involved in acute rat bladder nociception were examined. The nociceptive response was measured by analyzing both cardiovascular and visceromotor reflex responses to urinary bladder distension. The contributions of micro-opioid receptor, kappa-opioid receptor, sodium channels, muscarinic receptors, and cyclooxygenase, were explored with morphine, U50,488, mexiletine, oxybutynin, and naproxen, respectively. Female Sprague-Dawley rats were acutely instrumented with jugular venous, carotid arterial, and bladder cannulas. Needle electrodes were placed directly into the abdominal musculature to measure myoelectrical activity subsequent to repeated phasic urinary bladder distension (60 mmHg for 20 sec in 3 min intervals) under 1% isoflurane. Drugs were administered by i.v. bolus injection 2 min prior to distension. The analgesics morphine (ID50 0.69 mg/kg), U50,488 (1.34 mg/kg), and mexiletine (2.60 mg/kg) significantly inhibited the visceromotor reflex response to noxious urinary bladder distension. Oxybutynin also attenuated reflex responses to noxious urinary bladder distension to 41% of the maximal pressor response and 32% of the control visceromotor reflex response (3.01 and 5.05 mg/kg), respectively, indicating a role of muscarinic receptors in bladder nociception. Naproxen did not attenuate the pressor response, but moderately inhibited visceromotor reflex to 45% of control at 30 mg/kg (P < 0.05). Current results using the rat urinary bladder distension model are consistent with previous research demonstrating a role of the analgesics (morphine, U50,488, and mexiletine) in the inhibition of visceral nociceptive transmission. The utility of the reflex responses to urinary bladder distension may provide a method useful to examine mechanisms which target the bladder sensory pathway. (c) 2007 Wiley-Liss, Inc.

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

PubMed

Xu, Shi-Qiong; Buraschi, Simone; Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C; Gomella, Leonard G; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2015-05-10

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer.

Portable bladder ultrasound: an evidence-based analysis.

PubMed

2006-01-01

The aim of this review was to assess the clinical utility of portable bladder ultrasound. TARGET POPULATION AND CONDITION Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device's hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario's complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort.

Portable Bladder Ultrasound

PubMed Central

2006-01-01

Executive Summary Objective The aim of this review was to assess the clinical utility of portable bladder ultrasound. Clinical Need: Target Population and Condition Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. The Technology Being Reviewed Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. Review Strategy To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Summary of Findings Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device’s hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. Economic Analysis An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Considerations for Policy Development Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario’s complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort. PMID:23074481

Adipose-derived stem-cell-implanted poly(ϵ-caprolactone)/chitosan scaffold improves bladder regeneration in a rat model.

PubMed

Zhou, Zhe; Yan, Hao; Liu, Yidong; Xiao, Dongdong; Li, Wei; Wang, Qiong; Zhao, Yang; Sun, Kang; Zhang, Ming; Lu, Mujun

2018-04-01

The study investigated the feasibility of seeding adipose-derived stem cells (ASCs) onto a poly(ϵ-caprolactone)/chitosan (PCL/CS) scaffold for bladder reconstruction using a rat model of bladder augmentation. In the experimental group, the autologous ASCs were seeded onto the PCL/CS scaffold for bladder augmentation. An unseeded scaffold was used for bladder augmentation as control group. The sham group was also set. 8 weeks after implantation, more densely smooth muscles were detected in the experimental group with a larger bladder capacity and more intensive blood vessels. Immunofluorescence staining demonstrated that some of the smooth muscle cells were transdifferentiated from the ASCs. Our findings indicated that ASC-seeded PCL/CS may be a potential scaffold for bladder tissue engineering.

Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

ClinicalTrials.gov

2017-12-04

Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

Positive feedback loop for cystitis cystica: the effect of recurrent urinary tract infection on the number of bladder wall mucosa nodules.

PubMed

Vrljicak, Kristina; Turudić, Daniel; Bambir, Ivan; Gradiski, Ivan Pavao; Spajić, Borislav; Batinić, Danica; Topalović-Grković, Marija; Spajić, Marija; Batinić, Danko; Milosević, Danko

2013-12-01

The main purpose of this study was to demonstrate positive feedback loop between bladder wall nodules (nodules being one of the key diagnostic factors), bladder wall thickness, and recurrent urinary tract infections. Cystitis cystica was diagnosed in 115 prepubertal girls (mean age 7.79 +/- 3.05 years) by optic examination of bladder mucosal nodules and by ultrasonographic measurement of bladder wall thickness. Bladder wall thickness increased with the frequency of recurrent urinary tract infections as well as with the number of nodules on bladder wall mucosa (3.52 +/- 0.522 mm < or = 5 nodules vs. 4.42 +/- 0.429 mm 6-10 nodules vs. 5.20 +/- 0.610 mm > 10 nodules, respectively). Study results suggested that early control of urinary tract infections by chemoprophylaxis could prevent higher grades of bladder wall mucosal changes and consequently shorten the length of chemoprophylaxis.

Eviscerated urinary bladder via ruptured umbilical hernia: a rare occurrence.

PubMed

Pandey, A; Kumar, V; Gangopadhyay, A N; Upadhyaya, V D

2008-06-01

Umbilical hernia is a common problem encountered in children. Rupture and evisceration are very rare phenomena, and the usual content that is eviscerated is the bowel. We present an infant who had a ruptured umbilical hernia with eviscerated urinary bladder dome. As this is the first case of its kind, it is being reported with a brief review of literature.

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

PubMed Central

Gonzalez, Eric J.; Merrill, Liana

2014-01-01

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

Bladder cancer mapping in Libya based on standardized morbidity ratio and log-normal model

NASA Astrophysics Data System (ADS)

Alhdiri, Maryam Ahmed; Samat, Nor Azah; Mohamed, Zulkifley

2017-05-01

Disease mapping contains a set of statistical techniques that detail maps of rates based on estimated mortality, morbidity, and prevalence. A traditional approach to measure the relative risk of the disease is called Standardized Morbidity Ratio (SMR). It is the ratio of an observed and expected number of accounts in an area, which has the greatest uncertainty if the disease is rare or if geographical area is small. Therefore, Bayesian models or statistical smoothing based on Log-normal model are introduced which might solve SMR problem. This study estimates the relative risk for bladder cancer incidence in Libya from 2006 to 2007 based on the SMR and log-normal model, which were fitted to data using WinBUGS software. This study starts with a brief review of these models, starting with the SMR method and followed by the log-normal model, which is then applied to bladder cancer incidence in Libya. All results are compared using maps and tables. The study concludes that the log-normal model gives better relative risk estimates compared to the classical method. The log-normal model has can overcome the SMR problem when there is no observed bladder cancer in an area.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Lu, Daniel C.; Gerasimenko, Yury P.; Edgerton, V. Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury. PMID:25264607

Genome-wide association study identifies multiple loci associated with bladder cancer risk

PubMed Central

Figueroa, Jonine D.; Ye, Yuanqing; Siddiq, Afshan; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Prokunina-Olsson, Ludmila; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Tang, Wei; Bas Bueno-de-Mesquita, H.; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Lerner, Seth P.; Barton Grossman, H.; Lin, Jie; Gu, Jian; Pu, Xia; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Armenti, Karla R.; Hosain, G.M.; Andriole, Gerald; Grubb, Robert; Black, Amanda; Ryan Diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Haiman, Chris A.; Landi, Maria T.; Caporaso, Neil; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel

2014-01-01

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis. PMID:24163127

Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.

PubMed Central

Levine, S D; Levine, R D; Worthington, R E; Hays, R M

1976-01-01

Vasopressin increases the permeability of the total urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin. In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in to toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyflurane-treated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well. We conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea. PMID:184113

Primary nocturnal enuresis in children. Background and treatment.

PubMed

Wille, S

1994-01-01

The aim of the present studies was to investigate background factors and treatment in children with monosymptomatic primary nocturnal enuresis. The study material comprised enuretics, former enuretics and controls from the municipal community of Falkenberg on the west coast of Sweden. Whenever possible all investigations were made with the children staying in their own home environment. Different background factors have been suspected as being causative: sleep disturbances, behavioural or psychological disturbances, small bladder capacity, increased night diuresis and an insufficient production of the antidiuretic hormone during sleep. These factors have been investigated in these studies. The treatment of enuresis has been dominated by the alarm and antidiuretic treatment with DDAVP. Primary nocturnal monosymptomatic enuresis is a common problem in childhood. In this study the prevalence among 392 seven year old children was 7.3%. A prior history of enuresis was found in 65% of families of the enuretics compared to 25% in controls. The enuretic children showed no statistically significant differences in behavioural or psychological problems compared to non-enuretic children. Enuretic children were described as heavy sleepers by their parents and a wake-up test performed at home showed that they were statistically significantly harder to arouse than the controls. Children with nocturnal enuresis, former enuretics and controls did not differ in social or behavioural traits in an interview study. No signs of symptom substitution was found when enuresis was resolved. Enuretic children had a normal bladder capacity and no statistically significant difference was found compared to controls and former enuretics. The enuretic children showed a normal calcium-creatinine quota in the urine. Former enuretic children showed a significantly enhanced calcium/creatinine quota compared to enuretics and controls. Enuretic children had a statistically significant lower morning plasma level of the anti diuretic hormone vasopressin than non-enuretic children. Enuretic children were treated for 12 weeks with DDAVP or the alarm. DDAVP treated patients had a more rapid effect compared with alarm treated patients. Alarm treated children had a lower relapse frequency. Enuretic children were treated in a randomised, double blind, double dummy, cross over, placebo-controlled study with DDAVP 20 micrograms intranasally by a single dose pipette or 200 micrograms orally as a tablet. Both methods were equally effective in controlling enuresis, but significantly superior to placebo. Enuretic children are normal, well adjusted children with a normal bladder capacity, a high level of arousal threshold, and a low morning level of plasma vasopressin. The alarm and DDAVP are equally effective in treating enuresis.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-term safety, efficacy, and tolerability of imidafenacin in the treatment of overactive bladder: a review of the Japanese literature

PubMed Central

Masumori, Naoya

2013-01-01

Imidafenacin is an antimuscarinic agent with high affinity for the M3 and M1 muscarinic receptor subtypes and low affinity for the M2 subtype, and is used to treat overactive bladder. Several animal studies have demonstrated that imidafenacin has organ selectivity for the bladder over the salivary glands, colon, heart, and brain. In Phase I studies in humans, the approximately 2.9-hour elimination half-life of imidafenacin was shorter than that of other antimuscarinics such as tolterodine and solifenacin. Imidafenacin was approved for clinical use in overactive bladder in Japan in 2007 after a randomized, double-blind, placebo-controlled Phase II study and a propiverine-controlled Phase III study conducted in Japanese patients demonstrated that imidafenacin 0.1 mg twice daily was clinically effective for treating overactive bladder and was not inferior to propiverine for reduction of episodes of incontinence, with a better safety profile than propiverine. Several short-term clinical studies have demonstrated that imidafenacin also improves sleep disorders, nocturia, and nocturia-related quality of life. In addition, it is speculated that addon therapy with imidafenacin is beneficial for men with benign prostatic hyperplasia whose overactive bladder symptoms are not controlled by alpha-1 adrenoceptor antagonists. No cognitive impairment or influence of imidafenacin on the QTc interval has been observed. Although there have been very few relevant long-term clinical studies, the available information suggests the long-term efficacy, safety, and tolerability of imidafenacin, with less frequent severe adverse events, such as dry mouth and constipation. In addition, imidafenacin can be used safely for a long time even for cognitively vulnerable elderly patients with symptoms of overactive bladder. Thus, it is highly likely that imidafenacin is safe, efficacious, and tolerable to control symptoms of overactive bladder even over the long term. However, it remains unknown if the practical effectiveness of imidafenacin is applicable to ethnic groups other than Japanese. PMID:23390360

Non-alcoholic beverages and risk of bladder cancer in Uruguay

PubMed Central

De Stefani, Eduardo; Boffetta, Paolo; Deneo-Pellegrini, Hugo; Correa, Pelayo; Ronco, Alvaro L; Brennan, Paul; Ferro, Gilles; Acosta, Giselle; Mendilaharsu, María

2007-01-01

Background Bladder cancer is the fourth most frequent malignancy among Uruguayan men. A previous study from Uruguay suggested a high risk of bladder cancer associated with maté drinking. We conducted an additional case-control study in order to further explore the role of non-alcoholic beverages in bladder carcinogenesis. Methods In the time period 1996–2000, 255 incident cases with transitional cell carcinoma of the bladder and 501 patients treated in the same hospitals and in the same time period were frequency matched on age, sex, and residence. Both cases and controls were face-to-face interviewed on occupation, tobacco smoking, alcohol drinking and intake of maté, coffee, tea, and soft drinks. Statistical analysis was carried out by unconditional multiple logistic regression. Results Ever maté drinking was positively associated with bladder cancer (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.2–3.9) and the risk increased for increasing duration and amount of maté drinking. Both coffee and tea were strongly associated with bladder cancer risk (OR for coffee drinking 1.6, 95% CI 1.2–2.3; OR for tea drinking 2.3, 95% CI 1.5–3.4). These results were confirmed in a separate analysis of never-smokers. Conclusion Our results suggest that drinking of maté, coffee and tea may be risk factors for bladder carcinoma in Uruguay. PMID:17394632

Effects of fidarestat, an aldose reductase inhibitor, on nerve conduction velocity and bladder function in streptozotocin-treated female rats.

PubMed

Zotova, Elena G; Christ, George J; Zhao, Weixin; Tar, Moses; Kuppam, Srini D; Arezzo, Joseph C

2007-01-01

The effects of fidarestat, an aldose reductase inhibitor (ARI), were assessed on nerve conduction velocity (NCV) in somatic nerves and on multiple measures of bladder function in rats made hyperglycemic with streptozotocin (STZ) and in age-matched controls. Nerve conduction velocity was recorded at baseline and at 10, 20, 30, and 50 days after confirmation of the STZ-induced hyperglycemia in all rats (N=47); bladder function was assessed in a representative subset of rats (N=20) at Day 50. Caudal NCV was markedly slowed by STZ, and this effect was significantly reversed by fidarestat. The initial deficit and treatment-related improvement were especially evident for responses driven by high-frequency repetitive stimulation. Of the 11 parameters of bladder activity assessed, four measures-bladder capacity, micturition volume, micturition frequency, and bladder weight-were significantly different in the control and STZ-treated groups. These deficits were not affected by fidarestat. At Day 50, the induced deficits in bladder function were highly correlated with caudal NCV (r values ranging from 0.70 to 0.96; P values ranging from .02 to <.0001). These results suggested that fidarestat improved the slowing of somatic nerve NCV in hyperglycemic rats, but it was not effective in reversing associated bladder dysfunction, in spite of the highly significant correlation between these two diabetes-induced deficits. Possible explanations for this dissociation are discussed.

The association of lifetime physical inactivity with bladder and renal cancer risk: A hospital-based case-control analysis.

PubMed

Cannioto, Rikki; Etter, John Lewis; Guterman, Lauren Beryl; Joseph, Janine M; Gulati, Nicholas R; Schmitt, Kristina L; LaMonte, Michael J; Nagy, Ryan; Minlikeeva, Albina; Szender, James Brian; Moysich, Kirsten B

2017-08-01

Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk. In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk. In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively. In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pelvic floor muscle training in women with stress urinary incontinence causes hypertrophy of the urethral sphincters and reduces bladder neck mobility during coughing.

PubMed

McLean, Linda; Varette, Kevin; Gentilcore-Saulnier, Evelyne; Harvey, Marie-Andree; Baker, Kevin; Sauerbrei, Eric

2013-11-01

The purpose of this study was to determine the effect of a 12-week pelvic floor muscle (PFM) training program on urethral morphology and mobility in women with stress urinary incontinence (SUI). Forty women with SUI were randomly assigned to one of two groups: the treatment group received 12 weekly physiotherapy sessions during which they learned how to properly contract their pelvic floor muscles (PFMs) and a home exercise program was prescribed, reviewed, and progressed; the control group received no treatment. Before and after the 12-week study period, ultrasound imaging was used to evaluate bladder neck position and mobility during coughing and Valsalva maneuver in supine and in standing, as well as urethral morphology. Secondary outcome measures included a 3-day bladder diary, 30-min pad test, the Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Inventory (UDI-6). The women in the treatment group demonstrated reduced bladder neck mobility during coughing and increased cross-sectional area of their urethra after as compared to before the training. These changes were not evident in the control group. No differences in the resting position of the bladder neck or in bladder neck excursion during Valsalva maneuver were noted in either group. Concomitantly the women in the treatment group demonstrated significant improvements in the 3-day bladder diary and IIQ-7 after the PFM training and improved significantly more than the control group. Physiotherapist-supervised PFM training reduces bladder neck motion during coughing, and results in hypertrophy of the urethral sphincter in women who present with SUI. © 2013 Wiley Periodicals, Inc.

Androgen receptor activity modulates responses to cisplatin treatment in bladder cancer.

PubMed

Kashiwagi, Eiji; Ide, Hiroki; Inoue, Satoshi; Kawahara, Takashi; Zheng, Yichun; Reis, Leonardo O; Baras, Alexander S; Miyamoto, Hiroshi

2016-08-02

Cisplatin (CDDP)-based combination chemotherapy remains the mainstream treatment for advanced bladder cancer. However, its efficacy is often limited due to the development of resistance for which underlying mechanisms are poorly understood. Meanwhile, emerging evidence has indicated the involvement of androgen-mediated androgen receptor (AR) signals in bladder cancer progression. In this study, we aimed to investigate whether AR signals have an impact on sensitivity to CDDP in bladder cancer cells. UMUC3-control-short hairpin RNA (shRNA) cells with endogenous AR and AR-negative 647V/5637 cells stably expressing AR were significantly more resistant to CDDP treatment at its pharmacological concentrations, compared with UMUC3-AR-shRNA and 647V-vector/5637-vector control cells, respectively. A synthetic androgen R1881 significantly reduced CDDP sensitivity in UMUC3, 647V-AR, or 5637-AR cells, and the addition of an anti-androgen hydroxyflutamide inhibited the effect of R1881. In these AR-positive cells, R1881 treatment also induced the expression levels of NF-κB, which is known to involve CDDP resistance, and its phosphorylated form, as well as nuclear translocation of NF-κB. In CDDP-resistant bladder cancer sublines established following long-term culture with CDDP, the expression levels of AR as well as NF-κB and phospho-NF-κB were considerably elevated, compared with respective control sublines. In bladder cancer specimens, there was a strong trend to correlate between AR positivity and chemoresistance. These results suggest that AR activation correlates with CDDP resistance presumably via modulating NF-κB activity in bladder cancer cells. Targeting AR during chemotherapy may thus be a useful strategy to overcome CDDP resistance in patients with AR-positive bladder cancer.

Pelvic Floor Muscle Training in Women With Stress Urinary Incontinence Causes Hypertrophy of the Urethral Sphincters and Reduces Bladder Neck Mobility During Coughing

PubMed Central

McLean, Linda; Varette, Kevin; Gentilcore-Saulnier, Evelyne; Harvey, Marie-Andree; Baker, Kevin; Sauerbrei, Eric

2016-01-01

Aims The purpose of this study was to determine the effect of a 12-week pelvic floor muscle (PFM) training program on urethral morphology and mobility in women with stress urinary incontinence (SUI). Methods Forty women with SUI were randomly assigned to one of two groups: the treatment group received 12 weekly physiotherapy sessions during which they learned how to properly contract their pelvic floor muscles (PFMs) and a home exercise program was prescribed, reviewed, and progressed; the control group received no treatment. Before and after the 12-week study period, ultrasound imaging was used to evaluate bladder neck position and mobility during coughing and Valsalva maneuver in supine and in standing, as well as urethral morphology. Secondary outcome measures included a 3-day bladder diary, 30-min pad test, the Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Inventory (UDI-6). Results The women in the treatment group demonstrated reduced bladder neck mobility during coughing and increased cross-sectional area of their urethra after as compared to before the training. These changes were not evident in the control group. No differences in the resting position of the bladder neck or in bladder neck excursion during Valsalva maneuver were noted in either group. Concomitantly the women in the treatment group demonstrated significant improvements in the 3-day bladder diary and IIQ-7 after the PFM training and improved significantly more than the control group. Conclusion Physiotherapist-supervised PFM training reduces bladder neck motion during coughing, and results in hypertrophy of the urethral sphincter in women who present with SUI. PMID:23861324

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Hong, Jin Ki; Jang, Ja Yun; An, Jieun; Lee, Kyu-Sung; Kang, Tong Mook; Shin, Hyun Joon; Suh, Jun-Kyo Francis

2017-01-01

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

Biofabricated Structures Reconstruct Functional Urinary Bladders in Radiation-injured Rat Bladders.

PubMed

Imamura, Tetsuya; Shimamura, Mitsuru; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Silwal Gautam, Sudha; Ishizuka, Osamu

2018-05-08

The ability to repair damaged urinary bladders through the application of bone marrow-derived cells is in the earliest stages of development. We investigated the application of bone marrow-derived cells to repair radiation-injured bladders. We used a three-dimensional (3D) bioprinting robot system to biofabricate bone marrow-derived cell structures. We then determined if the biofabricated structures could restore the tissues and functions of radiation-injured bladders. The bladders of female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2-Gy once a week for 5 weeks. Adherent and proliferating bone marrow-derived cells harvested from the femurs of male 17-week-old green fluorescence protein-transfected Tg-SD rats were cultured in collagen-coated flasks. Bone marrow-derived cell spheroids were formed in 96-well plates. Three layers of spheroids were assembled by the bioprinter onto a 9x9 microneedle array. The assembled spheroids were perfusion cultured for 7 days, and then the microneedle array was removed. Two weeks after the last radiation treatment, the biofabricated structures were transplanted into an incision on the anterior wall of the bladders (n=10). Control rats received the same surgery but without the biofabricated structures (sham-structure, n=12). At 2 and 4 weeks after surgery, the sham-structure control bladder tissues exhibited disorganized smooth muscle layers, decreased nerve cells, and significant fibrosis with increased presence of fibrosis-marker P4HB-positive cells and hypoxia-marker HIF1α-positive cells. The transplanted structures survived within the recipient tissues, and blood vessels extended within them from the recipient tissues. The bone marrow-derived cells in the structures differentiated into smooth muscle cells and formed smooth muscle clusters. The recipient tissues near the transplanted structures had distinct smooth muscle layers and reconstructed nerve cells, and only minimal fibrosis with decreased presence of P4HB- and HIF1α-positive cells. At 4 weeks after surgery, the sham-structure control rats exhibited significant urinary frequency symptoms with irregular and short voiding intervals, and low micturition volumes. In contrast, the structure-transplanted rats had regular micturition with longer voiding intervals and higher micturition volumes compared to the control rats. Further, the residual volume of the structure-transplanted rats was lower than for the controls. Therefore, transplantation of biofabricated bone marrow-derived cell structures reconstructed functional bladders.

Problems arising in the diagnosis of primary ovarian transitional cell carcinoma after the occurrence of a transitional cell carcinoma of the bladder: a report of a difficult case and a critical review of literature.

PubMed

Raspollini, Maria Rosaria; Paglierani, Milena; Taddei, Gian Luigi

2009-03-01

Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer that morphologically resembles a TCC of the bladder. The most frequent metastases to ovaries come from the gastrointestinal tract and from breast carcinoma, but metastatic TCCs from the urinary tract to the ovary have been reported. TCC of the bladder is the sixth most common cancer in European and North American countries and its incidence has been increasing. We recently observed a woman, who previously had undergone endoscopic resection of a TCC of the bladder. She was affected by an ovarian bilateral tumor with features of malignant transitional cell tumor, characterized by papillae with multilayered transitional epithelium infiltrating the ovarian stroma. In this study, we showed the utility of WT1 and a panel of immunohistochemical markers in the difficult differential diagnosis between bladder and ovarian TCC.

Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hata, Masaharu; Miyanaga, Naoto; Tokuuye, Koichi

Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently,more » proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.« less

The significance of the open bladder neck associated with pelvic fracture urethral distraction defects.

PubMed

Iselin, C E; Webster, G D

1999-08-01

As a result of pelvic fracture urethral distraction defects, urinary continence relies predominantly on intact bladder neck function. Hence, when cystoscopy and/or cystography reveals an open bladder neck before urethroplasty, the probability of postoperative urinary incontinence may be significant. Unresolved issues are the necessity, the timing and the type of bladder neck repair. We report the outcome of various therapeutic options in patients with pelvic fracture urethral distraction defects and open bladder neck. We also attempt to identify prognostic factors of incontinence before urethroplasty. We retrospectively reviewed the records of 15 patients with a mean age of 30 years in whom an open bladder neck was identified before posterior urethroplasty between January 1981 and October 1997. Of the 15 patients 6 were continent and 8 were incontinent postoperatively. One patient underwent artificial urethral sphincter implantation simultaneously with pelvic fracture urethral distraction defect repair and was dry postoperatively without sphincter activation. Average bladder neck and prostatic urethral opening on the cystourethrogram before urethroplasty was significantly longer in incontinent (1.68 cm.) than in continent (0.9 cm.) patients. Of the 8 patients who were incontinent 6 underwent bladder neck reconstruction, 1 artificial urinary sphincter and 1 periurethral collagen implant. Five patients with bladder neck reconstruction are totally continent and 1 requires 1 pad daily. The patient who underwent collagen implant requires 2 pads daily and the patient who received an artificial urethral sphincter has minor urge leakage. Open bladder neck before urethroplasty may herald postoperative incontinence which may be predicted by radiographic and cystoscopic features. Evaluation of the risk of postoperative incontinence may be valuable, and eventually guide the necessity and timing of anti-incontinence surgery, although our preference remains to manage the pelvic fracture urethral distraction defects and bladder neck problem sequentially. Bladder neck reconstruction provides good postoperative continence rates and is our technique of choice.

Sensory feedback from the urethra evokes state-dependent lower urinary tract reflexes in rat.

PubMed

Danziger, Zachary C; Grill, Warren M

2017-08-15

The lower urinary tract is regulated by reflexes responsible for maintaining continence and producing efficient voiding. It is unclear how sensory information from the bladder and urethra engages differential, state-dependent reflexes to either maintain continence or promote voiding. Using a new in vivo experimental approach, we quantified how sensory information from the bladder and urethra are integrated to switch reflex responses to urethral sensory feedback from maintaining continence to producing voiding. The results demonstrate how sensory information regulates state-dependent reflexes in the lower urinary tract and contribute to our understanding of the pathophysiology of urinary retention and incontinence where sensory feedback may engage these reflexes inappropriately. Lower urinary tract reflexes are mediated by peripheral afferents from the bladder (primarily in the pelvic nerve) and the urethra (in the pudendal and pelvic nerves) to maintain continence or initiate micturition. If fluid enters the urethra at low bladder volumes, reflexes relax the bladder and evoke external urethral sphincter (EUS) contraction (guarding reflex) to maintain continence. Conversely, urethral flow at high bladder volumes, excites the bladder (micturition reflex) and relaxes the EUS (augmenting reflex). We conducted measurements in a urethane-anaesthetized in vivo rat preparation to characterize systematically the reflexes evoked by fluid flow through the urethra. We used a novel preparation to manipulate sensory feedback from the bladder and urethra independently by controlling bladder volume and urethral flow. We found a distinct bladder volume threshold (74% of bladder capacity) above which flow-evoked bladder contractions were 252% larger and evoked phasic EUS activation 2.6 times as often as responses below threshold, clearly demonstrating a discrete transition between continence (guarding) and micturition (augmenting) reflexes. Below this threshold urethral flow evoked tonic EUS activity, indicative of the guarding reflex, that was proportional to the urethral flow rate. These results demonstrate the complementary roles of sensory feedback from the bladder and urethra in regulating reflexes in the lower urinary tract that depend on the state of the bladder. Understanding the neural control of functional reflexes and how they are mediated by sensory information in the bladder and urethra will open new opportunities, especially in neuromodulation, to treat pathologies of the lower urinary tract. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Impact of solifenacin on diary-recorded and patient-reported urgency in patients with severe overactive bladder (OAB) symptoms.

PubMed

Serels, Scott R; Toglia, Marc R; Forero-Schwanhaeuser, Sergio; He, Weizhong

2010-10-01

It is widely recognized that patient perception of overactive bladder (OAB) symptoms can vary considerably from mild to severe bother. This post hoc analysis reports outcomes in patients with severe OAB symptoms at baseline taken from the VESIcare Efficacy and Safety in PatieNts with Urgency Study (VENUS). VENUS was a 12-week, randomized, double-blind, placebo-controlled trial of solifenacin (5 or 10 mg/day, flexibly dosed) in OAB patients. The primary endpoint in VENUS was mean change from baseline to study end in urgency episodes/day using 3-day bladder diaries. Secondary endpoints included other diary endpoints (frequency, incontinence, and nocturia), warning time (WT; time between first sensation of urgency to voiding), and patient-reported outcome (PRO) measures of urgency (the Indevus Urgency Severity Scale [IUSS] and Urgency Perception Scale [UPS]) and of symptom bother and health-related quality of life (HRQL) (the Patient Perception of Bladder Condition [PPBC] and Overactive Bladder Questionnaire). For this analysis, severe OAB was defined as baseline PPBC score ≥5 (1 = no problems, 6 = many severe problems). NCT00454896. In total, 158/707 (22.3%) patients in the full analysis set (FAS) reported severe OAB symptoms. Solifenacin reduced mean urgency episodes/day versus placebo in the severe subgroup (-4.6 vs. -3.1, p = 0.1150), similar to the significant reduction observed in the FAS (-3.9 vs. -2.7, p < 0.0001). Solifenacin also improved the other diary endpoints and PRO measures in the severe subgroup; these changes were consistent with the significant solifenacin- versus placebo-related improvements for the FAS. Treatment-emergent adverse events were mostly mild/moderate, and few patients taking solifenacin or placebo discontinued treatment in the severe subgroup (4.5% vs. 6.5%) or FAS (6.5% vs. 4.6%). Key limitations are that VENUS was not powered to detect treatment differences in subgroups, and that the lack of a standardized definition of OAB symptom severity may limit the generalizability of the findings. Patients with severe OAB symptoms showed objective and subjective improvements in symptoms, symptom bother, HRQL, and urgency severity with solifenacin similar to the FAS. Solifenacin was also well-tolerated in this subgroup.

Ba-Wei-Die-Huang-Wan (Hachimi-jio-gan) can ameliorate cyclophosphamide-induced ongoing bladder overactivity and acidic adenosine triphosphate solution-induced hyperactivity on rats prestimulated bladder.

PubMed

Lee, Wei-Chia; Wu, Chia-Ching; Chuang, Yao-Chi; Tain, You-Lin; Chiang, Po-Hui

2016-05-26

Ba-Wei-Die-Huang-Wan (BWDHW) is the traditional Chinese medicine formula containing eight ingredients, namely Rehmannia glutinosa (Gaetn.) DC., root, steamed & dried; Cornus officinalis Siebold & Zucc., fructus, dried; Dioscorea oppositifolia L., root, dried; Alisma plantago-aquatica, subsp. orientale (Sam.) Sam., tuber, dried; Poria cocos (Fr.) Wolf., sclerotium, dried; Paeonia×suffruticosa Andrews, bark, dried; Cinnamomum cassia (Nees & T.Nees) J. Presl, bark, dried; Aconitum carmichaeli Debeaux, lateral root, dried & processed. It has been used for diabetes and urinary frequency treatments. We investigate effects of BWDHW on cyclophosphamide (CYP)-induced ongoing bladder overactivity and acidic adenosine triphosphate (ATP) solution-induced hyperactivity on rat's prestimulated bladder. Female Wistar rats were injected with intraperitoneal CYP (100mg/kg) or saline respectively. Rats were treated with BWDHW (90mg/kg/day) or vehicle for the next five days. After treatments animals were evaluated both in metabolic cage model and then by cystometry. Acidic ATP solution (5mM, pH 3.3) was instilled to provoke bladder hyperactivity. Bladder mucosa and muscle proteins were assessed by Western blotting. As compared to the controls, the CYP group showed significantly decreased mean cystometric intercontractile interval and increased micturition frequency, whereas the CYP/BWDWH group did not. The CYP group had significant protein overexpression in mucosal M2, M3, P2X2, and P2X3 receptors as well as detrusor M2 and M3 receptors. However, the CYP/BWDWH group had insignificant changes from controls. In the provoking test, the control/BWDHW and CYP/BWDHW groups were less affected by acidic ATP stimulation of intercontractile interval changes than the control group. Compared to the control group, the control/BWDHW group showed significantly lower mucosal P2X3 protein expression and the CYP group showed significant mucosal TRPV1 protein upregulation after the provoking test. BWDHW treatment can ameliorate CYP-induced ongoing bladder overactivity and suppress mucosal P2X2, P2X3, M2, and M3 receptor protein overexpression, as well as detrusor M2 and M3 receptor protein overexpression. BWDHW pretreatment can reduce acidic ATP solution-provoked hyperactivity by preventing TRPV1 receptor overexpression in CYP-treated bladder mucosa and inhibiting P2X3 receptor overexpression in naïve bladder mucosa. Copyright © 2016. Published by Elsevier Ireland Ltd.

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

PubMed

Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

2016-12-01

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer.

PubMed

Ceylan, Gülay Güleç; Önalan, Ebru Etem; Kuloğlu, Tuncay; Aydoğ, Gülten; Keleş, İbrahim; Tonyali, Şenol; Ceylan, Cavit

2016-12-01

Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

Static postural stability in women with stress urinary incontinence: Effects of vision and bladder filling.

PubMed

Chmielewska, Daria; Stania, Magdalena; Słomka, Kajetan; Błaszczak, Edward; Taradaj, Jakub; Dolibog, Patrycja; Juras, Grzegorz

2017-11-01

This case-control study was designed to compare static postural stability between women with stress urinary incontinence and continent women and it was hypothesized that women with incontinence aged around 50 years also have balance disorders. Eighteen women with incontinence and twelve women without incontinence aged 50-55 years participated in two 60-s trials of each of four different testing conditions: eyes open/full bladder, eyes open/empty bladder, eyes closed/full bladder, eyes closed/empty bladder. The center of foot pressure (COP): sway range, root mean square, velocity (in the antero-posterior and medio-lateral directions), and COP area were recorded. The stabilograms were decomposed into rambling and trembling components. The groups of women with and without incontinence differed during the full bladder condition in antero-posterior COP sway range, COP area, and rambling trajectory (range in the antero-posterior and medio-lateral directions, root mean square in the antero-posterior and medio-lateral directions and velocity in the antero-posterior direction). The women with incontinence had more difficulty controlling their postural balance than continent women while standing with a full bladder. Therefore, developing therapeutic management focused on strengthening the women's core muscles and improving their postural balance seems advisable. © 2017 Wiley Periodicals, Inc.

Decreased expression of zonula occludens-1 and occludin in the bladder urothelium of patients with interstitial cystitis/painful bladder syndrome.

PubMed

Lee, Jane-Dar; Lee, Ming-Huei

2014-01-01

Unique barrier properties of the urothelial surface membrane permit urine storage without contents leak into the bloodstream. Previous reports suggested that the bladder urothelial barrier might be compromised in interstitial cystitis/painful bladder syndrome (IC/PBS). We examined the changes of tight junction proteins (zonula occludens-1 (ZO-1) and occludin) in IC/PBS patients. Bladder samples were derived from of 32 patients with IC/PBS and eight controls. We detected the tight junction proteins of ZO-1 and occludin expression by immunoblotting, immunohistochemical (IHC) staining and double immunofluorescent (IF) staining with confocal microscopy. Data were analyzed using the Mann-Whitney U-test. Expression of ZO-1 and occludin in the IC/PBS group was reduced compared to the control group by immunoblotting and IHC staining. Also, the thinning and denudation of urothelium were demonstrated in the IC/PBS group by histological study. IF staining showed the interruption of bladder urothelium in IC/PBS patients under confocal microscopy. Our data showed that decreased expression of tight junction proteins (ZO-1 and occludin) and interruption of bladder urothelium in IC/PBS patients. Treatment to repair the discontinuous urothelium may be useful to relieve some clinical symptoms of patients with IC/PBS. Copyright © 2012. Published by Elsevier B.V.

Predictive values of urinary bladder tumor markers survivin and soluble-Fas comparison with cystoscopy and bladder tumor antigen.

PubMed

Ganas, V; Kalaitzis, C; Sountoulides, P; Giannakopoulos, S; Touloupidis, S

2012-12-01

The aim of the study was to evaluate the predictive values of two novel urinary markers for bladder cancer: survivin and soluble-Fas (s-Fas). The study included 84 individuals divided in two groups. The first group contained 47 patients, who underwent transurethral bladder tumor resection and the second, control, group 20 patients with non-malignant conditions, who underwent cystoscopy and 17 health volunteers. Fresh, second morning voided urine was collected for measurement of s-Fas, survivin, BTA and for cytology. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated. Bladder tumor patients had significantly higher survivin urine levels in comparison to the controls. Survivin correlated also with the tumor stage. Combination of survivin with BTA had a sensitivity of 86.4% but still lower than that of cystoscopy (97.8%). Only the specificity of the combination between survivin and BTA was higher than that of cystoscopy (86.4% and 75.6%, respectively). Survivin was a better marker for tumor detection than s-Fas and was better enough to discriminate cancer stage. Combination of survivin and BTA had a specificity of 86.4% to exclude bladder malignancy and the combination of s-Fas with survivin and BTA had a sensitivity of 93.6% to detect bladder cancer.

A novel role for drebrin in regulating progranulin bioactivity in bladder cancer

PubMed Central

Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C.; Gomella, Leonard G.; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V.; Morrione, Andrea

2015-01-01

We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer. PMID:25839164

[Bladder injury during sling operation in the treatment of SUI--review of literature and case report].

PubMed

Gałczyński, Krzysztof; Futyma, Konrad; Bar, Krzysztof; Rechberger, Tomasz

2012-10-01

Sling operations have been performed for over 15 years. In recent years these operations have become the gold standard in the treatment of stress urinary incontinence (SUI) due to their efficacy safety and low invasiveness. Approximately 4% of women will undergo a surgery for SUI in the course of their life. As with any surgical intervention, there may be some technical problems, as well as intra- and postoperative complications, the most common of which is bladder injury Other complications encountered during mid-urethral slings procedures include bleeding (retropubic or vaginal hematomas), urethral perforation, urinary tract infections, postoperative vaginal or urethral erosions, bowel perforation, chronic pelvic pain, wound infection, nerve injury transient and persistent voiding dysfunction such as de novo urgency incomplete bladder emptying or urinary retention. Below we present a case of a patient with diagnosed vesicovaginal fistula after sling operation (TVT-tension-free vaginal tape). Upon admission the patient reported dysuria, persistent urinary leakage and abnormal, abundant vaginal discharge. Case report and review of literature concerning surgical treatment of stress urinary incontinence and its complications. Analysis of medical documentation of the patient treated at the Second Department of Gynecology Medical University of Lublin. Review of abstracts or papers in the Medline database related to surgical treatment of urinary incontinence and its complications. Bladder perforation is one of the most common complications of the retropubic approach for MUS placement. The presence of mesh within the bladder may arise from direct bladder perforation or from subsequent erosion of the sling. Such lesions do not cause any serious health consequences for patients on condition they are detected intraoperatively and appropriately repaired, but when unrecognized, they results in the development of considerable symptoms and negatively influence the quality of patient life. Improperly treated, it can lead to development of an abnormal communication between the urinary bladder and the anterior wall of the vagina -vesicovaginal fistula. We should suspect unrecognized bladder injury in case of patients with any persistent voiding symptoms after a sling procedure such as long lasting dysuria, persistent urinary leakage, hematuria, recurrent infections, chronic pain and voiding difficulties. Diagnosis and treatment of vesicovaginal fistula is long lasting and difficult for the patient and the surgeon. Füth-Mayo operation is an effective treatment method for the majority of vesicovaginal fistulas. During this operation we suture all layers of fistula separately (bladder perivesical fascia and vaginal wall). Although with this operation we solve one problem, the patient still might suffer from recurrent SUI. Alternative methods of treatment which can be offered to patients after unsuccessful SUI operation are periurethral injections with bulking agents or electrical stimulation of the pelvic floor muscles. Both methods are effective in the therapy of recurrent SUI. In our case periurtehral injection of Bulkamid did not provide a total cure. Therefore, we completed the treatment with electrical stimulation of the pelvic floor muscles using patient-controlled electrodes placed in the vagina to stimulate muscles with current frequency of 50 Hz, amperage between 0-60 mA and duration of 250 micros. This procedure produced a series of changes in the stimulated area and enabled to cure the incontinence.

Differential association for N-acetyltransferase 2 genotype and phenotype with bladder cancer risk in Chinese population.

PubMed

Quan, Lei; Chattopadhyay, Koushik; Nelson, Heather H; Chan, Kenneth K; Xiang, Yong-Bing; Zhang, Wei; Wang, Renwei; Gao, Yu-Tang; Yuan, Jian-Min

2016-06-28

N-acetyltransferase 2 (NAT2) is involved in both carcinogen detoxification through hepatic N-acetylation and carcinogen activation through local O-acetylation. NAT2 slow acetylation status is significantly associated with increased bladder cancer risk among European populations, but its association in Asian populations is inconclusive. NAT2 acetylation status was determined by both single nucleotide polymorphisms (SNPs) and caffeine metabolic ratio (CMR), in a population-based study of 494 bladder cancer patients and 507 control subjects in Shanghai, China. The CMR, a functional measure of hepatic N-acetylation, was significantly reduced in a dose-dependent manner among both cases and controls possessing the SNP-inferred NAT2 slow acetylation status (all P-values<5.0×10-10). The CMR-determined slow N-acetylation status (CMR<0.34) was significantly associated with a 50% increased risk of bladder cancer (odds ratio = 1.50, 95% confidence interval = 1.10-2.06) whereas the SNP-inferred slow acetylation statuses were significantly associated with an approximately 50% decreased risk of bladder cancer. The genotype-disease association was strengthened after the adjustment for CMR and was primarily observed among never smokers. The apparent differential associations for phenotypic and genetic measures of acetylation statuses with bladder cancer risk may reflect dual functions of NAT2 in bladder carcinogenesis because the former only measures the capacity of carcinogen detoxification pathway while the latter represents both carcinogen activation and detoxification pathways. Future studies are warranted to ascertain the specific role of N- and O-acetylation in bladder carcinogenesis, particularly in populations exposed to different types of bladder carcinogens.

Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.

PubMed

Nakai, Yasushi; Anai, Satoshi; Onishi, Sayuri; Masaomi, Kuwada; Tatsumi, Yoshihiro; Miyake, Makito; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2015-06-01

We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA). Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated. The differences in the bladder cancer group were significantly greater than those in the control group (p < 0.001). These differences were also significantly greater in patients with high-grade tumors than in those with low-grade tumors (p = 0.004), and also in patients with invasive bladder cancer than in those with noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84. Sensitivity and specificity of the method were 82% and 80%, respectively. We demonstrated that protoporphyrin IX levels in urinary cells treated with ALA could be quantitatively detected by spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use. Copyright © 2015 Elsevier B.V. All rights reserved.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.

PubMed

Krech, Eugen; Selinski, Silvia; Blaszkewicz, Meinolf; Bürger, Hannah; Kadhum, Thura; Hengstler, Jan G; Truss, Michael C; Golka, Klaus

2017-01-01

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.

Street ketamine-associated bladder dysfunction: an emerging health problem.

PubMed

Lee, Py; Ong, Ta; Chua, Cb; Lei, Ccm; Teh, Gc

2009-01-01

Ketamine is frequently abused nowadays as a recreational drug. Case reports are emerging since 2007 to describe a new clinical entity of severe bladder dysfunction associated with chronic abuse of street ketamine. Severe lower urinary tract symptoms of urinary frequency and urgency which are refractory to conventional treatment. Quality of life is adversely affected as a consequence. Chronic kidney disease will develop in advanced cases. Investigation findings: The urine is sterile on culture. Ultrasound will show reduced bladder capacity with thickened bladder wall. In advanced stage, hydronephrosis and renal impairment will develop. Patients should be advised to stop street ketamine use immediately. Anticholinergic medication could be tried to alleviate the symptoms. Refractory cases with dilatation of the upper urinary tract might need urinary diversion. Awareness of this new condition is essential in diagnosis. Early intervention offers better treatment outcome.

Trypanosoma cruzi infection induced changes in the innervation, structure and function of the murine bladder.

PubMed

Boczko, Judd; Tar, Moses; Melman, Arnold; Jelicks, Linda A; Wittner, Murray; Factor, Stephen M; Zhao, Dazhi; Hafron, Jason; Weiss, Louis M; Tanowitz, Herbert B; Christ, George J

2005-05-01

The involvement of the lower urinary tract in chronic Chagas' disease has received little attention. Therefore, we investigated pathology and functional alterations in the bladder of Trypanosoma cruzi infected mice. CD1 mice were infected with 5 x 10 T. cruzi trypomastigotes of the Brazil strain of T. cruzi. At day 100 after infection bladder structure and function were examined by pathological evaluation, magnetic resonance imaging and cystometric studies. The bladder in infected mice weighed more and were large, dilated, deformed, friable and thin walled compared with control mice. Magnetic resonance imaging confirmed these observations. Inflammation, fibrosis and ganglionitis was observed. Cystometric studies revealed that baseline, threshold and micturition pressures were increased in infected mice. Bladder overactivity and decreased bladder compliance were also noted in infected mice. There were no detectable differences in bladder capacity, micturition volume or residual volume between infected and uninfected mice. Bladder abnormalities may be a more common clinical sequelae of T. cruzi infection than previously appreciated.

[A simple and efficient method for establishing a mouse model of orthotopic MB49 bladder cancer].

PubMed

Liang, Zhong-kun; Zhang, Lin; Hu, Zhi-ming; Chen, Zhong; Huang, Xin; Shi, Xiang-hua; Tan, Wan-long; Gao, Ji-min

2009-04-01

To establish a simple and efficient method for establishing a mouse model of orthotopic superficial bladder cancer. C57BL/6 mice were anesthetized with sodium pentobarbital and catheterized with modified IV catheter (24 G). The mice were intravesically pretreated with HCl and then with NaOH, and after washing the bladders with phosphate-buffered saline (PBS), 100 microl (1 x 10(7)) MB49 cells were infused and allowed to incubate in the bladder for 2 h followed intravesical mitomycin C (MMC) administration. The tumor formation rate, survival, gross hematuria, and bladder weight were determined as the outcome variables, and the pathology of the bladders was observed. Instillation of MB49 tumor cells resulted in a tumor formation rates of 100% in all the pretreated groups while 0% in the control group without pretreatment. MMC significantly reduced the bladder weight as compared to PBS. We have successfully established a stable, reproducible, and reliable orthotopic bladder cancer model in mice.

Laparoendoscopic single-site repair of bladder rupture using a home-made single-port device: initial experience of treatment for a traumatic intraperitoneal bladder rupture.

PubMed

Lee, Joo Yong; Kang, Dong Hyuk; Lee, Seung Wook

2012-06-01

We report our initial experience with a laparoendoscopic single-site (LESS) repair of a bladder rupture using a home-made single-port device. A 37-year-old man presented to the emergency department with complaints of voiding difficulty and gross hematuria after blunt trauma. Cystography and computed tomography revealed an intraperitoneal bladder rupture. The patient underwent LESS repair of a bladder rupture using the Alexis wound retractor, which was inserted through the umbilical incision. A home-made single-port device was made by fixing 6½ surgical gloves to the outer rim of the retractor and securing the glove finger to the end of 3 trocars with a tie. Using the flexible laparoscopic instruments and rigid instruments, LESS surgery was performed using a procedure similar to conventional laparoscopic surgery. The patient did not have any voiding problem after removal of the urethral Foley catheter on the 10th postoperative day. To our knowledge, this is the first published report of LESS repair of a traumatic bladder rupture using a home-made single-port device in the literature.

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study.

PubMed

Nishikawa, Nobuyuki; Yago, Rie; Yamazaki, Yuichiro; Negoro, Hiromitsu; Suzuki, Mari; Imamura, Masaaki; Toda, Yoshinobu; Tanabe, Kazunari; Ogawa, Osamu; Kanematsu, Akihiro

2015-01-21

To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease. PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome). Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5-86.6%), median intravesical pressure at maximal capacity was 30 cmH2O (range 10-107 cmH2O), and median compliance was 3.93 ml/cmH2O (range 0.05-30.3 ml/cmH2O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases. Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.

Bladder volume-dependent excitatory and inhibitory influence of lumbosacral dorsal and ventral roots on bladder activity in rats

PubMed Central

Sugaya, Kimio; de Groat, William C.

2011-01-01

This study was undertaken to examine the role of the afferent and efferent pathways of the lumbosacral spinal nerve roots in the tonic control of bladder activity. Changes of isovolumetric bladder activity were recorded in 21 sympathectomized female rats under urethane anesthesia following transection of the dorsal (DRT) and ventral (VRT) lumbosacral spinal roots, and after intraperitoneal administration of hexamethonium. DRT altered the baseline intravesical pressure in a bladder volume-dependent manner in each animal. The percent change of baseline pressure after VRT following DRT was also dependent upon bladder volume. The percent change of baseline pressure after VRT alone was similarly dependent on bladder volume, but not after VRT followed by DRT. The percent change of baseline intravesical pressure (y)(−9 to +8 cm H2O, −56 to +46%) after DRT and VRT depended upon bladder volume (x)(y = 44.7 x −40.4) in all rats. Hexamethonium increased the amplitude of small myogenic bladder contractions after DRT and VRT. In conclusion, the bladder is tonically excited or inhibited by a local reflex pathway and by a parasympathetic reflex pathway that depends on connections with the lumbosacral spinal cord and the pelvic nerves. Both reflex mechanisms are influenced by bladder volume. PMID:17878597

Evidence of bladder oversensitivity in the absence of an infection in premenopausal women with a history of recurrent urinary tract infections.

PubMed

Arya, Lily A; Northington, Gina M; Asfaw, Tirsit; Harvie, Heidi; Malykhina, Anna

2012-07-01

Study Type - Prevalence (case control) Level of Evidence 4. What's known on the subject? and What does the study add? Urinary tract infections (UTIs) have been implicated in the aetiology of interstitial cystitis/painful bladder syndrome (IC/PBS). Prior studies have described symptoms and laboratory tests suggestive of UTI at the onset of IC/PBS as well as a significant history of childhood recurrent UTIs. However, the mechanism by which recurrent UTIs contribute to the development of IC/PBS is not clear. Our study shows that women with recurrent UTI suffer from bladder oversensitivity. Our findings have useful clinical implications. Women with bladder oversensitivity complain of urinary frequency which is often misdiagnosed as an infection and treated with unnecessary antibiotics. Additionally, there are no effective therapies for bladder oversensitivity. Therefore, women with recurrent UTI should undergo prompt evaluation and treatment of episodes of infection to prevent the development of bladder oversensitivity. Our findings also provide a possible mechanism for the development of IC/PBS. Whether women with recurrent UTI are at increased risk for developing IC/PBS in the future will need to be confirmed in future studies. • To compare the mean voided volume and bladder sensation during filling cystometry in women with a history of recurrent urinary tract infection (UTI) and controls. • This was a case-control study including adult women seen in the urogynaecology clinic. • The cases were 49 women with at least three documented positive urine cultures >105 colonies/mL in the previous 12 months and no active infection at the time of data collection. • Controls were 53 women with stress urinary incontinence and no history of recurrent UTI or coexistent urge urinary incontinence. • We compared bladder diary variables and filling cystometry data in the absence of an active infection. • There was no significant difference in the median age, parity and body mass index of women with a history of recurrent UTI and controls. • The median number of voids per day and median number of voids per litre of fluid intake was significantly greater in women with recurrent UTI than controls (12 vs 7 voids/day and 6 vs 4 voids/L, P= 0.005 and P= 0.004 respectively). • The median average voided volume was significantly lower in women with recurrent UTI than controls (155 vs 195 mL, P= 0.008). • On filling cystometry, median volumes of strong desire to void and maximum cystometric capacity were significantly lower in women with recurrent UTI than controls (all P < 0.05). • In the absence of an infection, premenopausal women with a history of recurrent UTI have significantly greater urinary frequency, lower average voided volume and a lower threshold of bladder sensitivity than controls. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

PubMed Central

Hagiwara, Akihiro; Imai, Norio; Doi, Yuko; Suguro, Mayuko; Kawabe, Mayumi; Furukawa, Fumio; Nagano, Kasuke; Fukushima, Shoji

2013-01-01

The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100–1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100–1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses. PMID:24526807

Bioadhesive drug delivery system using glyceryl monooleate for the intravesical administration of paclitaxel.

PubMed

Lee, Seung-Ju; Kim, Sae Woong; Chung, Hesson; Park, Yeong Taek; Choi, Young Wook; Cho, Yong-Hyun; Yoon, Moon Soo

2005-10-01

Many reports have shown that the efficacy of intravesical therapy for bladder cancer is in part limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer. Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed. 120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was decreased by 39.6 and 41.2% in the two experimental groups and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity. We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy. Copyright 2005 S. Karger AG, Basel.

Automobile industry occupations and bladder cancer: a population-based case-control study in southeastern Michigan, USA.

PubMed

Kobrosly, R W; Meliker, J R; Nriagu, J O

2009-10-01

To determine whether employees in the automobile industry in Michigan are at elevated risk of urinary bladder cancer. The authors conducted a population-based case-control study including 418 cases and 571 controls. History of employment within the automobile industry was coded according to the US Census Bureau Index of Occupations. Logistic regression analyses were adjusted for age at interview, cigarette smoking status, and highest education level, and used to assess associations between bladder cancer and (1) ever working in particular occupations within the automobile industry; and (2) usual occupation - defined as occupation of longest duration for each subject. Ever having worked in the automobile industry and usual employment within the industry exhibited elevated non-significant risks for bladder cancer among assembly line workers, painters and foremen. A higher risk was seen for those who worked for 20 or more years on the assembly line (OR = 2.10, 95% CI 1.15 to 3.80). Statistical interaction between usual employment on the assembly line and smoking status (>5 pack-years) was demonstrated (OR = 6.19, 95% CI 2.69 to 14.24). Among workers on the assembly line for at least 20 years, we observed an approximately twofold risk for bladder cancer. Heavy smokers working on the assembly line experience a sixfold risk for bladder cancer. Further research is necessary to verify this finding, identify the exposures that might be contributing to bladder cancer on the assembly line, and examine whether those exposures continue to persist in today's workplace.

[Correlation of infection with the physical and chemical characteristics of gall bladder contents].

PubMed

Sulaberidze, G T; Rachvelishvili, B Kh; Gelbakhiani, G P; Barbakadze, G G; Kapanadze, A G

2005-06-01

The aim of the study was to investigate pH and viscosity (h) of gall bladder contents during cholelithiasis and establishment of their correlation with bacterial and HBV infections. Seventy-eight patients undergone the planned cholecystectomy were investigated. 5 healthy persons (control group) were also involved into the study. In all cases the markers of HBV (Anti-HB core IgG, Anti-HB core IgM, HBsAg) in blood were detected, also bacteriological analysis of gall bladder tissue was performed. In 78 cases (I group) pH of gall bladder contents was measured, in 29 cases (II group), also viscosity of gall was studied. In the control group pH and viscosity were detected. Statistical analysis was performed using ANOVA method. Bacteriological study revealed presence of bacterial infection in gall bladder tissue in 34 cases (43,6%), in 30 patients Anti-HB core antibodies were found in the blood, in 13 cases (16,7%) coincidence of bacterial and HBV infection was documented. Mean indexes of pH and viscosity appeared to be significantly higher in the operated group (pH--7,30, h 2,1 mm(2)/sec), then in the control group (pH--6,74, h--1,34 mm(2)/sec); this indexes were highest in the infected patients. Thus, according to results of the study, changes of pH and viscosity of gall bladder contents could be considered as the useful indexes of initial stage of cholelithiasis and their values depend on the presence of bacterial or HBV infection of gall bladder.

Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics.

PubMed

Kuo, Hann-Chorng

2011-09-01

The purpose of this study was to evaluate the efficacy and safety of onabotulinumtoxinA injections at bladder base/trigone and compare with injections at bladder body or bladder body/trigone for the treatment of idiopathic detrusor overactivity (IDO) refractory to antimuscarinics. A single blind, randomized, paralleled, actively controlled trial was performed in patients with urodynamically proven IDO who failed antimuscarinic therapy. Patients were randomly assigned to receive intravesical injections of 100 U of onabotulinumtoxinA into three different bladder sites. All treatments were evaluated by voiding diary variables, urgency severity score, urodynamic studies, and patient perception of bladder condition. Long-term success rates over 12 months were also determined. Among the patients, 37 were randomized to injections in the bladder body, 35 into the bladder body/trigone, and 33 into the bladder base/trigone. Successful results were reported in 76 (72%) patients at 3 months: 26 (70%) in the bladder body group, 26 (74%) in the bladder body/trigone group, and 24 (73%) in the bladder base/trigone group. There were no significant differences in success rates, changes in urgency and urgency incontinence episodes, urodynamic variables, or long-term success rates among the three subgroups. The incidence of adverse events was similar among three groups. No vesicoureteral reflux was noted in all patients with or without involving trigone injection. Intravesical onabotulinumtoxinA injection is an effective treatment for IDO regardless of the bladder injection site. Bladder base/trigone injection is as safe and effective as bladder body injections with or without trigone involvement. Copyright © 2011 Wiley-Liss, Inc.

Analgesic and anti-inflammatory drug use and risk of bladder cancer: a population based case control study

PubMed Central

Fortuny, Joan; Kogevinas, Manolis; Zens, Michael S; Schned, Alan; Andrew, Angeline S; Heaney, John; Kelsey, Karl T; Karagas, Margaret R

2007-01-01

Background Use of phenacetin and other analgesic and non-steroidal anti-inflammatory drugs (NSAIDs) potentially influences bladder cancer incidence, but epidemiologic evidence is limited. Methods We analyzed data from 376 incident bladder cancer cases and 463 controls from a population-based case-control study in New Hampshire on whom regular use of analgesic drugs and NSAIDs was obtained. Odds ratios and 95% confidence intervals were computed using logistic regression with adjustment for potentially confounding factors. Separate models by tumor stage, grade and TP53 status were conducted. Results We found an elevated odds ratio (OR) associated with reported use of phenacetin-containing medications, especially with longer duration of use (OR >8 years = 3.00, 95% confidence interval (CI) = 1.4–6.5). In contrast, use of paracetamol did not relate overall to risk of bladder cancer. We also found that regular use of any NSAID was associated with a statistically significant decrease in bladder cancer risk (OR = 0.6, 95% CI = 0.4–0.9), and specifically use of aspirin. Further, the association with NSAID use was largely among invasive, high grade and TP53 positive tumors. Conclusion While these agents have been investigated in several studies, a number of questions remain regarding the effects of analgesic and NSAID use on risk of bladder cancer. PMID:17692123

Quantitative elasticity measurement of urinary bladder wall using laser-induced surface acoustic waves.

PubMed

Li, Chunhui; Guan, Guangying; Zhang, Fan; Song, Shaozhen; Wang, Ruikang K; Huang, Zhihong; Nabi, Ghulam

2014-12-01

The maintenance of urinary bladder elasticity is essential to its functions, including the storage and voiding phases of the micturition cycle. The bladder stiffness can be changed by various pathophysiological conditions. Quantitative measurement of bladder elasticity is an essential step toward understanding various urinary bladder disease processes and improving patient care. As a nondestructive, and noncontact method, laser-induced surface acoustic waves (SAWs) can accurately characterize the elastic properties of different layers of organs such as the urinary bladder. This initial investigation evaluates the feasibility of a noncontact, all-optical method of generating and measuring the elasticity of the urinary bladder. Quantitative elasticity measurements of ex vivo porcine urinary bladder were made using the laser-induced SAW technique. A pulsed laser was used to excite SAWs that propagated on the bladder wall surface. A dedicated phase-sensitive optical coherence tomography (PhS-OCT) system remotely recorded the SAWs, from which the elasticity properties of different layers of the bladder were estimated. During the experiments, series of measurements were performed under five precisely controlled bladder volumes using water to estimate changes in the elasticity in relation to various urinary bladder contents. The results, validated by optical coherence elastography, show that the laser-induced SAW technique combined with PhS-OCT can be a feasible method of quantitative estimation of biomechanical properties.

N-acetyltransferase 2 gene polymorphism as a biomarker for susceptibility to bladder cancer in Bangladeshi population.

PubMed

Hosen, Md Bayejid; Islam, Jahidul; Salam, Md Abdus; Islam, Md Fakhrul; Hawlader, M Zakir Hossain; Kabir, Yearul

2015-03-01

To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods. Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor. N-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. © 2014 Wiley Publishing Asia Pty Ltd.

Chromium in urothelial carcinoma of the bladder.

PubMed

Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

2017-12-23

Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

Electrical stimulation of anal sphincter or pudendal nerve improves anal sphincter pressure.

PubMed

Damaser, Margot S; Salcedo, Levilester; Wang, Guangjian; Zaszczurynski, Paul; Cruz, Michelle A; Butler, Robert S; Jiang, Hai-Hong; Zutshi, Massarat

2012-12-01

Stimulation of the pudendal nerve or the anal sphincter could provide therapeutic options for fecal incontinence with little involvement of other organs. The goal of this project was to assess the effects of pudendal nerve and anal sphincter stimulation on bladder and anal pressures. Ten virgin female Sprague Dawley rats were randomly allocated to control (n = 2), perianal stimulation (n = 4), and pudendal nerve stimulation (n = 4) groups. A monopolar electrode was hooked to the pudendal nerve or placed on the anal sphincter. Aballoon catheter was inserted into the anus to measure anal pressure, and a catheter was inserted into the bladder via the urethra to measure bladder pressure. Bladder and anal pressures were measured with different electrical stimulation parameters and different timing of electrical stimulation relative to spontaneous anal sphincter contractions. Increasing stimulation current had the most dramatic effect on both anal and bladder pressures. An immediate increase in anal pressure was observed when stimulating either the anal sphincter or the pudendal nerve at stimulation values of 1 mA or 2 mA. No increase in anal pressure was observed for lower current values. Bladder pressure increased at high current during anal sphincter stimulation, but not as much as during pudendal nerve stimulation. Increased bladder pressure during anal sphincter stimulation was due to contraction of the abdominal muscles. Electrical stimulation caused an increase in anal pressures with bladder involvement only at high current. These initial results suggest that electrical stimulation can increase anal sphincter pressure, enhancing continence control.

The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice.

PubMed

Kadekawa, Katsumi; Majima, Tsuyoshi; Shimizu, Takahiro; Wada, Naoki; de Groat, William C; Kanai, Anthony J; Goto, Momokazu; Yoshiyama, Mitsuharu; Sugaya, Kimio; Yoshimura, Naoki

2017-09-01

We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1 ) spinal intact (SI)-control, 2 ) SI-capsaicin pretreatment (Cap), 3 ) SCI-control, and 4 ) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously 4 days before the experiments. In the SI-Cap group, 100 mg/kg capsaicin pretreatment significantly increased bladder capacity and decreased the silent period duration of EUS/EMG compared with the SI-control group. In the SCI-Cap group, 50 and 100 mg/kg capsaicin pretreatment decreased the number of nonvoiding contractions (NVCs) and the duration of reduced EUS activity during voiding, respectively, compared with the SCI-control group. In SCI mice, hexamethonium, a ganglionic blocker, almost completely blocked NVCs, suggesting that they are of neurogenic origin. Patch-clamp recordings in capsaicin-sensitive bladder afferent neurons from SCI mice showed hyperexcitability, which was evidenced by decreased spike thresholds and increased firing rate compared with SI mice. These results indicate that capsaicin-sensitive C-fiber afferent pathways, which become hyperexcitable after SCI, can modulate bladder and urethral sphincter activity in awake SI and SCI mice. Detrusor overactivity as shown by NVCs in SCI mice is significantly but partially dependent on capsaicin-sensitive C-fiber afferents, whereas the EUS relaxation during voiding is enhanced by capsaicin-sensitive C-fiber bladder afferents in SI and SCI mice. Copyright © 2017 the American Physiological Society.

A placebo-controlled efficacy study of the intravesical immunomodulators TMX-101 and TMX-202 in an orthotopic bladder cancer rat model.

PubMed

Falke, Johannes; Hulsbergen-van de Kaa, Christina A; Maj, Roberto; Oosterwijk, Egbert; Witjes, J Alfred

2018-05-16

TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model. Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically. No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant (p = 0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle (p = 0.005). TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.

Rapidly quantifying the relative distention of a human bladder

NASA Technical Reports Server (NTRS)

Companion, John A. (Inventor); Heyman, Joseph S. (Inventor); Mineo, Beth A. (Inventor); Cavalier, Albert R. (Inventor); Blalock, Travis N. (Inventor)

1991-01-01

A device and method was developed to rapidly quantify the relative distention of the bladder of a human subject. An ultrasonic transducer is positioned on the human subject near the bladder. A microprocessor controlled pulser excites the transducer by sending an acoustic wave into the human subject. This wave interacts with the bladder walls and is reflected back to the ultrasonic transducer where it is received, amplified, and processed by the receiver. The resulting signal is digitized by an analog to digital converter, controlled by the microprocessor again, and is stored in data memory. The software in the microprocessor determines the relative distention of the bladder as a function of the propagated ultrasonic energy. Based on programmed scientific measurements and the human subject's past history as contained in program memory, the microprocessor sends out a signal to turn on any or all of the available alarms. The alarm system includes and audible alarm, the visible alarm, the tactile alarm, and the remote wireless alarm.

Association between the high risk occupations and bladder cancer in Iran: a case-control study.

PubMed

Khoubi, Jamshid; Pourabdian, Siamak; Mohebbi, Iraj; Tajvidi, Mina; Zaroorian, Omid; Giahi, Omid

2013-04-01

The objective of this work was to identify the high-risk occupations in Iran and to re-inspect occupations that were related to bladder cancer. In the study, 300 patients suffering from bladder cancer and 500 control individuals were interviewed. Demographic information, occupational history, and history of exposure to chemical compounds such as aromatic amines for each participant were collected. ORs and 95% CIs were calculated using unconditional logistic regression for each occupation. There was a significantly increased risk of bladder cancer among truck and bus drivers (OR = 11.3), skilled agricultural, forestry and fishery workers (OR = 6.0), metal industry workers (OR = 6.0), domestic housekeepers (OR = 5.9), and construction workers (OR = 3.8). The study showed a strong correlation between truck and bus drivers, skilled agricultural, forestry and fishery workers, metal industry workers, domestic housekeepers, as well as construction workers and the increased risk of bladder cancer in these occupations.

Study protocol: patient reported outcomes for bladder management strategies in spinal cord injury.

PubMed

Patel, Darshan P; Lenherr, Sara M; Stoffel, John T; Elliott, Sean P; Welk, Blayne; Presson, Angela P; Jha, Amitabh; Rosenbluth, Jeffrey; Myers, Jeremy B

2017-10-10

The majority of spinal cord injury (SCI) patients have urinary issues, such as incontinence, retention, and frequency. These problems place a significant burden on patients' physical health and quality of life (QoL). There are a wide variety of bladder management strategies available to patients with no clear guidelines on appropriate selection. Inappropriate bladder management can cause hospitalizations and serious complications, such as urosepsis and renal failure. Patients believe that both independence and ability to carry out daily activities are just as important as physical health in selecting the right bladder-management strategy but little is known about patient's QoL with different bladder managements. Our study's aim is to assess patient reported QoL measures with various bladder managements after SCI. This manuscript describes the approach, study design and common data elements for our central study. This is a multi-institutional prospective cohort study comparing three different bladder-management strategies (clean intermittent catheterization, indwelling catheters, and surgery). Information collected from participants includes demographics, past medical and surgical history, injury characteristics, current and past bladder management, and SCI /bladder-related complications. Patient reported outcomes and QoL questionnaires were administered at enrollment and every 3 months for 1 year. Aims of this study protocol are: (1) to assess baseline QoL differences between the three different bladder-management strategies; (2) determine QoL impact when those using either form of catheter management undergo a surgery over the 1 year of follow-up among patients eligible for surgery; (3) assess the effects of changes in bladder management and complications on QoL over a 1-year longitudinal follow-up. By providing information about patient-reported outcomes associated with different bladder management strategies after SCI, and the impact of bladder management changes and complications on QoL, this study will provide essential information for shared decision-making and guide future investigation. Trial registration number: www.clinicaltrials.gov : Identifier: NCT0261608; U.S. National Library of Medicine, wwwcf.nlm.nih.gov : Identifier: HSRP20153564.

[Plastic closure of a bladder wall defect by use of a pedicled auto-alloplastic prosthesis in experiments].

PubMed

Sedlarik, K; Stanulla, H; Samohýl, J

1975-01-01

The problems of substituting larger areas of the bladder wall are not definitely solved. Experiments on implantation of auto-allografts resulted in complications, which prevented correct epithelization of the interior surface, due to ischemia. In successful experiments on 34 rabbits, the authors obtained sufficient blood supply of the implantate and re-epithelization of the graft's interior surface in a two-stage operation.

Gulf War Women’s Health Cohort

DTIC Science & Technology

2017-10-01

suggested excess rates of woman’s health problems, e.g., breast cysts, abnormal Papanicolaou (Pap) smears, yeast infections, and bladder infections...e.g., breast cysts, abnormal Papanicolaou (Pap) smears, yeast infections, and bladder infections (4-6). However, in the 25 years since the war...lumps or cysts in the breasts, abnormal Pap tests) compared to women deployed elsewhere. In a further follow-up survey of this cohort of USAF

Bladder cancer and occupation: a case-control study in northern Italy.

PubMed Central

Porru, S; Aulenti, V; Donato, F; Boffetta, P; Fazioli, R; Cosciani Cunico, S; Alessio, L

1996-01-01

OBJECTIVES--A hospital based case-control study was conducted between 1992 and 1993 in the province of Brescia, a highly industrialised area in northern Italy, to evaluate occupational risk factors of bladder cancer. METHODS--The study evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80 women) and 579 controls affected by urological non-neoplastic diseases (397 men, 182 women). Lifetime occupational history, smoking and drinking habits, and sociodemographic characteristics were recorded by means of a structured questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking, alcohol and coffee consumption, education, and place of residence. RESULTS--A significant (P < 0.05) increase of risk of bladder cancer were found in men for labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI) 1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9). Increased risks, although not significant, were found for various other occupations and industries such as machinery mechanics, metal processers and polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased risk with increasing duration of employment was found. CONCLUSIONS--Occupational exposures seem to contribute to bladder cancer risk in the area under study. PMID:8563860

Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies.

PubMed

Hukkanen, V; Haarala, M; Nurmi, M; Klemi, P; Kiilholma, P

1996-01-01

Microbes may be involved in the pathogenesis of interstitial cystitis (IC). Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder and they are causative agents for hemorrhagic cystitis. We therefore studied the presence of adenovirus and BKV genomes in urinary bladder tissue specimens of patients with IC using polymerase chain reaction (PCR) and in situ hybridization (ISH). Controls were specimens from cases with transitional cell carcinoma of the bladder. Nucleic acids were extracted from paraffin sections of the bladder tissue for PCR. Primers detecting all adenovirus types were used. In situ hybridization was carried out for the paraffin sections using digoxigenin-labeled DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one to two infected cells/specimen. All the seven IC cases studied and six controls were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was also considered negative in IC cases and controls. The specimens which were negative in PCR tests yielded a signal with beta-globin primers, thus being amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic role in interstitial cystitis.

Management of transitional cell carcinoma of the urinary bladder in dogs: a review.

PubMed

Fulkerson, Christopher M; Knapp, Deborah W

2015-08-01

Transitional cell carcinoma (TCC), also referred to as urothelial carcinoma, is the most common form of urinary bladder cancer in dogs, affecting tens of thousands of dogs worldwide each year. Canine TCC is usually a high grade invasive cancer. Problems associated with TCC include urinary tract obstruction, distant metastases in >50% of affected dogs, and clinical signs that are troubling both to the dogs and to their owners. Risk factors for TCC include exposure to older types of flea control products and lawn chemicals, obesity, female sex, and a very strong breed-associated risk. This knowledge is allowing pet owners to take steps to reduce the risk of TCC in their dog. The diagnosis of TCC is made by histopathology of tissue biopsies obtained by cystoscopy, surgery, or catheter. Percutaneous aspirates and biopsies should be avoided due to the risk of tumor seeding. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Medical treatment is the mainstay for TCC therapy in dogs. Although TCC is not usually curable in dogs, multiple drugs have activity against it. Approximately 75% of dogs respond favorably to TCC treatment and can enjoy several months to a year or more of good quality life. Many promising new therapies for TCC are emerging and with the close similarity between TCC in dogs and high grade invasive bladder cancer in humans, new treatment strategies found to be successful in canine studies are expected to help dogs and to be subsequently translated to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulation of the release of ( sup 3 H)norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somogyi, G.T.; de Groat, W.C.

Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activationmore » of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.« less

Association between N-Acetyltransferase 2 Polymorphism and Bladder Cancer Risk: a Meta-Analysis in a Single Ethnic Group.

PubMed

Xu, Wan-Jiang; Wen, Li-Ping; Jiang, Xiang-Xin; Ye, Li-Yin; Meng, Fan-Hua; Guan, Sheng; Qian, Ying-Jun; Wei, Jing-Feng

2017-02-01

Many studies have evaluated the correlation between N-acetyltransferase 2 (NAT2) slow acetylation genotype and bladder cancer risk. However, the results are inconsistent and remain to be confirmed in each ethnic group. To assess the effects of NAT2 acetylation status on the risk of bladder cancer in the Chinese population, a meta-analysis was performed. Studies were identified using PubMed and Chinese databases through February 2016. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). This meta-analysis included 10 studies with 896 bladder cancer cases and 1188 controls. In the overall analysis, NAT2 slow acetylation phenotype was significantly associated with an increased risk of bladder cancer in the Chinese population (OR = 1.68, 95% CI = 1.11 - 2.53). In the subgroup analyses by geographic areas and sources of controls, significant risk was found in Mainland China (OR = 1.83, 95% CI = 1.04 - 3.20) and hospitalbased studies (OR = 1.74, 95% CI = 1.27 - 2.38), but not in Taiwan China. This meta-analysis suggested that the NAT2 slow acetylation genotype is associated with an increased bladder cancer risk in Chinese individuals.

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia

PubMed Central

Peh, Wendy Yen Xian; Mogan, Roshini; Thow, Xin Yuan; Chua, Soo Min; Rusly, Astrid; Thakor, Nitish V.; Yen, Shih-Cheng

2018-01-01

The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential peripheral targets for stimulation to treat dysfunctional bladders, but typical electrical stimulation of pelvic nerves activates both the parasympathetic efferent pathway to excite the bladder, as well as the sensory afferent pathway that causes unwanted sphincter contractions. Thus, a novel pelvic nerve stimulation paradigm is required. In anesthetized female rats, we combined a low frequency (10 Hz) stimulation to evoke bladder contraction, and a more proximal 20 kHz stimulation of the pelvic nerve to block afferent activation, in order to produce micturition with reduced bladder-sphincter dyssynergia. Increasing the phase width of low frequency stimulation from 150 to 300 μs alone was able to improve voiding outcome significantly. However, low frequency stimulation of pelvic nerves alone evoked short latency (19.9–20.5 ms) dyssynergic EUS responses, which were abolished with a non-reversible proximal central pelvic nerve cut. We demonstrated that a proximal 20 kHz stimulation of pelvic nerves generated brief onset effects at lower current amplitudes, and was able to either partially or fully block the short latency EUS responses depending on the ratio of the blocking to stimulation current. Our results indicate that ratios >10 increased the efficacy of blocking EUS contractions. Importantly, we also demonstrated for the first time that this combined low and high frequency stimulation approach produced graded control of the bladder, while reversibly blocking afferent signals that elicited dyssynergic EUS contractions, thus improving voiding by 40.5 ± 12.3%. Our findings support advancing pelvic nerves as a suitable neuromodulation target for treating bladder dysfunction, and demonstrate the feasibility of an alternative method to non-reversible nerve transection and sub-optimal intermittent stimulation methods to reduce dyssynergia. PMID:29618971

Neural control of Substance P-induced upregulation and release of macrophage migration inhibitory factor in the rat bladder

PubMed Central

Vera, Pedro L.; Wang, Xihai; Meyer-Siegler, Katherine L.

2009-01-01

OBJECTIVE Macrophage migration inhibitory factor (MIF) is increased in the intraluminal fluid after experimental inflammation and mediates pro-inflammatory effects on the bladder. We examined the contribution of nerve activity and of specific neurotransmitter systems on the mechanism of MIF release from the bladder during inflammation. MATERIALS & METHODS Male Sprague-Dawley rats were anesthetized, bladders were emptied and filled with saline. Rats received saline (s.c.; control; 0.1 ml/100 g bodyweight) or substance P (40 μg/kg in saline; s.c.; 0.1 ml/100 g bodyweight) and also received hexamethonium (50 mg/kg;i.p.; in saline; 0.1 ml/100 g body weight); intravesical lidocaine (2%; 0.3 ml), atropine (3 mg/kg in saline; i.v.; 0.1 ml/100 g body weight), propranolol (3 mg/kg in saline; i.v.; 0.1 ml/100 g body weight) or phentolamine (10 mg/kg in saline; i.v.; 0.1 ml/100 g body weight). After of 1 hour, the intravesical fluid was removed and the bladder was excised. MIF levels in the intraluminal fluid were measured by ELISA and Western-blotting. MIF expression in bladder homogenates was examined using RT-PCR. RESULTS Either intravesical lidocaine or ganglionic blockage with hexamethonium prevented Substance P-induced MIF release. In addition, pretreatment with atropine and phentolamine, but not propranolol, also prevented MIF release. MIF upregulation in the bladder, while increased with Substance P treatment, was only prevented by intravesical lidocaine. CONCLUSION Substance P-induced MIF release in the bladder is mediated through nerve activation. Post-ganglionic parasympathetic (via muscarinic receptors) and sympathetic (via alpha-adrenergic receptors) fibers mediate MIF release while activation of bladder afferent nerve terminals upregulate MIF. PMID:18499160

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

PubMed

Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

2011-12-01

This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

The urinary bladder of spontaneously hypertensive rat demonstrates bladder hypertrophy, inflammation, and fibrosis but not hyperplasia

PubMed Central

Shen, Shanwei; Xia, Chun-mei; Qiao, Li-Ya

2014-01-01

The present study aims to systemically characterize the factors that are associated with urinary bladder organ enlargement in the spontaneously hypertensive rats (SHR). Material and Methods We compared the SHR to age-matched normotensive Wistar-Kyoto (WKY) control rats in the levels of bladder pro-inflammatory factors, collagen expression (type I), and detrusor smooth muscle growth. Key Findings Our results showed that enhanced inflammatory responses and fibrosis were key factors that were closely associated with bladder wall thickening in SHR. Specifically the mRNA levels of inflammatory factors interleukin (IL)-1α, IL-6 and TNFα were significantly higher in SHR than those in WKY. The SHR also had a higher number of mast cells in the suburothelium space. Type I collagen production was also significantly higher in SHR when compared to those in control rats. However, the smooth muscle content stayed the same in SHR and WKY rats. This was shown as that the ratio of α-smooth muscle actin (SMA) to the nuclear protein histone H3 showed no difference between these two rat strains. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) also showed no change in the urinary bladder of SHR and WKY. Further study showed that the phosphorylation level of Akt in the urinary bladder was not changed in SHR when compared to WKY. In contrast, the phosphorylation level of ERK1/2 was significantly higher in SHR bladder when compared to WKY. Significance These results suggest that inflammation and fibrosis are primary factors that may lead to urinary bladder hypertrophy in SHR. PMID:25445218

Cigarette Smoking and the Risk of Bladder Cancer in Men and Women

PubMed Central

Quirk, Jeffrey T; Li, Qiang; Natarajan, Nachimuthu; Mettlin, Curtis J; Cummings, K Michael

2004-01-01

Although cigarette smoking is a principal risk factor for bladder cancer in both men and women, few studies have statistically evaluated whether gender modifies the effect of smoking on bladder cancer risk. We initiated the present case-control study at Roswell Park Cancer Institute in Buffalo, New York, U.S., to provide further data on this important issue. We observed similar risk estimates for men and women with comparable smoking exposures, but did not observe a statistically significant interaction between gender and lifetime smoking exposure. We conclude that cigarette smoking is a major risk factor for bladder cancer in both sexes, but that gender does not modify the effect of smoking on bladder cancer risk.

Symposium on Spina Bifida (Denver, Colorado, November, 1969).

ERIC Educational Resources Information Center

Colorado Univ., Denver. Medical Center.

The objectives of the symposium were to define the problems of the child with spina bifida and to present practical means of management, using a multi-disciplinary team approach. Eight papers defining the problem cover the epidemiology of spina bifida, pathophysiology, musculoskeletal defects, incontinence of bladder and bowel, problems of…

Differential Expression of Renal Outer Medullary K+ Channel and Voltage-gated K+ Channel 7.1 in Bladder Urothelium of Patients With Interstitial Cystitis/Painful Bladder Syndrome.

PubMed

Lee, Jane-Dar; Lee, Ming-Huei; Yang, Wen-Kai; Wang, Kuan-Lin; Lee, Tsung-Han

2017-03-01

To investigate the changes including expression and localization of 2 potassium channels, renal outer medullary K + channel (ROMK) and voltage-gated K + channel 7.1 (KCNQ1), after increased urinary potassium leakage in patients with interstitial cystitis/painful bladder syndrome (IC/PBS). The study group included 24 patients with IC/PBS and a control group consisting of 12 volunteers without any IC/PBS symptoms. Bladder biopsies were taken from both groups. We determined the protein expression and distribution of potassium channels using immunoblotting, immunohistochemistry, and immunofluorescent staining under confocal laser microscopy. The results revealed that ROMK was predominantly expressed in apical cells of the bladder urothelium at significantly higher levels (3.3-fold) in the study group than in the control group. In contrast, KCNQ1 was expressed in the basolateral membrane according to confocal microscopy results and did not significantly differ between groups. Our data showed that the abundance of ROMK protein in apical cells was increased in the IC/PBS group, whereas KCNQ1, which was distributed in the basolateral membrane of the bladder urothelium, showed similar abundance between groups. These results suggest that upregulation of the ROMK channel in apical cells might permit avid potassium flux into the bladder lumen to maintain intracellular K + homeostasis in the dysfunctional urothelium. Copyright © 2016 Elsevier Inc. All rights reserved.

Loxoprofen inhibits facilitated micturition reflex induced by acetic acid urinary bladder infusion of the rats.

PubMed

Shinozaki, Sachiyo; Saito, Motoaki; Kawatani, Masahito

2005-02-01

Prostaglandins (PGs) are well known as one of the chemical mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs), PG synthesis inhibitors, are used for anti-nociception and/or anti-inflammation. We examine the effect of loxoprofen, an NSAID, on micturiton in acetic acid-induced bladder inflammation of the rats. In cystometrogram study with saline infusion into the urinary bladder, loxoprofen did not alter the interval of bladder contraction (IC, 107% of the control). IC was shortened by acetic acid infusion (65% of the control) and loxoprofen prolonged the IC (162% of acetic acid infused period). This prolonged IC was approximately same as the control. Loxoprofen did not alter the threshold pressure and the maximal voiding pressure. These data suggest that PGE2 might not play a part of normal micturition and may play a part of the micturition reflex during acetic acid infusion. That is, loxoprofen might be useful for pathological hyperreflex of the micturition.

Orthotopic AY-27 rat bladder urothelial cell carcinoma model presented an elevated methemoglobin proportion in the increased total hemoglobin content when evaluated in vivo by single-fiber reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Sun, Tengfei; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.; Piao, Daqing

2017-02-01

In vivo single-fiber reflectance spectroscopy (SfRS) was performed on an orthotopic AY-27 rat bladder urothelial cell carcinoma model to explore potential spectroscopic features revealing neoplastic changes. AY-27 bladder tumor cells were intravesically instilled in four rats and allowed to implant and grow for one week, with two additional rats as the control. A total of 107 SfRS measurements were taken from 27 sites on two control bladders and 80 from four AY-27 treated bladders. The spectral profiles obtained from AY-27 treated bladders revealed various levels of a methemoglobin (MetHb) characteristic spectral feature around 635nm. A multisegment spectral analysis method estimated concentrations of five chromophore compositions including oxyhemoglobin, deoxyhemoglobin, MetHb, lipid and water. The total hemoglobin concentration ([HbT]), the MetHb proportion in the total hemoglobin and the lipid volume content showed possible correlations. The 80 measurements from the AY-27 treated bladders could separate to three sub-sets according to the MetHb proportion. Specifically, 72 were in subset 1 with low proportion (5.3%<[MetHb]<7%), 6 in subset 2 with moderate proportion (7%<[MetHb]<30%), and 2 in subset 3 with significant proportion (>30%). When grouped according to [MetHB], the [HbT] increased from 368 μM of subset 1 to 488 μM of subset 2 to 541 μM of subset 3, in comparison to the 285 μM of the control. The increased total hemoglobin and the elevation of MetHb proportion may signify angiogenesis and degradation in hemoglobin oxygen-transport. Additionally, the lipid volume content decreased from 2.58% in the control to <0.2% in the tumor groups, indicating disruption of subepithelium tissue architecture.

An animal model for the neuromodulation of neurogenic bladder dysfunction.

PubMed

Zvara, P; Sahi, S; Hassouna, M M

1998-08-01

To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

Swim bladder function and buoyancy control in pink snapper (Pagrus auratus) and mulloway (Argyrosomus japonicus).

PubMed

Stewart, John; Hughes, Julian M

2014-04-01

Physoclist fish are able to regulate their buoyancy by secreting gas into their hydrostatic organ, the swim bladder, as they descend through the water column and by resorbing gas from their swim bladder as they ascend. Physoclists are restricted in their vertical movements due to increases in swim bladder gas volume that occur as a result of a reduction in hydrostatic pressure, causing fish to become positively buoyant and risking swim bladder rupture. Buoyancy control, rates of swim bladder gas exchange and restrictions to vertical movements are little understood in marine teleosts. We used custom-built hyperbaric chambers and laboratory experiments to examine these aspects of physiology for two important fishing target species in southern Australia, pink snapper (Pagrus auratus) and mulloway (Argyrosomus japonicus). The swim bladders of pink snapper and mulloway averaged 4.2 and 4.9 % of their total body volumes, respectively. The density of pink snapper was not significantly different to the density of seawater (1.026 g/ml), whereas mulloway were significantly denser than seawater. Pink snapper secreted gas into their swim bladders at a rate of 0.027 ± 0.005 ml/kg/min (mean ± SE), almost 4 times faster than mulloway (0.007 ± 0.001 ml/kg/min). Rates of swim bladder gas resorption were 11 and 6 times faster than the rates of gas secretion for pink snapper and mulloway, respectively. Pink snapper resorbed swim bladder gas at a rate of 0.309 ± 0.069 ml/kg/min, 7 times faster than mulloway (0.044 ± 0.009 ml/kg/min). Rates of gas exchange were not affected by water pressure or water temperature over the ranges examined in either species. Pink snapper were able to acclimate to changes in hydrostatic pressure reasonably quickly when compared to other marine teleosts, taking approximately 27 h to refill their swim bladders from empty. Mulloway were able to acclimate at a much slower rate, taking approximately 99 h to refill their swim bladders. We estimated that the swim bladders of pink snapper and mulloway ruptured after decreases in ~2.5 and 2.75 times the hydrostatic pressure to which the fish were acclimated, respectively. Differences in buoyancy, gas exchange rates, limitations to vertical movements and acclimation times between the two species are discussed in terms of their differing behaviour and ecology.

Efficacy of bladder neck incision on urodynamic abnormalities in patients with posterior urethral valves.

PubMed

Sarin, Yogesh K; Sinha, Shalini

2013-04-01

This study aims to study the efficacy of simultaneous endoscopic bladder neck incision (BNI) and primary endoscopic valve incision (PEVI) in patients with posterior urethral valves (PUV). Nine PUV patients underwent PEVI and BNI over a year. They were compared to nine comparable historical controls that had undergone only PEVI. Trends in renal function tests, urodynamics and changes in the upper urinary tracts were evaluated after 3 months during which no pharmacotherapy was given. The incidence of bladder dysfunction in the two groups was similar-55.5 % in case group and 66.6 % in control group. Hypocompliant, high-pressure bladder was the predominant cystometric finding in both groups. Three patients in the case group and two patients in the control group had high end infusion pressure (EIP) with poor compliance. Detrusor overactivity (DOA) was seen in 23.1 % patients in the case group as compared to 55.5 % patients in the control group (P = 0.3348). Five patients in both groups were later started on anticholinergics due to raised EIP, small capacity bladder and/or DOA. Although BNI should theoretically improve the outcome of PUV patients, the current pilot study failed to demonstrate any significant difference. A larger sample size and longer follow-up are required to prove or disprove its efficacy.

Telomerase activity in solid transitional cell carcinoma, bladder washings, and voided urine.

PubMed

Lance, R S; Aldous, W K; Blaser, J; Thrasher, J B

1998-03-04

Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in patients with benign urologic diseases, especially those with symptomatic benign prostatic hyperplasia. An additional study of a larger number of both bladder cancer patients and those at risk is necessary to determine if telomerase activity could play a role as a diagnostic and/or surveillance marker of TCC. Published by Elsevier Science Inc.

Toward Self-Control Systems for Neurogenic Underactive Bladder: A Triboelectric Nanogenerator Sensor Integrated with a Bistable Micro-Actuator.

PubMed

Arab Hassani, Faezeh; Mogan, Roshini P; Gammad, Gil G L; Wang, Hao; Yen, Shih-Cheng; Thakor, Nitish V; Lee, Chengkuo

2018-04-24

Aging, neurologic diseases, and diabetes are a few risk factors that may lead to underactive bladder (UAB) syndrome. Despite all of the serious consequences of UAB, current solutions, the most common being ureteric catheterization, are all accompanied by serious shortcomings. The necessity of multiple catheterizations per day for a physically able patient not only reduces the quality of life with constant discomfort and pain but also can end up causing serious complications. Here, we present a bistable actuator to empty the bladder by incorporating shape memory alloy components integrated on flexible polyvinyl chloride sheets. The introduction of two compression and restoration phases for the actuator allows for repeated actuation for a more complete voiding of the bladder. The proposed actuator exhibits one of the highest reported voiding percentages of up to 78% of the bladder volume in an anesthetized rat after only 20 s of actuation. This amount of voiding is comparable to the common catheterization method, and its one time implantation onto the bladder rectifies the drawbacks of multiple catheterizations per day. Furthermore, the scaling of the device for animal models larger than rats can be easily achieved by adjusting the number of nitinol springs. For neurogenic UAB patients with degraded nerve function as well as degenerated detrusor muscle, we integrate a flexible triboelectric nanogenerator sensor with the actuator to detect the fullness of the bladder. The sensitivity of this sensor to the filling status of the bladder shows its capability for defining a self-control system in the future that would allow autonomous micturition.

Does increased urination frequency protect against bladder cancer?

PubMed

Silverman, Debra T; Alguacil, Juan; Rothman, Nathaniel; Real, Francisco X; Garcia-Closas, Montserrat; Cantor, Kenneth P; Malats, Nuria; Tardon, Adonina; Serra, Consol; Garcia-Closas, Reina; Carrato, Alfredo; Lloreta, Josep; Samanic, Claudine; Dosemeci, Mustafa; Kogevinas, Manolis

2008-10-01

Experimental studies suggest that increased urination frequency may reduce bladder cancer risk if carcinogens are present in the urine. Only 2 small studies of the effect of increased urination frequency on bladder cancer risk in humans have been conducted with conflicting results. Our purpose was to evaluate the effect of urination frequency on risk of bladder cancer in a large, multicenter case-control study. We analyzed data based on interviews conducted with 884 patients with newly diagnosed, bladder cancer and 996 controls from 1998 to 2001 in Spain. We observed a consistent, inverse trend in risk with increasing nighttime voiding frequency in both men (p = 0.0003) and women (p = 0.07); voiding at least 2 times per night was associated with a significant, 40-50% risk reduction. The protective effect of nocturia was apparent among study participants with low, moderate and high water consumption. The risk associated with cigarette smoking was reduced by nocturia. Compared with nonsmokers who did not urinate at night, current smokers who did not urinate at night had an OR of 7.0 (95% CI = 4.7-10.2), whereas those who voided at least twice per night had an OR of 3.3 (95% CI = 1.9-5.8) (p value for trend = 0.0005). Our findings suggest a strong protective effect of nocturia on bladder cancer risk, providing evidence in humans that bladder cancer risk is related to the contact time of the urothelium with carcinogens in urine. Increased urination frequency, coupled with possible dilution of the urine from increased water intake, may diminish the effect of urinary carcinogens on bladder cancer risk.

Dysfunction of the lower urinary and distal gastrointestinal tracts in pediatric patients with known spinal cord problems.

PubMed

Churchill, B M; Abramson, R P; Wahl, E F

2001-12-01

Destruction of the urinary tract in children with elimination, storage, and holding dysfunction of the lower urinary and the distal GI tracts is caused primarily by high intravesical pressure. UTI accelerates this process. The LPP and the status of the urethral control mechanism and its relationship to the detrusor are the primary determinants of intravesical pressure. Intravesical pressures of more than 40 cm H2O are dangerous because they cause a pressure gradient that is transmitted proximally to the renal papillae, which results in the cessation of renal blood flow and a loss of renal function over time. Hydroureteronephrosis, VUR, UTI, urinary incontinence, and calculi formation also may occur. If these dangerously high intravesical pressures remain untreated, renal failure is likely to occur over time. These children then require dialysis or renal transplantation to survive, which is tragic and represents an enormous economic cost to society. Renal failure and upper urinary tract damage is nearly 100% preventable with early and appropriate evaluation and treatment. CIC is a crucial part of the management of these children and has been shown to be safe and effective, even in newborn boys. The use of the Credé maneuver (i.e., manual compression) to empty the bladder is obsolete and should be abandoned. The distal GI tract is inseparable from the lower urinary tract and must be treated simultaneously. Failure to treat the distal GI tract yields poor clinical results and much patient dissatisfaction and makes it difficult or impossible to treat the child's urinary tract problem successfully. Bowel-management programs must include daily high water and fiber intake, together with digital perianal stimulation or fecal extraction. Neuropathic bladder and bowel problems that are intractable to conservative medical and mechanical (i.e., CIC and digital perianal stimulation or fecal extraction, respectively) management almost always can be corrected surgically with high success rates in cooperative patients. Finally, neuropathic bladder and bowel problems can be extremely isolating and debilitating problems. Psychologic counseling and emotional support must be provided as needed. The care that these patients receive must be organized, comprehensive, and correlated with these patients' lifestyles. If these children are evaluated and treated early, they have the potential to live long, healthy, and productive lives.

Catheter-associated UTI

MedlinePlus

... UTI; Health care-associated UTI; Catheter-associated bacteriuria; Hospital acquired-UTI Images Bladder catheterization, female Bladder catheterization, male References Calfee DP. Prevention and control of health care-associated infections. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

Biospectral analysis of the bladder channel point in chronic low back pain patients

NASA Astrophysics Data System (ADS)

Vidal, Alberto Espinosa; Nava, Juan José Godina; Segura, Miguel Ángel Rodriguez; Bastida, Albino Villegas

2012-10-01

Chronic pain is the main cause of disability in the productive age people and is a public health problem that affects both the patient and society. On the other hand, there isn't any instrument to measure it; this is only estimated using subjective variables. The healthy cells generate a known membrane potential which is part of a network of biologically closed electric circuits still unstudied. It is proposed a biospectral analysis of a bladder channel point as a diagnosis method for chronic low back pain patients. Materials and methods: We employed a study group with chronic low back pain patients and a control group without low back pain patients. The visual analog scale (VAS) to determine the level of pain was applied. Bioelectric variables were measured for 10 seconds and the respective biostatistical analyses were made. Results: Biospectral analysis on frequency domain shows a depression in the 60-300 Hz frequency range proportional to the chronicity of low back pain compared against healthy patients.

Treatment of Overactive Bladder Syndrome with Urethral Calibration in Women

PubMed Central

Sato, Renee L; Matsuura, Grace HK; Wei, David C; Chen, John J

2013-01-01

Our objective was to determine whether urethral calibration with Walther's urethral sounds may be an effective treatment for overactive bladder syndrome. The diagnosis of overactive bladder syndrome is a clinical one based on the presence of urgency, with or without urge incontinence, and is usually accompanied by frequency and nocturia in the absence of obvious pathologic or metabolic disease. These symptoms exert a profound effect on the quality of life. Pharmacologic treatment is generally used to relieve symptoms, however anticholinergic medications may be associated with several undesirable side effects. There are case reports of symptom relief following a relatively quick and simple office procedure known as urethral dilation. It is hypothesized that this may be an effective treatment for the symptoms of overactive bladder. Women with clinical symptoms of overactive bladder were evaluated. Eighty-eight women were randomized to either urethral calibration (Treatment), or placebo (Control) treatment. Women's clinical outcomes at two and eight weeks were assessed and compared between the two treatment arms. Eight weeks after treatment, 31.1% (n=14) of women who underwent urethral calibration were responsive to the treatment versus 9.3% (n=4) of the Control group. Also, 51.1% (n=23) of women within the Treatment group showed at least a partial response versus 20.9% (n=9) of the Control group. Our conclusion is that Urethral calibration significantly improves the symptoms of overactive bladder when compared to placebo and may be an effective alternative treatment method. PMID:24167769

Resveratrol improves urinary dysfunction in rats with chronic prostatitis and suppresses the activity of the stem cell factor/c-Kit signaling pathway.

PubMed

Yu, Yang; Jiang, Jiang; He, Yi; Wang, Wei; Shen, Chen; Yang, Bo

2017-08-01

Chronic prostatitis (CP) is a common urological disorder, with bladder voiding dysfunction being the primary clinical manifestation. Resveratrol is polyphenolic compound isolated from numerous plants, with widely‑reported anti-inflammatory properties. The present study aimed to investigate whether resveratrol may improve overactive bladder in rats with CP and to investigate the underlying molecular mechanisms. Furthermore, the potential pharmacological synergy between resveratrol and solifenacin was also investigated as a potential treatment for CP. Following the successful establishment of a rat model of CP by subcutaneously injecting DPT vaccine, rats were treated with resveratrol or a combination of resveratrol + solifenacin. Bladder pressure and volume tests were performed to investigate the effect of resveratrol and solifenacin on urinary dysfunction in rats with chronic prostatitis. Western blot analysis and immunohistochemical staining were used to examine the expression of c‑Kit receptor, stem cell factor (SCF), AKT and phosphorylated‑AKT (p‑AKT) in the bladder tissue. The results of the bladder pressure and volume test indicated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure in the control group were 0.57 ml, 0.17 ml and 29.62 cm H2O, respectively. These values were increased by 71, 27 and 206% in rats in the CP group compared with the control group. Following treatment with resveratrol, the results in the resveratrol group were reduced by 25.77, 44.23 and 13.32% compared with the CP group. The results of western blot analysis, immunohistochemical staining and immunofluorescence labeling demonstrate that the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats in the CP group was 4.32, 6.13 and 6.31 times higher compared with the control group, respectively. Following treatment with resveratrol, protein expression was significantly reduced. However, no significant differences were observed between the protein expression of the SCF, c‑Kit and p‑AKT in the bladder between the resveratrol and combination groups. In conclusion, resveratrol may improve overactive bladder by downregulating the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats with CP. Furthermore, a combination of resveratrol and solifenacin may have potential pharmacological synergy as a treatment for patients with CP.

Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder.

PubMed

Suadicani, Sylvia O; Urban-Maldonado, Marcia; Tar, Moses T; Melman, Arnold; Spray, David C

2009-06-01

To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X(1)R, and increase in P2X(7)R expression. There was decreased Cx43 and increased P2Y(4)R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X(1)R expression levels, and a positive correlation between bladder spontaneous activity and P2Y(4)R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y(2)R, P2X(4)R and increase in P2X(1)R expression in the corpora, and by a doubling in Cx43 and P2Y(2)R, and significant increase in P2Y(4)R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.

CHILDHOOD BLADDER STONES-AN ENDEMIC DISEASE OF DEVELOPING COUNTRIES.

PubMed

Lal, Bhamar; Paryani, Jai Pal; Memon, Shafique-ur-Rehman

2015-01-01

Bladder calculi are one of the commonest health problems in young children especially in rural and underprivileged areas. All children of bladder stones operated at District Headquarter Hospital Mithi from July 2009 to June 2012 were included in this cross-sectional study. Data was collected regarding age, sex, address (rural or urban), body weight, duration of breast feeding, weaning, detailed dietary history regarding milk type, volume, amount of water intake, recurrent diarrhoea, urinary tract infection (UTI), family history, and socioeconomic history. Urine analysis, complete blood count (CBC), renal function, ultra sound abdomen, X-ray kidney, ureter, and bladder (KUB) was done in all patients. All patients had cystolithotomy and were followed up till complete recovery. A total of 113 children (97 males and 16 females) operated at District Headquarter Hospital Mithi Tharparker were included in study. All patients belonged to local desert areas of Tharparker. Age ranged from 18 months to 14 year (mean age 8.6 year). Most frequent symptom was difficulty in micturition in 76 (67.25%) patients, urinary retention in 18 (15.9%) and stone with pyuria and fever in 12 (10.6%) patients. Recurrent episodes of diarrhoea (more than 3 episodes per year) in 73(65%) patients, recurrent UTI in 51 (45.6%), family history of stone disease in 6 (5%) and associated rectal prolapse in 3 (2.6%) patients. On x-ray KUB 111 (98%) patients had single stone in bladder, 2 (2%) had multiple stones and an associated renal and ureteric stone in 5 (4.5%). Mild anaemia (Hb 7-10 gm%) was seen in 35 (39.55%) patients, moderate anaemia (Hb 5-7 gm %) was seen in 21(24%) and severe anaemia (Hb less than 5 gm%) was seen in 14 (16%) patients. All patients had open cystolithotomy for removal of stones under general anaesthesia. Bladder stones are public health problem. Majority of affected patients were less than 5 years old. Low protein diet, dehydration, use of goat milk and poor socio-economic conditions were major risk factors identified for development of bladder stones.

Cigarette Smoking and the Risk of Bladder Cancer in Men and Women

PubMed Central

Quirk, Jeffrey T; Li, Qiang; Natarajan, Nachimuthu; Mettlin, Curtis J; Cummings, K Michael

2004-01-01

Although cigarette smoking is a principal risk factor for bladder cancer in both men and women, few studies have statistically evaluated whether gender modifies the effect of smoking on bladder cancer risk. We initiated the present case-control study at Roswell Park Cancer Institute in Buffalo, New York, U.S., to provide further data on this important issue. We observed similar risk estimates for men and women with comparable smoking exposures, but did not observe a statistically significant interaction between gender and lifetime smoking exposure. We conclude that cigarette smoking is a major risk factor for bladder cancer in both sexes, but that gender does not modify the effect of smoking on bladder cancer risk. PMID:19570280

Wolfram (DIDMOAD) syndrome: a multidisciplinary clinical study in nine Turkish patients and review of the literature.

PubMed

Simsek, E; Simsek, T; Tekgül, S; Hosal, S; Seyrantepe, V; Aktan, G

2003-01-01

To study Wolfram syndrome (WFS) with multidisciplinary consultations and compare the results with the literature. Nine patients fulfilled the ascertainment criteria of WFS (insulin-dependent diabetes mellitus and optic atrophy). All patients were evaluated by the departments of paediatrics, ophthalmology, audiology, urology and medical biology. The earliest manifestation of WFS was insulin-dependent diabetes mellitus (at a median age of 6.9 y), followed by optic atrophy (8.9 y), diabetes insipidus (10.2 y) and deafness (10.5 y). Short stature was found in five cases, delayed puberty in two cases and hypergonadotropic hypogonadism in one case. Audiography disclosed hearing loss at high frequency in all patients (100%), but only five patients had clinical subjective hearing problems. Intravenous pyelography revealed hydroureteronephrosis in eight patients. Urodynamics revealed a normal bladder in only one patient. Three patients had a low-capacity, low-compliance bladder, detrusor external sphincteric dyssynergia and emptying problem, while five had an atonic bladder. Ocular findings were optic atrophy, low visual acuity and colour vision defects. Visual field tests revealed concentric and/or peripheral diminution in five patients. Visual evoked potentials were abnormal (reduced amplitude to both flash and pattern stimulation) in seven patients. Cranial magnetic resonance imaging showed mild or moderate atrophy of the optic nerves, chiasm, cerebellum, basal ganglia and brainstem in six patients; there was a partially empty sella in one case. There was no evidence of mitochondrial tRNA(Leu) (UUR) A to G (nucleotide 3243) mutation. Wolfram syndrome should be evaluated in a multidisciplinary manner. Some specific and dynamic tests are necessary to make a more precise estimate of the prevalence and median age of the components of WFS. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotropic. Bladder dysfunction does not always present as a large atonic bladder in WFS. A low-capacity, high-pressure bladder with sphincteric dyssynergia is also common.

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

Overactive bladder symptom severity, bother, help-seeking behavior, and quality of life in patients with type 2 diabetes: a path analysis.

PubMed

Xu, Dongjuan; Zhao, Meng; Huang, Liqun; Wang, Kefang

2018-01-02

This study aimed to investigate the relationships among overactive bladder (OAB) symptom severity, bother, help-seeking behavior, and quality of life (QOL) in patients with type 2 diabetes. A total of 127 diabetic patients, aged at least 18 years, with overactive bladder from a hospital in Shandong Province, China, were recruited for this study. Symptom severity, bother, and quality of life were assessed using the Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder Condition (PPBC), and Overactive Bladder Questionnaire Short Form (OAB-q SF), respectively. Help-seeking behavior was assessed by asking patients whether they consulted health care professionals or received treatment for their bladder problems. A two-step path analysis was performed to analyze the data. OAB symptom severity was directly associated with lower levels of QOL, and the strength of this association was no longer significant when taking bother and help-seeking behavior into account. Bother increased with OAB symptom severity, and patients with bothersome OAB tended to have lower levels of QOL. Moreover, bother increased help-seeking behavior; however, patients who sought help tended to have lower levels of QOL. Our findings highlight the role of bother and help-seeking behavior in the relationship between OAB symptom severity and QOL. To improve a patient's QOL, health care providers should focus not only on symptom bother but also on dysfunctional help-seeking patterns.

Do patients with OAB experience bladder sensations in the same way as healthy volunteers? A focus group investigation.

PubMed

Heeringa, R; van Koeveringe, G A; Winkens, B; van Kerrebroeck, P E V; de Wachter, S G G

2012-04-01

To describe the terminology and pattern of bladder sensations experienced during non-invasive rapid bladder filling in a controlled setting in patients with OAB and to compare these results with a previous study conducted in healthy volunteers. Three groups of patients with OAB, in total 10 patients, participated in three consecutive focus group sessions. Before each session a strict water loading protocol was given. During the first two sessions, participants described how they experienced their bladder sensations in daily life and during a non-invasive bladder filling with constant focus on their bladder. The third session focused on verifying the interpretation of the data gathered and describing the pattern of sensations. Patients describe their bladder sensations as a pressure or a tingling sensation and the pattern can be described by terms ranging from no sensation to an absolute need to void. The absolute need to void may develop suddenly or more slowly progressive. The mean development of bladder sensation is significantly different between patients and healthy volunteers as well as their average diuresis. Patients with OAB describe their bladder sensations as a pressure or a tingling sensation. There appear to be two types of urgency: a sudden absolute need to void and a slowly developing absolute need to void. Furthermore bladder sensation develops significantly different in volunteers than in OAB patients. Copyright © 2012 Wiley Periodicals, Inc.

Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

PubMed

Beckham, Carla J; Olsen, Jayme; Yin, Peng-Nien; Wu, Chia-Hao; Ting, Huei-Ju; Hagen, Fred K; Scosyrev, Emelian; Messing, Edward M; Lee, Yi-Fen

2014-08-01

High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical utility of urinary soluble Fas in screening for bladder cancer.

PubMed

Srivastava, Anupam Kumar; Singh, Pankaj Kumar; Singh, Dhramveer; Dalela, Divakar; Rath, Srikanta Kumar; Bhatt, Madan Lal Brahma

2016-06-01

Early diagnosis of carcinoma of urinary bladder remains a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Soluble Fas (sFas), a cell-surface receptor and member of the tumor necrosis factor superfamily, is frequently expressed in urinary bladder carcinoma. The objective of this study was to investigate the urinary sFas for diagnosis of transitional cell carcinoma (TCC) of urinary bladder. We examined urinary sFas concentration in 74 controls and 117 cases of TCC, both primary and recurrent disease, by using enzyme-linked immunosorbent assay and compared it with urinary cytology. Urinary sFas concentration was found to be significantly higher in the patient as compared to control group (P < 0.05). An optimal cutoff value of 174.0 pg/mL was proposed. The urinary sFas level was found to have an approximate sensitivity and specificity of 88.03% and 89.19% (P < 0.001), whereas urine cytology had sensitivity of 66.67% and specificity of 95.95%. sFas had better sensitivity in higher grade and both primary and recurrent cases of urinary bladder cancer in comparison with cytology. Out of 15 node positive bladder cancer cases, 13 had high urinary sFas levels, whereas 12 were urinary cytology positive for malignancy. Urinary sFas can be used as a non-invasive diagnostic biomarker for TCC of urinary bladder, both for primary and recurrent disease. © 2014 Wiley Publishing Asia Pty Ltd.

PLK-1 Silencing in Bladder Cancer by siRNA Delivered With Exosomes.

PubMed

Greco, Kristin A; Franzen, Carrie A; Foreman, Kimberly E; Flanigan, Robert C; Kuo, Paul C; Gupta, Gopal N

2016-05-01

To use exosomes as a vector to deliver small interfering ribonucleic acid (siRNA) to silence the polo-like kinase 1 (PLK-1) gene in bladder cancer cells. Exosomes were isolated from both human embryonic kidney 293 (HEK293) cell and mesenchymal stem cell (MSC) conditioned media. Fluorescently labeled exosomes were co-cultured with bladder cancer and normal epithelial cells and uptake was quantified by image cytometry. PLK-1 siRNA and negative control siRNA were loaded into HEK293 and MSC exosomes using electroporation. An invasive bladder cancer cell line (UMUC3) was co-cultured with the electroporated exosomes. Quantitative reverse transcriptase polymerase chain reaction was performed. Protein analysis was performed by Western blot. Annexin V staining and MTT assays were used to investigate effects on apoptosis and viability. Bladder cancer cell lines internalize an increased percentage of HEK293 exosomes when compared to normal bladder epithelial cells. Treatment of UMUC3 cells with exosomes electroporated with PLK-1 siRNA achieved successful knockdown of PLK-1 mRNA and protein when compared to cells treated with negative control exosomes. HEK293 and MSC exosomes were effectively used as a delivery vector to transport PLK-1 siRNA to bladder cancer cells in vitro, resulting in selective gene silencing of PLK-1. The use of exosomes as a delivery vector for potential intravesical therapy is attractive. Copyright © 2016 Elsevier Inc. All rights reserved.

Thermal dosimetry for bladder hyperthermia treatment. An overview.

PubMed

Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

2016-06-01

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM.

PubMed

Bryan, R T; Regan, H L; Pirrie, S J; Devall, A J; Cheng, K K; Zeegers, M P; James, N D; Knowles, M A; Ward, D G

2015-03-17

Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

The modern staged repair of classic bladder exstrophy: a detailed postoperative management strategy for primary bladder closure.

PubMed

Stec, Andrew A; Baradaran, Nima; Schaeffer, Anthony; Gearhart, John P; Matthews, Ranjiv I

2012-10-01

Successful primary bladder closure of classic bladder exstrophy sets the stage for development of adequate bladder capacity and eventual voided continence. The postoperative pathway following primary bladder closure at the authors' institution is quantitatively and qualitatively detailed. Sixty-five consecutive newborns (47 male) undergoing primary closure of classic bladder exstrophy were identified and data were extracted relating to immediate postoperative care. Overall success rate was utilized to validate the pathway. Mean age at time of primary closure was 4.6 days and mean hospital stay was 35.8 days. Osteotomy was performed in 19 patients (mean age 8.8 days), and was not required in 39 infants (mean age 2.9 days). All patients were immobilized for 4 weeks. Tunneled epidural analgesia was employed in 61/65 patients. All patients had ureteral catheters and a suprapubic tube, along with a comprehensive antibiotic regimen. Postoperative total parenteral nutrition was commonly administered, and enteral feedings started around day 4.6. Our success rate of primary closure was 95.4%. A detailed and regimented plan for bladder drainage, immobilization, pain control, nutrition, antimicrobial prophylaxis, and adequate healing time is a cornerstone for the postoperative management of the primary closure of bladder exstrophy. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

[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.

Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

PubMed

Jacquez, Geoffrey M; Shi, Chen; Meliker, Jaymie R

2015-01-01

In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation. Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race. Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed. Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of Oakland and Ingham counties, and to the City of Jackson.

Health Related Quality of Life Following Radical Cystectomy: Comparative Analysis from the Medicare Health Outcomes Survey.

PubMed

Winters, Brian R; Wright, Jonathan L; Holt, Sarah K; Dash, Atreya; Gore, John L; Schade, George R

2017-09-05

Health related quality of life after radical cystectomy and ileal conduit is not well quantified at the population level. We evaluated health related quality of life in patients with bladder cancer compared with noncancer controls and patients with colorectal cancer using data from SEER (Surveillance, Epidemiology and End Results)-MHOS (Medicare Health Outcomes Survey). SEER-MHOS data from 1998 to 2013 were used to identify patients with bladder cancer and those with colorectal cancer who underwent extirpative surgery with ileal conduit or colostomy creation, respectively. A total of 166 patients with bladder cancer treated with radical cystectomy were propensity matched 1:5 to 830 noncancer controls and compared with 154 patients with colorectal cancer. Differences in Mental and Physical Component Summary scores as well as component subscores were determined between patients with bladder cancer, patients with colorectal cancer and noncancer controls. SEER-MHOS patients were more commonly male and white with a mean ± SD age of 77 ± 6 years. Patients treated with radical cystectomy had significantly lower Physical Component Summary scores, select physical subscale scores and all mental subscale scores compared with noncancer controls. These findings were similar in the subset of 40 patients treated with radical cystectomy who had available preoperative and postoperative survey data. Global Mental Component Summary scores did not differ significantly between the groups. No significant differences were observed in global Mental Component Summary, Physical Component Summary or subscale scores between patients with bladder cancer and patients with colorectal cancer. Patients with bladder cancer who undergo radical cystectomy have significant declines in multiple components of physical and mental health related quality of life vs noncancer controls, which mirror those of patients with colorectal cancer. Further longitudinal study is required to better codify the effectors of poor health related quality of life after radical cystectomy to improve patient expectations and outcomes. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prevention of postpartum stress incontinence in primigravidae with increased bladder neck mobility: a randomised controlled trial of antenatal pelvic floor exercises.

PubMed

Reilly, E T C; Freeman, R M; Waterfield, M R; Waterfield, A E; Steggles, P; Pedlar, F

2014-12-01

To test whether supervised pelvic floor exercises antenatally will reduce the incidence of postpartum stress incontinence in at-risk primigravidae with bladder neck mobility, ultrasonically proven. Single blind, randomised controlled trial. Antenatal clinic in a UK NHS Trust Hospital. Two hundred and sixty-eight primigravidae attending an antenatal clinic at approximately 20 weeks of gestation with bladder neck mobility, on standardised valsalva, of 5 mm or more linear movement. The median age was 28, ranging from 16 to 47 years. Patients randomised to supervised pelvic floor exercises (n = 139) attended a physiotherapist at monthly intervals from 20 weeks until delivery. The exercises comprised three repetitions of eight contractions each held for six seconds, with two minutes rest between repetitions. These were repeated twice daily. At 34 weeks of gestation the number of contractions per repetition was increased to 12. Both the untreated control group and the study group received verbal advice on pelvic floor exercises from their midwives antenatally. Subjective reporting of stress incontinence at three months postpartum. Pelvic floor strength, using perineometry, and bladder neck mobility measured by perineal ultrasound. Of the 268 women enrolled, information on the main outcome variable was available for 110 in the control group and 120 in the study group. Fewer women in the supervised pelvic floor exercise group reported postpartum stress incontinence, 19.2% compared with 32.7% in the control group (RR 0.59 [0.37-0.92]). There was no change in bladder neck mobility and no difference in pelvic floor strength between groups after exercise, although all those developing postpartum stress incontinence had significantly poorer perineometry scores than those who were continent. The findings suggest that antenatal supervised pelvic floor exercises are effective in reducing the risk of postpartum stress incontinence in primigravidae with bladder neck mobility. © RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology.

A case-control study of bladder cancer in the United States rubber and tyre industry.

PubMed

Checkoway, H; Smith, A H; McMichael, A J; Jones, F S; Monson, R R; Tyroler, H A

1981-08-01

A case-control study of bladder cancer was conducted in five United States rubber and tyre companies to determine if there were high-risk jobs and work areas within the industry. The study included 220 male cases of bladder cancer, of whom 107 were identified from hospital record reviews and 113 from death certificates. Each case was matched individually with two industry controls by sex, race, year of birth, and company. One control was matched additionally by year of hire and duration of employment. Comparisons of cases and controls not matched by year of hire and age of hire showed no differences for those variables, which suggests that age and calendar period of first exposure to the industry were not risk determinants. When the work histories of both cases and controls were contrasted it was found that cases were more likely than controls to have worked in milling (odds ratio (OR) = 1.91) and calender operation (OR = 2.21) jobs. The relative risk estimates for milling and calender operation both exhibited linear trends of increase with duration of exposure. Milling and calender operation jobs entail potential exposures to volatilised reaction products from heated rubber stock. A better understanding of aetiological associations with job type will require more detailed characterisation of the work environment with regard to the sources and levels of aromatic amines and other suspected bladder carcinogens.

A case-control study of bladder cancer in the United States rubber and tyre industry.

PubMed Central

Checkoway, H; Smith, A H; McMichael, A J; Jones, F S; Monson, R R; Tyroler, H A

1981-01-01

A case-control study of bladder cancer was conducted in five United States rubber and tyre companies to determine if there were high-risk jobs and work areas within the industry. The study included 220 male cases of bladder cancer, of whom 107 were identified from hospital record reviews and 113 from death certificates. Each case was matched individually with two industry controls by sex, race, year of birth, and company. One control was matched additionally by year of hire and duration of employment. Comparisons of cases and controls not matched by year of hire and age of hire showed no differences for those variables, which suggests that age and calendar period of first exposure to the industry were not risk determinants. When the work histories of both cases and controls were contrasted it was found that cases were more likely than controls to have worked in milling (odds ratio (OR) = 1.91) and calender operation (OR = 2.21) jobs. The relative risk estimates for milling and calender operation both exhibited linear trends of increase with duration of exposure. Milling and calender operation jobs entail potential exposures to volatilised reaction products from heated rubber stock. A better understanding of aetiological associations with job type will require more detailed characterisation of the work environment with regard to the sources and levels of aromatic amines and other suspected bladder carcinogens. PMID:7272236

Genome-wide interaction study of smoking and bladder cancer risk

PubMed Central

Figueroa, Jonine D.; Han, Summer S.; Garcia-Closas, Montserrat; Baris, Dalsu; Jacobs, Eric J.; Kogevinas, Manolis; Schwenn, Molly; Malats, Nuria; Johnson, Alison; Purdue, Mark P.; Caporaso, Neil; Landi, Maria Teresa; Prokunina-Olsson, Ludmila; Wang, Zhaoming; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Vineis, Paolo; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Bueno-de-Mesquita, H.Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Karagas, Margaret R.; Schned, Alan; Armenti, Karla R.; Hosain, G.M.Monawar; Haiman, Chris A.; Fraumeni, Joseph F.; Chanock, Stephen J.; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T.

2014-01-01

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10− 5 were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20–1.50, P value = 5.18 × 10− 7]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67–0.84, P value = 6.35 × 10− 7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers—including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene–environment interactions for tobacco and bladder cancer. PMID:24662972

Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer

PubMed Central

Yuan, Jian-Min; Chan, Kenneth K.; Coetzee, Gerhard A.; Castelao, J.Esteban; Watson, Mary A.; Bell, Douglas A.; Wang, Renwei; Yu, Mimi C.

2008-01-01

Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual’s susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case–control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19–48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19–1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12–1.81) and 1.71 (1.25–2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12–3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype. PMID:18544563

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

Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics.

PubMed

Sin, Mandy L Y; Mach, Kathleen E; Sinha, Rahul; Wu, Fan; Trivedi, Dharati R; Altobelli, Emanuela; Jensen, Kristin C; Sahoo, Debashis; Lu, Ying; Liao, Joseph C

2017-07-15

Purpose: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. Experimental Design: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients ( n = 13) and controls ( n = 10). Eight bladder cancer specific and 3 reference genes identified by RNA-seq were quantitated by qPCR in a training cohort of 102 urine samples. A diagnostic model based on the training cohort was constructed using multiple logistic regression. The model was further validated in an independent cohort of 101 urines. Results: A total of 418 genes were found to be differentially expressed between bladder cancer and controls. Validation of a subset of these genes was used to construct an equation for computing a probability of bladder cancer score (P BC ) based on expression of three markers ( ROBO1, WNT5A , and CDC42BPB ). Setting P BC = 0.45 as the cutoff for a positive test, urine testing using the three-marker panel had overall 88% sensitivity and 92% specificity in the training cohort. The accuracy of the three-marker panel in the independent validation cohort yielded an AUC of 0.87 and overall 83% sensitivity and 89% specificity. Conclusions: Urine-based molecular diagnostics using this three-marker signature could provide a valuable adjunct to cystoscopy and may lead to a reduction of unnecessary procedures for bladder cancer diagnosis. Clin Cancer Res; 23(14); 3700-10. ©2017 AACR . ©2017 American Association for Cancer Research.

Pneumovesical ureteric reimplantation using T-fastener: A modification for bladder wall anchorage.

PubMed

Lau, Chin Tung; Lan, Lawrence Chuen Leung; Wong, Kenneth Kak Yuen; Tam, Paul

2017-06-01

Bladder anchoring during pneumovesical ureteric reimplantation (PUR) can be difficult. Here we describe our new technique using a T-fastener (Kimberly Clark, Irving, TX, USA) to tackle this problem. A T-fastener has been applied to all patients who underwent PUR in our center since 2011. Seventeen consecutive cases were performed between 2011 and 2015. No bladder dislodgement or air leak was observed in any of the operations. No morbidity or mortality has been associated with the use of T-fasteners. In our experience, this technique is simple to learn and transferrable. It decreases intraoperative complications and helps to climb the learning curve. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Restoration of bladder function in spastic neuropathic bladder using sacral deafferentation and different techniques of neurostimulation.

PubMed

Schumacher, S; Bross, S; Scheepe, J R; Alken, P; Jünemann, K P

1999-01-01

Conventional sacral anterior root stimulation (SARS) results in simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation induced detrusor-sphincter-dyssynergia and to achieve a physiological voiding. The literature was reviewed on different techniques of sacral anterior root stimulation of the bladder and the significance of posterior rhizotomy in patients with supraconal spinal cord injury suffering from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. The achievement of selective detrusor activation would improve current sacral neurostimulation of the bladder, including the principle of "poststimulus voiding". This is possible with the application of selective neurostimulation in techniques of anodal block, high frequency block, depolarizing prepulses and cold block. Nowadays, sacral deafferentation is a standard therapy in combination with neurostimulation of the bladder because in conclusion advantages of complete rhizotomy predominate. The combination of sacral anterior root stimulation and sacral deafferentation is a successful procedure for restoration of bladder function in patients with supraconal spinal cord injury. Anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphincter-dyssynergia and thus improve stimulation induced voiding.

Morphological examination of the effects of defibrotide on experimentally induced bladder injury and its relation to interstitial cystitis.

PubMed

Aydin, H; Ercan, F; Cetinel, S; San, T

2001-08-01

This morphological study aims to investigate the effects of defibrotide, a deoxyribonucleic acid derivative drug with cytoprotective, immunosuppressive and vasorelaxant effects, on protamine sulfate induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or, either protamine sulfate (bladder injury group) or protamine sulfate+defibrotide (bladder injury+defibrotide group) dissolved in phosphate buffered solution. The morphology of the urinary bladder was investigated using light and electron microscopy. The number of mast cells in the mucosa, mucosal alterations, intercellular junctions, surface topography and the glycosaminoglycan (GAG) layer as well as microvillus formation on the luminal surface were evaluated. In the bladder injury group, ulcerated areas, irregularity of the GAG layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli and dilatations in the intercellular spaces in the urothelium were observed. In the bladder injury+defibrotide group a relatively normal urothelial topography, GAG layer and a few mast cells in the mucosa, some dilatations between the intercellular areas, less uniform microvilli, regular perinuclear cistern and tight junctions were observed. These results show that defibrotide can inhibit PS induced bladder damage.

ATP during early bladder stretch is important for urgency in detrusor overactivity patients.

PubMed

Cheng, Y; Mansfield, K J; Allen, W; Chess-Williams, R; Burcher, E; Moore, K H

2014-01-01

ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤ 200 mL) than in those with higher FDV (> 200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid.

An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat.

PubMed

Rahman, Nadeem U; Phonsombat, Surat; Bochinski, Derek; Carrion, Rafael E; Nunes, Lora; Lue, Tom F

2007-09-01

To present evidence that rats fed a high-fat diet could serve as a useful animal model to study both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), as recent epidemiological studies have shown a strong association between LUTS and ED but the physiological basis behind this relationship is unknown. In all, 24 male Sprague-Dawley rats were divided into two groups: nine controls were fed a 'normal' diet and 15 were fed a high-fat diet (hyperlipidaemic rats). After 6 months all the rats had bladder and erectile functions evaluated using awake cystometry and cavernosal nerve electrostimulation, respectively. After the functional studies were completed, the penis, prostate and bladder were collected for immunohistochemical analysis. The hyperlipidaemic rats had significantly higher serum cholesterol and low-density lipoprotein than the controls (P < 0.05). The hyperlipidaemic rats also had significantly worse erectile function (P = 0.004) and developed more bladder overactivity (P = 0.004) than the controls. In the hyperlipidaemic rats there was significant muscle hypertrophy in the peri-urethral lobe of the prostate (P < 0.001) and in the bladder (P < 0.05). There was also greater P2X(1) (purinoceptor) staining as well as other molecular changes in the bladder of the hyperlipidaemic rats. In this hyperlipidaemic rat model three abnormalities were consistently detected: prostatic enlargement, bladder overactivity, and ED. This rat model could be a useful research tool for understanding the common causes of LUTS and ED, as well as facilitating the development of preventive measures and better therapies to treat both conditions.

Male bladder cancer risk and occupational exposure according to a job-exposure matrix-a case-control study in British Columbia, Canada.

PubMed

Richardson, Kathryn; Band, Pierre R; Astrakianakis, George; Le, Nhu D

2007-12-01

The authors investigated the risk of bladder cancer in association with exposure to over 12 000 occupational chemical agents, complex mixtures, and other substances (hereafter referred to as chemical agents). Adult males diagnosed with cancer between 1983 and 1990 in British Columbia, Canada, were surveyed. Detailed occupational histories and confounding information was provided by a self-administered questionnaire. Cancer controls were matched to bladder cancer cases, resulting in 1062 cases and 8057 controls for the analysis. An extensive United-States-based job-exposure matrix was applied to estimate cumulative exposure to occupational chemical agents. Odds ratios for bladder cancer due to exposure to chemical agents were estimated via conditional logistic regression analyses, adjusted for important confounders. A significantly (P<0.05) increased risk was detected for ever exposure to 635 chemical agents, and 341 chemical agents exhibited a significantly increasing dose-response relationship. Adjustment for multiple comparisons resulted in a subset of 29 chemical agents that continued to show significant results. A principal components analysis classified these 29 chemical agents into five independent groups, distinguished mainly by job. Exposures to these chemical agents were largely due to employment in the logging and construction industries and occupations involving motor vehicles. Consistent results were observed for bladder carcinogens reported in the literature. This study suggests that several specific chemical agents were significantly associated with the risk of bladder cancer. The chemical agents were mainly derivatives or combustion products of fossil fuels. The results corroborate important findings from the literature and document a risk for specific chemical agents not previously reported.

Multi-center randomized controlled trial of cognitive treatment, placebo, oxybutynin, bladder training, and pelvic floor training in children with functional urinary incontinence.

PubMed

van Gool, Jan D; de Jong, Tom P V M; Winkler-Seinstra, Pauline; Tamminen-Möbius, Tytti; Lax, Hildegard; Hirche, Herbert; Nijman, Rien J M; Hjälmås, Kelm; Jodal, Ulf; Bachmann, Hannsjörg; Hoebeke, Piet; Walle, Johan Vande; Misselwitz, Joachim; John, Ulrike; Bael, An

2014-06-01

Functional urinary incontinence causes considerable morbidity in 8.4% of school-age children, mainly girls. To compare oxybutynin, placebo, and bladder training in overactive bladder (OAB), and cognitive treatment and pelvic floor training in dysfunctional voiding (DV), a multi-center controlled trial was designed, the European Bladder Dysfunction Study. Seventy girls and 27 boys with clinically diagnosed OAB and urge incontinence were randomly allocated to placebo, oxybutynin, or bladder training (branch I), and 89 girls and 16 boys with clinically diagnosed DV to either cognitive treatment or pelvic floor training (branch II). All children received standardized cognitive treatment, to which these interventions were added. The main outcome variable was daytime incontinence with/without urinary tract infections. Urodynamic studies were performed before and after treatment. In branch I, the 15% full response evolved to cure rates of 39% for placebo, 43% for oxybutynin, and 44% for bladder training. In branch II, the 25% full response evolved to cure rates of 52% for controls and 49% for pelvic floor training. Before treatment, detrusor overactivity (OAB) or pelvic floor overactivity (DV) did not correlate with the clinical diagnosis. After treatment these urodynamic patterns occurred de novo in at least 20%. The mismatch between urodynamic patterns and clinical symptoms explains why cognitive treatment was the key to success, not the added interventions. Unpredictable changes in urodynamic patterns over time, the response to cognitive treatment, and the gender-specific prevalence suggest social stress might be a cause for the symptoms, mediated by corticotropin-releasing factor signaling pathways. © 2013 Wiley Periodicals, Inc.

The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer.

PubMed

Shakhssalim, Nasser; Houshmand, Massoud; Kamalidehghan, Behnam; Faraji, Abolfazl; Sarhangnejad, Reza; Dadgar, Sepideh; Mobaraki, Maryam; Rosli, Rozita; Sanati, Mohammad Hossein

2013-12-05

Bladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues. The DNA from blood, tumoral tissues and adjacent non-tumoral tissues of twenty-six patients with bladder cancer and DNA from blood of 504 healthy controls from different ethnicities were investigated to determine sequence variation in the mitochondrial D-loop region using multiplex polymerase chain reaction (PCR), DNA sequencing and southern blotting analysis. From a total of 110 variations, 48 were reported as new mutations. No deletions were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not significantly correlated with bladder cancer, the C16069T variation was significantly present in patient samples compared to control samples (p < 0.05). Interestingly, there was no significant difference (p > 0.05) of C variations, including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between patients and control samples. Our study suggests that 16069 mitochondrial DNA D-Loop mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer.

Central control of visceral pain and urinary tract function.

PubMed

Lovick, Thelma A

2016-10-01

Afferent input from Aδ and C-fibres innervating the urinary bladder are processed differently by the brain, and have different roles in signaling bladder sensation. Aδ fibres that signal bladder filling activate a spino-bulbo-spinal loop, which relays in the midbrain periaqueductal grey (PAG) and pontine micturition centre (PMC). The excitability of this circuitry is regulated by tonic GABAergic inhibitory processes. In humans and socialised animals micturition is normally under volitional control and influenced by a host of psychosocial factors. Higher nervous decision-making in a social context to 'go now' or 'do not go' probably resides in frontal cortical areas, which act as a central control switch for micturition. Exposure to psychosocial stress can have profoundly disruptive influence on the process and lead to maladaptive changes in the bladder. During sleeping the voiding reflex threshold appears to be reset to a higher level to promote urinary continence. Under physiological conditions C-fibre bladder afferents are normally silent but are activated in inflammatory bladder states and by intense distending pressure. Following prolonged stimulation visceral nociceptors sensitise, leading to a lowered threshold and heightened sensitivity. In addition, sensitization may occur within the central pain processing circuitry, which outlasts the original nociceptive insult. Visceral nociception may also be influenced by genetic and environmental influences. A period of chronic stress can produce increased sensitivity to visceral pain that lasts for months. Adverse early life events can produce even longer lasting epigenetic changes, which increase the individual's susceptibility to developing visceral pain states in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

Spina Bifida

MedlinePlus

... brain. Some people with spina bifida may have learning problems, but most have normal intelligence. Most kids with spina bifida have some problems with their bowels and bladder. The nerves that send and receive messages from the brain can't do their job, so it's hard for kids to know when ...

Crowdsourcing Disease Biomarker Discovery Research: The IP4IC Study.

PubMed

Chancellor, Michael B; Bartolone, Sarah N; Veerecke, Andrew; Lamb, Laura E

2018-05-01

Biomarker discovery is limited by readily assessable, cost efficient human samples available in large numbers that represent the entire heterogeneity of the disease. We developed a novel, active participation crowdsourcing method to determine BP-RS (Bladder Permeability Defect Risk Score). It is based on noninvasive urinary cytokines to discriminate patients with interstitial cystitis/bladder pain syndrome who had Hunner lesions from controls and patients with interstitial cystitis/bladder pain syndrome but without Hunner lesions. We performed a national crowdsourcing study in cooperation with the Interstitial Cystitis Association. Patients answered demographic, symptom severity and urinary frequency questionnaires on a HIPAA (Health Insurance Portability and Accountability Act) compliant website. Urine samples were collected at home, stabilized with a preservative and sent to Beaumont Hospital for analysis. The expression of 3 urinary cytokines was used in a machine learning algorithm to develop BP-RS. The IP4IC study collected a total of 448 urine samples, representing 153 patients (147 females and 6 males) with interstitial cystitis/bladder pain syndrome, of whom 54 (50 females and 4 males) had Hunner lesions. A total of 159 female and 136 male controls also participated, who were age matched. A defined BP-RS was calculated to predict interstitial cystitis/bladder pain syndrome with Hunner lesions or a bladder permeability defect etiology with 89% validity. In this novel participation crowdsourcing study we obtained a large number of urine samples from 46 states, which were collected at home, shipped and stored at room temperature. Using a machine learning algorithm we developed BP-RS to quantify the risk of interstitial cystitis/bladder pain syndrome with Hunner lesions, which is indicative of a bladder permeability defect etiology. To our knowledge BP-RS is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome and one of the first biomarker assays to be developed using crowdsourcing. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

NASA Astrophysics Data System (ADS)

Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

2011-10-01

The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor Alpha in Cancer Bladder: Schistosomal and Non-Schistosomal

PubMed Central

Badawy, Afkar A.; El-Hindawi, Ali; Hammam, Olfat; Moussa, Mona; Helal, Noha S.; Kamel, Amira

2017-01-01

Introduction Overexpression of epidermal growth factor receptor (EGFR) has been described in several solid tumors including bladder cancer. Transforming growth factor alpha (TGFα) is frequently deregulated in neoplastic cells and plays a role in the development of bladder cancer. TGFα-EGFR ligand-receptor combination constitutes an important event in multistep tumorigenesis. Methods This study was done on 30 bladder biopsies from patients with urothelial carcinoma, 15 with squamous cell carcinoma, 10 with cystitis and 5 normal control bladder specimens. All were immuohistochemically stained with EGFR and TGFα antibodies. Results EGFR and TGFα were over-expressed in higher grades and late stages of bladder cancer. Moreover, they show higher expression in squamous cell carcinoma compared to urothelial carcinoma and in schistosomal associated lesions than in non-schistosomal associated lesions. Conclusion EGFR and TGFα could be used as prognostic predictors in early stage and grade of bladder cancer cases, especially those with schistosomal association. In addition they can help in selecting patients who can get benefit from anti-EGFR molecular targeted therapy. PMID:28413380

Neuromodulation in a rat model of the bladder micturition reflex

PubMed Central

Nickles, Angela; Nelson, Dwight E.

2012-01-01

A rat model of bladder reflex contraction (BRC) was used to determine the optimal frequency and intensity of spinal nerve (SN) stimulation to produce neuromodulation of bladder activity and to assess the therapeutic mechanisms of this neuromodulation. In anesthetized female rats (urethane 1.2 g/kg ip), a wire electrode was used to produce bilateral stimulation of the L6 SN. A cannula was placed into the bladder via the urethra, and the urethra was ligated to ensure an isovolumetric bladder. Saline infusion induced BRC. Electrical stimulation of the SN produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. Ten-herz stimulation produced maximal inhibition; lower and higher stimulation frequency produced less attenuation of BRC. Attenuation of bladder contraction frequency was directly proportional to the current intensity. At 10 Hz, stimulation using motor threshold pulses (Tmot) produced a delayed inhibition of the frequency of bladder contractions to 34 ± 11% of control. Maximal bladder inhibition appeared at 10 min poststimulation. High current intensity at 0.6 mA (∼6 * Tmot) abolished bladder contraction during stimulation, and the inhibition was sustained for 10 min poststimulation (prolonged inhibition). Furthermore, in rats pretreated with capsaicin (125 mg/kg sc), stimulation produced a stronger inhibition of BRC. The inhibitory effects on bladder contraction may be mediated by both afferent and efferent mechanisms. Lower intensities of stimulation may activate large, fast-conducting fibers and actions through the afferent limb of the micturition reflex arc in SN neuromodulation. Higher intensities may additionally act through the efferent limb. PMID:22049401

Pentosanpolysulfate coating of silicone reduces encrustation.

PubMed

Zupkas, P; Parsons, C L; Percival, C; Monga, M

2000-08-01

A significant problem associated with catheterization in the urinary tract is the encrustation of the catheter materials. One approach to reducing encrustation is to alter the surface properties of the catheters. We evaluated the effectiveness of coating with pentosanpolysulfate (PPS), a semisynthetic polysaccharide similar to heparin, in reducing encrustation and the foreign-body inflammatory response to silicone stents in the bladders of male New Zealand White rabbits. Sixteen rabbits were divided into three groups to receive placement in their bladders of uncoated (N = 7), PPS-coated (N = 7), or sham matrix-processed silicone rings (N = 2) via open cystotomy. After 50 days of maintenance on normal food and water, all rabbits were sacrificed, and the air-dried, unfixed silicone ring surfaces were examined by scanning electron microscopy. Bladders and remaining silicone rings were removed and preserved separately. Silicone rings, cleaned of all encrustation, were stained with toluidene blue to determine the presence or absence of PPS coating on the surface. Histologic examination revealed normal tissue in bladder sections exposed to coated silicone rings and an inflammatory response in sections from bladders having uncoated silicone rings. Coating with PPS was associated with an eightfold reduction in the amount of encrustation of silicone and a marked reduction in the inflammatory response of the bladder wall to the foreign body. A PPS coating may be useful in reducing the encrustation of long-term indwelling silicone stents or catheters in the human urinary tract.

Complications and salvage options after laser lithotripsy for a vesical calculus in a tetraplegic patient: a case report.

PubMed

Vaidyanathan, Subramanian; Singh, Gurpreet; Selmi, Fahed; Hughes, Peter L; Soni, Bakul M; Oo, Tun

2015-01-01

Laser lithotripsy of vesical calculi in tetraplegic subjects with long-term urinary catheters is fraught with complications because of bladder wall oedema, infection, fragile urothelium, bladder spasms, and autonomic dysreflexia. Severe haematuria should be anticipated; failure to institute measures to minimise bleeding and prevent clot retention can be catastrophic. We present an illustrative case. A tetraplegic patient underwent laser lithotripsy of vesical stone under general anaesthesia. During lithotripsy, severe bladder spasms and consequent rise in blood pressure occurred. Bleeding continued post-operatively resulting in clot retention. CT revealed clots within distended but intact bladder. Clots were sucked out and continuous bladder irrigation was commenced. Bleeding persisted; patient developed repeated clot retention. Cystoscopy was performed to remove clots. Patient developed abdominal distension. Bladder rupture was suspected; bed-side ultrasound scan revealed diffuse small bowel dilatation with mild peritoneal effusion; under-filled bladder containing small clot. Patient developed massive abdominal distension and ileus. Two days later, CT with oral positive contrast revealed intra-peritoneal haematoma at the dome of bladder with perforation at the site of haematoma. Free fluid was noted within the peritoneal cavity. This patient was managed by gastric drainage and intravenous fluids. Patient's condition improved gradually with urethral catheter drainage. Follow-up CT revealed resolution of bladder rupture, perivesical haematoma, and intra-peritoneal free fluid. If bleeding occurs, bladder irrigation should be commenced immediately after surgery to prevent clot retention. When bladder rupture is suspected, CT of abdomen should be done instead of ultrasound scan, which may not reveal bladder perforation. It is debatable whether laparotomy and repair of bladder rupture is preferable to nonoperative management in tetraplegics. Anti-muscarinic drugs should be prescribed prior to lithotripsy to control bladder spasms; aspirin and ibuprofen should be omitted. If significant bleeding occurs during lithotripsy, procedure should be stopped and rescheduled. Percutaneous cystolithotripsy using a wide channel could be quicker to clear stones, as larger fragments could be retrieved; lesser stimulant for triggering autonomic dysreflexia, as it avoids urethral manipulation. But in patients with small, contracted bladder, and protuberant abdomen, percutaneous access to urinary bladder may be difficult and can result in injury to bowels.

Effects of ageing and streptozotocin–induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder

PubMed Central

Suadicani, Sylvia O.; Urban–Maldonado, Marcia; Tar, Moses T.; Melman, Arnold; Spray, David C.

2012-01-01

OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X1R, and increase in P2X7R expression. There was decreased Cx43 and increased P2Y4R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X1R expression levels, and a positive correlation between bladder spontaneous activity and P2Y4R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y2R, P2X4R and increase in P2X1R expression in the corpora, and by a doubling in Cx43 and P2Y2R, and significant increase in P2Y4R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. CONCLUSION Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats. PMID:19154470

Virtual 3D bladder reconstruction for augmented medical records from white light cystoscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lurie, Kristen L.; Zlatev, Dimitar V.; Angst, Roland; Liao, Joseph C.; Ellerbee, Audrey K.

2016-02-01

Bladder cancer has a high recurrence rate that necessitates lifelong surveillance to detect mucosal lesions. Examination with white light cystoscopy (WLC), the standard of care, is inherently subjective and data storage limited to clinical notes, diagrams, and still images. A visual history of the bladder wall can enhance clinical and surgical management. To address this clinical need, we developed a tool to transform in vivo WLC videos into virtual 3-dimensional (3D) bladder models using advanced computer vision techniques. WLC videos from rigid cystoscopies (1280 x 720 pixels) were recorded at 30 Hz followed by immediate camera calibration to control for image distortions. Video data were fed into an automated structure-from-motion algorithm that generated a 3D point cloud followed by a 3D mesh to approximate the bladder surface. The highest quality cystoscopic images were projected onto the approximated bladder surface to generate a virtual 3D bladder reconstruction. In intraoperative WLC videos from 36 patients undergoing transurethral resection of suspected bladder tumors, optimal reconstruction was achieved from frames depicting well-focused vasculature, when the bladder was maintained at constant volume with minimal debris, and when regions of the bladder wall were imaged multiple times. A significant innovation of this work is the ability to perform the reconstruction using video from a clinical procedure collected with standard equipment, thereby facilitating rapid clinical translation, application to other forms of endoscopy and new opportunities for longitudinal studies of cancer recurrence.

Immunohistochemical study of parathyroid hormone-related protein in vesical transitional epithelium of patients with spinal cord injury.

PubMed

Vaidyanathan, S; McCreavy, D T; McDicken, I W; Soni, B M; Mansour, P; Wlodarski, B; Carron, J A; Fraser, W D; Singh, G; Sett, P; Gallagher, J A

1999-11-01

Parathyroid hormone-related protein (PTHrP), in addition to the well-established role in endochrondral bone development, is believed to be an important mediator of cellular growth and differentiation in a number of non-bony tissues. To compare the immunohistochemical staining of vesical transitional epithelium to antibodies raised to synthetic peptides of PTHrP composed of amino acid sequences 43 - 52 and 127 - 138 in patients with spinal cord injury (SCI) and neuropathic bladder (n=14), and control patients with intact neuraxis and no history of bladder cancer (n=10). Male SCI patients registered with Regional Spinal Injuries Centre, Southport, England. Endoscopic cold cup biopsy from the trigone of the urinary bladder was taken from patients with SCI while they were undergoing a therapeutic procedure in the urinary bladder. The control samples of bladder biopsies were taken from the archives of the Department of Histopathology, District General Hospital, Southport. Immunohistochemistry was performed using rabbit antibodies raised against synthetic peptides of human PTHrP (43 - 52) and PTHrP (127 - 138). The biopsies were examined for immunostaining of transitional epithelium. Of the 14 biopsies of SCI patients, positive immunostaining using antibodies to both the PTHrP peptides was found in four cases; five biopsies showed positive immunostaining only to anti-PTHrP (43 - 52); and five biopsies showed no immunostaining with either of the PTHrP peptides. In contrast, transitional epithelium in the biopsy specimens of ten control subjects with no history of bladder cancer showed no immunostaining with either of the PTHrP peptides. This study revealed that the transitional epithelium of neuropathic urinary bladder exhibits increased predilection for positive immunohistochemical staining for PTHrP (43 - 52), and to a lesser extent, to PTHrP (127 - 138), as compared to the vesical transitional epithelium of able bodied individuals with no history of vesical malignancy. The possible role of PTHrP in the cellular differentiation of urothelium of neuropathic bladder, and thereby, in the pathogenesis of cystitis in SCI patients, needs to be explored.

Prostaglandins as mediators of acidification in the urinary bladder of Bufo marinus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frazier, L.W.; Yorio, T.

1990-05-01

Experiments were performed to determine whether prostaglandins (PG) play a role in H+ and NH4+ excretion in the urinary bladder of Bufo marinus. Ten paired hemibladders from normal toads were mounted in chambers. One was control and the other hemibladder received PGE2 in the serosal medium (10(-5) M). H+ excretion was measured by change in pH in the mucosal fluid and reported in units of nmol (100 mg tissue)-1 (min)-1. NH4+ excretion was measured colorimetrically and reported in the same units. The control group H+ excretion was 8.4 +/- 1.67, while the experimental group was 16.3 +/- 2.64 (P lessmore » than 0.01). The NH4+ excretion in the experimental and control group was not significantly different. Bladders from toads in a 48-hr NH4+Cl acidosis (metabolic) did not demonstrate this response to PGE2 (P greater than 0.30). Toads were put in metabolic acidosis by gavaging with 10 ml of 120 mM NH4+Cl 3 x day for 2 days. In another experiment, we measured levels of PG in bladders from control (N) and animals placed in metabolic acidosis (MA). Bladders were removed from the respective toad, homogenized, extracted, and PG separated using high-pressure liquid chromatography and quantified against PG standards. The results are reported in ng (mg tissue)-1. PGE2 fraction in N was 1.09 +/- 0.14 and in MA was 3.21 +/- 0.63 (P less than 0.01). PGF1 alpha, F2 alpha and I2 were not significantly different in N and MA toads. Bladders were also removed from N and MA toads, and incubated in Ringer's solution containing (3H)arachidonic acid (0.2 microCi/ml) at 25 degrees C for 2 hr. Bladders were then extracted for PG and the extracts separated by thin layer chromatography. PG were identified using standards and autoradiography, scraped from plates, and counted in a scintillation detector. The results are reported in cpm/mg tissue x hr +/- SEM.« less

Bioimpedance harmonic analysis as a tool to simultaneously assess circulation and nervous control.

PubMed

Mudraya, I S; Revenko, S V; Nesterov, A V; Gavrilov, I Yu; Kirpatovsky, V I

2011-07-01

Multicycle harmonic (Fourier) analysis of bioimpedance was employed to simultaneously assess circulation and neural activity in visceral (rat urinary bladder) and somatic (human finger) organs. The informative value of the first cardiac harmonic of the bladder impedance as an index of bladder circulation is demonstrated. The individual reactions of normal and obstructive bladders in response to infusion cystometry were recorded. The potency of multicycle harmonic analysis of bioimpedance to assess sympathetic and parasympathetic neural control in urinary bladder is discussed. In the human finger, bioimpedance harmonic analysis revealed three periodic components at the rate of the heart beat, respiration and Mayer wave (0.1 Hz), which were observed under normal conditions and during blood flow arrest in the hand. The revealed spectrum peaks were explained by the changes in systemic blood pressure and in regional vascular tone resulting from neural vasomotor control. During normal respiration and circulation, two side cardiac peaks were revealed in a bioimpedance amplitude spectrum, whose amplitude reflected the depth of amplitude respiratory modulation of the cardiac output. During normal breathing, the peaks corresponding to the second and third cardiac harmonics were split, reflecting frequency respiratory modulation of the heart rate. Multicycle harmonic analysis of bioimpedance is a novel potent tool to examine the interaction between the respiratory and cardiovascular system and to simultaneously assess regional circulation and neural influences in visceral and somatic organs.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case–control study in Michigan, USA

PubMed Central

Slotnick, Melissa J.; AvRuskin, Gillian A.; Schottenfeld, David; Jacquez, Geoffrey M.; Wilson, Mark L.; Goovaerts, Pierre; Franzblau, Alfred; Nriagu, Jerome O.

2014-01-01

Objective Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose–response relationships for arsenic exposures below 100 µg/L remain equivocal. We conducted a population-based case–control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 µg/L. Methods This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants’ person-years. Results Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 µg/L when compared with a reference group exposed to <1 µg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 µg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). Conclusions We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure. PMID:20084543

Dynamic graciloplasty for urinary incontinence: the potential for sequential closed-loop stimulation.

PubMed

Zonnevijlle, Erik D H; Perez-Abadia, Gustavo; Stremel, Richard W; Maldonado, Claudio J; Kon, Moshe; Barker, John H

2003-11-01

Muscle tissue transplantation applied to regain or dynamically assist contractile functions is known as 'dynamic myoplasty'. Success rates of clinical applications are unpredictable, because of lack of endurance, ischemic lesions, abundant scar formation and inadequate performance of tasks due to lack of refined control. Electrical stimulation is used to control dynamic myoplasties and should be improved to reduce some of these drawbacks. Sequential segmental neuromuscular stimulation improves the endurance and closed-loop control offers refinement in rate of contraction of the muscle, while function-controlling stimulator algorithms present the possibility of performing more complex tasks. An acute feasibility study was performed in anaesthetised dogs combining these techniques. Electrically stimulated gracilis-based neo-sphincters were compared to native sphincters with regard to their ability to maintain continence. Measurements were made during fast bladder pressure changes, static high bladder pressure and slow filling of the bladder, mimicking among others posture changes, lifting heavy objects and diuresis. In general, neo-sphincter and native sphincter performance showed no significant difference during these measurements. However, during high bladder pressures reaching 40 cm H(2)O the neo-sphincters maintained positive pressure gradients, whereas most native sphincters relaxed. During slow filling of the bladder the neo-sphincters maintained a controlled positive pressure gradient for a prolonged time without any form of training. Furthermore, the accuracy of these maintained pressure gradients proved to be within the limits set up by the native sphincters. Refinements using more complicated self-learning function-controlling algorithms proved to be effective also and are briefly discussed. In conclusion, a combination of sequential stimulation, closed-loop control and function-controlling algorithms proved feasible in this dynamic graciloplasty-model. Neo-sphincters were created, which would probably provide an acceptable performance, when the stimulation system could be implanted and further tested. Sizing this technique down to implantable proportions seems to be justified and will enable exploration of the possible benefits.

Bladder outlet obstruction triggers neural plasticity in sensory pathways and contributes to impaired sensitivity in erectile dysfunction.

PubMed

Malykhina, Anna P; Lei, Qi; Chang, Shaohua; Pan, Xiao-Qing; Villamor, Antonio N; Smith, Ariana L; Seftel, Allen D

2013-05-15

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in aging males worldwide. The objective of this work was to evaluate the effects of bladder neck nerve damage induced by partial bladder outlet obstruction (PBOO) on sensory innervation of the corpus cavernosum (CC) and CC smooth muscle (CCSM) using a rat model of PBOO induced by a partial ligation of the bladder neck. Retrograde labeling technique was used to label dorsal root ganglion (DRG) neurons that innervate the urinary bladder and CC. Contractility and relaxation of the CCSM was studied in vitro, and expression of nitric oxide synthase (NOS) was evaluated by Western blotting. Concentration of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide was measured by ELISA. Partial obstruction of the bladder neck caused a significant hypertrophy of the urinary bladders (2.5-fold increase at 2 wk). Analysis of L6-S2 DRG sections determined that sensory ganglia received input from both the urinary bladder and CC with 5-7% of all neurons double labeled from both organs. The contractile responses of CC muscle strips to KCl and phenylephrine were decreased after PBOO, followed by a reduced relaxation response to nitroprusside. A significant decrease in neuronal NOS expression, but not in endothelial NOS or protein kinase G (PKG-1), was detected in the CCSM of the obstructed animals. Additionally, PBOO caused some impairment to sensory nerves as evidenced by a fivefold downregulation of SP in the CC (P ≤ 0.001). Our results provide evidence that PBOO leads to the impairment of bladder neck afferent innervation followed by a decrease in CCSM relaxation, downregulation of nNOS expression, and reduced content of sensory neuropeptides in the CC smooth muscle. These results suggest that nerve damage in PBOO may contribute to LUTS-ED comorbidity and trigger secondary changes in the contraction/relaxation mechanisms of CCSM.

Microwave radiometry for non-invasive detection of vesicoureteral reflux (VUR) following bladder warming

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolotti, Piero; Snow, Brent

2011-03-01

Background: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. Results: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. Conclusion: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects >=2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

Two differentially structured collagen scaffolds for potential urinary bladder augmentation: proof of concept study in a Göttingen minipig model.

PubMed

Leonhäuser, Dorothea; Stollenwerk, Katja; Seifarth, Volker; Zraik, Isabella M; Vogt, Michael; Srinivasan, Pramod K; Tolba, Rene H; Grosse, Joachim O

2017-01-04

The repair of urinary bladder tissue is a necessity for tissue loss due to cancer, trauma, or congenital abnormalities. Use of intestinal tissue is still the gold standard in the urological clinic, which leads to new problems and dysfunctions like mucus production, stone formation, and finally malignancies. Therefore, the use of artificial, biologically derived materials is a promising step towards the augmentation of this specialised tissue. The aim of this study was to investigate potential bladder wall repair by two collagen scaffold prototypes, OptiMaix 2D and 3D, naïve and seeded with autologous vesical cells, as potential bladder wall substitute material in a large animal model. Six Göttingen minipigs underwent cystoplastic surgery for tissue biopsy and cell isolation followed by implantation of unseeded scaffolds. Six weeks after the first operation, scaffolds seeded with the tissue cultured autologous urothelial and detrusor smooth muscle cells were implanted into the bladder together with additional unseeded scaffolds for comparison. Cystography and bladder ultrasound were performed to demonstrate structural integrity and as leakage test of the implantation sites. Eighteen, 22, and 32 weeks after the first operation, two minipigs respectively were sacrificed and the urinary tract was examined via different (immunohistochemical) staining procedures and the usage of two-photon laser scanning microscopy. Both collagen scaffold prototypes in vivo had good ingrowth capacity into the bladder wall including a quick lining with urothelial cells. The ingrowth of detrusor muscle tissue, along with the degradation of the scaffolds, could also be observed throughout the study period. We could show that the investigated collagen scaffolds OptiMaix 2D and 3D are a potential material for bladder wall substitution. The material has good biocompatible properties, shows a good cell growth of autologous cells in vitro, and a good integration into the present bladder tissue in vivo.

Microwave Radiometry for Non-Invasive Detection of Vesicoureteral Reflux (VUR) Following Bladder Warming.

PubMed

Stauffer, Paul R; Maccarini, Paolo F; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K; Bardati, Fernando; Tognolatti, Piero; Snow, Brent

2011-01-01

BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. METHODS: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. RESULTS: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

Aging and recurrent urinary tract infections are associated with bladder dysfunction in type 2 diabetes.

PubMed

Lin, Tzu-Li; Chen, Gin-Den; Chen, Yi-Ching; Huang, Chien-Ning; Ng, Soo-Cheen

2012-09-01

The objective of this study was to demonstrate the diversity of urodynamic findings and temporal effects on bladder dysfunction in diabetes as well as to evaluate the predisposing factors that attenuate the storage and voiding function of diabetic women. In this prospective study, 181 women with type 2 diabetes mellitus (DM) and lower urinary tract dysfunction underwent complete urogynecological evaluations and urodynamic studies. The patients' histories of DM and the treatment agents used were documented from chart records and interviews. The urodynamic diagnoses were recategorized into two groups for comparison, namely overactive detrusor (detrusor overactivity and/or increased bladder sensation as well as mixed incontinence) and voiding dysfunction (detrusor hyperactivity with insufficient contractility and detrusor underactivity with poor voiding efficiency) in order to evaluate the temporal effect of DM on diabetic bladder dysfunction. The development of bladder dysfunction showed a trend involving time-dependent progression, beginning with storage problems (i.e. advancing from urodynamic stress incontinence to detrusor overactivity and/or increased bladder sensation) and eventually led to impaired voiding function. The duration of DM relative to the urodynamic diagnoses of these women was longer in women with voiding dysfunction (6.8 ± 2.8 years with urodynamic stress incontinence, 7.3 ± 6.5 years with detrusor overactivity and/or increased bladder sensation, and 10.4 ± 8.3 years with women with voiding dysfunction). Notwithstanding these findings, stepwise logistic regression analysis indicated that age and recurrent urinary tract infections were the two independent factors associated with developing voiding dysfunction. The urodynamic study revealed a temporal effect on bladder function, and women with diabetic voiding dysfunction were found to have had a longer duration of DM than women with an overactive detrusor. However, aging and recurrent urinary tract infections are the two independent factors that contribute to impaired voiding function and diabetic bladder dysfunction. Copyright © 2012. Published by Elsevier B.V.

Association of N-acetyltransferase 1 polymorphism and bladder cancer risk: an updated meta-analysis and trial sequential analysis.

PubMed

Xu, Zicheng; Li, Xiao; Qin, Zhiqiang; Xue, Jianxin; Wang, Jingyuan; Liu, Zhentao; Cai, Hongzhou; Yu, Bin; Xu, Ting; Zou, Qin

2017-07-24

Individual studies of the association between N-acetyltransferase 1 (NAT1)*10 allele and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of any such relationship, we performed this systemic review and updated meta-analysis based on 17 publications. A total of 17 studies were investigated with 4,322 bladder cancer cases and 4,944 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Subgroup analyses were conducted based on ethnicity, sex, source of controls and detecting methods. Then trial sequential analysis was performed to evaluate whether the evidence of the results was sufficient and reduce the risk of type I error. There was no association between NAT1*10 allele and bladder cancer risk in a random-effects model (OR = 0.96, 95% CI, 0.84-1.10) or in a fixed-effects model (OR = 0.95, 95% CI, 0.87-1.03). In addition, no significantly increased risk of bladder cancer was found in any other subgroup analysis. Then, trial sequential analyses demonstrated that the results of our study need to be further verified. Despite its limitations, the results of the present meta-analysis suggested that there was no association between NAT1*10 allele and bladder cancer risk. More importantly, our findings need to be further validated regarding whether being without the NAT1*10 allele could in the future be shown to be a potential marker for the risk of bladder cancer.

Genetic variation in the base excision repair pathway and bladder cancer risk.

PubMed

Figueroa, Jonine D; Malats, Núria; Real, Francisco X; Silverman, Debra; Kogevinas, Manolis; Chanock, Stephen; Welch, Robert; Dosemeci, Mustafa; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Castaño-Vinyals, Gemma; Rothman, Nathaniel; García-Closas, Montserrat

2007-04-01

Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.

Quantification of effectiveness of bilateral and unilateral neuromodulation in the rat bladder rhythmic contraction model

PubMed Central

2013-01-01

Background Using the isovolumetric bladder rhythmic contraction (BRC) model in anesthetized rats, we have quantified the responsiveness to unilateral and bilateral stimulation of the L6 spinal nerve (SN) and characterized the relationship between stimulus intensity and inhibition of the bladder micturition reflex. Methods A wire electrode was placed under either one or both of the L6 SN roots. A cannula was placed into the bladder via the urethra and the urethra was ligated. Saline infusion induced BRC. Results At motor threshold (Tmot) intensity, SN stimulation of both roots (10 Hz) for 10 min reduced bladder contraction frequency from 0.63 ± 0.04 to 0.17 ± 0.09 contractions per min (26 ± 14% of baseline control; n = 10, p < 0.05). However, the same intensity of unilateral stimulation (n = 15) or sequential stimulation of both SNs (e.g. 5 min per side alternatively for a total of 10 min or 20 min) was less efficacious. The greater sensitivity to bilateral stimulation is not dependent upon precise bilateral timing of the stimulation pulses. Bilateral stimulation also produced both acute and prolonged- inhibition on bladder contractions in a stimulation intensity dependent fashion. Conclusions Using the bladder rhythmic contraction model, bilateral stimulation was more effective than unilateral stimulation of the SN. Clinical testing should be conducted to further compare efficacies of unilateral and bilateral stimulation. Bilateral stimulation may allow the use of lower stimulation intensities to achieve higher efficacy for neurostimulation therapies on urinary tract control. PMID:23866931

The relationship between promoter methylation of p16 gene and bladder cancer risk: a meta-analysis

PubMed Central

Qi, Defeng; Li, Jinhui; Jiang, Mei; Liu, Chenli; Hu, Yuan; Li, Mengxi; Su, Jialin; Que, Biao; Ji, Weidong

2015-01-01

Purpose: Many scientific evidences suggested that the methylation of p16INK4a (p16) was associated with bladder cancer, but some existing studies have yielded inconclusive results about the relationship between p16 promoter methylation and pathological features or the tumor grade of bladder cancer. This meta-analysis of studies aims to evaluate the clinical and prognostic significance of p16 methylation in bladder carcinogenesis. Methods: Studies were systemically searched via PubMed and Google Scholar in English up to Sept 2015 and a total of ten appropriate studies (693 cases and 290 controls) with an average NOS score of 6.8 were included. The quality of the appropriate studies was measured by the Newcastle-Ottawa Scale (NOS) assessment. Results: The meta-analysis results revealed that the methylation state of p16 was statistically significantly associated with an increased risk of bladder cancer (OR=6.71, 95% CI=3.79-11.87) compared to control, and there is no statistically significantly association between the p16 methylation and the tumor pTNM staging (OR=0.59, 95% CI=0.22-1.60) or the tumor grade (OR=1.01, 95% CI=0.52-1.94) in p16 methylated patients compared to unmethylated patients. Conclusions: our meta-analysis indicates that p16 promoter methylation may be a promising biomarker for the diagnosis of bladder cancer and the inactivation of p16 may be an early event in bladder carcinogenesis. More studies with larger numbers of participants worldwide are needed to further identify the obvious association above. PMID:26884993

Adjuvant photodynamic therapy (PDT) with photosensitizer photosens for superficial bladder cancer: experimental investigations to treat prostate cancer by PDT with photosens

NASA Astrophysics Data System (ADS)

Apolikhin, Oleg I.; Chernishov, Igor V.; Sivkov, Andrey V.; Altunin, Denis V.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

2007-07-01

14 patients with transional-cell bladder cancer in stage T1N0M0G2 after transurethral bladder resection were offered adjuvant treatment with PDT. Adjuvant PDT was performed 1-1.5 months after transurethral bladder resection for superficial bladder cancer. Prior to PDT conventional and fluorescent cystoscopy were performed. In the absence of inflammation and after full epitalisation of postoperative wound a session of therapy was performed. 24 hours prior to PDT-session photosensitizer Photosens was injected intravenously in the dose of 0.8 mg per kg of body weight. Prior to PDT local anesthesia of urethra with lidocain-gel was performed. Cystoscopy was carried out. PDT was performed with diode laser "Biospec" (675 nm). During the session the place of standing diffuser and the volume of a bladder were controlled. After 7 months of observation no tumor recidivists were observed. Registered side effects were not life-threatened. 5 patients had pain or discomfort in suprapubic area, ceasing spontaneously or requiring administration of analgetics. No systemic side-effects or allergic reactions were observed. The method can be used in out-patient practice. Absence of early recidivists shows efficiency of PDT in the treatment of superficial bladder cancer. Further study is necessary to estimate optimal regimen of PDT. The further controlling of condition on the patients in this group is required. At the laboratory animals' experiment, we conducted the explorations devoted to the influence of the photodynamic effect at the prostate's tissues.

Sealed-bladdered chemical processing method and apparatus

DOEpatents

Harless, D. Phillip

1999-01-01

A method and apparatus which enables a complete multi-stepped chemical treatment process to occur within a single, sealed-bladdered vessel 31. The entire chemical process occurs without interruption of the sealed-bladdered vessel 31 such as opening the sealed-bladdered vessel 31 between various steps of the process. The sealed-bladdered vessel 31 is loaded with a batch to be dissolved, treated, decanted, rinsed and/or dried. A pressure filtration step may also occur. The self-contained chemical processing apparatus 32 contains a sealed-bladder 32, a fluid pump 34, a reservoir 20, a compressed gas inlet, a vacuum pump 24, and a cold trap 23 as well as the associated piping 33, numerous valves 21,22,25,26,29,30,35,36 and other controls associated with such an apparatus. The claimed invention allows for dissolution and/or chemical treatment without the operator of the self-contained chemical processing apparatus 38 coming into contact with any of the process materials.

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators.

PubMed

Hassani, Faezeh Arab; Peh, Wendy Yen Xian; Gammad, Gil Gerald Lasam; Mogan, Roshini Priya; Ng, Tze Kiat; Kuo, Tricia Li Chuen; Ng, Lay Guat; Luu, Percy; Yen, Shih-Cheng; Lee, Chengkuo

2017-11-01

Underactive bladder or detrusor underactivity (DU) is defined as a reduction of contraction strength or duration of the bladder wall. Despite the serious healthcare implications of DU, there are limited solutions for affected individuals. A flexible 3D printed implantable device driven by shape memory alloys (SMA) actuators is presented here for the first time to physically contract the bladder to restore voluntary control of the bladder for individuals suffering from DU. This approach is used initially in benchtop experiments with a rubber balloon acting as a model for the rat bladder to verify its potential for voiding, and that the operating temperatures are safe for the eventual implantation of the device in a rat. The device is then implanted and tested on an anesthetized rat, and a voiding volume of more than 8% is successfully achieved for the SMA-based device without any surgical intervention or drug injection to relax the external sphincter.

[THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

PubMed

Mikhailenko, D S; Kushlinskii, N E

2016-02-01

All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

[The role of telomerase activity in non-invasive diagnostics of bladder cancer].

PubMed

Glybochko, P V; Alyaev, J G; Potoldykova, N V; Polyakovsky, K A; Vinarov, A Z; Glukhov, A I; Gordeev, S A

2016-08-01

To evaluate the potentials of determining the telomerase activity (TA) in the cellular material of the urine for noninvasive diagnosis of bladder cancer (BC). Evaluation of TA was performed in the urine of 48 patients with bladder cancer (study group) before and after transurethral resection of the bladder wall (n=38), an open resection of the bladder (n=4), and cystectomy (n=6). TA was also evaluated in 48 tumor tissue samples obtained from these patients during removal of the bladder tumor. Each sample of the tumor tissue was separated into two parts, one of which was subjected to histological examination, and the latter was used to determine the telomerase activity. In all cases, the diagnosis of bladder cancer was confirmed morphologically. Determination of TA in the samples was performed by the modified TRAP-method (telomerase repeat amplification protocol), RT-PCR, PCR, and electrophoresis. As a control, cell material of the urine and tissue in 12 patients with chronic cystitis was investigated. TA before surgery was found in 45 (93.75%) of 48 samples of cellular material of the urine from patients with suspected bladder cancer. BC was histologically verified in all patients in this group. In the postoperative period, TA was not observed in the 48 samples of cellular material of the urine from patients with BC. In the control group of patients with histologically verified cystitis, weak TA was determined only in one sample of cellular material of the urine. The analysis indicates statistically significant predominance of patients with bladder cancer in case of TA in the urine (P=0.001). TA was detected in all samples of tumor tissue. We also analyzed the dependence of TA levels in urine and tissue on the degree of BC differentiation. In patients with highly differentiated BC, mean AT in the cellular materials of the urine was 0,61% (n=15), in patients with moderately differentiated BC - 0.95% (n=23), in patients with low-grade bladder cancer - 1.33% (n=10); in other words, increase in the TA levels with decreasing the degree of differentiation was observed. This finding can be used in the prognosis of the course of disease based on determining the TA level in these patients. Preliminary data indicate the possibility of use of determining the TA in cellular material of the urine for the diagnosis and monitoring of bladder cancer recurrence.

Meta-analysis demonstrates lack of association of the hOGG1 Ser326Cys polymorphism with bladder cancer risk.

PubMed

Zhong, D Y; Chu, H Y; Wang, M L; Ma, L; Shi, D N; Zhang, Z D

2012-09-26

The functional polymorphism Ser326Cys (rs1052133) in the human 8-oxoguanine DNA glycosylase (hOGG1) gene has been implicated in bladder cancer risk. However, reports of this association between the Ser326Cys polymorphism and bladder cancer risk are conflicting. In order to help clarify this relationship, we made a meta-analysis of seven case-control studies, summing 2521 cases and 2408 controls. We used odds ratios (ORs) with 95% confidence intervals (95%CIs) to assess the strength of the association. Overall, no significant association between the hOGG1 Ser326Cys polymorphism and bladder cancer risk was found for Cys/Cys vs Ser/Ser (OR = 1.10, 95%CI = 0.74-1.65), Ser/Cys vs Ser/Ser (OR = 1.07, 95%CI = 0.81-1.42), Cys/Cys + Ser/Cys vs Ser/Ser (OR = 1.08, 95%CI = 0.87-1.33), and Cys/Cys vs Ser/Cys + Ser/Ser (OR = 1.04, 95%CI = 0.65-1.69). Even when stratified by ethnicity, no significant association was observed. We concluded that the hOGG1 Ser326Cys polymorphism does not contribute to susceptibility to bladder cancer.

Leak detection system and control using non-rigid bladder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pillette, K.P.

1980-11-11

A portable system for early detection of leaks from suspect piping fittings, for example, as used on the ''christmas tree'' portion of a gas well provides an encapsulating bladder which sealably encapsulates the suspect fitting and collects leaks from the fitting. The apparatus provides, in the preferred embodiment, a bladder which can encase any suspect portion of the christmas tree (Or like piping system), such as for example, the choke jacket or other like fittings where maximum turbulence occurs as when gas or oil mixed with sand flows through the fitting. In the preferred embodiment, the collection of a leakmore » within the bladder causes a regulator to operate a control valve and halt the flow of gas, oil, or like flowing material through the piping system of which the suspect fitting is a part. The system can be applied to any other similar existing and operating piping arrangement where the detection of leaks from suspect fittings is desirable. The portable bladder and shut off arrangement of the present invention has particular application in the offshore oil and gas industry, where it can perform a safety function on unmanned gas/oil well platforms.« less

The Role of Rac1 on Carbachol-induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin-induced Diabetic Rats.

PubMed

Evcim, Atiye Sinem; Micili, Serap Cilaker; Karaman, Meral; Erbil, Guven; Guneli, Ensari; Gidener, Sedef; Gumustekin, Mukaddes

2015-06-01

This study was designed to determine the role of the small GTPase Rac1 on carbachol-induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)-induced diabetic rat model, three study groups were composed of control, diabetic and insulin-treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8-12 weeks after STZ injection. Carbachol (CCh) (10(-9) -10(-4) M) concentration-response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 μM). Diabetes-related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose-dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh-induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin-treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh-induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes-related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Genetics Home Reference: bladder cancer

MedlinePlus

... events in bladder tumors. Researchers believe that several genes that control cell growth and division are probably located on chromosome 9 . ... Kwast TH, Zwarthoff EC, Radvanyi F. Novel fibroblast growth factor receptor ... identified in non-lethal skeletal disorders. Eur J Hum Genet. 2002 Dec;10( ...

Egg consumption and risk of bladder cancer: a meta-analysis.

PubMed

Li, Fei; Zhou, You; Hu, Rui-ting; Hou, Li-na; Du, Yue-Jun; Zhang, Xin-ji; Olkkonen, Vesa M; Tan, Wan-long

2013-01-01

The findings of epidemiologic studies on the association between egg consumption and bladder cancer risk remain conflicting. We conducted a meta-analysis to clarify the potential association between egg consumption and bladder cancer risk. Four cohort studies and 9 case-control studies in the PubMed database through February 2012 were identified on egg consumption and risk of bladder cancer involving 2715 cases and 184,727 participants. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest compared with the lowest category of egg consumption. In addition, we performed stratified analyses and sensitivity and dose-response analyses to examine the association. Overall, no significant association was observed between egg consumption and bladder cancer (SRRE = 1.11 95% CI: 0.90-1.35). However, increased risk of bladder cancer was detected in North/South America (SRRE = 1.40 95% CI: 1.05-1.86) and, moreover, fried egg intake positively associated with bladder cancer as well (SRRE = 2.04, 95% CI: 1.41-2.95). In conclusion, our findings suggest no significant association between egg consumption and bladder cancer risk, except for a possible positive relationship with the intake of fried eggs based on the limited number of studies. Additional studies, especially large prospective cohort studies, are warranted to confirm these findings.

Chronobiology of micturition: putative role of the circadian clock.

PubMed

Negoro, Hiromitsu; Kanematsu, Akihiro; Yoshimura, Koji; Ogawa, Osamu

2013-09-01

Mammals urinate less frequently during the sleep period than the awake period. This is modulated by a triad of factors, including decreased arousal in the brain, a decreased urine production rate in the kidneys and increased functional bladder capacity during sleep. The circadian clock is genetic transcription-translation feedback machinery. It exists in most organs and cells, termed the peripheral clock, which is orchestrated by the central clock in the suprachiasmatic nucleus of the brain. We discuss the linkage between the day and night change in micturition frequency and the genetic rhythm maintained by the circadian clock system, focusing on the brain, kidney and bladder. We performed an inclusive review of the literature on the diurnal change in micturition frequency, urine volume, functional bladder capacity and urodynamics in humans and rodents, relating this to recent basic biological findings about the circadian clock. In humans various behavioral studies demonstrated a diurnal functional change in the kidney and bladder. Conversely, patients with nocturnal enuresis and nocturia showed impairment in this triad of factors. Rats and mice, which are nocturnal animals, also have a micturition frequency rhythm that is decreased during the day, which is the sleep phase for them. Mice with a genetically defective circadian clock system show impaired physiological rhythms in the triad of factors. The existence of the circadian clock has been proven in the brain, kidney and bladder, in which thousands of circadian oscillating genes exist. In the kidney they include genes involved in the regulation of water and major electrolytes. In the bladder they include connexin 43, a gene associated with the regulation of bladder capacity. Recent progress in molecular biology about the circadian clock provides an opportunity to investigate the genetic basis of the micturition rhythm or impairment of the rhythm in nocturnal enuresis and nocturia. If this approach is to be translated clinically, a strategy is to analyze and treat the triad of micturition factors as separate parts of 1 problem. The other way could be to cope with this triad of problems simultaneously, if possible, by treating the circadian physiological rhythm itself. The discoveries reviewed point toward further investigation of the micturition rhythm by basic and translational chronobiology. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Urinary bladder organ hypertrophy is partially regulated by Akt1-mediated protein synthesis pathway.

PubMed

Qiao, Li-Ya; Xia, Chunmei; Shen, Shanwei; Lee, Seong Ho; Ratz, Paul H; Fraser, Matthew O; Miner, Amy; Speich, John E; Lysiak, Jeffrey J; Steers, William D

2018-05-15

The present study aims to investigate the role of Akt in the regulation of urinary bladder organ hypertrophy caused by partial bladder outlet obstruction (pBOO). Male rats were surgically induced for pBOO. Real-time PCR and western blot were used to examine the levels of mRNA and protein. A phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to inhibit the activity of endogenous Akt. The urinary bladder developed hypertrophy at 2 weeks of pBOO. The protein but not mRNA levels of type I collagen and α-smooth muscle actin (αSMA) were increased in pBOO bladder when compared to sham control. The phosphorylation (activation) levels of Akt1 (p-Ser 473 ), mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and 4E-BP1 were also increased in pBOO bladder. LY294002 treatment reduced the phosphorylation levels of Akt1 and 4E-BP1, and the protein levels of type I collagen and αSMA in pBOO bladder. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) were increased in pBOO bladder, and PCNA up-regulation occurred in urothelial not muscular layer. LY294002 treatment had no effect on the mRNA and protein levels of PCNA in pBOO bladder. LY294002 treatment partially reduced the bladder weight caused by pBOO. pBOO-induced urinary bladder hypertrophy is attributable to fibrosis, smooth muscle cellular hypertrophy, and urothelium cell hyper-proliferation. Akt1-mediated protein synthesis in pBOO bladder contributes to type I collagen and αSMA but not PCNA up-regulation. Target of Akt1 is necessary but not sufficient in treatment of urinary bladder hypertrophy following pBOO. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

PubMed

Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D; Resnick, Neil M

2015-09-01

Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Tobacco use, occupation, coffee, various nutrients, and bladder cancer.

PubMed

Howe, G R; Burch, J D; Miller, A B; Cook, G M; Esteve, J; Morrison, B; Gordon, P; Chambers, L W; Fodor, G; Winsor, G M

1980-04-01

In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.

Differences in Receipt of Three Preventive Health Care Services by Race/Ethnicity in Medicare Advantage Plans: Tracking the Impact of Pay for Performance, 2010 and 2013

PubMed Central

Palta, Mari; Smith, Maureen; Oliver, Thomas R.; DuGoff, Eva H.

2016-01-01

Introduction In 2012, the Centers for Medicare and Medicaid Services (CMS) introduced the Quality Bonus Payment Demonstration, a pay-for-performance (P4P) program, into Medicare Advantage plans. Previous studies documented racial/ethnic disparities in receipt of care among participants in these plans. The objective of this study was to determine whether P4P incentives have affected these disparities in Medicare Advantage plans. Methods We studied 411 Medicare Advantage health plans that participated in the Medicare Health Outcome Survey in 2010 and 2013. Preventive health care was defined as self-reported receipt of health care provider communication or treatment to reduce risk of falling, improve bladder control, and monitor physical activity among individuals reporting these problems. Logistic regression stratified by health care plan was used to examine racial/ethnic disparities in receipt of preventive health care before and after the introduction of the P4P program in 2012. Results We found similar racial/ethnic differences in receipt of preventive health care before and after the introduction of P4P. Blacks and Asians were less likely than whites to receive advice to improve bladder control and more likely to receive advice to reduce risk of falling and improve physical activity. Hispanics were more likely to report receiving advice about all 3 health issues than whites. After the introduction of P4P, the gap decreased between Hispanics and whites for improving bladder control and monitoring physical activity and increased between blacks and whites for monitoring physical activity. Conclusion Racial/ethnic differences in receipt of preventive health care are not always in the expected direction. CMS should consider developing a separate measure of equity in preventive health care services to encourage health plans to reduce gaps among racial/ethnic groups in receiving preventive care services. PMID:27609303

Differences in Receipt of Three Preventive Health Care Services by Race/Ethnicity in Medicare Advantage Plans: Tracking the Impact of Pay for Performance, 2010 and 2013.

PubMed

Jung, Daniel H; Palta, Mari; Smith, Maureen; Oliver, Thomas R; DuGoff, Eva H

2016-09-08

In 2012, the Centers for Medicare and Medicaid Services (CMS) introduced the Quality Bonus Payment Demonstration, a pay-for-performance (P4P) program, into Medicare Advantage plans. Previous studies documented racial/ethnic disparities in receipt of care among participants in these plans. The objective of this study was to determine whether P4P incentives have affected these disparities in Medicare Advantage plans. We studied 411 Medicare Advantage health plans that participated in the Medicare Health Outcome Survey in 2010 and 2013. Preventive health care was defined as self-reported receipt of health care provider communication or treatment to reduce risk of falling, improve bladder control, and monitor physical activity among individuals reporting these problems. Logistic regression stratified by health care plan was used to examine racial/ethnic disparities in receipt of preventive health care before and after the introduction of the P4P program in 2012. We found similar racial/ethnic differences in receipt of preventive health care before and after the introduction of P4P. Blacks and Asians were less likely than whites to receive advice to improve bladder control and more likely to receive advice to reduce risk of falling and improve physical activity. Hispanics were more likely to report receiving advice about all 3 health issues than whites. After the introduction of P4P, the gap decreased between Hispanics and whites for improving bladder control and monitoring physical activity and increased between blacks and whites for monitoring physical activity. Racial/ethnic differences in receipt of preventive health care are not always in the expected direction. CMS should consider developing a separate measure of equity in preventive health care services to encourage health plans to reduce gaps among racial/ethnic groups in receiving preventive care services.

A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder

PubMed Central

Ma, Emily; Vetter, Joel; Bliss, Laura; Lai, H. Henry; Mysorekar, Indira U.

2016-01-01

Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis. PMID:27029431

Associations of dietary carbohydrates, glycaemic index and glycaemic load with risk of bladder cancer: a case-control study.

PubMed

Augustin, Livia S A; Taborelli, Martina; Montella, Maurizio; Libra, Massimo; La Vecchia, Carlo; Tavani, Alessandra; Crispo, Anna; Grimaldi, Maria; Facchini, Gaetano; Jenkins, David J A; Botti, Gerardo; Serraino, Diego; Polesel, Jerry

2017-11-01

Carbohydrate foods with high glycaemic index (GI) and load (GL) may negatively influence cancer risk. We studied the association of dietary carbohydrates, GI, GL, intake of bread and pasta with risk of bladder cancer using data from an Italian case-control study. The study included 578 men and women with histologically confirmed bladder cancer and 608 controls admitted to the same hospitals as cases for acute, non-neoplastic conditions. OR were estimated by logistic regression models after allowance for relevant confounding factors. OR of bladder cancer for the highest v. the lowest quantile of intake were 1·52 (95 % CI 0·85, 2·69) for available carbohydrates, 1·18 (95 % CI 0·83, 1·67) for GI, 1·96 (95 % CI 1·16, 3·31, P trend<0·01) for GL, 1·58 (95 % CI 1·09, 2·29, P trend=0·03) for pasta and 1·92 (95 % CI 1·28, 2·86, P trend<0·01) for bread. OR for regular consumption of legumes and whole-grain products were 0·78 (95 % CI 0·60, 1·00) and 0·82 (95 % CI 0·63, 1·08), respectively. No heterogeneity in risks emerged across strata of sex. This case-control study showed that bladder cancer risk was directly associated with high dietary GL and with consumption of high quantity of refined carbohydrate foods, particularly bread. These associations were apparently stronger in subjects with low vegetable consumption.

Quality control and primo-diagnosis of transurethral bladder resections with full-field OCT

NASA Astrophysics Data System (ADS)

Montagne, P.; Ducesne, I.; Anract, J.; Yang, C.; Sibony, M.; Beuvon, F.; Delongchamps, N. B.; Dalimier, E.

2017-02-01

Transurethral resections are commonly used for bladder cancer diagnosis, treatment and follow-up. Cancer staging relies largely on the analysis of muscle in the resections; however, muscle presence is uncertain at the time of the resection. An extemporaneous quality control tool would be of great use to certify the presence of muscle in the resection, and potentially formulate a primo-diagnosis, in order to ensure optimum patient care. Full-field optical coherence tomography (FFOCT) offers a fast and non-destructive method of obtaining images of biological tissues at ultrahigh resolution (1μm in all 3 directions), approaching traditional histological sections. This study aimed to evaluate the potential of FFOCT for the quality control and the primo-diagnosis of transurethral bladder resections. Over 70 transurethral bladder resections were imaged with FFOCT within minutes, shortly after excision, and before histological preparation. Side-by-side comparison with histology allowed to establish reading criteria for the presence of muscle and cancer in particular. Images of 24 specimens were read blindly by three non-pathologists readers: two resident urologists and a junior bio-medical engineer, who were asked to notify the presence of muscle and tumor. Results showed that after appropriate training, 96% accuracy could be obtained on both tumour and muscle detection. FFOCT is a fast and nondestructive imaging technique that provides analysis results concordant with histology. Its implementation as a quality control and primo-diagnosis tool for transurethral bladder resections in the urology suite is feasible and lets envision high value for the patient.

[Reconstructive treatment of female urethral estenosis secondary to erosion by suburethral tape].

PubMed

Angulo, J C; Mateo, E; Lista, F; Andrés, G

2011-04-01

Female urethral stricture secondary to erosión by suburethral sling is an unfrequent problem of difficult solution. Ventral vaginal rotation flaps or buccal mucosa dorsal grafts are not useful because this type of stricture is very proximal (close to the bladder neck) and the vagina is thinned. We present our experience to manage this problem using excision of disease urethral tract, associated to bladder mucosa flap and vaginal sling using transverse vaginal flap to repair the weakened vaginal wall. Three females with urethral stricture secondary to urethral erosion of their sling were treated with a technique of combined urethroplasty with bladder flap and vaginal reinforcement with pediculated vaginal flap transferred in a mini-sling fashion. Two of the patients suffered chronic urinary retention and preoperative placement of urethral catheter was not possible. The patients were evaluated 12, 36 and 55 months after surgery, respectively. Surgery was performed without complications. Results were satisfactory in all the patients, reaching good micturition postoperative caliber and being without incontinence at follow-up. Patients with suburethral erosion by a synthetic sling and secondary severe urethral stricture need total extirpation of the mesh and complete reconstruction of the urethro-vaginal septum. Tension-free urethral suture and use of vaginal sling with the technique here described are two useful technical tips for this problem. Copyright © 2011 AEU. Published by Elsevier Espana. All rights reserved.

Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer

PubMed Central

Dai, Xiaoyu; Fang, Xiangming; Ma, Ying; Xianyu, Jianbo

2016-01-01

Abstract Benign prostatic hyperplasia (BPH) has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The aim of this study was to investigate the association between BPH and urologic cancers. MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched for potential eligible studies. We included case-control studies or cohort studies, which evaluated the association between BPH and urologic cancers (including prostate cancer, bladder cancer, kidney cancer, testicular cancer, or penile cancer). Overall effect estimates were calculated using the DerSimonian–Laird method for a random-effects model. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This systematic review included 16 case-control studies and 10 cohort studies evaluating the association of BPH and prostate or bladder cancer; we did not identify any study about other urologic cancers. Meta-analyses demonstrated that BPH was associated with an increased incidence of prostate cancer (case-control study: RR = 3.93, 95% CI = 2.18–7.08; cohort-study: RR = 1.41, 95% CI = 1.00–1.99) and bladder cancer (case-control study: RR = 2.50, 95% CI = 1.63–3.84; cohort-study: RR = 1.58, 95% CI = 1.28–1.95). Subgroup analysis by ethnicity suggested that the association between BPH and prostate cancer was much stronger in Asians (RR = 6.09, 95% CI = 2.96–12.54) than in Caucasians (RR = 1.54, 95% CI = 1.19–2.01). Egger's tests indicated low risk of publication bias (prostate cancer: P = 0.11; bladder cancer: P = 0.95). BPH is associated with an increased risk of prostate cancer and bladder cancer. The risk of prostate cancer is particularly high in Asian BPH patients. Given the limitations of included studies, additional prospective studies with strict design are needed to confirm our findings. PMID:27149447

Increased expression of GGN promotes tumorigenesis in bladder cancer and is correlated with poor prognosis.

PubMed

Wang, Wentao; Li, Changfu; Chen, Yongsheng; Teng, Lichen; Cao, Yan; Xu, Yongpeng; Pan, Hongxin; An, Ruihua

2018-04-30

Bladder cancer has shown great challenge for people's life. Traditional therapeutics against bladder cancer including surgery could not bring much benefit for patients, particularly for the late stage patients. So it is necessary to keep in mind why and how bladder cancer cells survive in our body. In this study, we explored the function and the molecular mechanism of GGN gene in bladder cancer. GGN was shown to be expressed at a high level in bladder cancer tissues compared to the control and was associated with the unsatisfactory survival rate of patients. GGN was also expressed abundantly in bladder cancer cell lines such as T24, 5637 and BIU87. Then GGN was knocked down in 5637 cells and T24 cells at both RNA and protein level. In accordance, aberrant growth and proliferation were demonstrated in bladder cancer cells. The ability of migration and invasion of bladder cancer cells was also inhibited. The in vivo data further proved that the xenograft tumor growth was dramatically suppressed by GGN knockdown. Then we demonstrated that the level of IκB, bax and truncated caspase3 was upregulated after GGN was knocked down in 5637 cells. In contrast, expression level of NFκB, IKK, c-Myc, cyclin D1 and Bcl-2 was reduced. Further, the phosphorylation level of IκB was also downregulated. These data suggest that NFκB/caspase3-mediated apoptosis signaling was regulated by GGN. Conclusively, GGN played a tumor-promoting role in bladder cancer through regulation of NFκB/caspase3-mediated apoptosis signaling. This study provides a new clue for the treatment of patients with bladder cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Cyclophosphamide-induced hemorrhagic cystitis in rats that underwent colocystoplasty: experimental study.

PubMed

Rodó, J; Farré, X; Martín, E

2001-02-01

Cyclophosphamide and its derivatives induce hemorrhagic cystitis. A substantial number of patients receive bladder augmentation or replacements using bowel. If patients who have undergone colocystoplasty need treatment with cyclophosphamide before or after the operation, does hemorrhagic cystitis develop? We evaluated the histological changes produced in the colon wall and bladder related to cyclophosphamide and its derivatives in rats that underwent colocystoplasty. Sprague-Dawley rats of each sex were grouped according to whether they received a single 200 mg./kg. dose of cyclophosphamide, underwent colocystoplasty, underwent each technique or served as controls. The technique of colocystoplasty was the same in all groups. Results were analyzed according to previously reported criteria, by the gross appearance of the bladder and colon segment used for colocystoplasty, and by histological changes. Two weeks after surgery colocystoplasty had not resulted in secondary changes in the implanted colon segment or original bladder, while there were only nonspecific changes of an inflammatory type in the anastomotic area. After cyclophosphamide administration the animals lost considerable weight and in the bladder area we observed hemorrhagic cystitis that was greater in males than in females, and greater in isolated bladder than when the bladder was sutured to the colon segment. In the colon there was no inflammation or hemorrhage damage of the hemorrhagic cystitis type in the bladder. A total of 12 days after colocystoplasty there were no secondary histological changes except in the anastomotic area. A single 200 mg./kg. dose of cyclophosphamide caused substantial weight loss and hemorrhagic cystitis. Cystitis was quantitatively greater in males than in females and greater in isolated bladder than in bladder anastomosed to the colon. Administering a single dose of cyclophosphamide did not result in lesions in the colon segment used for colocystoplasty analogous to those of the bladder, such as hemorrhagic cystitis.

Combined cystometrography and electromyography of the external urethral sphincter following complete primary repair of bladder exstrophy.

PubMed

Borer, Joseph G; Strakosha, Ruth; Bauer, Stuart B; Diamond, David A; Pennison, Melanie; Rosoklija, Ilina; Khoshbin, Shahram

2014-05-01

Concern in patients with bladder exstrophy after reconstruction regarding potential injury to pelvic neurourological anatomy and a resultant functional deficit prompted combined (simultaneous) cystometrography and electromyography after complete primary repair of bladder exstrophy. We determined whether complete primary repair of bladder exstrophy would adversely affect the innervation controlling bladder and external urethral sphincter function. Complete primary repair of bladder exstrophy was performed via a modified Mitchell technique in newborns without osteotomy. Postoperative evaluation included combined cystometrography and needle electrode electromyography via the perineum, approximating the external urethral sphincter muscle complex. Electromyography was done to evaluate the external urethral sphincter response to sacral reflex stimulation and during voiding. Nine boys and 4 girls underwent combined cystometrography/electromyography after complete primary repair of bladder exstrophy. Age at study and time after complete primary repair of bladder exstrophy was 3 months to 10 years (median 11.5 months). Cystometrography revealed absent detrusor overactivity and the presence of a sustained detrusor voiding contraction in all cases. Electromyography showed universally normal individual motor unit action potentials of biphasic pattern, amplitude and duration. The external urethral sphincter sacral reflex response was intact with a normal caliber with respect to Valsalva, Credé, bulbocavernosus and anocutaneous (bilateral) stimulation. Synergy was documented by abrupt silencing of external urethral sphincter electromyography activity during voiding. After complete primary repair of bladder exstrophy combined cystometrography/electromyography in patients with bladder exstrophy showed normal neurourological findings, including sacral reflex responses, sustained detrusor voiding contraction and synergic voiding, in all patients postoperatively. These findings confirm the safety of complete primary repair of bladder exstrophy. Based on our results we have discontinued routine electromyography in these patients. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Urothelial acetylcholine involvement in ATP-induced contractile responses of the rat urinary bladder.

PubMed

Stenqvist, Johanna; Winder, Michael; Carlsson, Thomas; Aronsson, Patrik; Tobin, Gunnar

2017-08-15

Both acetylcholine and adenosine 5'-triphosphate (ATP) are released from the urothelium. In in vivo experiments ATP has been shown to evoke contractile responses that are significantly reduced by atropine. Currently, we aimed to examine the cholinergic part of the ATP-evoked contractile response of normal and inflamed (cyclophosphamide-treated rats) bladders. A whole bladder preparation that enabled drug administration either outside or inside the urinary bladder was used. The responses were examined in bladders from control and cyclophosphamide-treated rats that were either intact or urothelium-denuded. The expression of choline acetyltransferase and carnitine acetyltransferase were examined by Western blotting of normal and inflamed bladders. Methacholine evoked larger contractions when administered to the outside of the bladder in comparison to instillation. For ATP, an opposite trend emerged. While atropine substantially reduced the ATP-induced responses at internal administration (7.4±1.1 and 3.7±0.9 mN at 10 -3 M; n=13; P<0.001), it had no effect when administered outside the bladder. The removal of the urothelium caused a similar reduction of the responses to internal administration of ATP as caused by atropine. In cyclophosphamide-treated rats, neither atropine nor urothelium-denudation had any effect on the ATP-evoked responses. No changes in the expressions of the acetylcholine synthesising enzymes were observed. The current study shows that ATP induces a release of urothelial acetylcholine that contributes to the purinergic contractile response in the rat urinary bladder. This atropine-sensitive part of the purinergic contractile response is absent in the inflamed bladder. This may be one pathological mechanism involved in bladder dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

PubMed

Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

2017-01-01

Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

Role for pAKT in rat urinary bladder with cyclophosphamide (CYP)-induced cystitis

PubMed Central

Arms, Lauren

2011-01-01

AKT phosphorylation following peripheral nerve injury or inflammation may play a role in somatic pain processes and visceral inflammation. To examine such a role in micturition reflexes with bladder inflammation, we induced bladder inflammation in adult female Wistar rats (200–300 g) by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every third day for 10 days) time points. Western blot analyses of whole urinary bladders showed significant increases (P ≤ 0.01) in phosphorylated (p) AKT at all time points; however, the magnitude of AKT phosphorylation varied with duration of CYP treatment. Immunohistochemical analyses of pAKT immunoreactivity (pAKT-IR) in cryostat bladder sections demonstrated duration-dependent, significant (P ≤ 0.01) increases in pAKT-IR in both the urothelium and detrusor smooth muscle of CYP-inflamed bladders. Additionally, a suburothelial population of pAKT-IR macrophages (CD68-, MAC2-, and F4/80-positive) was present in chronic CYP-treated bladders. The functional role of pAKT in micturition was evaluated using open, conscious cystometry with continuous instillation of saline in conjunction with administration of an inhibitor of AKT phosphorylation, deguelin (1.0 μg/10 μl), or vehicle (1% DMSO in saline) in control (no inflammation) and CYP (48 h)-treated rats. Bladder capacity, void volume, and intercontraction void interval increased significantly (P ≤ 0.05) following intravesical instillation of deguelin in CYP (48 h)-treated rats. These results demonstrate increased AKT phosphorylation in the urinary bladder with urinary bladder inflammation and that blockade of AKT phosphorylation in the urothelium improves overall bladder function. PMID:21632956

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

PubMed Central

Zhang, Fan; Mally, Abhijith D.; Ogagan, P. Dafe; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.

2012-01-01

Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3–7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50–60% of the saline control capacity. Tramadol administered alone in low doses (0.3–1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3–7 mg/kg) increased bladder capacity (50–60%). TNS in combination with tramadol (3–7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects. PMID:22496406

[Constipation in patients with diabetes mellitus].

PubMed

Rossol, Siegbert

2007-11-01

Up to 60% of the patients with diabetes mellitus suffer from gastrointestinal tract symptoms that arise pathogenetically from a disturbance of the autonomous nervous system. Patient age, disease duration and poor control of diabetes mellitus correlate positively with the presence of gastrointestinal symptoms. Chronic constipation, in addition to diarrhoea, gall bladder dysfunction and incontinence, is increasingly regarded as a serious problem and for the first time, is now considered in the current guidelines of the professional societies. Modern diagnosis and treatment facilitate systematic control of the symptoms. Treatment necessitates long-term intake of laxatives, proper diabetes control and other accompanying general measures such as adequate amounts of liquids, dietary fibre and exercise. Motility and secretion-stimulating, osmotically active or locally applied laxatives are used. Slow transit constipation, which is typically observed in diabetics, can be best controlled with polyethylene glycol, bisacodyl or sodium picosulphate.

Citrus fruit intake and bladder cancer risk: a meta-analysis of observational studies.

PubMed

Liang, Sudong; Lv, Gaofei; Chen, Weikai; Jiang, Jianxin; Wang, Jingqun

2014-11-01

Epidemiological studies have investigated the association between citrus fruit and bladder cancer risk; however, the results are inconsistent. To assess these issues, we conducted a meta-analysis of currently available studies. We identified relevant articles by searching the MEDLINE and EMBASE databases. We calculated the summary relative risk (RR) with 95% confidence interval (95% CI) using a random effect model. We included eight case-control studies and six cohort studies in the meta-analysis. There was a significant inverse association between citrus fruit intake and bladder cancer risk in all pooled studies (RR: 0.85; 95% CI, 0.76-0.94) and case-control studies (RR: 0.77; 95% CI, 0.64-0.92), but not in the cohort studies (RR: 0.96; 95% CI, 0.87-1.07). Our results suggest that citrus fruit intake is related to decreased bladder cancer risk. Subsequent well-designed, large prospective studies are needed to obtain better understanding of this relationship.

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

PubMed Central

Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

2017-01-01

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

Diabetes attenuates urothelial modulation of detrusor contractility and spontaneous activity.

PubMed

Wang, Yi; Tar, Moses T; Fu, Shibo; Melman, Arnold; Davies, Kelvin P

2014-10-01

To investigate the effect of diabetes on urothelial modulation of bladder contractility. Bladder strips (urothelium intact or denuded) were prepared from 8-week-old streptozotocin-induced diabetic (n = 19) and non-diabetic control rats (n = 10). The effect of modulators of MaxiK (iberiotoxin and tetraethylammonium) and Kv7 (XE991 and retigabine) potassium channel activity were investigated for their effects on both carbachol-induced force generation and spontaneous contractile activity. In bladder strips from non-diabetic animals, the presence of the urothelium resulted in marked sensitivity to carbachol-induced force generation by modulators of MaxiK and Kv7 channel activity, whereas in the diabetic animal urothelial sensitivity to these agents was significantly diminished. Urothelial-intact bladder strips from non-diabetic animals were more sensitive to modulators of Kv7 activity in reducing the amplitude of spontaneous phasic contractions than urothelial-denuded bladder strips, whereas in diabetic animals the presence or absence of the urothelium did not alter the sensitivity to modulators of Kv7 activity. Spontaneous activity in the presence of tetraethylammonium was not affected by the urothelium in bladder strips from either diabetic or non-diabetic animals. The presence of the urothelium in bladders from non-diabetic animals modulates the activity of potassium blockers to affect bladder contractility, whereas in the diabetic bladder this effect is attenuated. These findings could help to explain the lack of success of pharmaceutical treatments targeting potassium channels to treat bladder pathology in patients with diseases imparing urothelial function. © 2014 The Japanese Urological Association.

Effect of glycine on recovery of bladder smooth muscle contractility after acute urinary retention in rats.

PubMed

Hong, Sung K; Son, Hwancheol; Kim, Soo W; Oh, Seung-June; Choi, Hwang

2005-12-01

To investigate the effects of glycine on the recovery of bladder smooth muscle contractility after acute urinary retention. Bladder overdistension was induced in Sprague-Dawley rats by an infusion of saline (twice the threshold volume), maintained for 2 h. From 15 min before emptying of the bladder until 2 h after, saline or glycine solution was infused i.v. At 30 min, 2 h and 1 week after bladder emptying, samples of bladder tissue were taken for muscle strip study, malondialdehyde (MDA) assay, ATP assay, Western blotting for apoptosis-related molecules (Bcl-2, Bax, Caspase-3), and histological analysis including terminal deoxynucleotidyl transferase-mediated nick-end labelling staining. The results were compared among normal control, saline-treated and glycine-treated rats. In the glycine-treated group, muscle strip contractile responses induced by electrical-field stimulation and carbachol were both significantly greater at 1 week after bladder emptying than in the saline-treated group. The results of the ATP assay appeared to correspond with those of the muscle strip study. The saline-treated group had significantly higher MDA levels at 30 min after bladder emptying than the glycine-treated group. At 2 h after bladder emptying, there was significantly more apoptosis and greater leukocyte infiltration in the saline-treated group than in the glycine-treated group. While pro-apoptotic Bax and caspase-3 were down-regulated, Bcl-2 was up-regulated in the glycine-treated group. Glycine infusions might improve the contractile responses of bladder smooth muscle after acute urinary retention by reducing oxidative damage and apoptosis.

Chronic Infections of the Urinary Tract and Bladder Cancer Risk: a Systematic Review.

PubMed

Anderson-Otunu, Oghenetejiri; Akhtar, Saeed

2016-01-01

Literature on the relationship between recurrent urinary tract infections and urinary bladder carcinoma risk has been inconsistent. Therefore, we carried out this systematic review of observational studies to ascertain if there is any association between chronic urinary tract infection and urinary bladder carcinoma. A total of 10 databases were searched using Boolean: CINAHL, PUBMED, Google Scholar, Medline, Science Direct, SCIRUS, Cochrane, UK PubMed central, NHS evidence and WHO-website. The search yielded an initial hit of 3,518 articles and after screening and critical appraisal, seven studies were included for this review. Four articles reported an association between chronic urinary tract infections and bladder cancer while three concluded a weak or no association at least in one gender. Main findings in this review were that most of the studies reported an association between chronic urinary tract infections and bladder cancer risk. However, inferences about the causal association between chronic urinary tract infections and bladder cancer risk should be drawn cautiously considering the methodological limitations of case-control studies included in this review. Therefore, more empirical evidence is needed to determine the causal nature of relationships between chronic urinary tract infections and bladder cancer risk.

A meta-analysis of tea consumption and the risk of bladder cancer.

PubMed

Wang, Xiao; Lin, Yi-Wei; Wang, Shuai; Wu, Jian; Mao, Qi-Qi; Zheng, Xiang-Yi; Xie, Li-Ping

2013-01-01

Previous studies on the association between tea consumption and bladder cancer risk have only illustrated contradictory results. The role of tea in bladder carcinogenesis still remains conflicting. In order to illustrate the potential relationship between tea consumption and bladder cancer, a meta-analysis of case-control and cohort studies was conducted. Eligible studies were retrieved via both computerized searches and review of references. Stratified analyses on types of tea, gender, study design, ethnicity and smoking status were performed. Fixed- or random-effect models were used to summarize the estimates of OR with 95% CIs. Seventeen studies were eligible for our analysis. No statistical significance was detected between tea consumption and bladder cancer risk when comparing the highest with the lowest intake of tea (OR = 0.825, 95% CI 0.652-1.043). In the subgroup of green tea, we observed it illustrated a protective effect on bladder cancer (OR = 0.814, 95% CI 0.678-0.976). Our analysis indicated that green tea may have a protective effect on bladder cancer in Asian people. Further studies need to be conducted to better clarify the biological mechanisms. Copyright © 2012 S. Karger AG, Basel.

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin.

PubMed

Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C; Gomella, Leonard G; Belfiore, Antonino; Black, Peter C; Iozzo, Renato V; Morrione, Andrea

2016-06-28

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer.

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin

PubMed Central

Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C.; Gomella, Leonard G.; Belfiore, Antonino; Black, Peter C.; Iozzo, Renato V.; Morrione, Andrea

2016-01-01

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer. PMID:27220888

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies.

PubMed

Palma, Jose-Alberto; Kaufmann, Horacio

2018-03-01

Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Health-Related Quality of Life after Cystectomy and Urinary Diversion for Bladder Cancer

PubMed Central

Shih, Cheryl; Porter, Michael P.

2011-01-01

With multiple options for urinary diversion after radical cystectomy for bladder cancer that have comparable cancer control and complication rates, health-related quality of life (HRQOL) has become an important consideration. This article reviews the methods for defining HRQOL, the challenges in measuring HRQOL in bladder cancer, and the literature comparing HRQOL after various methods of urinary diversion. Recent contributions include the validation of HRQOL instruments specific to bladder cancer and the publication of several prospective studies measuring HRQOL outcomes after cystectomy and urinary diversion. There is no convincing evidence from existing literature that any particular method of urinary diversion offers superior HRQOL outcomes. Rather, there is growing evidence that good HRQOL can be achieved with patient education and consideration of each patient's clinical and psychosocial situation. Future research should utilize the validated bladder cancer specific HRQOL instruments and perhaps explore the impact of preoperative counseling on postoperative HRQOL. PMID:21826139

Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk.

PubMed

Tang, Li; Zirpoli, Gary R; Guru, Khurshid; Moysich, Kirsten B; Zhang, Yuesheng; Ambrosone, Christine B; McCann, Susan E

2008-04-01

Cruciferous vegetables contain isothiocyanates, which show potent chemopreventive activity against bladder cancer in both in vitro and in vivo studies. However, previous epidemiologic studies investigating cruciferous vegetable intake and bladder cancer risk have been inconsistent. Cooking can substantially reduce or destroy isothiocyanates, and could account for study inconsistencies. In this hospital-based case-control study involving 275 individuals with incident, primary bladder cancer and 825 individuals without cancer, we examined the usual prediagnostic intake of raw and cooked cruciferous vegetables in relation to bladder cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with unconditional logistic regression, adjusting for smoking and other bladder cancer risk factors. We observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable intake (adjusted OR for highest versus lowest category = 0.64; 95% CI, 0.42-0.97), with a significant trend (P = 0.003); there were no significant associations for fruit, total vegetables, or total cruciferous vegetables. The associations observed for total raw crucifers were also observed for individual raw crucifers. The inverse association remained significant among current and heavy smokers with three or more servings per month of raw cruciferous vegetables (adjusted ORs, 0.46 and 0.60; 95% CI, 0.23-0.93 and 0.38-0.93, respectively). These data suggest that cruciferous vegetables, when consumed raw, may reduce the risk of bladder cancer, an effect consistent with the role of dietary isothiocyanates as chemopreventive agents against bladder cancer.

Protease-Activated Receptor 4 Induces Bladder Pain through High Mobility Group Box-1

PubMed Central

Kouzoukas, Dimitrios E.; Ma, Fei; Meyer-Siegler, Katherine L.; Westlund, Karin N.; Hunt, David E.; Vera, Pedro L.

2016-01-01

Pain is the significant presenting symptom in Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS). Activation of urothelial protease activated receptor 4 (PAR4) causes pain through release of urothelial macrophage migration inhibitory factor (MIF). High Mobility Group Box-1 (HMGB1), a chromatin-binding protein, mediates bladder pain (but not inflammation) in an experimental model (cyclophosphamide) of cystitis. To determine if PAR4-induced bladder hypersensitivity depends on HMGB1 downstream, we tested whether: 1) bladder PAR4 stimulation affected urothelial HMGB1 release; 2) blocking MIF inhibited urothelial HMGB1 release; and 3) blocking HMGB1 prevented PAR4-induced bladder hypersensitivity. HMGB1 release was examined in immortalized human urothelial cultures (UROtsa) exposed to PAR4-activating peptide (PAR4-AP; 100 μM; 2 hours) or scrambled control peptide. Female C57BL/6 mice, pretreated with a HMGB1 inhibitor (glycyrrhizin: 50 mg/kg; ip) or vehicle, received intravesical PAR4-AP or a control peptide (100 μM; 1 hour) to determine 1) HMGB1 levels at 1 hour in the intravesical fluid (released HMGB1) and urothelium, and 2) abdominal hypersensitivity to von Frey filament stimulation 24 hours later. We also tested mice pretreated with a MIF blocker (ISO-1: 20 mg/kg; ip) to determine whether MIF mediated PAR4-induced urothelial HMGB1 release. PAR4-AP triggered HMGB1 release from human (in vitro) and mice (in vivo) urothelial cells. Intravesical PAR4 activation elicited abdominal hypersensitivity in mice that was prevented by blocking HMGB1. MIF inhibition prevented PAR4-mediated HMGB1 release from mouse urothelium. Urothelial MIF and HGMB1 represent novel targets for therapeutic intervention in bladder pain conditions. PMID:27010488

Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huddart, Robert A., E-mail: robert.huddart@icr.ac.uk; Hall, Emma; Hussain, Syed A.

2013-10-01

Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. Themore » primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.« less

Bladder cancer and occupational exposure to diesel and gasoline engine emissions among Canadian men.

PubMed

Latifovic, Lidija; Villeneuve, Paul J; Parent, Marie-Élise; Johnson, Kenneth C; Kachuri, Linda; Harris, Shelley A

2015-12-01

The International Agency for Research on Cancer has classified diesel exhaust as a carcinogen based on lung cancer evidence; however, few studies have investigated the effect of engine emissions on bladder cancer. The purpose of this study was to investigate the association between occupational exposure to diesel and gasoline emissions and bladder cancer in men using data from the Canadian National Enhanced Cancer Surveillance System; a population-based case-control study. This analysis included 658 bladder cancer cases and 1360 controls with information on lifetime occupational histories and a large number of possible cancer risk factors. A job-exposure matrix for engine emissions was supplemented by expert review to assign values for each job across three dimensions of exposure: concentration, frequency, and reliability. Odds ratios (OR) and their corresponding 95% confidence intervals were estimated using logistic regression. Relative to unexposed, men ever exposed to high concentrations of diesel emissions were at an increased risk of bladder cancer (OR = 1.64, 0.87-3.08), but this result was not significant, and those with >10 years of exposure to diesel emissions at high concentrations had a greater than twofold increase in risk (OR = 2.45, 1.04-5.74). Increased risk of bladder cancer was also observed with >30% of work time exposed to gasoline engine emissions (OR = 1.59, 1.04-2.43) relative to the unexposed, but only among men that had never been exposed to diesel emissions. Taken together, our findings support the hypothesis that exposure to high concentrations of diesel engine emissions may increase the risk of bladder cancer. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Effects of Cyclooxygenase on the Urothelium of the Urinary Bladder of Mice Exposed to Pelvic Radiation.

PubMed

Ozbilgin, M Kemal; Onal, Tuna; Ozcan, Cemil; Temel, Merve; Aktas, Caner; Gareveran, Manuchehr Salehi; Uluer, Elgin Turkoz; Inan, Sevinc; Kurtman, Cengiz

2016-04-01

To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p < 0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p < 0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p < 0.005). COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium.

A Randomized Pilot Trial of Dietary Modification for the Chemoprevention of Non-invasive Bladder Cancer: The Dietary Intervention in Bladder Cancer Study (DIBS)

PubMed Central

Parsons, J. Kellogg; Pierce, John P.; Natarajan, Loki; Newman, Vicky A.; Barbier, Leslie; Mohler, James; Rock, Cheryl L.; Heath, Dennis D.; Guru, Khurshid; Jameson, Michael B.; Li, Hongying; Mirheydar, Hossein; Holmes, Michael A.; Marshall, James

2013-01-01

Epidemiological data suggest robust associations of high vegetable intake with decreased risks of bladder cancer incidence and mortality, but translational prevention studies have yet to be performed. We designed and tested a novel intervention to increase vegetable intake in patients with non-invasive bladder cancer. We randomized 48 patients aged 50 to 80 years with biopsy-proven non-invasive (Ta, T1, or carcinoma in situ) urothelial cell carcinoma to telephone- and Skype-based dietary counseling or a control condition that provided print materials only. The intervention behavioral goals promoted 7 daily vegetable servings, with at least 2 of these as cruciferous vegetables. Outcome variables were self-reported diet and plasma carotenoid and 24-hour urinary isothiocyanate (ITC) concentrations. We used 2-sample t-tests to assess between-group differences at 6-month follow-up. After 6 months, intervention patients had higher daily intakes of vegetable juice (p=0.02), total vegetables (p=0.02), and cruciferous vegetables (p=0.07); lower daily intakes of energy (p=0.007), (p=0.002) and energy from fat (p=0.06); and higher plasma alpha-carotene concentrations (p=0.03). Self-reported cruciferous vegetable intake correlated with urinary ITC concentrations at baseline (p<0.001) and at 6 months (p=0.03). Although urinary ITC concentrations increased in the intervention group and decreased in the control group, these changes did not attain between-group significance (p=0.32). In patients with non-invasive bladder cancer, our novel intervention induced diet changes associated with protective effects against bladder cancer. These data demonstrate the feasibility of implementing therapeutic dietary modifications to prevent recurrent and progressive bladder cancer. PMID:23867158

Deformable structure registration of bladder through surface mapping.

PubMed

Xiong, Li; Viswanathan, Akila; Stewart, Alexandra J; Haker, Steven; Tempany, Clare M; Chin, Lee M; Cormack, Robert A

2006-06-01

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractions of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.

Is Detrusor Contraction during Rapid Bladder Filling Caused by Cold or Warm Water? A Randomized, Controlled, Double-Blind Trial.

PubMed

Kozomara, Marko; Mehnert, Ulrich; Seifert, Burkhardt; Kessler, Thomas M

2018-01-01

We investigated whether detrusor contraction during rapid bladder filling is provoked by cold or warm water. Patients with neurogenic lower urinary tract dysfunction were included in this randomized, controlled, double-blind trial. At the end of a standard urodynamic investigation patients underwent 2 bladder fillings using a 4C ice water test or a 36C warm water test saline solution at a filling speed of 100 ml per minute. The order was randomly selected, and patients and investigators were blinded to the order. The primary outcome measure was detrusor overactivity, maximum detrusor pressure and maximum bladder filling volume during the ice and warm water tests. Nine women and 31 men were the subject of data analysis. Neurogenic lower urinary tract dysfunction was caused by spinal cord injury in 33 patients and by another neurological disorder in 7. Irrespective of test order detrusor overactivity occurred significantly more often during the ice water test than during the warm water test (30 of 40 patients or 75% vs 25 of 40 or 63%, p = 0.02). When comparing the ice water test to the warm water test, maximum detrusor pressure was significantly higher and maximum bladder filling volume was significantly lower during the ice water test (each p <0.001). The order of performing the tests (ice water first vs warm water first) had no effect on the parameters. Our findings imply that the more frequent detrusor overactivity, higher maximum detrusor pressure and lower bladder filling volume during the ice water test compared to the warm water test were caused by cold water. This underlies the theory of a C-fiber mediated bladder cooling reflex in humans. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder catheterization in Greek nursing education: An audit of the skills taught.

PubMed

Theofanidis, Dimitrios; Fountouki, Antigoni

2011-02-01

The auditing of nurse teaching is in its infancy in Greece. One area urgently in need of audit is the teaching of male catheterization. To assess the current educational model regarding male bladder catheterization at a sole tertiary education nursing establishment in a major Greek city and to improve nurse undergraduate training by implementing appropriate recommendations for change to the current educational module and support these changes in the long term. A systematic search of international databases for guidelines or best practice regarding bladder catheterization was conducted. Audit measures included direct observation of the teaching process and compilation of a checklist. The shortcomings are discussed under the following headings: patient pre-preparation, choice and quality of materials used, appropriate aseptic techniques, catheter withdrawal, connecting and handling the drainage bag, diminishing risk of Catheter Associated Urinary Track Infections (CAUTIs), no problem solving trouble-shooting training, textbook and educational resources, lack of national guidelines, setting of the educational experience. The main problem with the teaching process exposed by the audit is entrenched use of an outmoded textbook with little effort to enrich teaching with current evidence base practices. Copyright © 2010 Elsevier Ltd. All rights reserved.

Optimal graph search segmentation using arc-weighted graph for simultaneous surface detection of bladder and prostate.

PubMed

Song, Qi; Wu, Xiaodong; Liu, Yunlong; Smith, Mark; Buatti, John; Sonka, Milan

2009-01-01

We present a novel method for globally optimal surface segmentation of multiple mutually interacting objects, incorporating both edge and shape knowledge in a 3-D graph-theoretic approach. Hard surface interacting constraints are enforced in the interacting regions, preserving the geometric relationship of those partially interacting surfaces. The soft smoothness a priori shape compliance is introduced into the energy functional to provide shape guidance. The globally optimal surfaces can be simultaneously achieved by solving a maximum flow problem based on an arc-weighted graph representation. Representing the segmentation problem in an arc-weighted graph, one can incorporate a wider spectrum of constraints into the formulation, thus increasing segmentation accuracy and robustness in volumetric image data. To the best of our knowledge, our method is the first attempt to introduce the arc-weighted graph representation into the graph-searching approach for simultaneous segmentation of multiple partially interacting objects, which admits a globally optimal solution in a low-order polynomial time. Our new approach was applied to the simultaneous surface detection of bladder and prostate. The result was quite encouraging in spite of the low saliency of the bladder and prostate in CT images.

In vitro release of adenosine triphosphate from the urothelium of human bladders with detrusor overactivity, both neurogenic and idiopathic.

PubMed

Kumar, Vivek; Chapple, Christopher R; Rosario, Derek; Tophill, Paul R; Chess-Williams, Russell

2010-06-01

There is increased evidence to suggest a role for nonadrenergic-noncholinergic neurotransmission in the pathogenesis of bladder dysfunction. In this set of experiments, we have assessed the contribution of the urothelium to purinergic activity by quantifying the amount of adenosine triphosphate (ATP) released from the urothelium of patients with idiopathic detrusor overactivity (IDO) and with neurogenic detrusor overactivity (NDO) and comparing these releases to those of controls. Bladder tissue with urodynamically and clinically proven NDO (n=8) and IDO (n=8) were included in this study. The carefully dissected urothelium was stimulated by mechanically stretching as well as electrically stimulating and the ATP; thus, release was quantified. We used a Lucy Anthos 1 luminometre (Anthos Labtec Instruments GmBH, Wals, Austria) to perform the assay. The results were analysed using Stingray software (Dazdaq Ltd, Brighton, UK). Both mechanical stretch and electric field stimulation (EFS) led to increased ATP release in both sets of tissues with overactivity compared to the controls; this rise was even more significant for the IDO urothelium (2416.7±479.8 pmol/g [p<0.005]) than for the NDO urothelium (133.1±22.4 pmol/g [p<0.01]); values for the controls were 77.6±16.2 pmol/g. ATP release following mechanical stretch was more sensitive to tetrodotoxin in bladders with NDO compared to those with IDO as well as to the controls, with ATP levels falling from 233.5±20.7 pmol/g to 107.2±11.6 pmol/g, expressed as percentage of basal levels (p<0.002). The experiments were performed in vitro, and the female patients were a mix of peri- and postmenopausal states. These experiments suggested a significant rise in ATP release from the urothelium of bladders with NDO as well as those with IDO in comparison to controls. Most of the ATP released from bladders with NDO is primarily from neuronal sources. Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Trajectories of urinary incontinence in childhood and bladder and bowel symptoms in adolescence: prospective cohort study

PubMed Central

Heron, Jon; Grzeda, Mariusz T; von Gontard, Alexander; Wright, Anne; Joinson, Carol

2017-01-01

Objectives To identify different patterns (trajectories) of childhood urinary incontinence and examine which patterns are associated with bladder and bowel symptoms in adolescence. Design Prospective cohort study. Setting General community. Participants The starting sample included 8751 children (4507 men and 4244 women) with parent-reported data on frequency of bedwetting and daytime wetting for at least three of five time points (4½, 5½, 6½, 7½ and 9½ years—hereafter referred to as 4–9 years). Study children provided data on a range of bladder and bowel symptoms at age 14 (data available for 5899 participants). Outcome measures Self-reported bladder and bowel symptoms at 14 years including daytime wetting, bedwetting, nocturia, urgency, frequent urination, low voided volume, voiding postponement, passing hard stools and low stool frequency. Results We extracted 5 trajectories of urinary incontinence from 4 to 9 years using longitudinal latent class analysis: (1) normative development of daytime and night-time bladder control (63.0% of the sample), (2) delayed attainment of bladder control (8.6%), (3) bedwetting alone (no daytime wetting) (15.6%), (4) daytime wetting alone (no bedwetting) (5.8%) and (5) persistent wetting (bedwetting with daytime wetting to age 9) (7.0%). The persistent wetting class generally showed the strongest associations with the adolescent bladder and bowel symptoms: OR for bedwetting at 14 years=23.5, 95% CI (15.1 to 36.5), daytime wetting (6.98 (4.50 to 10.8)), nocturia (2.39 (1.79 to 3.20)), urgency (2.10 (1.44 to 3.07)) and passing hard stools (2.64 (1.63 to 4.27)) (reference category=normative development). The association with adolescent bedwetting was weaker for children with bedwetting alone (3.69 (2.21 to 6.17)). Conclusions Trajectories of childhood urinary incontinence are differentially associated with adolescent bladder and bowel symptoms. Children exhibiting persistent bedwetting with daytime wetting had the poorest outcomes in adolescence. PMID:28292756

Contribution of GABAA, Glycine, and Opioid Receptors to Sacral Neuromodulation of Bladder Overactivity in Cats.

PubMed

Jiang, Xuewen; Fuller, Thomas W; Bandari, Jathin; Bansal, Utsav; Zhang, Zhaocun; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

2016-12-01

In α-chloralose-anesthetized cats, we examined the role of GABA A , glycine, and opioid receptors in sacral neuromodulation-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.5% acetic acid (AA). AA irritation significantly (P < 0.01) reduced bladder capacity to 59.5 ± 4.8% of saline control. S1 or S2 dorsal root stimulation at threshold intensity for inducing reflex twitching of the anal sphincter or toe significantly (P < 0.01) increased bladder capacity to 105.3 ± 9.0% and 134.8 ± 8.9% of saline control, respectively. Picrotoxin, a GABA A receptor antagonist administered i.v., blocked S1 inhibition at 0.3 mg/kg and blocked S2 inhibition at 1.0 mg/kg. Picrotoxin (0.4 mg, i.t.) did not alter the inhibition induced during S1 or S2 stimulation, but unmasked a significant (P < 0.05) poststimulation inhibition that persisted after termination of stimulation. Naloxone, an opioid receptor antagonist (0.3 mg, i.t.), significantly (P < 0.05) reduced prestimulation bladder capacity and removed the poststimulation inhibition. Strychnine, a glycine receptor antagonist (0.03-0.3 mg/kg, i.v.), significantly (P < 0.05) increased prestimulation bladder capacity but did not reduce sacral S1 or S2 inhibition. After strychnine (0.3 mg/kg, i.v.), picrotoxin (0.3 mg/kg, i.v.) further (P < 0.05) increased prestimulation bladder capacity and completely blocked both S1 and S2 inhibition. These results indicate that supraspinal GABA A receptors play an important role in sacral neuromodulation of bladder overactivity, whereas glycine receptors only play a minor role to facilitate the GABA A inhibitory mechanism. The poststimulation inhibition unmasked by blocking spinal GABA A receptors was mediated by an opioid mechanism. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Tissue Engineering of Urinary Bladder and Urethra: Advances from Bench to Patients

PubMed Central

Bouhout, Sara; Chabaud, Stéphane; Bolduc, Stéphane

2013-01-01

Urinary tract is subjected to many varieties of pathologies since birth including congenital anomalies, trauma, inflammatory lesions, and malignancy. These diseases necessitate the replacement of involved organs and tissues. Shortage of organ donation, problems of immunosuppression, and complications associated with the use of nonnative tissues have urged clinicians and scientists to investigate new therapies, namely, tissue engineering. Tissue engineering follows principles of cell transplantation, materials science, and engineering. Epithelial and muscle cells can be harvested and used for reconstruction of the engineered grafts. These cells must be delivered in a well-organized and differentiated condition because water-seal epithelium and well-oriented muscle layer are needed for proper function of the substitute tissues. Synthetic or natural scaffolds have been used for engineering lower urinary tract. Harnessing autologous cells to produce their own matrix and form scaffolds is a new strategy for engineering bladder and urethra. This self-assembly technique avoids the biosafety and immunological reactions related to the use of biodegradable scaffolds. Autologous equivalents have already been produced for pigs (bladder) and human (urethra and bladder). The purpose of this paper is to present a review for the existing methods of engineering bladder and urethra and to point toward perspectives for their replacement. PMID:24453796

Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction.

PubMed

Eberli, Daniel; Horst, Maya; Mortezavi, Ashkan; Andersson, Karl-Erik; Gobet, Rita; Sulser, Tullio; Simon, Hans-Uwe; Salemi, Souzan

2018-05-24

To explore whether autophagy plays a role in the remodeling of bladder smooth muscle cells (SMCs) in children with neurogenic lower urinary tract dysfunction (NLUTD), we investigated the effect of autophagy in NLUTD in the paediatric population. Bladder biopsies were taken from children with NLUTD and healthy donors as controls. Samples were labeled with the SMC markers calponin, smoothelin, and the autophagy proteins LC3, ATG5, and Beclin1. The contractile ability of bladder derived SMCs was investigated. ATG5 gene and protein was upregulated in NLUTD muscle tissue compared to normal bladder. NLUTD muscle exhibited a punctated immunostaining pattern for LC3 in a subset of the SMCs, confirming the accumulation of autophagosomes. Pronounced elevation of ATG5 in the SMC in NLUTD tissue was associated with a downregulation of the key contractile proteins smoothelin and calponin. Pharmacological blocking of autophagy completely stopped the cells growth in normal bladder SMCs. Inhibition of autophagy in the NLUTD SMCs, with already elevated levels of ATG5, resulted in a reduction of ATG5 protein expression to the basal level found in normal controls. Our study suggests that autophagy is an important factor affecting the remodeling of SMCs and the alteration of functionality in bladder smooth muscle tissue in the NLUTD. Since autophagy can be influenced by oral medication, this finding might lead to novel strategies preventing the deterioration of NLUTD muscle. © 2018 Wiley Periodicals, Inc.

Determinants of Quality of Interview and Impact on Risk Estimates in a Case-Control Study of Bladder Cancer

PubMed Central

Silverman, Debra T.; Malats, Núria; Tardon, Adonina; Garcia-Closas, Reina; Serra, Consol; Carrato, Alfredo; Fortuny, Joan; Rothman, Nathaniel; Dosemeci, Mustafa; Kogevinas, Manolis

2009-01-01

The authors evaluated potential determinants of the quality of the interview in a case-control study of bladder cancer and assessed the effect of the interview quality on the risk estimates. The analysis included 1,219 incident bladder cancer cases and 1,271 controls recruited in Spain in 1998–2001. Information on etiologic factors for bladder cancer was collected through personal interviews, which were scored as unsatisfactory, questionable, reliable, or high quality by the interviewers. Eight percent of the interviews were unsatisfactory or questionable. Increasing age, lower socioeconomic status, and poorer self-perceived health led to higher proportions of questionable or unreliable interviews. The odds ratio for cigarette smoking, the main risk factor for bladder cancer, was 6.18 (95% confidence interval: 4.56, 8.39) overall, 3.20 (95% confidence interval: 1.13, 9.04) among unsatisfactory or questionable interviews, 6.86 (95% confidence interval: 4.80, 9.82) among reliable interviews, and 7.70 (95% confidence interval: 3.64, 16.30) among high-quality interviews. Similar trends were observed for employment in high-risk occupations, drinking water containing elevated levels of trihalomethanes, and use of analgesics. Higher quality interviews led to stronger associations compared with risk estimation that did not take the quality of interview into account. The collection of quality of interview scores and the exclusion of unreliable interviews probably reduce misclassification of exposure in observational studies. PMID:19478234

Gender Identity and Sex Role of Patients Operated on for Bladder Exstrophy-Epispadias.

PubMed

Taskinen, Seppo; Suominen, Janne S; Mattila, Aino K

2016-08-01

We evaluated whether genital deformity has an impact on gender identity and sex role in patients operated on for bladder exstrophy-epispadias complex. A total of 62 adolescents and adults operated on for bladder exstrophy-epispadias complex were mailed questionnaires evaluating gender identity (Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults) and sex role (Bem Sex Role Inventory). Of the patients 33 responded and the results were compared with 99 gender matched controls. On the gender identity questionnaire female patients had median scores similar to those of their gender matched controls (4.93 vs 4.89, p = 0.412) but in males the score was lower compared to controls (4.87 vs 4.96, p = 0.023), indicating somewhat more conflicted gender identity. However, no patient had gender dysphoria. Female sex role index was higher in female patients vs controls (5.9 vs 5.3, p = 0.003) but was comparable between male patients and controls (5.2 vs 5.0, p = 0.459). Masculine sex role indices were comparable between female patients and controls as well as between male patients and controls. Of 32 patients 17 were considered to have androgynous sex role, as were 24 of 97 controls (p = 0.004). The exact diagnosis (bladder exstrophy or epispadias) or dissatisfaction with appearance of the genitals had no impact on gender identity or on sex role indices. Male patients had lower gender identity scores compared to controls and female sex role was enhanced among female patients. Androgynous sex role was more common in patients vs controls. Gender dysphoria was not noted in any patient. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Mental health diagnoses in patients with interstitial cystitis/painful bladder syndrome and chronic prostatitis/chronic pelvic pain syndrome: a case/control study.

PubMed

Clemens, J Quentin; Brown, Sheila O; Calhoun, Elizabeth A

2008-10-01

We compared the rate of mental health disorders in male and female patients with pelvic pain and control subjects. Male patients with chronic prostatitis/chronic pelvic pain syndrome (174) and female patients with interstitial cystitis/painful bladder syndrome (111) were identified from a urology tertiary care clinic population. A control group consisting of 72 men and 175 women was also recruited. Subjects completed self-administered questionnaires that included items about demographics, medical history, medication use and urological symptoms. The Patient Health Questionnaire was used to identify depression and panic disorder. Multiple logistic regression was used to determine odds ratios for the presence of a mental health diagnosis. Mental health disorders were identified in 13% of the chronic prostatitis/chronic pelvic pain syndrome cases and 4% of male controls (OR 2.0, p = 0.04), as well as in 23% of interstitial cystitis/painful bladder syndrome cases and 3% of female controls (OR 8.2, p <0.0001). Disease status (case vs control) (OR 10.4, p = 0.001) and income greater than $50,000 (OR 0.34, p = 0.008) were the only 2 variables independently predictive of the presence of a mental health diagnosis. Age, gender, race/ethnicity and education were not predictive. Medications for anxiety, depression or stress were being taken by 18% of patients with chronic prostatitis/chronic pelvic pain syndrome, 37% of those with interstitial cystitis/painful bladder syndrome, 7% of male controls and 13% of female controls. Depression and panic disorder are significantly more common in men and women with pelvic pain conditions than in controls. Medication use data suggest that anxiety and depression may be more difficult to treat in patients with urological pain syndromes than in controls.

Long-term micturition problems of asymptomatic postpartum urinary retention: a prospective case-control study.

PubMed

Mulder, Femke E M; Hakvoort, Robert A; de Bruin, Jan-Peter; Janszen, Erica W; van der Post, Joris A M; Roovers, Jan-Paul W R

2018-04-01

Covert (asymptomatic) postpartum urinary retention (PUR) is defined as post-void residual volume (PVRV) ≥150 mL. Although often supposed to be a common and harmless phenomenon, no data are available on the potential long-term micturition problems of increased PVRV after vaginal delivery. After the first spontaneous void post-vaginal delivery, PVRV was measured using a portable scanning device. Micturition symptoms were compared using validated questionnaires between women with PVRV < 150 mL and those with PVRV ≥150 mL until 1 year after delivery. Women with PVRV ≥ 150 mL were followed until complete bladder emptying was achieved. Data of 105 patients with PVRV < 150 mL and 119 with PVRV ≥ 150 mL were available for analysis. 75% of all patients included had PVRV ≥ 250 mL. More primiparous patients had PVRV ≥ 150 mL (p < 0.02). 92% of women with PVRV ≥ 150 mL after delivery were able to adequately empty their bladder within 4 days. One year after delivery, no statistically significant differences were found. Covert PUR according to the definition of PVRV ≥ 150 mL, is a common and transient phenomenon that does not result in more lower urinary tract symptoms 1 year after delivery. Although the current definition is not useful in identifying postpartum women with a pathological condition, we suggest that the definition of covert PUR should be change to: "PVRV≥500 mL after the first spontaneous void after (vaginal) delivery." This cut-off value is the value at which some women do need more time to normalise emptying of the bladder. The exact clinical implications of covert PUR need to be further studied in this subcategory of women.

Women's toileting behaviour related to urinary elimination: concept analysis.

PubMed

Wang, Kefang; Palmer, Mary H

2010-08-01

This paper is a report of analysis of the concept of women's toileting behaviour related to urinary elimination. Behaviours related to emptying urine from the bladder can contribute to bladder health problems. Evidence exists that clinical interventions focusing on specific behaviours that promote urine storage and controlled emptying are effective in reducing lower urinary tract symptoms. The concept of women's toileting behaviour related to urinary elimination has not been well-developed to guide nursing research and intervention. The CINAHL, Medline, PsycInfo and ISI Citation databases were searched for publications between January, 1960 and May, 2009, using combinations of keywords related to women's toileting behaviour. Additional publications were identified by examining the reference lists in the papers identified. Johnson's behavioural system model provided the conceptual framework to identify the concept. Walker and Avant's method was used for this concept analysis. Women's toileting behaviour related to urinary elimination can be defined as voluntary actions related to the physiological event of emptying the bladder, which is comprised of specific attributes including voiding place, voiding time, voiding position and voiding style. This behaviour is also influenced by the physical and social environments. An explicit definition of women's toileting behaviour can offer a basis for nurses to understand the factors involved in women's toileting behaviour. It also facilitates the development of an instrument to assess women's toileting behaviour better, and to facilitate development of behavioural interventions designed to prevent, eliminate, reduce and manage female lower urinary tract symptoms.

Adenoviral receptor expression of normal bladder and transitional cell carcinoma of the bladder.

PubMed

Buscarini, Maurizio; Quek, Marcus L; Gilliam-Hegarich, Susan; Kasahara, Nori; Bochner, Bernard

2007-01-01

The insertion of absent or underexpressed genes into cancer cells to alter their malignant phenotype is an important potential application of available gene therapy technology. One of the more common viral vector systems that has been extensively studied for this purpose are the replication-deficient adenoviruses (Ad). Adenoviral infection of cells is mediated through a complex pathway, initiated following viral-cell attachment. Adenoviral-cell attachment occurs following interactions with a 46-kDa transmembrane protein with high affinity for both the Coxsackie and adenovirus, designated the CAR (Coxsackie and adenoviral receptor). Additional important cell-viral interactions that occur involve the alpha(v)-based integrins, specifically alpha(v)beta3 and alpha(v)beta5. The purpose of the present study was to determine the extent of expression and localization of the known Ad receptor proteins (CAR, alpha(v)beta3, and alpha(v)beta5) in normal and cancerous human bladders. Frozen tissue samples of normal bladder and invasive transitional cell cancers of the bladder were evaluated. Tissue blocks containing muscle-invasive transitional cell carcinoma (TCC) were obtained following radical cystectomy, which were performed at our institution. Thirty-two invasive transitional cell bladder tumors were evaluated, each with a matched sample of histologically normal-appearing bladder used as a control. Four additional samples of normal bladder were obtained from patients with no evidence of disease of the bladder and served as further controls. Three additional cases of invasive bladder cancer with no matching normal tissue were also evaluated. Identification of the CAR receptor was performed using the anti-CAR mouse monoclonal antibody designated RmBC. The integrins alpha(v)beta3 and alpha(v)beta5 were identified using the mouse monoclonal antibodies designated LM609 and P1F6 respectively. All slides were evaluated by two of the authors (M.B., B.B.) without knowledge of the clinical and pathological data. Normal bladder: Normal bladder mucosa demonstrated a marked positivity for CAR in 29/35 (82.8%) cases. In contrast, normal transitional epithelial cells were uniformly negative when tested for the integrins alpha(v)beta3 and alpha(v)beta5. Subepithelial tissues, specifically the connective tissue components of the lamina propria and deep muscle wall of the bladder, were positive for alpha(v)beta3 and for alpha(v)beta5 in 61 and 75% of samples, respectively. Endothelial cells associated with the various layers throughout the bladder uniformly expressed both integrins and served as a consistent internal control for both antibodies. An almost identical staining pattern of the endothelium was observed using LM609 and P1F6 in all samples tested. Bladder transitional cell carcinoma: CAR immunoreactivity against TCC cells was uniformly decreased compared to normal transitional cells. Nine tumors exhibited a weak positivity for CAR while the remaining samples were negative. In some cases, the absence of CAR positivity was associated with histological evidence of carcinoma in situ. In 6 cases, it led to the identification of small regions of carcinoma in situ that were not noted on primary pathological evaluation. Peritumoral connective tissue expressed both integrins in the majority of cases, similar to the pattern described above for normal bladder. Transitional cell cancers demonstrated a similar pattern of expression of alpha(v)beta5, in which all tumor cells exhibited minimal or no staining. The success of all viral-mediated gene therapy strategies relies on the ability of the vector to efficiently deliver its genetic material to a target cell population. In the current study, we demonstrate that the bladder epithelial layer consistently expresses high levels of CAR. Deeper layers of the epithelium also express CAR, including the basal layer cells. A decrease in the expression of CAR appears as an early event in bladder carcinogenesis. We observed that both alpha(v)beta3 and alpha(v)beta5 are strongly expressed in muscle cells surrounding the neoplastic cells, as well as within the peritumoral connective tissue. In cases of invasive bladder cancer that have lost CAR expression, an adenoviral vector may still be utilized through the less efficient interactions with the integrins. Bladder tumor tissue may be less susceptible to an adenoviral-mediated gene therapy approach in which a significant percentage of tumor cells require transduction. Adenoviral uptake by tumor or peritumoral cells with subsequent gene transfer could be predicted by the level of CAR and alpha(v)-based integrin expression. This would enhance our ability to identify those patients whose tumors would be more susceptible to Ad-mediated gene delivery as part of an antitumor treatment. 2007 S. Karger AG, Basel

Genetic Variants in the Wnt/β-Catenin Signaling Pathway as Indicators of Bladder Cancer Risk.

PubMed

Pierzynski, Jeanne A; Hildebrandt, Michelle A; Kamat, Ashish M; Lin, Jie; Ye, Yuanqing; Dinney, Colin P N; Wu, Xifeng

2015-12-01

Genetic factors that influence bladder cancer risk remain largely unknown. Previous research has suggested that there is a strong genetic component underlying the risk of bladder cancer. The Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation through its regulation of stem cell homeostasis. Furthermore, variants in the Wnt/β-catenin signaling pathway have been implicated in the development of other cancers, leading us to believe that this pathway may have a vital role in bladder cancer development. A total of 230 single nucleotide polymorphisms in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls. A total of 20 single nucleotide polymorphisms were nominally significant for risk. Individuals with 2 variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer in the recessive model in the initial analysis (OR 0.76, 95% CI 0.58-0.99, p=0.039). This was validated using the bladder genome-wide association study chip (OR 0.51, 95% CI 0.27-1.00, p=0.049 and for combined analysis p=0.007). Together these findings implicate variants in the Wnt/β-catenin stem cell pathway as having a role in bladder cancer etiology. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

New treatments for incontinence.

PubMed

MacLachlan, Lara S; Rovner, Eric S

2015-07-01

Urinary incontinence (UI) is a common, yet underdetected and under-reported, health problem that can significantly affect quality of life. UI may also have serious medical and economic ramifications for untreated or undertreated patients, including perineal dermatitis, worsening of pressure ulcers, urinary tract infections, and falls. To prevent incontinence, the urethral sphincter must maintain adequate closure to resist the flow of urine from the bladder at all times until voluntary voiding is initiated and the bladder must accommodate increasing volumes of urine at a low pressure. UI can be categorized as a result of urethral underactivity (stress UI), bladder overactivity (urge UI), a combination of the 2 (mixed incontinence), or urethral overactivity/bladder underactivity (overflow incontinence). The main goal of therapy for the management of UI is to reduce the number of UI episodes, prevent complications, and, if possible, restore continence. This review highlights the existing treatment of stress, urge, mixed, and overflow UI in adult men and women and discusses many of the novel treatments including potential future or emerging therapies. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer.

PubMed

Ferreccio, Catterina; Yuan, Yan; Calle, Jacqueline; Benítez, Hugo; Parra, Roxana L; Acevedo, Johanna; Smith, Allan H; Liaw, Jane; Steinmaus, Craig

2013-11-01

Millions of people worldwide are exposed to arsenic in drinking water, and many are likely coexposed to other agents that could substantially increase their risks of arsenic-related cancer. We performed a case-control study of multiple chemical exposures in 538 lung and bladder cancer cases and 640 controls in northern Chile, an area with formerly high drinking water arsenic concentrations. Detailed information was collected on lifetime arsenic exposure, smoking, secondhand smoke, and other known or suspected carcinogens, including asbestos, silica, and wood dust. Very high lung and bladder cancer odds ratios (ORs), and evidence of greater than additive effects, were seen in people exposed to arsenic concentrations >335 µg/L and who were tobacco smokers (OR = 16, 95% confidence interval = 6.5-40 for lung cancer; and OR = 23 [8.2-66] for bladder cancer; Rothman Synergy Indices = 4.0 [1.7-9.4] and 2.0 [0.92-4.5], respectively). Evidence of greater than additive effects were also seen in people coexposed to arsenic and secondhand tobacco smoke and several other known or suspected carcinogens, including asbestos, silica, and wood dust. These findings suggest that people coexposed to arsenic and other known or suspected carcinogens have very high risks of lung or bladder cancer.

Reduced energy and volume air pump for a seat cushion

DOEpatents

Vaughn, M.R.; Constantineau, E.J.; Groves, G.E.

1997-08-19

An efficient pump system is described for transferring air between sets of bladders in a cushion. The pump system utilizes a reversible piston within a cylinder in conjunction with an equalizing valve in the piston which opens when the piston reaches the end of travel in one direction. The weight of a seated user then forces air back across the piston from an inflated bladder to the previously deflated bladder until the pressure is equalized. In this fashion the work done by the pump is cut in half. The inflation and deflation of the different bladders is controlled to vary the pressure on the several pressure points of a seated user. A principal application is for wheel chair use to prevent pressure ulcers. 12 figs.

Interstitial cystitis intravesical therapy

PubMed Central

2017-01-01

Interstitial cystitis (IC) is a progressive bladder disorder that presents with symptoms of bladder urgency, frequency and pain. The aetiology of the disease remains uncertain, but it is postulated that there is an initial infective insult which damages the glycosaminoglycan (GAG) layer of the bladder urothelium. This defect allows an influx of ions, particularly potassium, which initiates an inflammatory reaction in the bladder wall, which incites the symptoms described above. Treatment initially involves behavioural and oral medication, with second line being intravesical instillation therapy. Treatment strategies focus on restoring lower urinary tract epithelial function, inhibiting neural activation, controlling allergies and relieving symptoms. In this review, current intravesical therapy will be discussed, as well as what lies on the horizon for intravesical therapy in IC. PMID:28791236

Reduced energy and volume air pump for a seat cushion

DOEpatents

Vaughn, Mark R.; Constantineau, Edward J.; Groves, Gordon E.

1997-01-01

An efficient pump system for transferring air between sets of bladders in a cushion. The pump system utilizes a reversible piston within a cylinder in conjunction with an equalizing valve in the piston which opens when the piston reaches the end of travel in one direction. The weight of a seated user then forces air back across the piston from an inflated bladder to the previously deflated bladder until the pressure is equalized. In this fashion the work done by the pump is cut in half. The inflation and deflation of the different bladders is controlled to vary the pressure on the several pressure points of a seated user. A principal application is for wheel chair use to prevent pressure ulcers.

Neuroprostheses to treat neurogenic bladder dysfunction: current status and future perspectives.

PubMed

Rijkhoff, Nico J M

2004-02-01

Neural prostheses are a technology that uses electrical activation of the nervous system to restore function to individuals with neurological or sensory impairment. This article provides an introduction to neural prostheses and lists the most successful neural prostheses (in terms of implanted devices). The article then focuses on neurogenic bladder dysfunction and describes two clinically available implantable neural prostheses for treatment of neurogenic bladder dysfunction. Special attention is given to the usage of these neural prostheses in children. Finally, three new developments that may lead to a new generation of implantable neural prostheses for bladder control are described. They may improve the neural prostheses currently available and expand further the population of patients who can benefit from a neural prosthesis.

Longitudinal associations between mental health conditions and overactive bladder in women veterans.

PubMed

Bradley, Catherine S; Nygaard, Ingrid E; Hillis, Stephen L; Torner, James C; Sadler, Anne G

2017-10-01

One in 5 recently deployed US women veterans report overactive bladder symptoms. Mental health conditions such as depression and anxiety commonly co-occur in women with overactive bladder, but temporal relationships between these outcomes have not been well studied, and the mechanism behind this association is unknown. The Women Veterans Urinary Health Study, a nationwide longitudinal study in recently deployed women veterans, was designed to better understand relationships between overactive bladder and mental health conditions. We sought to estimate the 1-year incidence and remission of overactive bladder and to identify the impact of depression, anxiety, posttraumatic stress disorder, and prior sexual assault on 1-year overactive bladder incidence and remission rates. Participants of this 1-year prospective cohort study were female veterans separated from military service who had returned from Iraq or Afghanistan deployment within the previous 2 years. Eligible women were identified through the Defense Manpower Data Center and recruited by mail and telephone. Telephone screening confirmed participants were ambulatory, community-dwelling veterans and excluded those with urinary tract fistula, congenital abnormality, or cancer; pelvic radiation; spinal cord injury; multiple sclerosis; Parkinson disease; stroke; or current/recent pregnancy. Data collection included computer-assisted telephone interviews performed at enrollment and 1 year later. The interview assessed demographic and military service characteristics; urinary symptoms and treatment; depression, anxiety, and posttraumatic stress disorder symptoms and treatment; and a lifetime history of sexual assault. Overactive bladder was identified if at least moderately bothersome urgency urinary incontinence and/or urinary frequency symptoms were reported on Urogenital Distress Inventory items. Exposures included depression, anxiety, posttraumatic stress disorder, and lifetime sexual assault, assessed at baseline using validated questionnaires (including the Patient Health Questionnaire and Posttraumatic Stress Disorder Checklist). Associations between exposures and overactive bladder incidence and remission were estimated using propensity score adjusted logistic regression models. In all, 1107 (88.0%) of 1258 eligible participants completed 1-year interviews. Median age was 29 (range 20-67) years and 53% were nulliparous. Overactive bladder was identified at baseline in 242 (22%), and 102 (9.2%), 218 (19.7%), 188 (17.0%), and 287 (25.9%) met criteria for baseline depression, anxiety, posttraumatic stress disorder, and lifetime sexual assault, respectively. At 1 year, overactive bladder incidence was 10.5% (95% confidence interval, 8.6-12.8%), and remission of overactive bladder was 36.9% (95% confidence interval, 30.8-43.4%). New overactive bladder occurred more often in women with baseline anxiety (21% vs 9%), posttraumatic stress disorder (19% vs 9%) and lifetime sexual assault (16% vs 9%) (all: P < .01). After adjustment, anxiety (odds ratio, 2.4; 95% confidence interval, 1.4-4.1) and lifetime sexual assault (odds ratio, 1.7; 95% confidence interval, 1.0-2.8) predicted 1-year incident overactive bladder. Overactive bladder remission occurred less often in those with baseline depression (19% vs 41%, P < .01) and anxiety (29% vs 42%, P = .03). After adjustment, depression decreased 1-year overactive bladder remission risk (odds ratio, 0.37; 95% confidence interval, 0.16-0.83). Overactive bladder treatment was uncommon and not associated with remission. Anxiety, depression, and prior sexual assault-common postdeployment problems for women veterans-influence the natural history of overactive bladder. Providers should screen for mental health conditions and sexual assault in women with newly diagnosed or persistent overactive bladder. Copyright © 2017 Elsevier Inc. All rights reserved.

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.

PubMed

Chaudhry, Rajeev; Madden-Fuentes, Ramiro J; Ortiz, Tara K; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S; Ross, Sherry S; Seed, Patrick C

2014-05-01

Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pudendal nerve stimulation and block by a wireless-controlled implantable stimulator in cats.

PubMed

Yang, Guangning; Wang, Jicheng; Shen, Bing; Roppolo, James R; de Groat, William C; Tai, Changfeng

2014-07-01

The study aims to determine the functionality of a wireless-controlled implantable stimulator designed for stimulation and block of the pudendal nerve. In five cats under α-chloralose anesthesia, the stimulator was implanted underneath the skin on the left side in the lower back along the sacral spine. Two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves in addition to one bipolar cuff electrode that was implanted on the left side central to the tripolar cuff electrode. The stimulator provided high-frequency (5-20 kHz) biphasic stimulation waveforms to the two tripolar electrodes and low-frequency (1-100 Hz) rectangular pulses to the bipolar electrode. Bladder and urethral pressures were measured to determine the effects of pudendal nerve stimulation (PNS) or block. The maximal (70-100 cmH2O) urethral pressure generated by 20-Hz PNS applied via the bipolar electrode was completely eliminated by the pudendal nerve block induced by the high-frequency stimulation (6-15 kHz, 6-10 V) applied via the two tripolar electrodes. In a partially filled bladder, 20-30 Hz PNS (2-8 V, 0.2 ms) but not 5 Hz stimulation applied via the bipolar electrode elicited a large sustained bladder contraction (45.9 ± 13.4 to 52.0 ± 22 cmH2O). During cystometry, the 5 Hz PNS significantly (p < 0.05) increased bladder capacity to 176.5 ± 27.1% of control capacity. The wireless-controlled implantable stimulator successfully generated the required waveforms for stimulation and block of pudendal nerve, which will be useful for restoring bladder functions after spinal cord injury. © 2013 International Neuromodulation Society.

[Risk factors for bladder injuries during cesarean section].

PubMed

Alcocer Urueta, Jaime; Bonilla Mares, Marcela; Gorbea Chávez, Viridiana; Velázquez Valassi, Beatriz

2009-01-01

To identify risk factors for bladder injury during cesarean delivery, to let patients and doctors know them and their importance. We conducted a case-control study of women undergoing cesarean delivery at the Instituto Nacional de PerinatologíaIsidro Espinosa de los Reyes between January 2001 and December 2007. Cases were women with bladder injuries at the time of cesarean section. Two controls per case were selected randomly. Medical records were reviewed for clinical and demographic data to compare them. Twenty-one bladder injuries were identified among 24, 057 cesarean sections, (incidence 0.087%), only 19 were analized. Prior cesarean section was more prevalent among cases than controls (63% vs 42% p 0.134), with an OR of 2.35 (95% CI 0.759-7.319), when we take only patients with one cesarea in contrast with no cesarea the OR is 3.75 (95% CI 1.002- 14.07). Statistically significant differences (P values < .05) between cases and controls were found in gestacional age (38.16 vs 37.35 weeks), prior cesareans (42% vs 18%), adhesions (79% vs 5%), Odds ratio of 67.5 (95% CI 11.14- 408), VBAC (31.5 vs 3%), median skin incisión (16% vs 68%), Pfannenstiel (84% vs 32%), blood loss (744cc vs 509cc) and length of surgery 135 vs 58 minutes). No differences were found among age, BMI, prior surgery, labor, premature rupture of membranes, station, chorioamnioitis, induction, uterine incision, timing of delivery, uterine rupture. Prior cesarean section and adhesions are risk factors for bladder injury at the time of repeat cesarean delivery. Elective cesarean delivery is valid but it is duty of physicians to inform patients the risks of it.

The concept of peripheral modulation of bladder sensation

PubMed Central

Eastham, Jane E; Gillespie, James I

2013-01-01

It is recognized that, as the bladder fills, there is a corresponding increase in sensation. This awareness of the volume in the bladder is then used in a complex decision making process to determine if there is a need to void. It is also part of everyday experience that, when the bladder is full and sensations strong, these sensations can be suppressed and the desire to void postponed. The obvious explanation for such altered perceptions is that they occur centrally. However, this may not be the only mechanism. There are data to suggest that descending neural influences and local factors might regulate the sensitivity of the systems within the bladder wall generating afferent activity. Specifically, evidence is accumulating to suggest that the motor-sensory system within the bladder wall is influenced in this way. The motor-sensory system, first described over 100 years ago, appears to be a key component in the afferent outflow, the afferent “noise,” generated within the bladder wall. However, the presence and possible importance of this complex system in the generation of bladder sensation has been overlooked in recent years. As the bladder fills the motor activity increases, driven by cholinergic inputs and modulated, possibly, by sympathetic inputs. In this way information on bladder volume can be transmitted to the CNS. It can be argued that the ability to alter the sensitivity of the mechanisms generating the motor component of this motor-sensory system represents a possible indirect way to influence afferent activity and so the perception of bladder volume centrally. Furthermore, it is emerging that the apparent modulation of sensation by drugs to alleviate the symptoms of overactive bladder (OAB), the anti-cholinergics and the new generation of drugs the β3 sympathomimetics, may be the result of their ability to modulate the motor component of the motor sensory system. The possibility of controlling sensation, physiologically and pharmacologically, by influencing afferent firing at its point of origin is a “new” concept in bladder physiology. It is one that deserves careful consideration as it might have wider implications for our understanding of bladder pathology and in the development of new therapeutic drugs. In this overview, evidence for the concept peripheral modulation of bladder afferent outflow is explored. PMID:23917648

Risks on N-acetyltransferase 2 and bladder cancer: a meta-analysis.

PubMed

Zhu, Zongheng; Zhang, Jinshan; Jiang, Wei; Zhang, Xianjue; Li, Youkong; Xu, Xiaoming

2015-01-01

It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2). The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer. The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis. The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled odds ratio was 1.31 (95% confidence interval: 1.11-1.55). The status of NAT2 slow N-acetylation is associated with bladder cancer risks, and may increase the risk of bladder cancer.

Activation of P2Y6 receptors increases the voiding frequency in anaesthetized rats by releasing ATP from the bladder urothelium.

PubMed

Carneiro, Inês; Timóteo, M Alexandrina; Silva, Isabel; Vieira, Cátia; Baldaia, Catarina; Ferreirinha, Fátima; Silva-Ramos, Miguel; Correia-de-Sá, Paulo

2014-07-01

Despite the abundant expression of the UDP-sensitive P2Y6 receptor in urothelial cells and sub-urothelial myofibroblasts its role in the control of bladder function is not well understood. We compared the effects of UDP and of the selective P2Y6 receptor agonist, PSB0474, on bladder urodynamics in anaesthetized rats; the voided fluid was tested for ATP bioluminescence. The isolated urinary bladder was used for in vitro myographic recordings and [(3) H]-ACh overflow experiments. Instillation of UDP or PSB0474 into the bladder increased the voiding frequency (VF) without affecting the amplitude (A) and the duration (Δt) of bladder contractions; an effect blocked by the P2Y6 receptor antagonist, MRS2578. Effects mediated by urothelial P2Y6 receptors required extrinsic neuronal circuitry as they were not detected in the isolated bladder. UDP-induced bladder hyperactvity was also prevented by blocking P2X3 and P2Y1 receptors, respectively, with A317491 and MRS2179 applied i.v.. UDP decreased [(3) H]-ACh release from stimulated bladder strips with urothelium, but not in its absence. Inhibitory effects of UDP were converted into facilitation by the P2Y1 receptor antagonist, MRS2179. The P2Y6 receptor agonist increased threefold ATP levels in the voided fluid. Activation of P2Y6 receptors increased the voiding frequency indirectly by releasing ATP from the urothelium and activation of P2X3 receptors on sub-urothelial nerve afferents. Bladder hyperactivity may be partly reversed following ATP hydrolysis to ADP by E-NTPDases, thereby decreasing ACh release from cholinergic nerves expressing P2Y1 receptors. © 2014 The British Pharmacological Society.

Down-regulation of annexin A1 in the urothelium decreases cell survival after bacterial toxin exposure.

PubMed

Monastyrskaya, Katia; Babiychuk, Eduard B; Draeger, Annette; Burkhard, Fiona C

2013-07-01

We examined the role of annexins in bladder urothelium. We characterized expression and distribution in normal bladders, biopsies from patients with bladder pain syndrome, cultured human urothelium and urothelial TEU-2 cells. Annexin expression in bladder layers was analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunofluorescence. We assessed cell survival after exposure to the pore forming bacterial toxin streptolysin O by microscopy and alamarBlue® assay. Bladder dome biopsies were obtained from 8 asymptomatic controls and 28 patients with symptoms of bladder pain syndrome. Annexin A1, A2, A5 and A6 were differentially distributed in bladder layers. Annexin A6 was abundant in detrusor smooth muscle and low in urothelium, while annexin A1 was the highest in urothelium. Annexin A2 was localized to the lateral membrane of umbrella cells but excluded from tight junctions. TEU-2 cell differentiation caused up-regulation of annexin A1 and A2 and down-regulation of annexin A6 mRNA. Mature urothelium dedifferentiation during culture caused the opposite effect, decreasing annexin A1 and increasing annexin A6. Annexin A2 influenced TEU-2 cell epithelial permeability. siRNA mediated knockdown of annexin A1 in TEU-2 cells caused significantly decreased cell survival after streptolysin O exposure. Annexin A1 was significantly reduced in biopsies from patients with bladder pain syndrome. Several annexins are expressed in human bladder and TEU-2 cells, in which levels are regulated during urothelial differentiation. Annexin A1 down-regulation in patients with bladder pain syndrome might decrease cell survival and contribute to compromised urothelial function. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder cancer incidence among workers exposed to o-toluidine, aniline and nitrobenzene at a rubber chemical manufacturing plant

PubMed Central

Carreón, Tania; Hein, Misty J; Hanley, Kevin W; Viet, Susan M; Ruder, Avima M

2015-01-01

Background An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation. Methods Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking. Results Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence. Conclusions Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits. PMID:24368697

Effects of low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model.

PubMed

Wang, Hung-Jen; Lee, Wei-Chia; Tyagi, Pradeep; Huang, Chao-Cheng; Chuang, Yao-Chi

2017-08-01

Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. We examined the effects of LESW on the expression of inflammatory molecules, pain behavior, and bladder function in a rat cystitis model. Control and experimental animals were injected with saline or cyclophosphamide (CYP; 75 mg/kg intraperitoneally) on day 1 and 4. After lower midline incision, the bladders were exposed to LESW (300 pulses, 0.12 mJ/mm 2 ) or sham operation on day 2. In study 1 (N = 12, 4 for each group), the nociceptive effects of CYP were evaluated for 30 min by behavioral assessment on day 4 one hour after CYP injection. In study 2 (N = 21, 7 for each group), continuous cystometry (CMG) was performed on day 8. The bladder was harvested after behavioral assessment or CMG for histology and Western blotting. CYP-induced upregulation of COX2 and IL6 expression, caused pain behavior (eye closing and hypolocomotion), and bladder inflammation was noted on days 4 and 8 along with bladder hyperactivity. LESW treatment reduced pain behavior and downregulated the NGF expression (33.3%, P < 0.05) on day 4 and IL6 (40.9%, P < 0.05). LESW treatment suppressed bladder overactivity (intercontraction interval 77.8% increase, P < 0.05) by decreasing inflammation and COX2 (38.6%, P < 0.05) expression and NGF expression (25.2%, P = 0.0812). CYP-induced bladder pain, inflammation, and overactivity involves activation of IL6, NGF, and COX2 expression. These changes are suppressed by LESW, indicating it as a potential candidate for relieving bladder inflammatory conditions and overactivity. © 2016 Wiley Periodicals, Inc.

Bladder Cancer Mortality in the United States: A Geographic and Temporal Analysis of Socioeconomic and Environmental Factors.

PubMed

Smith, Norm D; Prasad, Sandip M; Patel, Amit R; Weiner, Adam B; Pariser, Joseph J; Razmaria, Aria; Maene, Chieko; Schuble, Todd; Pierce, Brandon; Steinberg, Gary D

2016-02-01

We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender. NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings. Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p <0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05). Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Medical Tests for Prostate Problems

MedlinePlus

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Bladder irrigation and urothelium disruption: a reminder apropos of a case of fatal fluid absorption.

PubMed

Di Paolo, Marco; Bugelli, Valentina; Di Luca, Alessandro; Turillazzi, Emanuela

2014-11-20

Irrigation or washouts of the bladder are usually performed in various clinical settings. In the 1980s Elliot and colleagues argued that urothelial damage could occur after washouts and irrigations of the bladder. The exact mechanism underlying urothelial damage has not yet been discovered. To our knowledge, this is the first report of fatal fluid overload and pulmonary edema, due to urothelium disruption occurring during bladder irrigation, approached performing complete histological and immunohistochemical investigation on bladder specimens. The exposed case deserves attention since it demonstrates that, although very rarely, irrigation or washouts of the bladder may have unexpected serious clinical consequences. An 85 year-old Caucasian man, unable to eat independently and whose fluid intake was controlled, underwent continuous bladder irrigation with a 3-way catheter due to a severe episode of macrohematuria. During the third day of hospitalization, while still undergoing bladder irrigation, he suddenly experienced extreme shortness of breath, breathing difficulties, and cough with frothy sputum. His attending nurse immediately noted that there was no return of the fluid (5 liters) introduced through bladder irrigation. He was treated urgently with hemodialysis. At the beginning of the dialysis treatment, the patient had gained 7.4 kg since the previous measurement (24 hours prior) without any clear explanation. Although a significant weight loss (from 81 to 76 kg) due to the dialysis procedure, the patient died shortly after the final treatment. The autopsy revealed that the brain and the lungs were heavily edematous. Microscopic examination of bladder specimens revealed interstitial and mucosal swelling, and loss of the superficial cell layer. Intermediate and basal urothelial cells were preserved. Altogether the above mentioned findings were suggestive of a diffuse disruption of the urothelium. In conclusion the death of the man was attributed to an acute severe pulmonary edema due to massive fluid absorption. Our case demonstrates that urothelium disruption may occur during irrigation and washouts of the bladder, also in the absence of other well-known predisposing conditions. Inappropriate use of bladder irrigation should be avoided and a close attention is required of the fluid balance is mandatory when irrigating the bladder.

The role of metabotropic glutamate receptor mGlu5 in control of micturition and bladder nociception.

PubMed

Hu, Youmin; Dong, Li; Sun, Biying; Guillon, Marlene A; Burbach, Leah R; Nunn, Philip A; Liu, Xingrong; Vilenski, Olga; Ford, Anthony P D W; Zhong, Yu; Rong, Weifang

2009-01-23

In micturition control, the roles of ionotropic glutamate (iGlu) receptors NMDA and AMPA are well established, whereas little is known about the function of metabotropic glutamate (mGlu) receptors. Since antagonists for mGlu5 receptors are efficacious in animal models of inflammatory and neuropathic pain, we examined whether mGlu5 receptors play a role in the voiding reflex and bladder nociception and, if so, via centrally or peripherally localized receptors. The mGlu5 receptor antagonist MPEP dose-dependently increased the micturition threshold (MT) volume in the volume-induced micturition reflex (VIMR) model in anesthetized rats. Following doses of 5.2, 15.5 and 51.7micromol/kg of MPEP (intraduodenal), the MT was increased by 24.7+/-5.0%, 97.2+/-12.5% (P<0.01) and 128.0+/-28.3% (P<0.01) from the baseline, respectively (n=4-5; compared with 0.8+/-9.1% in the vehicle group). Infusing MPEP (0.3, 1mM) directly into the bladder also raised MT. However, the efficacious plasma concentrations of MPEP following intravesical dosing were similar to that after intraduodenal dosing (EC(50) of 0.11 and 0.27microM, respectively, P>0.05). MPEP also dose-dependently attenuated the visceromotor responses (VMR, total number of abdominal EMG spikes during phasic bladder distension) in anesthetized rats. The VMR was decreased to 1332.4+/-353.9 from control of 2886.5+/-692.2 spikes/distension (n=6, P<0.01) following MPEP (10micromol/kg, iv). Utilizing the isolated mouse bladder/pelvic nerve preparation, we found that neither MPEP (up to 3microM) nor MTEP (up to 10microM) affected afferent discharge in response to bladder distension (n=4-6). In contrast, MPEP attenuated the responses of the mesenteric nerves to distension of the mouse jejunum in vitro. These data suggest that mGlu5 receptors play facilitatory roles in the processing of afferent input from the urinary bladder, and that central rather than peripheral mGlu5 receptors appear to be responsible.

Occupation and Bladder Cancer in a Population-Based Case-control Study in Northern New England

PubMed Central

Colt, Joanne S.; Karagas, Margaret R.; Schwenn, Molly; Baris, Dalsu; Johnson, Alison; Stewart, Patricia; Verrill, Castine; Moore, Lee E.; Lubin, Jay; Ward, Mary H.; Samanic, Claudine; Rothman, Nathaniel; Cantor, Kenneth P.; Beane Freeman, Laura E.; Schned, Alan; Cherala, Sai; Silverman, Debra T.

2010-01-01

Objectives We used data from a large, population-based case-control study in New England to examine relationships between occupation, industry, and bladder cancer risk. Methods Lifetime occupational histories were obtained by personal interview from 1,158 patients newly diagnosed with urothelial carcinoma of the bladder between 2001 and 2004 among residents of Maine, New Hampshire, and Vermont, and from 1,402 population controls selected from Department of Motor Vehicle records (ages 30 to 64 years) or Medicare beneficiary records (65 to 79 years). Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for demographic factors, smoking, and employment in high-risk occupations other than the one being analyzed. Results Male precision metalworkers and metalworking/plasticworking machine operators had significantly elevated risks and significant trends in risk with duration of employment (precision metalworkers: OR=2.2; CI: 1.4, 3.4, Ptrend =0.0065; metalworking/plasticworking machine operators: OR=1.6; CI: 1.01, 2.6, Ptrend=0.047). Other occupations/industries for which risk increased significantly with duration of employment included: for men, textile machine operators, mechanics/repairers, automobile mechanics, plumbers, computer systems analysts, information clerks, and landscape and horticultural services industry workers; and for women, service occupations, health services, cleaning and building services, management-related occupations, electronic components and accessories manufacturing, and transportation equipment manufacturing. Men reporting use of metalworking fluids (MWF) had a significantly elevated bladder cancer risk (OR=1.7; 95% CI: 1.1, 2.5), Conclusions Our findings for metalworkers and for MWF exposure support the hypothesis that some component(s) of MWF may be carcinogenic to the bladder in humans. Our results also corroborate many other previously-reported associations between bladder cancer risk and various occupations. More detailed analyses using information collected in job-specific questionnaires administered in this study may help to identify components of MWF that may be carcinogenic, and other bladder carcinogens to which people are exposed in a variety of occupations. PMID:20864470

Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

NASA Astrophysics Data System (ADS)

Khurram, Abeer; Ross, Shani E.; Sperry, Zachariah J.; Ouyang, Aileen; Stephan, Christopher; Jiman, Ahmad A.; Bruns, Tim M.

2017-06-01

Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

Genome-wide association studies in bladder cancer: first results and potential relevance.

PubMed

Kiemeney, Lambertus A; Grotenhuis, Anne J; Vermeulen, Sita H; Wu, Xifeng

2009-09-01

The role of genetic susceptibility in the development of urinary bladder cancer is unclear, as it is in many other types of cancer. Since 2007, however, an innovative research approach (i.e. genome-wide association studies or GWASs) has led to the identification of numerous genomic loci that harbor susceptibility factors for one or more cancer sites. All GWASs have been published in high-impact journals and the strengths of the design are acknowledged by all experts, but there is criticism about the relevance of the results. Late 2008, the first GWAS in bladder cancer was published. In this review, the principles of GWASs are explained, as well as their strengths and limitations. The study in bladder cancer among 4000 cases and 38,000 controls identified three new susceptibility loci at 8q24, 3q28, and 5p15 that increase the risk of bladder cancer by 22, 19, and 16%, respectively. The results of two other GWASs in bladder cancer are expected to appear this year. Joint analysis of the three studies will probably identify additional susceptibility loci. The results of bladder cancer GWASs may point the way to yet unknown disease mechanisms. So far, the findings are not sufficiently discriminative for risk predictions to be used in clinical care or public health.

Central control of micturition in women: Brain-bladder pathways in continence and urgency urinary incontinence.

PubMed

Arya, Nisha G; Weissbart, Steven J

2017-04-01

Urinary incontinence disproportionately affects women. Anatomical textbooks typically describe continence mechanisms in women in the context of the pelvic floor support of the urinary bladder and the urethral sphincters. However, the urinary bladder and urethral sphincters are under the central control of the brain through a complex network of neurons that allow storage of urine followed by voiding when socially appropriate. Recent studies suggest that the most common type of urinary incontinence in women, urgency urinary incontinence, involves significant dysfunction of the central control of micturition. In this paper, we review the anatomy and functional connectivity of the nervous system structures involved in the control of micturition. Clinical application of this anatomy in the context of urgency urinary incontinence is also discussed. Understanding the anatomy of the neural structures that control continence will allow clinicians to better understand the underlying pathology of urge incontinence and consider new ways of treating this distressing condition. Clin. Anat. 30:373-384, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Application of Multi-SNP Approaches Bayesian LASSO and AUC-RF to Detect Main Effects of Inflammatory-Gene Variants Associated with Bladder Cancer Risk

PubMed Central

Calle, M. Luz; Rothman, Nathaniel; Urrea, Víctor; Kogevinas, Manolis; Petrus, Sandra; Chanock, Stephen J.; Tardón, Adonina; García-Closas, Montserrat; González-Neira, Anna; Vellalta, Gemma; Carrato, Alfredo; Navarro, Arcadi; Lorente-Galdós, Belén; Silverman, Debra T.; Real, Francisco X.; Wu, Xifeng; Malats, Núria

2013-01-01

The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk. PMID:24391818

Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

PubMed

Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

2010-08-01

Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

Measurement of DNA damage in rat urinary bladder transitional cells: improved selective harvest of transitional cells and detailed Comet assay protocols.

PubMed

Wang, Amy; Robertson, John L; Holladay, Steven D; Tennant, Alan H; Lengi, Andrea J; Ahmed, S Ansar; Huckle, William R; Kligerman, Andrew D

2007-12-01

Urinary bladder transitional epithelium is the main site of bladder cancer, and the use of transitional cells to study carcinogenesis/genotoxicity is recommended over the use of whole bladders. Because the transitional epithelium is only a small fraction of the whole bladder, the alkaline single cell gel electrophoresis assay (Comet assay), which requires only a small number of cells per sample, is especially suitable for measuring DNA damage in transitional cells. However, existed procedures of cell collection did not yield transitional cells with a high purity, and pooling of samples was needed for Comet assay. The goal of this study was to develop an optimized protocol to evaluate DNA damage in the urinary bladder transitional epithelium. This was achieved by an enzymatic stripping method (trypsin-EDTA incubation plus gentle scraping) to selectively harvest transitional cells from rat bladders, and the use of the alkaline Comet assay to detect DNA strand breaks, alkaline labile sites, and DNA-protein crosslinks. Step by step procedures are reported here. Cells collected from a single rat bladder were sufficient for multiple Comet assays. With this new protocol, increases in DNA damage were detected in transitional cells after in vitro exposure to the positive control agents, hydrogen peroxide or formaldehyde. Repair of the induced DNA damage occurred within 4h. This indicated the capacity for DNA repair was maintained in the harvested cells. The new protocol provides a simple and inexpensive method to detect various types of DNA damage and to measure DNA damage repair in urinary bladder transitional cells.

Tadalafil attenuates hypotonicity-induced Ca2+ influx via TRPV2 and TRPV4 in primary rat bladder urothelial cell cultures.

PubMed

Dong, Xiao; Nakagomi, Hiroshi; Miyamoto, Tatsuya; Ihara, Tatsuya; Kira, Satoru; Sawada, Norifumi; Mitsui, Takahiko; Takeda, Masayuki

2018-03-22

To investigate the localization of phosphodiesterase 5 (PDE5) and the molecular mechanism underlying the effect of the PDE5 inhibitor tadalafil in signal transduction in the bladder urothelium. PDE5 expression in rat bladder tissues and cultured primary rat bladder urothelial cells was evaluated using immunochemistry and western blot assays. Ca 2+ influx in cells exposed to isotonic solution, hypotonic solution, a selective transient receptor potential vanilloid 2 (TRPV2) channel agonist (cannabidiol), a selective TRPV4 channel agonist (GSK1016790A), a TRP cation channel melastatin 7 (TRPM7) channel agonist (PIP2), or a purinergic receptor agonist (ATP) in the presence or absence of 10 µM tadalafil was evaluated using calcium imaging techniques. We also evaluated stretch-induced changes in ATP concentration in the mouse bladder in the presence or absence of 100 µM tadalafil. Immunochemistry and western blot analyses demonstrated that PDE5 is abundantly expressed in the bladder urothelium and in primary rat urothelial cells. Ca 2+ influx induced by hypotonic stimulation, GSK1016790A, or cannabidiol was significantly inhibited by tadalafil, whereas ATP-induced Ca 2+ influx was unaffected by tadalafil. PIP2 did not induce Ca2+ influx. ATP release in tadalafil-pretreated bladders significantly decreased compared to control bladders. Tadalafil attenuates Ca 2+ influx via TRPV4 and TRPV2, and inhibits ATP release in the bladder urothelium. These findings indicate that tadalafil functions as an inhibitor of urothelial signal transduction. © 2018 Wiley Periodicals, Inc.

Bladder accumulated dose in image-guided high-dose-rate brachytherapy for locally advanced cervical cancer and its relation to urinary toxicity

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Gaudet, Marc; Aquino-Parsons, Christina; Spadinger, Ingrid

2016-12-01

The purpose of this study was to estimate locally accumulated dose to the bladder in multi-fraction high-dose-date (HDR) image-guided intracavitary brachytherapy (IG-ICBT) for cervical cancer, and study the locally-accumulated dose parameters as predictors of late urinary toxicity. A retrospective study of 60 cervical cancer patients who received five HDR IG-ICBT sessions was performed. The bladder outer and inner surfaces were segmented for all sessions and a bladder-wall contour point-set was created in MATLAB. The bladder-wall point-sets for each patient were registered using a deformable point-set registration toolbox called coherent point drift (CPD), and the fraction doses were accumulated. Various dosimetric and volumetric parameters were calculated using the registered doses, including r{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} (minimum dose to the most exposed n-cm3 volume of bladder wall), r V n Gy (wall volume receiving at least m Gy), and r\\text{EQD}{{2}n \\text{c{{\\text{m}}\\text{3}}}} (minimum equivalent biologically weighted dose to the most exposed n-cm3 of bladder wall), where n  =  1/2/5/10 and m  =  3/5/10. Minimum dose to contiguous 1 and 2 cm3 hot-spot volumes was also calculated. The unregistered dose volume histogram (DVH)-summed equivalent of r{{\\text{D}}n \\text{c{{\\text{m}}3}}} and r\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} parameters (i.e. s{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} and s\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} ) were determined for comparison. Late urinary toxicity was assessed using the LENT-SOMA scale, with toxicity Grade 0-1 categorized as Controls and Grade 2-4 as Cases. A two-sample t-test was used to identify the differences between the means of Control and Case groups for all parameters. A binomial logistic regression was also performed between the registered dose parameters and toxicity grouping. Seventeen patients were in the Case and 43 patients in the Control group. Contiguous values were on average 16 and 18% smaller than parameters for 1 and 2 cm3 volumes, respectively. Contiguous values were on average 26 and 27% smaller than parameters. The only statistically significant finding for Case versus Control based on both methods of analysis was observed for r V3 Gy (p  =  0.01). DVH-summed parameters based on unregistered structure volumes overestimated the bladder dose in our patients, particularly when contiguous high dose volumes were considered. The bladder-wall volume receiving at least 3 Gy of accumulated dose may be a parameter of interest in further investigations of Grade 2+  urinary toxicity.

THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

PubMed

Kehinde, E O; Al-Maghrebi, M; Anim, J T; Kapila, K; George, S S; Al-Juwaiser, A; Memon, A

2013-01-01

To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. Prospective study Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

PubMed

Offiah, Ifeoma; Didangelos, Athanasios; Dawes, John; Cartwright, Rufus; Khullar, Vik; Bradbury, Elizabeth J; O'Sullivan, Suzanne; Williams, Dic; Chessell, Iain P; Pallas, Kenny; Graham, Gerry; O'Reilly, Barry A; McMahon, Stephen B

2016-08-01

Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Robotic-assisted versus open radical cystectomy in bladder cancer: A meta-analysis of four randomized controlled trails.

PubMed

Tang, Jin-Qiu; Zhao, Zhihong; Liang, Yiwen; Liao, Guixiang

2018-02-01

Robot-assisted radical cystectomy (RARC) is increasing annually for treatment of bladder cancer. The objective of this meta-analysis was to compare the safety and efficacy of RARC and open radical cystectomy (ORC) for bladder cancer. Our meta-analysis searches were conducted using PubMed, Web of Science, and Cochrane Library databases to identify randomized controlled trials (RCT) assessing the two techniques. Four RCT studies were identified, including 239 cases. Our studies indicated that RARC was associated with longer operative time (WMD: 69.69, 95% CI:17.25 to122.12; P= 0.009), lower estimated blood loss (WMD: -299.83, 95% CI:-414.66to -184.99; P<0.00001). The two groups had no significant difference in overall perioperative complications, length of hospital stay, lymph node yield and positive surgical margins. RARC is mini-invasive alternative to ORC for bladder cancer. The advantage of RARC was reduced estimated blood loss. More studies are needed to compare the two techniques. Copyright © 2017 John Wiley & Sons, Ltd.

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

Role of potassium ion channels in detrusor smooth muscle function and dysfunction

PubMed Central

Petkov, Georgi V.

2013-01-01

Contraction and relaxation of the detrusor smooth muscle (DSM), which makes up the wall of the urinary bladder, facilitates the storage and voiding of urine. Several families of K+ channels, including voltage-gated K+ (KV) channels, Ca2+-activated K+ (KCa) channels, inward-rectifying ATP-sensitive K+ (Kir, KATP) channels, and two-pore-domain K+ (K2P) channels, are expressed and functional in DSM. They control DSM excitability and contractility by maintaining the resting membrane potential and shaping the action potentials that determine the phasic nature of contractility in this tissue. Defects in DSM K+ channel proteins or in the molecules involved in their regulatory pathways may underlie certain forms of bladder dysfunction, such as overactive bladder. K+ channels represent an opportunity for novel pharmacological manipulation and therapeutic intervention in human DSM. Modulation of DSM K+ channels directly or indirectly by targeting their regulatory mechanisms has the potential to control urinary bladder function. This Review summarizes our current state of knowledge of the functional role of K+ channels in DSM in health and disease, with special emphasis on current advancements in the field. PMID:22158596

Muscarinic receptor subtypes involved in urothelium-derived relaxatory effects in the inflamed rat urinary bladder.

PubMed

Andersson, M; Aronsson, P; Doufish, D; Lampert, A; Tobin, G

2012-09-25

Functional studies have shown altered cholinergic mechanisms in the inflamed bladder, which partly depend on muscarinic receptor-induced release of nitric oxide (NO). The current study aimed to characterize which muscarinic receptor subtypes that are involved in the regulation of the nitrergic effects in the bladder cholinergic response during cystitis. For this purpose, in vitro examinations of carbachol-evoked contractions of inflamed and normal bladder preparations were performed. The effects of antagonists with different selectivity for the receptor subtypes were assessed on intact and urothelium-denuded bladder preparations. In preparations from cyclophosphamide (CYP; in order to induce cystitis) pre-treated rats, the response to carbachol was about 75% of that of normal preparations. Removal of the urothelium or administration of a nitric oxide synthase inhibitor re-established the responses in the inflamed preparations. Administration of 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) inhibited the carbachol-induced contractile responses of preparations from CYP pre-treated rats less potently than controls. Pirenzepine and p-fluoro-hexahydro-sila-diphenidol (pFHHSiD) affected the carbachol-induced contractile responses to similar extents in preparations of CYP pre-treated and control rats. However, the Schild slopes for the three antagonists were all significantly different from unity in the preparations from CYP pre-treated rats. Again, L-NNA or removal of the urothelium eliminated any difference compared to normal preparations. This study confirms that muscarinic receptor stimulation in the inflamed rat urinary bladder induces urothelial release of NO, which counteracts detrusor contraction. Copyright © 2012 Elsevier B.V. All rights reserved.

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras.

PubMed

Ehrhardt, Annette; Wang, Bin; Yung, Andrew C; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W

2015-01-01

Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras-/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly 'layered' with age in Mras-/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras-/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras-/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras-/- males were increased, and Mras-/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras-/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice.

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

PubMed Central

Ehrhardt, Annette; Wang, Bin; Yung, Andrew C.; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W.

2015-01-01

Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras -/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly ‘layered’ with age in Mras -/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras -/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras -/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras -/- males were increased, and Mras -/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras -/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. PMID:26516777

Incontinence in children with treated attention-deficit/hyperactivity disorder.

PubMed

Niemczyk, J; Equit, M; Hoffmann, L; von Gontard, A

2015-06-01

Attention-deficit/hyperactivity disorder (ADHD) and incontinence (nocturnal enuresis, daytime urinary incontinence and fecal incontinence) are common disorders in childhood. Both disorders are strongly associated with each other. ADHD can affect compliance to incontinence therapy in a negative way; it can also affect outcome. The aim of the present study was to assess the prevalence of incontinence, age of bladder and bowel control, and psychological symptoms in children having treatment for ADHD compared to a control group. Forty children having treatment for ADHD (75% boys, mean age 11.4 years) and 43 matched controls (60.5% boys, mean age 10.7 years) were assessed. Their parents filled out questionnaires to assess: child psychopathology (Child Behavior Checklist), incontinence (Parental Questionnaire: Enuresis/Urinary Incontinence; Encopresis Questionnaire - Screening Version) and symptoms of the lower urinary tract (International-Consultation-on-Incontinence-Questionnaire - Pediatric Lower Urinary Tract Symptoms). The ICD-10 diagnoses and children's IQ were measured by standardized instruments (Kinder-DIPS, Coloured Progressive Matrices/Standard Progressive Matrices). Rates of incontinence in the ADHD group (5% nocturnal enuresis, 5% daytime urinary incontinence, 2.5% fecal incontinence) did not differ significantly from incontinence rates in the control group (4.7% daytime urinary incontinence). More children in the ADHD group had Child Behavior Checklist scores in the clinical range. Further ICD-10 disorders were present in eight children with ADHD and in one control child. More children with ADHD had delayed daytime and nighttime bladder control, as well as delayed bowel control, than the controls. The present study showed that if children are treated for their ADHD, according to standard practice guidelines, incontinence rates are similar to those without ADHD. More children with ADHD reached continence at a later age than the controls, which could be an indicator of maturational deficits in the central nervous system. Additionally, children with ADHD showed higher rates of clinically relevant psychological symptoms. This study provides further information of the association between ADHD and incontinence. Treatment of ADHD may be associated with positive effects on incontinence outcomes. Therefore, children with ADHD should always be screened for incontinence problems and children with incontinence problems should also be screened for ADHD if symptoms of hyperactivity, inattention and/or impulsivity are also present. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Spatio-Temporal Distribution of Smads and Role of Smads/TGF-β/BMP-4 in the Regulation of Mouse Bladder Organogenesis

PubMed Central

Islam, Syed S.; Mokhtari, Reza Bayat; Kumar, Sushil; Maalouf, Joe; Arab, Sara; Yeger, Herman; Farhat, Walid A.

2013-01-01

Although Shh, TGF-β and BMP-4 regulate radial patterning of the bladder mesenchyme and smooth muscle differentiation, it is not known what transcription factors, local environmental cues or signaling cascades mediate bladder smooth muscle differentiation. We investigated the expression patterns of signaling mediated by Smad2 and Smad3 in the mouse embryonic bladder from E12.5 to E16.5 by using qRT-PCR, in situ hybridization and antibodies specifically recognizing individual Smad proteins. The role of Smad2 and Smad3 during smooth muscle formation was examined by disrupting the Smad2/3 signaling pathway using TβR1 inhibitor SB-431542 in organ culture system. qRT-PCR results showed that R-Smads, Co-Smad and I-Smads were all expressed during bladder development. RNA ISH for BMP-4 and immunostaining of TGF-β1 showed that BMP-4 and TGF-β1 were expressed in the transitional epithelium, lamina propia and muscularis mucosa. Smad1, Smad5 and Smad8 were first expressed in the bladder epithelium and continued to be expressed in the transitional epithelium, muscularis mesenchyme and lamina propia as the bladder developed. Smad2, Smad3 and Smad4 were first detected in the bladder epithelium and subsequently were expressed in the muscularis mesenchyme and lamina propia. Smad6 and Smad7 showed overlapping expression with R-Smads, which are critical for bladder development. In bladder explants (E12.5 to E16.5) culture, Smad2 and Smad3 were found localized within the nuclei, suggesting critical transcriptional regulatory effects during bladder development. E12.5 to E16.5 bladders were cultured with and without TβR1 inhibitor SB-431542 and assessed by qRT-PCR and immunofluorescence. After three days in culture in SB-431542, α-SMA, Smad2 and Smad3 expressions were significantly decreased compared with controls, however, with no significant changes in the expression of smooth muscle myosin heavy chain (SM-Myh. Based on the Smad expression patterns, we suggest that individual or combinations of Smads may be necessary during mouse bladder organogenesis and may be critical mediators for bladder smooth muscle differentiation. PMID:23620745

Validation of non-rigid point-set registration methods using a porcine bladder pelvic phantom

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Spadinger, Ingrid

2016-01-01

The problem of accurate dose accumulation in fractionated radiotherapy treatment for highly deformable organs, such as bladder, has garnered increasing interest over the past few years. However, more research is required in order to find a robust and efficient solution and to increase the accuracy over the current methods. The purpose of this study was to evaluate the feasibility and accuracy of utilizing non-rigid (affine or deformable) point-set registration in accumulating dose in bladder of different sizes and shapes. A pelvic phantom was built to house an ex vivo porcine bladder with fiducial landmarks adhered onto its surface. Four different volume fillings of the bladder were used (90, 180, 360 and 480 cc). The performance of MATLAB implementations of five different methods were compared, in aligning the bladder contour point-sets. The approaches evaluated were coherent point drift (CPD), gaussian mixture model, shape context, thin-plate spline robust point matching (TPS-RPM) and finite iterative closest point (ICP-finite). The evaluation metrics included registration runtime, target registration error (TRE), root-mean-square error (RMS) and Hausdorff distance (HD). The reference (source) dataset was alternated through all four points-sets, in order to study the effect of reference volume on the registration outcomes. While all deformable algorithms provided reasonable registration results, CPD provided the best TRE values (6.4 mm), and TPS-RPM yielded the best mean RMS and HD values (1.4 and 6.8 mm, respectively). ICP-finite was the fastest technique and TPS-RPM, the slowest.

Air pollution and risk of urinary bladder cancer in a case-control study in Spain.

PubMed

Castaño-Vinyals, Gemma; Cantor, Kenneth P; Malats, Núria; Tardon, Adonina; Garcia-Closas, Reina; Serra, Consol; Carrato, Alfredo; Rothman, Nathaniel; Vermeulen, Roel; Silverman, Debra; Dosemeci, Mustafa; Kogevinas, Manolis

2008-01-01

Air pollution has been associated with an increased risk for lung cancer. We examined whether long-term air pollution is associated with bladder cancer risk. Information from a case-control study in Spain that included 1219 incident cases and 1271 hospital controls was used. Information on residential history including several indicators of exposure to air pollution and other potential risk factors was collected in a face-to-face computerised personal interview. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, smoking, occupation, water contaminants and diet. Living more than 40 years in a city with a population of more than 100 000 was associated with an increased risk for bladder cancer overall (OR 1.30, 95% CI 1.04 to 1.63). Emissions of polycyclic aromatic hydrocarbons and diesel from industries near the residence, as evaluated by experts, were associated with an increased risk (OR 1.29, 95% CI 0.85 to 1.98), while lower or no excess risks were observed for other pollution-related variables. Odds ratios among never smokers tended to be higher than among smokers. The small to moderate positive associations found for several indices of air pollution and bladder cancer, while suggestive of excess risk, require further evaluation in other settings.

A Review of ERCC1 Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy.

PubMed

Kawashima, Atsunari; Takayama, Hitoshi; Tsujimura, Akira

2012-01-01

The excision repair cross-complementing group 1 (ERCC1) gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.

Expression of HSP 70 and its mRNAS during ischemia-reperfusion in the rat bladder.

PubMed

Saito, Motoaki; Tominaga, Lika; Nanba, Eiji; Kinoshita, Yukako; Housi, Daisuke; Miyagawa, Ikuo; Satoh, Keisuke

2004-08-27

HSP 70 is an important protein that repairs damaged tissue after injury. In the present study, we investigated the expression of HSP 70 and its mRNAs during ischemia-reperfusion in the rat bladder. Rat abdominal aorta was clamped with a small clip to induce ischemia-reperfusion injury in the bladder dome. Male Wistar rats, 8 weeks old, were divided into six groups: controls, 30-min ischemia, 30-min ischemia and 30-, 60-minute, 1- and 7-day reperfusion, groups A, B, C, D, E, and F, respectively. In functional studies, contractile responses to carbachol were measured in these groups. The expression of HSP 70-1/2 mRNAs was quantified using a real-time PCR method, and that of HSP 70 proteins was measured using ELISA in the bladders. In the functional study, Emax values of carbachol to bladders in the A, B, C, D, E and F groups were 9.3 +/- 1.3, 7.9 +/- 1.7, 4.3 +/- 0.8, 4.2 +/- 0.7, 4.5 +/- 0.6, and 8.1 +/- 1.2 g/mm2, respectively. In the control group, the expression of HSP 70-1/2 mRNA was detected, and the expression of HSP 70-1 mRNAs was significantly higher than that of HSP 70-2 mRNAs in each group. The expression of HSP 70-1 mRNA increased in groups B and C, but decreased in groups D, E, and F. The expression of HSP 70-2 mRNA in group C was significantly higher than that of groups A, D, E, and F. The expression of HSP 70-1/2 mRNAs after 1 day or 1 week of reperfusion was similar to control levels. The expression of HSP 70 proteins was increased shortly after the expression of their mRNAs. The expression of HSP 70 after 1 day or 1 week of reperfusion was almost identical to control levels. Our data indicate that contractile responses of the bladder were decreased by ischemia reperfusion, and that expression of HSP 70 and its mRNAs appeared to increase after a short period of the insult.

Small bowel injury after suprapubic catheter insertion presenting 3 years after initial insertion

PubMed Central

Gallagher, Kevin M; Good, Daniel W; Brush, John P; Al-hasso, Ammar; Stewart, Grant D

2013-01-01

A 77-year-old woman was referred to urology with blockages of her suprapubic catheter (SPC). The catheter was replaced easily in the emergency department, however, no urine was draining, only a cloudy green fluid was visible. On cystoscopy bilious material was identified in the bladder. There was no catheter visible. There seemed to be a fistulous tract entering the bladder at the left dome. The urethra was dilated, a urethral catheter was placed and the SPC was removed. A CT demonstrated that the SPC tract transfixed a loop of pelvic small bowel and entered the bladder with no intraperitoneal contrast leak. The patient recovered well and did not require laparotomy. This case emphasises that bowel perforation, although rare, must be considered as a complication of SPC placement even years after initial insertion when catheter problems arise. Unusually, we learn that this complication may not present with abdominal pain or peritonism. PMID:24326435

[Urinary incontinence].

PubMed

Kuhn, Annette

2010-01-01

Incontinence is a common age-dependent and increasing problem in women that may mainly present as stress incontinence, overactive bladder, mixed incontinence or other forms. A thorough history, gynaecological and neurological examination and urinalysis as initial step will lead to the diagnosis and treatment. If midstream urine is difficult to receive, a catheter urine will be easy to obtain. Further investigations as urodynamics, cystoscopy and ultrasound may be required. As initial step, stress incontinence should be treated with physiotherapy and pelvic floor exercises, if not successful with operations as suburethral slings. Slings have good long-term success rates of approximately 85 % with a low morbidity and can even be inserted under local anaesthetic. The treatment of idiopathic overactive bladder consists of bladder training, a behavioural therapy, and mainly anticholinergics. Anticholinergics may cause side effects particularly in the elderly who are under several medications that may add anticholinergic effects as antidepressants, antibiotics or antihistaminics.

Lower urinary tract symptoms in patients with Niigata Minamata disease: a case-control study 50 years after methyl mercury pollution.

PubMed

Hara, Noboru; Saito, Hisashi; Takahashi, Kota; Takeda, Masayuki

2013-06-01

To clarify the prevalence of lower urinary tract symptoms and overactive bladder in patients with chronic methyl mercury poisoning. A total of 151 patients (61 men and 90 women; mean age 72.1 years) with Niigata Minamata disease were enrolled. An age- and sex-matched group of 150 participants was used as control. Patients reported their International Prostate Symptom Score and overactive bladder symptom score. In men, the total, storage and voiding International Prostate Symptom Score scores were higher in the Niigata Minamata disease group than in the control group (10.6 ± 7.8 vs 5.0 ± 5.0, 4.5 ± 3.3 vs 2.4 ± 2.4 and 6.1 ± 5.1 vs 2.7 ± 3.1, respectively, P < 0.001 in all). In women, these scores were also higher in the Niigata Minamata disease group than in the control group (8.9 ± 7.3 vs 4.0 ± 4.0, 4.4 ± 3.2 vs 2.8 ± 2.4 and 4.5 ± 5.0 vs 1.3 ± 2.0, respectively, P < 0.001 in all). The prevalence of overactive bladder was more frequent in the Niigata Minamata disease group compared with that in the control group (51.7% vs 26.7%, P < 0.001). In both men and women, the overactive bladder symptom score was higher in the Niigata Minamata disease group than in the control group (4.1 ± 3.0 vs 2.4 ± 2.9, P = 0.002 and 4.6 ± 3.6 vs 2.7 ± 2.9, P < 0.001, respectively). The International Prostate Symptom Score and overactive bladder symptom score in the Niigata Minamata disease group were highest in patients aged 60-69 years (P < 0.001 in both), whereas these increased in an age-dependent manner in the control group. Lower urinary tract symptoms and overactive bladder are severe and highly prevalent conditions among patients with methyl mercury poisoning. The higher prevalence of lower urinary tract symptoms among patients aged 60-69 years might be related to the fact that they were exposed to methyl mercury during their childhood/development. © 2012 The Japanese Urological Association.

Nerve supply to the pelvis (image)

MedlinePlus

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal ... be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems ...

Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin.

PubMed

Ratliff, T L; Palmer, J O; McGarr, J A; Brown, E J

1987-04-01

Intravesical Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial bladder cancer. Although the mechanisms by which BCG inhibits tumor growth are not known, previous studies have shown that systemic immunization to BCG and the local expression of the immune response in the bladder are associated with a favorable response to BCG therapy. We have investigated the conditions required for the initiation of an immunological response after the intravesical instillation of BCG. Initial histological studies showed that BCG attached to the bladder wall only in areas where the urothelium was damaged by electrocautery and suggested that attachment was associated with the fibrin clot. Quantitative studies verified the histological observations. Minimal BCG attachment (mean less than 10(2) colony forming units) was observed in normal bladders in contrast with a mean of 1.42 X 10(4) colony forming units/bladder in bladders damaged by electrocautery (10 separate experiments). BCG attachment to the bladder wall was durable since organisms were observed in bladders 48 h after instillation. To investigate the proteins to which BCG attached, we tested the binding of BCG to extracellular matrix and inflammatory proteins which comprise a significant portion of the fibrin clot. BCG bound in vitro to coverslips coated in vivo with extracellular matrix proteins but did not bind to control albumin-coated coverslips. BCG also bound to coverslips coated with purified plasma fibronectin but not to coverslips coated with other purified extracellular matrix proteins including laminin, fibrinogen, and type IV collagen. BCG attachment to coverslips coated with either extracellular matrix proteins or purified fibronectin was inhibited by antibodies specific for fibronectin. Moreover, BCG attachment to cauterized bladders in vivo was inhibited by antifibronectin antibodies. These results demonstrate that fibronectin mediates the attachment of BCG to surfaces and suggest that it is the primary component mediating attachment within the bladder. Moreover, the data suggest that the BCG-fibronectin interaction may be a requisite first step for the initiation of the antitumor activity in intravesical BCG for bladder cancer.

Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction

PubMed Central

Kiss, Bernhard; Moltzahn, Felix; Keller, Irene; Rehrauer, Hubert; Fournier, Catharine Aquino; Burkhard, Fiona C.

2017-01-01

Bladder outlet obstruction (BOO) induces significant organ remodeling, leading to lower urinary tract symptoms accompanied by urodynamic changes in bladder function. Here, we report mRNA and miRNA transcriptome sequencing of bladder samples from human patients with different urodynamically defined states of BOO. Patients’ miRNA and mRNA expression profiles correlated with urodynamic findings. Validation of RNA sequencing results in an independent patient cohort identified combinations of 3 mRNAs (NRXN3, BMP7, UPK1A) and 3 miRNAs (miR-103a-3p, miR-10a-5p, miR-199a-3p) sufficient to discriminate between bladder functional states. All BOO patients shared cytokine and immune response pathways, TGF-β and NO signaling pathways, and hypertrophic PI3K/AKT signaling pathways. AP-1 and NFkB were dominant transcription factors, and TNF-α was the top upstream regulator. Integrated miRNA-mRNA expression analysis identified pathways and molecules targeted by differentially expressed miRNAs. Molecular changes in BOO suggest an increasing involvement of miRNAs in the control of bladder function from the overactive to underactive/acontractile states. PMID:28138557

The assessment of bladder neck position and mobility in continent nullipara, mulitpara, forceps-delivered and incontinent women using perineal ultrasound: a future office procedure?

PubMed

Meyer, S; De Grandi, P; Schreyer, A; Caccia, G

1996-01-01

The purpose of this study was to assess the effects of spontaneous and instrumented deliveries, the baby's birthweight, the presence of stress incontinence and the woman's age and weight on bladder neck (BN) position and mobility using perineosonography, a simple non-invasive method, and to compare these results with those from continent nulliparous controls. Two hundred and fourteen women, including 74 nullipara, 29 para-1, 64 para-2 and 3, 16 with previous forceps deliveries and 32 with stress incontinence, underwent perineosonography with measurements of BN position and backwards/downwards displacement of BN using a two-axis calculation system. Results showed that bladder neck position undergoes a significantly backwards and downwards displacement on assuming an upright position. When compared with nulliparous controls, the bladder neck position at rest was the same in all groups of parous women in the supine/standing positions, but lower in patients having undergone forceps delivery (standing position) and in stress incontinent patients (both supine and standing); the bladder neck position during Valsalva was significantly lower in all groups of patients in the standing position, but the only significant difference in the supine position was seen in stress incontinent patients; the extent of bladder neck displacement was not significantly different between the groups, except in stress incontinent patients. A strong correlation (r = 0.66) was found between the relative importance of backwards and downwards displacement, but no correlation was found between bladder neck displacement and baby's birth-weight or patient's weight. It was concluded that compared to nulliparous continent patients, normal and instrumented delivery induces no modifications of BN position at rest, but is responsible for a lower bladder neck position during Valsalva in the standing position only. The extent of BN displacement is virtually the same in all groups of patients in both positions, except for stress incontinent patients, who have a significantly lower and more mobile bladder neck, the values of which overlap to a great extent (sensitivity of 78%/75% for a displacement > 14 mm) within those seen in continent nulliparous women. The correlation between the importance of backwards and downwards displacement is strong, making superfluous a two-dimensional coordinate system for routine BN position/mobility assessment.

Salt adaptation in Bufo bufo

PubMed Central

Ferreira, H. G.; Jesus, C. H.

1973-01-01

1. The capacity of adaptation of toads (Bufo bufo) to environments of high salinity was studied and the relative importance of skin, kidney and urinary bladder in controlling the balance of water and salt was assessed. 2. Toads were kept in NaCl solutions of 20, 50, 110, 150 and 220 mM and studied in their fourth week of adaptation. A group of animals considered as `control' was kept in wet soil with free access to water. Plasma, ureter urine, and bladder and colon contents were analysed for sodium, potassium, chloride and osmolality, and total body sodium and water were determined. Absorption of water and 22Na through the skin, and water flow and sodium excretion through the ureter, of intact animals was studied. Hydrosmotic water transport through the isolated urinary bladder of `control' and adapted animals was determined. The effects of pitressin and aldosterone on the water and sodium balance are described. 3. The survival rates of toads kept in saline concentrations up to 150 mM were identical to that of `control' animals, but half of the animals kept in 220 mM died within 4 weeks. 4. There is a linear correlation between the sodium concentrations and osmolality of plasma and of the external media. 5. The sodium concentration in colon contents rose with rising external concentrations, up to values higher than the values in plasma. 6. Sodium concentrations and osmolalities of ureter and bladder urine increased in adapted animals, the values for bladder urine becoming much higher than those for ureter urine in animals adapted to 110, 150 and 220 mM. 7. Total body water, as a percentage of total weight was kept within very narrow limits, although the total body sodium increased with adaptation. 8. Absorption of water through the skin for the same osmotic gradients was smaller in adapted than in `control' animals. 9. The ureteral output of water of toads adapted to 110 and 150 mM-NaCl was larger than the water absorption through the skin. 10. Skin absorption of sodium was lower in animals adapted to concentrated saline solutions than in `control' animals. 11. Sodium output by the ureter was identical to skin absorption in `control' animals adapted to 20, 50 and 110 mM-NaCl but was higher in animals adapted to 150 mM-NaCl. 12. Aldosterone increased the absorption of sodium in `control' and adapted toads, but at all dose levels absorption by control was greater than by adapted animals. 13. The stimulation of water absorption by vasopressin in vivo or in isolated bladders was not modified in animals adapted to high salinities. PMID:4633911

The role of matrix metalloproteinase MMP-9 and TIMP-2 tissue inhibitor of metalloproteinases as serum markers of bladder cancer.

PubMed

Ramón de Fata, F; Ferruelo, A; Andrés, G; Gimbernat, H; Sánchez-Chapado, M; Angulo, J C

2013-09-01

The diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer. Quantification of the serum levels of MMP-2, MMP-9 and TIMP-2 in a series of 42 individuals (31 patients with bladder cancer in different stages and 11 healthy controls) using the ELISA technique was carried out. The determinations were compared between cases and controls (Mann-Whitney U) and between different groups of tumors (Mann-Whitney U or Kruskal-Wallis), according to the clinical-pathological characteristics (age, gender, T category, M category or grade). Diagnostic yield of these markers was evaluated by analysis of the ROC curves. There is a correlation between the determinations of MMP-2 and TIMP-2 (R=.699; P>.0001) and MMP-9 and TIMP-2 (R=.305; P=.049). Patients with bladder cancer have higher levels of MMP-9 (p<0.0001) and TIMP-2 (P=.047) than the controls. Furthermore, the MMP-9/TIMP-2 ratio is also superior in cancer patients (P<.001). Differences were not detected between cancer and controls regarding age (P=.64) or gender (P=.64). Differences were also not detected regarding MMP-2 (P=.35) or MMP-2/TIMP-2 rate (P=.45). Within the cancer patient population, the MMP-2 and MMP-9 values differ according to T category (P=.022 and P=.038, respectively) and those of the TIMP-2 according to M category (P=.036). ROC curve analysis showed that both MMP-9 and the MMP-9/TIMP-2 ratio discriminate patients with cancer and controls, with equivalent diagnostic accuracy (ABC 0.953) and cut offs of 3.93 ng/mL (S 90%; Sp 81%) and 0.053 ng/mL (S 96%; Sp 84%), respectively. The results obtained suggest that both serum MMP-9 and TIMP-2 would have an application in the prediction of the development and progression of bladder cancer, and a potential utility as clinical markers of the disease. Multicenter, prospective studies that confirm their preliminary results are necessary. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

SU-E-J-221: A Novel Expansion Method for MRI Based Target Delineation in Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruiz, B; East Carolina University, Greenville, NC; Feng, Y

Purpose: To compare a novel bladder/rectum carveout expansion method on MRI delineated prostate to standard CT and expansion based methods for maintaining prostate coverage while providing superior bladder and rectal sparing. Methods: Ten prostate cases were planned to include four trials: MRI vs CT delineated prostate/proximal seminal vesicles, and each image modality compared to both standard expansions (8mm 3D expansion and 5mm posterior, i.e. ∼8mm) and carveout method expansions (5mm 3D expansion, 4mm posterior for GTV-CTV excluding expansion into bladder/rectum followed by additional 5mm 3D expansion to PTV, i.e. ∼1cm). All trials were planned to total dose 7920 cGy viamore » IMRT. Evaluation and comparison was made using the following criteria: QUANTEC constraints for bladder/rectum including analysis of low dose regions, changes in PTV volume, total control points, and maximum hot spot. Results: ∼8mm MRI expansion consistently produced the most optimal plan with lowest total control points and best bladder/rectum sparing. However, this scheme had the smallest prostate (average 22.9% reduction) and subsequent PTV volume, consistent with prior literature. ∼1cm MRI had an average PTV volume comparable to ∼8mm CT at 3.79% difference. Bladder QUANTEC constraints were on average less for the ∼1cm MRI as compared to the ∼8mm CT and observed as statistically significant with 2.64% reduction in V65. Rectal constraints appeared to follow the same trend. Case-by-case analysis showed variation in rectal V30 with MRI delineated prostate being most favorable regardless of expansion type. ∼1cm MRI and ∼8mm CT had comparable plan quality. Conclusion: MRI delineated prostate with standard expansions had the smallest PTV leading to margins that may be too tight. Bladder/rectum carveout expansion method on MRI delineated prostate was found to be superior to standard CT based methods in terms of bladder and rectal sparing while maintaining prostate coverage. Continued investigation is warranted for further validation.« less

Regulation of IGF-1 but not TGF-β1 by NGF in the smooth muscle of the inflamed urinary bladder

PubMed Central

Zhang, Qing L.; Qiao, Li-Ya

2012-01-01

Intraperitoneal injection of cyclophosphamide (CYP) causes haemorrhagic cystitis with excess growth of muscular layer leading to bladder hypertrophy; this could be attributable to changes in the expression profiles of growth factors in the inflamed urinary bladder. The growth factors characterized in the current study include nerve growth factor (NGF), insulin-like growth factor (IGF)-1, and transforming growth factor (TGF)-β1. We found that following CYP injection for 8h and 48h, the mRNA levels of all three factors were increased in the inflamed bladder when compared to control. The level of NGF mRNA was mainly increased in the urothelium layer while the levels of IGF-1 mRNA and TGF-β1 mRNA were increased in the smooth muscle layer. The level of NGF high affinity receptor TrkA mRNA was also increased in both the urothelium and the smooth muscle layers during bladder inflammation. When we blocked NGF action with NGF neutralizing antibody in vivo, we found that the up-regulation of IGF-1 in the inflamed bladder was reversed while the up-regulation of TGF-β1 was not affected by NGF neutralization. The effect of NGF on regulating IGF-1 expression was further confirmed in bladder smooth muscle culture showing that exogenous NGF increased the mRNA level of IGF-1 after 30 min to 1h stimulation. These results suggest that bladder inflammation induced region-specific changes in the expression profiles of NGF, IGF-1 and TGF-β1. The up-regulation of NGF in the urothelium may have a role in affecting bladder smooth muscle cell physiology by regulating IGF-1 expression. PMID:22579999

C-reactive protein levels in girls with lower urinary tract symptoms.

PubMed

Tarhan, H; Ekin, R G; Can, E; Cakmak, O; Yavascan, O; Mutlubas Ozsan, F; Helvaci, M; Zorlu, F

2016-04-01

Daytime lower urinary tract (LUT) conditions are identified as daytime incontinence problems for children in whom any cause of neuropathy and uropathy has been excluded. C-reactive protein (CRP) is a common marker of acute or chronic inflammation and infection. Increased CRP levels have been detected in the studies conducted on adults diagnosed with overactive bladders and interstitial cystitis. This study aimed to investigate the role of serum CRP levels in girls suffering from daytime LUT conditions. Out of the 752 patients who presented to the outpatient clinics with lower urinary tract symptoms, 709 were excluded due to: being boys, having previous urinary tract surgery, an active urinary tract infection, a neurological anomaly, a urinary system anomaly, having rheumatic disease, any chronic disease, any febrile infection over the past week, a history of constipation, and enuresis nocturna. Forty-three girls with LUT conditions and aged 8-10 years were included in the study as the patient group. Forty girls who attended the urology outpatient clinic without LUT conditions, or active urinary tract infections and any chronic disease requiring follow-up constituted the control group. Under the control of the parents, all subjects were asked to fill out 3-day voiding diaries. The voiding diaries identified frequency, urgency, urgency urinary incontinence, and functional bladder capacity data. All subjects also completed a dysfunctional voiding scoring system (DVSS). The serum CRP levels of all subjects were measured. There was a significant difference in serum CRP levels and DVSS between the patient group and the control group (P = 0.001, P = 0.001). The mean serum CRP levels showed a significant increase when frequency and urgency scores were ≥8, the urge incontinence score was ≥2 and the DVS score DVSS was ≥14 in the voiding diaries of the patient group (Table). Lower urinary tract dysfunction is defined as a condition involving abnormalities of filling and/or emptying of the bladder. This frequently encountered problem constitutes >40% of all pediatric urology outpatient visits. The relationship between LUT conditions and serum CRP in both genders has been detected. However, it is believed that to our knowledge, this is the first study looking at the relationship between daytime LUTS and increased CRP levels in children. The most important limitations of the study were: having a small number of patients, and the sample consisting of only one gender and a specific age group. The serum CRP levels were significantly higher in the girls with daytime LUT conditions than in the control group. Also, the CRP levels significantly increased as DVSS, frequency, urgency, and urge incontinence scores increased. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Validation of deformable image registration algorithms on CT images of ex vivo porcine bladders with fiducial markers.

PubMed

Wognum, S; Heethuis, S E; Rosario, T; Hoogeman, M S; Bel, A

2014-07-01

The spatial accuracy of deformable image registration (DIR) is important in the implementation of image guided adaptive radiotherapy techniques for cancer in the pelvic region. Validation of algorithms is best performed on phantoms with fiducial markers undergoing controlled large deformations. Excised porcine bladders, exhibiting similar filling and voiding behavior as human bladders, provide such an environment. The aim of this study was to determine the spatial accuracy of different DIR algorithms on CT images of ex vivo porcine bladders with radiopaque fiducial markers applied to the outer surface, for a range of bladder volumes, using various accuracy metrics. Five excised porcine bladders with a grid of 30-40 radiopaque fiducial markers attached to the outer wall were suspended inside a water-filled phantom. The bladder was filled with a controlled amount of water with added contrast medium for a range of filling volumes (100-400 ml in steps of 50 ml) using a luer lock syringe, and CT scans were acquired at each filling volume. DIR was performed for each data set, with the 100 ml bladder as the reference image. Six intensity-based algorithms (optical flow or demons-based) implemented in theMATLAB platform DIRART, a b-spline algorithm implemented in the commercial software package VelocityAI, and a structure-based algorithm (Symmetric Thin Plate Spline Robust Point Matching) were validated, using adequate parameter settings according to values previously published. The resulting deformation vector field from each registration was applied to the contoured bladder structures and to the marker coordinates for spatial error calculation. The quality of the algorithms was assessed by comparing the different error metrics across the different algorithms, and by comparing the effect of deformation magnitude (bladder volume difference) per algorithm, using the Independent Samples Kruskal-Wallis test. The authors found good structure accuracy without dependency on bladder volume difference for all but one algorithm, and with the best result for the structure-based algorithm. Spatial accuracy as assessed from marker errors was disappointing for all algorithms, especially for large volume differences, implying that the deformations described by the registration did not represent anatomically correct deformations. The structure-based algorithm performed the best in terms of marker error for the large volume difference (100-400 ml). In general, for the small volume difference (100-150 ml) the algorithms performed relatively similarly. The structure-based algorithm exhibited the best balance in performance between small and large volume differences, and among the intensity-based algorithms, the algorithm implemented in VelocityAI exhibited the best balance. Validation of multiple DIR algorithms on a novel physiological bladder phantom revealed that the structure accuracy was good for most algorithms, but that the spatial accuracy as assessed from markers was low for all algorithms, especially for large deformations. Hence, many of the available algorithms exhibit sufficient accuracy for contour propagation purposes, but possibly not for accurate dose accumulation.

Intravesical application of rebamipide suppresses bladder inflammation in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-04-01

We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Investigation of urinary management after removal of indwelling urethral catheters in a general hospital: associations between bedridden state and impaired bladder emptying].

PubMed

Tsuchiyama, Katsuki; Ueki, Osamu; Minami, Hidero; Kawaguchi, Kouhei; Aoki, Yoshitaka; Yokoyama, Osamu

2010-06-01

In this study we investigated the influences of decreased levels of activities of daily living (ADL), especially in bedridden patients,on lower urinary tract dysfunction and urinary management during hospital care. All 1,106 non-urological inpatients (896 non-bedridden patients and 210 bedridden patients) with an indwelling urethral catheter treated at Noto General Hospital between April 2006 and October 2009 were retrospectively evaluated. Maximum bladder capacity and post-void residual urine volume (PVR) were evaluated with uroflowmetry or voiding cystourethrography at the time the catheter was removed. Clean intermittent catheterization (CIC) and drug administration were performed for patients who had a PVR of 100 ml or more. Bedridden patients required urinary interventions at a higher rate than did non-bedridden patients (bedridden : 29.0%,non-bedridden : 17.6%). Although indwelling urethral catheters were reinserted in 13 patients in the bedridden group and 16 patients in the non-bedridden group,many patients in both groups could be free from the catheter. Our results indicate that patients with low ADL are vulnerable to impaired bladder emptying,and early diagnosis of impaired bladder emptying and active urinary management are required to solve their urinary problems.

Bladder and bowel dysfunctions in 1748 children referred to pelvic physiotherapy: clinical characteristics and locomotor problems in primary, secondary, and tertiary healthcare settings.

PubMed

van Engelenburg-van Lonkhuyzen, Marieke L; Bols, Esther M J; Benninga, Marc A; Verwijs, Wim A; de Bie, Rob A

2017-02-01

The aims of this study are to evaluate in a pragmatic cross-sectional study, the clinical characteristics of childhood bladder and/or bowel dysfunctions (CBBD) and locomotor problems in the primary through tertiary health care setting. It was hypothesized that problems would increase, going from primary to tertiary healthcare. Data were retrieved from patient-records of children (1-16 years) presenting with CBBD and visiting pelvic physiotherapists. Prevalence's of dysfunctions were compared between healthcare settings and gender using ANOVA and chi-square test. Agreement between physicians' diagnoses and parent-reported symptoms was evaluated (Cohen's Kappa). One thousand seventy hundred forty-eight children (mean age 7.7 years [SD 2.9], 48.9% boys) were included. Daytime urinary incontinence (P = 0.039) and enuresis (P < 0.001) were more diagnosed in primary healthcare, whereas constipation (P < 0.001) and abdominal pain (P = 0.009) increased from primary to tertiary healthcare. All parent-reported symptoms occurred more frequently than indicated by the physicians. Poor agreement between physicians' diagnoses and parent-reported symptoms was found (k = 0.16). Locomotor problems prevailed in all healthcare settings, motor skills (P = 0.041) and core stability (P = 0.015) significantly more in tertiary healthcare. Constipation and abdominal pain (physicians' diagnoses) and the parent-reported symptoms hard stools and bloating increased from primary to tertiary healthcare. Discrepancies exist between the prevalence's of physicians' diagnoses and parent-reported symptoms. Locomotor problems predominate in all healthcare settings. What is Known: • Childhood bladder and/or bowel dysfunctions (CCBD) are common. • Particularly tertiary healthcare characteristics of CBBD are available What is New: • Characteristics of CBBD referred to pelvic physiotherapy are comparable in primary, secondary, and tertiary healthcare settings. • Concomitant CBBD appeared to be more prevalent than earlier reported. • Discrepancies exist between referring physicians' diagnoses and parent-reported symptoms.

Efficacy of butylscopolamine for the treatment of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study.

PubMed

Ryu, J H; Hwang, J W; Lee, J W; Seo, J H; Park, H P; Oh, A Y; Jeon, Y T; Do, S H

2013-12-01

Catheter-related bladder discomfort (CRBD) secondary to intraoperative catheterization of urinary bladder is one of the most distressing symptoms during recovery from anaesthesia. Butylscopolamine, a peripheral antimuscarinic agent, is effective for relieving the pain, which is because of smooth muscle contraction. The aim of this study was to assess the efficacy and safety profiles of butylscopolamine in treating CRBD after urological surgeries. Adult male patients undergoing urological surgery requiring urinary bladder catheterization intraoperatively were enrolled. Induction and maintenance of anaesthesia were standardized. Patients were randomized into two groups after complaining of CRBD in the post-anaesthesia care unit. The control group (n=29) received normal saline and the butylscopolamine group (n=28) was administered butylscopolamine 20 mg i.v. The severity of CRBD, postoperative pain, and adverse effects were assessed at baseline, 20 min, 1, 2, and 6 h after administration of the study drug. The severity of CRBD observed in the butylscopolamine group was significantly lower than that of the control group at 1, 2, and 6 h after administration of the study drug [59 (12), 50 (16), 40 (21) in the control group vs 41 (22), 32 (25), 23 (18) in the butylscopolamine group, P<0.01]. Rescue analgesics were required less in the butylscopolamine group than in the control group (P=0.001). Adverse events were comparable between the two groups. Butylscopolamine 20 mg administered i.v. after complaining CRBD during recovery reduced both the severity of CRBD and the need for rescue analgesics without adverse effects in patients undergoing urologic surgeries.

A Pilot Study Combining a GC-Sensor Device with a Statistical Model for the Identification of Bladder Cancer from Urine Headspace

PubMed Central

Khalid, Tanzeela; White, Paul; De Lacy Costello, Ben; Persad, Raj; Ewen, Richard; Johnson, Emmanuel; Probert, Chris S.; Ratcliffe, Norman

2013-01-01

There is a need to reduce the number of cystoscopies on patients with haematuria. Presently there are no reliable biomarkers to screen for bladder cancer. In this paper, we evaluate a new simple in–house fabricated, GC-sensor device in the diagnosis of bladder cancer based on volatiles. Sensor outputs from 98 urine samples were used to build and test diagnostic models. Samples were taken from 24 patients with transitional (urothelial) cell carcinoma (age 27-91 years, median 71 years) and 74 controls presenting with urological symptoms, but without a urological malignancy (age 29-86 years, median 64 years); results were analysed using two statistical approaches to assess the robustness of the methodology. A two-group linear discriminant analysis method using a total of 9 time points (which equates to 9 biomarkers) correctly assigned 24/24 (100%) of cancer cases and 70/74 (94.6%) controls. Under leave-one-out cross-validation 23/24 (95.8%) of cancer cases were correctly predicted with 69/74 (93.2%) of controls. For partial least squares discriminant analysis, the correct leave-one-out cross-validation prediction values were 95.8% (cancer cases) and 94.6% (controls). These data are an improvement on those reported by other groups studying headspace gases and also superior to current clinical techniques. This new device shows potential for the diagnosis of bladder cancer, but the data must be reproduced in a larger study. PMID:23861976

Perceptions of School Toilets as a Cause for Irregular Toilet Habits among Schoolchildren Aged 6 to 16 Years

ERIC Educational Resources Information Center

Lundblad, Barbro; Hellstrom, Anna-Lena

2005-01-01

Irregular bladder and bowel habits can contribute to urinary and bowel problems. Schoolchildren undergoing treatment for these problems often do not follow the recommendation of regular toilet visits at school, claiming negative perceptions of school toilets. This study examined 6- to 16-year-old schoolchildren's perceptions of school toilets and…

An Unusual Complication of Ventriculoperitoneal Shunt: Urinary Bladder Stone Case Report and Literature Review.

PubMed

Xu, Songtao; Sheng, Weixin; Qiu, Yufa; Wang, Jianguo

2016-01-01

Ventriculoperitoneal (V-P) shunt surgery is the most common technique used for the treatment of hydrocephalus. The migration of ventriculoperitoneal shunt to the bladder is rare. Only two cases have been previously reported in the literature. We report on a 38-year-old male who had hydrocephalus and V-P shunt for 12 years. Two years ago, he found himself with recurrent urinary tract infections, haematuria and urges incontinence, and then he was diagnosed with bladder perforation and merge stones. The patient had an abdominal operation to cut off and take out the shunt catheter, as well as a transurethral holmium laser lithotripsy. Bladder perforation and stones are rare examples of complications in V-P surgical procedures. Controlling the effective length of the terminal V-P shunt and modifying it appropriately can effectively reduce these complications.

Systematic Review of Studies Reporting Positive Surgical Margins After Bladder Neck Sparing Radical Prostatectomy.

PubMed

Bellangino, Mariangela; Verrill, Clare; Leslie, Tom; Bell, Richard W; Hamdy, Freddie C; Lamb, Alastair D

2017-11-07

Bladder neck preservation (BNP) during radical prostatectomy (RP) has been proposed as a method to improve early recovery of urinary continence after radical prostatectomy. However, there is concern over a possible increase in the risk of positive surgical margins and prostate cancer recurrence rate. A recent systematic review and meta-analysis reported improved early recovery and overall long-term urinary continence without compromising oncologic control. The aim of our study was to perform a critical review of the literature to assess the impact on bladder neck and base margins after bladder neck sparing radical prostatectomy. We carried out a systematic review of the literature using Pubmed, Scopus and Cochrane library databases in May 2017 using medical subject headings and free-text protocol according to PRISMA guidelines. We used the following search terms: bladder neck preservation, prostate cancer, radical prostatectomy and surgical margins. Studies focusing on positive surgical margins (PSM) in bladder neck sparing RP pertinent to the objective of this review were included. Overall, we found 15 relevant studies reporting overall and site-specific positive surgical margins rate after bladder neck sparing radical prostatectomy. This included two RCTs, seven prospective comparative studies, two retrospective comparative studies and four case series. All studies were published between 1993 and 2015 with sample sizes ranging between 50 and 1067. Surgical approaches included open, laparoscopic and robot-assisted radical prostatectomy. The overall and base-specific PSM rates ranged between 7-36% and 0-16.3%, respectively. Mean base PSM was 4.9% in those patients where bladder neck sparing was performed, but only 1.85% in those without sparing. Bladder neck preservation during radical prostatectomy may increase base-positive margins. Further studies are needed to better investigate the impact of this technique on oncological outcomes. A future paradigm could include modification of intended approach to bladder neck dissection when anterior base lesions are identified on pre-operative MRI.

Activation of P2Y6 receptors increases the voiding frequency in anaesthetized rats by releasing ATP from the bladder urothelium

PubMed Central

Carneiro, Inês; Timóteo, M Alexandrina; Silva, Isabel; Vieira, Cátia; Baldaia, Catarina; Ferreirinha, Fátima; Silva-Ramos, Miguel; Correia-de-Sá, Paulo

2014-01-01

BACKGROUND AND PURPOSE Despite the abundant expression of the UDP-sensitive P2Y6 receptor in urothelial cells and sub-urothelial myofibroblasts its role in the control of bladder function is not well understood. EXPERIMENTAL APPROACH We compared the effects of UDP and of the selective P2Y6 receptor agonist, PSB0474, on bladder urodynamics in anaesthetized rats; the voided fluid was tested for ATP bioluminescence. The isolated urinary bladder was used for in vitro myographic recordings and [3H]-ACh overflow experiments. KEY RESULTS Instillation of UDP or PSB0474 into the bladder increased the voiding frequency (VF) without affecting the amplitude (A) and the duration (Δt) of bladder contractions; an effect blocked by the P2Y6 receptor antagonist, MRS2578. Effects mediated by urothelial P2Y6 receptors required extrinsic neuronal circuitry as they were not detected in the isolated bladder. UDP-induced bladder hyperactvity was also prevented by blocking P2X3 and P2Y1 receptors, respectively, with A317491 and MRS2179 applied i.v.. UDP decreased [3H]-ACh release from stimulated bladder strips with urothelium, but not in its absence. Inhibitory effects of UDP were converted into facilitation by the P2Y1 receptor antagonist, MRS2179. The P2Y6 receptor agonist increased threefold ATP levels in the voided fluid. CONCLUSIONS AND IMPLICATIONS Activation of P2Y6 receptors increased the voiding frequency indirectly by releasing ATP from the urothelium and activation of P2X3 receptors on sub-urothelial nerve afferents. Bladder hyperactivity may be partly reversed following ATP hydrolysis to ADP by E-NTPDases, thereby decreasing ACh release from cholinergic nerves expressing P2Y1 receptors. PMID:24697602

Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

PubMed

Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

2013-03-01

Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder and Bowel Control in Children with Cerebral Palsy: Case-Control Study

PubMed Central

Ozturk, Mustafa; Oktem, Faruk; Kisioglu, Nesimi; Demirci, Mustafa; Altuntas, Irfan; Kutluhan, Suleyman; Dogan, Malik

2006-01-01

Aim To determine the age of development of bladder and bowel control and the frequency of enuresis, encopresis, and urinary infections in children with cerebral palsy. Methods The study included 45 children with cerebral palsy who regularly attended a rehabilitation center in Isparta, Turkey, and two groups of age- and sex-matched children, 37 siblings of the children with cerebral palsy and 37 healthy children. Demographic data and information on the age of development of total bladder and bowel control and presence of possible urinary symptoms in children were collected from their caregivers by use of a questionnaire. Frequency of enuresis and encopresis was estimated among the children aged ≥5 years. A mid-way urinary sample was obtained from 40, 22, and 21 children in the cerebral palsy, siblings, and healthy children, respectively. Results The mean age of nighttime bladder and bowel control development was 47 months (95% confidence interval [CI], 35-58) and 45 (36-55) months, respectively, for the children with cerebral palsy, 35 months (95% CI, 24-46) and 26 months (95% CI, 24-28), respectively, for their siblings, and 27 months (95% CI, 22-33) and 25 months (95% CI, 23-27) months, respectively, for the healthy children. Among the children aged ≥5 years, enuresis was present in 11 of 34 children with cerebral palsy, 7 of 30 siblings, and 4 of 30 healthy children (P = 0.200), whereas encopresis was present in 5 children with cerebral palsy, one sibling, and one healthy child. Constipation was significantly more present in chidlren with cerebral palsy than in other two groups (P<0.001). Urine culture was positive in 13 children with cerebral palsy, 1 sibling, and 2 healthy chidlren (P = 0.024). There were no significant differences in other urinary symptoms and laboratory findings among the three groups. Conclusion The children with cerebral palsy gained bladder and bowel control at older age in comparison with their siblings and healthy children. They also had more frequent enuresis and urinary infections. PMID:16625691

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer.

PubMed

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-10-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer

PubMed Central

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-01-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer. PMID:28943911

Effects of Bladder Training and Pelvic Floor Muscle Training in Female Patients with Overactive Bladder Syndrome: A Randomized Controlled Trial.

PubMed

Rizvi, Raheela Mohsin; Chughtai, Novera Ghayoor; Kapadia, Naheed

2018-01-01

The purpose of our study was to see the efficacy of 3 different modes of treatment for overactive bladder (OAB) in symptoms reduction and quality of life improvement. We conducted a 12-week single-blinded randomized controlled trial of women aged 22-65 years with clinical diagnosis of OAB. Arm A (n = 47) received bladder training, arm B (n = 50) received pelvic floor muscle training (PFMT), and arm C (n = 50) received PFMT with biofeedback. Bladder diary was used to assess the difference in urinary frequency, urgency, and leak accidents before and after treatment. Initial and final assessment was made using -validated urogenital distress inventory short form 6 (UDI-SF6) and incontinence impact questionnaire short form 7 (IIQ-SF7). UDI-SF6 scores showed significant improvement in all arms. There was a reduction in UDI-6 scores from 8.38 ± 4.3 to 4.77 ± 5.5 with a mean difference of 3.61 ± 7.4 in patients in arm A (p = 0.002), arm B (p = 0.01), and arm C (p = 0.016). All patients in arms A, B, and C reported significant improvement in quality of life as assessed by IIQ-SF7 scores with significant p values of 0.009, 0.051, and 0.001, respectively. Bladder diary results using paired t test showed the significant difference in day time urinary frequency in arm A after treatment, as well as the reduction in both leak accidents and urgency score in all 3 arms. All 3 arms of study showed significant results and can be used as the first line of management. © 2018 S. Karger AG, Basel.

Modulating the internalization of bacille Calmette-Guérin by cathelicidin in bladder cancer cells.

PubMed

Choi, Se Young; Kim, Soon-Ja; Chi, Byung Hoon; Kwon, Jong Kyou; Chang, In Ho

2015-04-01

To confirm the role of cathelicidin (LL-37) in the internalization of bacille Calmette-Guérin (BCG) into bladder cancer cells. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction analysis evaluated the changes in protein and messenger ribonucleic acid (RNA) expression with BCG incubation after LL-37 pretreatment in 5637 and T24 human bladder cancer cells. The internalization rate was evaluated by a double immunofluorescence assay, and confocal microscopy confirmed the function of LL-37 in BCG internalization. We also investigated the difference in internalization rates and cell viability between LL-37, anti-LL-37 antibody, and LL-37 plus anti-LL-37 antibody. The levels of LL-37 increased after BCG exposure in bladder cancer cells in dose- and time-dependent manners. Increasing LL-37 levels using recombinant LL-37 protein further dose dependently decreased BCG internalization in both cell lines. The internalization rates of BCG after LL-37 instillation were lower compared with the controls, and the internalization rate of BCG after anti-LL-37 antibody instillation was significantly higher compared with the controls in both cell lines (P <.05). Viability of LL-37 plus BCG group was higher compared with the BCG-alone group. The anti-LL-37 antibody plus BCG group had decreased cell viability compared with the BCG-alone group in both cell lines. Bladder cancer cells produce cathelicidin when infected with BCG and upregulate cathelicidin to defend against BCG by inhibiting its internalization. Blocking the action of cathelicidin may increase the internalization and effectiveness of BCG in reducing bladder cancer cell proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Xiong; Viswanathan, Akila; Stewart, Alexandra J.

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractionsmore » of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.« less

Bladder control training in girls with lower urinary tract dysfunction.

PubMed

Amira, Peco-Antić; Dušan, Paripović; Gordana, Miloševski-Lomić; Sandra, Trojanović; Ivaniševic, Ivana

2013-01-01

To evaluate the efficacy of standard and biofeedback bladder control training (BCT) on the resolution of dysfunctional elimination syndrome (primary outcome), and on the reduction of urinary tract infections (UTI) and the use of medications such as antibacterial prophylaxis and/or anticholinergic/alpha-blockers (secondary outcome) in girls older than aged least 5 years. 72 girls, median age of 8 years (interquartile range, IQR 7-10) were subjected to standard BCT (cognitive, behavioural and constipation treatment) and 12 one-hour sessions of animated biofeedback using interactive computer games within 8 weeks. Fifty patients were reevaluated after median 11 (IQR, 6-17) months. Effectiveness of BCT was determined by reduction of dysfunctional voiding score (DVS), daytime urinary incontinence (DUI), constipation, UTI, nocturnal enuresis (NE), post void residual (PVR), and improvements in bladder capacity and uroflow/EMG patterns. BCT resulted in significant normalization of DUI, NE, constipation, bladder capacity, uroflow/EMG, while decrease of PVR didn't reach statistical significance. In addition, the incidence of UTI, antibacterial prophylaxis and medical urotherapy significantly decreased. There were no significant differences in DVS, DVI, NE, bladder capacity and voiding pattern at the end of the BCT and at the time of reevaluation. The success on BCT was supported by parenteral perception of the treatment response in 63.9% and full response in additional 15.3% of the patients. Combination of standard and biofeedback BCT improved dysfunctional elimination syndrome and decreased UTI with discontinuation of antibacterial prophylaxis and/or anticholinergic/alpha-blockers in the majority of the patients. Better training results are expected in patients with higher bladder wall thickness as well as in those with vesicoureteral reflux, while presence of nocturnal enuresis may be a negative predictor of the training effect.

Aquatic models for the study of renal transport function and pollutant toxicity.

PubMed Central

Miller, D S

1987-01-01

Studies of renal cell transport mechanisms and their impairment by xenobiotics are often limited by technical difficulties related to renal tubule complexity. Problems include the juxtaposition of multiple tubule segments with different transport functions and severely limited access to the tubular lumen. Some limitations can be overcome by the careful selection of an appropriate aquatic experimental system. Two aquatic models for the vertebrate proximal segment are discussed here. The first is the kidney from certain marine flounder, which offers the following advantages: long-term viability, little tissue of nonproximal origin, and easy tubule isolation. Data are presented to demonstrate how studies with flounder kidney can be used to elucidate cellular mechanisms whereby different classes of toxic pollutants may interact. Results from these experiments indicate that the excretion of certain anionic xenobiotics can be delayed by other anionic xenobiotics that compete for secretory transport sites and by compounds that disrupt cellular ion gradients and energy metabolism needed to drive transport. The second system is the crustacean urinary bladder, a simple, flatsheet epithelium. Bladder morphology and transport physiology closely resemble those of vertebrate proximal segment. Electron micrographs show a brush border membrane at the luminal surface, numerous mitochondria, and an infolded serosal membrane, while in vivo and in vitro transport studies show reabsorption of NaCl, nutrients and water and secretion of organic cations; organic anions are secreted in bladders from some species and reabsorbed in others. Moreover, since bladders can be mounted as flat sheets in flux chambers, studies with this tissue avoid the problems of complex renal tubule geometry and tissue heterogeneity that limit transport studies in proximal tubule. Images FIGURE 3. FIGURE 6. PMID:3297665

Consequences of interstitial cystitis/bladder pain symptoms on women's work participation and income: results from a national household sample.

PubMed

Beckett, Megan K; Elliott, Marc N; Clemens, J Quentin; Ewing, Brett; Berry, Sandra H

2014-01-01

We describe differences in work participation and income by bladder symptom impact and comorbidities among women with interstitial cystitis/bladder pain syndrome. Cross-sectional data from 2,767 respondents younger than 65 years identified with interstitial cystitis/bladder pain syndrome symptoms were analyzed. The data were taken from the RAND Interstitial Cystitis Epidemiology (RICE) survey, and included retrospective self-reports of interstitial cystitis/bladder pain syndrome impact, severity, years since onset, related comorbidities (depressive symptomatology, number of conditions), work participation and income, and personal characteristics. Multiple regressions predicted 5 current work outcomes of works now, kept from working by pain, missed work days, days worked when bothered by symptoms and real income change since symptom onset. Controlling for work status at symptom onset and personal characteristics, greater bladder symptom impact predicted a greater likelihood of not now working, kept more days from working by pain, missed more work days and working more days with symptoms. More depressive symptomatology and greater number of comorbidities predicted reduced work participation. Women experienced no growth in real income since symptom onset. Measures of symptom severity were not associated with any of the economic outcomes. Greater interstitial cystitis/bladder pain syndrome symptom impact, depressive symptomatology and count of comorbidities (but not symptom severity) were each associated with less work participation and leveling of women's long-term earnings. Management of bladder symptom impact on nonwork related activities and depressive symptomatology may improve women's work outcomes. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Diffusion and localization of hematoporphyrin derivative in the normal bladder wall of a pig and a rat after local administration

NASA Astrophysics Data System (ADS)

Bisson, Jean F.; Notter, Dominique; Labrude, P.; Vigneron, C.; Guillemin, Francois H.

1996-04-01

Photochemotherapy using I.V. administered porphyrin photosensitizers has been used to treat superficial bladder cancers. In order to avoid cutaneous photosensitivity, lasting 6 - 8 weeks, we instilled the photosensitizer intravesically. After first studying the diffusion and localization of HpD in aqueous phase (5 mg/ml) in vitro through the bladder wall of pig by spectrofluorimetry ((lambda) ex equals 392 nm and (lambda) em equals 612.8 nm) and fluorescence microscopy, we determined the biodistribution of HpD in vivo in the rat bladder wall, 2 and 4 hours after bladder instillation of 0.4 ml of HpD: (1) the controls show only a weak autofluorescence restricted to the urothelium after 2 hours (24 micrometers plus or minus 5 micrometers, n equals 3) as well as after 4 hours (29.5 micrometers plus or minus 5 micrometers, n equals 3); (2) on the test preparation a higher fluorescence was observed: after 2 hours, HpD was localized in the urothelium and a very small part of the chorion (55 micrometers plus or minus 9 micrometers, n equals 9) whereas after 4 hours, it penetrated almost completely in the bladder wall (960 micrometers plus or minus 118 micrometers, n equals 9). In conclusion, a bladder instillation of 2 hours seems to be the optimal time of application in the rat since superficial bladder cancers, like carcinoma in situ, particularly occur in the urothelium (stage 0, pTa) or in the chorion (stage 1, pT1).

Effect of intravesical Resiniferatoxin (RTX) on lower urinary tract symptoms, urodynamic parameters, and quality of life of patients with urodynamic increased bladder sensation.

PubMed

Apostolidis, Apostolos; Gonzales, Gwendoline E; Fowler, Clare J

2006-12-01

Intravesical resiniferatoxin (RTX) has been used with variable efficacy in the treatment of detrusor overactivity (DO). Patients with interstitial cystitis (IC) failed to benefit from this treatment, but a single placebo-controlled study in patients with non-IC painful bladders showed that RTX was effective in the short-term. We investigated the efficacy of intravesical RTX in patients with urgency and frequency due to increased bladder sensation. Patients with intractable urgency and frequency, with or without urgency incontinence or bladder pain/discomfort, and with no urodynamic evidence of DO were recruited. After a single intravesical instillation of 100ml 50 nM RTX solution, patients were followed at 1, 3, and 6 mo for changes in urodynamics, bladder diary, the King's Health Questionnaire (KHQ), and degree of bladder pain. Fifteen patients (mean age, 52.5 yr) were treated. RTX significantly improved maximum cystometric capacity, volume at first desire to void, mean micturition volume, 24-h frequency, and daytime frequency for up to 6 mo after treatment. The overall KHQ score improved at all time points, with sustained improvements in the Symptom Severity, Incontinence Impact, and Personal Relationships domains. A >50% decrease in pain was reported by five of seven patients with painful bladders at 1 mo, but only one of seven at 6 mo. In our small open-label study, a single administration of intravesical RTX in patients with frequency and urgency due to increased bladder sensation significantly improved lower urinary tract symptoms, urodynamic parameters, and quality of life for up to 6 mo.

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

Proteomic analysis of urine in patients with intestinal segments transposed into the urinary tract.

PubMed

Nabi, Ghulam; N'Dow, James; Hasan, Tahseen S; Booth, Ian R; Cash, Phil

2005-04-01

Intestinal segments are used to replace or reconstruct the urinary bladder when it has become dysfunctional or develops life-threatening disease such as cancer. The quality of life in patients with intestinal segments used to either enlarge or completely replace the native bladder is adversely affected by recurrent urinary tract infections, excessive mucus production and the occasional development of malignancy. At present, there is no reliable method of predicting or noninvasively monitoring these patients for the development of these complications. The characterisation of proteins secreted into urine from the transposed intestinal segments could serve as important indicators of these clinical complications. Urine is an ideal source of material in which to search for biomarkers, since it bathes the affected tissues and can be obtained relatively easily by noninvasive methods. The urinary proteome of patients with intestinal segments transposed into the urinary tract is unknown and we present the first global description of the urinary protein profile in these patients. Sample preparation is a critical step in achieving accurate and reliable data. We describe a method to prepare urinary proteins that was compatible with their subsequent analysis using two-dimensional polyacrylamide gel electrophoresis. This method helped to overcome some of the technical problems encountered in analysing urine from this patient cohort. The method was used to analyse urinary proteins recovered from five healthy controls and ten patients with intestinal segments transposed into the urinary tract. Four low molecular weight proteins were found to be present in nine out of ten for the patient group but for none of the healthy controls. The four proteins were identified as lithostathine-1 alpha precursor, pancreatitis associated protein-1 precursor, liver fatty acid binding protein and testis expressed protein-12. The role of these proteins as potential biomarkers of intestinal cell activity within the reconstructed bladder is discussed.

Intake of α-linolenic acid and other fatty acids in relation to the risk of bladder cancer: results from the New Hampshire case–control study

PubMed Central

Brinkman, Maree T.; Karagas, Margaret R.; Zens, Michael S.; Schned, Alan R.; Reulen, Raoul C.; Zeegers, Maurice P.

2012-01-01

The role of dietary fat in bladder cancer aetiology is currently unclear due to few studies, equivocal findings and a lack of information on important dietary fatty acids. The aim of the present study was to investigate the association between the intake of major dietary fats and fatty acids and the risk of bladder cancer. A case–control study was conducted in New Hampshire, USA. Dietary data were collected from 322 cases and 239 controls, and OR and 95 % CI were calculated using unconditional logistic regression. Adjustment was made for potential confounders: sex, age, smoking status, pack-years smoked, cholesterol and energy intake. Statistically significant reduced odds of bladder cancer were observed for high intakes (highest quartile v. lowest quartile) of α-linolenic acid (ALA) (OR 0.26, 95% CI 0.10, 0.65; P for trend=0.01) and vegetable fat (OR 0.39, 95% CI 0.18, 0.86; P for trend=0.03). Borderline statistically significant reduced odds were detected for polyunsaturated fat (OR 0.43, 95% CI 0.19, 0.98; P for trend=0.07) and linoleic acid (OR 0.43, 95% CI 0.19, 0.96; P for trend=0.06). These fats and fatty acids were highly correlated and following adjustment for each other, the only potential inverse association to remain was for ALA. The present findings suggest that ALA may have a protective role against developing bladder cancer; however, further investigation and replication in other epidemiological studies are required. Future research should focus on the type, source and quantities of different dietary fatty acids consumed. PMID:21736846

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer

PubMed Central

Liang, Li-Guo; Kong, Meng-Qi; Zhou, Sherry; Sheng, Ye-Feng; Wang, Ping; Yu, Tao; Inci, Fatih; Kuo, Winston Patrick; Li, Lan-Juan; Demirci, Utkan; Wang, ShuQi

2017-01-01

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30–200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings. PMID:28436447

[Biodegradable catheters for fistula prevention in hypospadias. Experimental preliminary study].

PubMed

Ramos, J L; Aldazabal, P; Zuza, E; Sarasúa, J R; Arrieta, A; Villanueva, A; Eizaguirre, I

2013-04-01

Continuous technical innovations are not enough to resolve the high incidence of fistula after hypospadias repair. A urethral catheter-tutor made of reabsorbable polymeric biomaterial (RPB) which could be left in situ long enough could reduce the complications. To investigate in an animal model differents RPB to be used in urology. CRL Wistar rats, males, divided into 5 equal groups according to the used polymers: polylactide; lactic-coprolactone copolymer; lactic-glycolic copolymer; simulated; control silicones. Three individuals were sacrificed per group at 4th, 10th and 16th week. In all animals (exceptuating the simulated group), biomaterial was fixed to the bladder wall bylaparotomy. Animals remained in individual housing and kept under daily control of hematuria during the first 15 days and weekly weight and urine control for pH and lactate. After being slaughtered, remaining polymer was collected for chemical analysis and bladder tissue for hystologic study. There was no mortality, hematuria nor other clinical signs. The bladder wall showed a mild foreign body reaction. The values of lactate and pH in urine did not reach toxic levels. Lactic-glycolic was totally reabsorbed by the 10th week and had the lowest degree of calcification. Polylactide and lactic-coprolactone remained intact. The model of urinary bladder has proven useful for studying the degradation of bioresorbable polymers. The analyzed polymers have spent long time to be reabsorbed, so we will have to study new others.

Dog as an animal model for neurostimulation.

PubMed

Hassouna, M; Li, J S; Elhilali, M

1994-01-01

The dog provides an important model to study the effect of neural stimulation of different parts of the central and peripheral nervous systems. A multitude of experiments on neurostimulation and neuromodulation to ensure bladder evacuation have been conducted on dogs. The present article reviews the most prominent contributions in the English literature related to neurostimulation using the dog as an experimental model. The various modes of stimulation using dogs as a model and the rationale for their use as well as their shortcomings will be examined. The prominent anatomic features in the neural control of the bladder and the technical aspects involved in neurostimulation of the canine bladder will be reviewed.

Wireless, Ultra-Low-Power Implantable Sensor for Chronic Bladder Pressure Monitoring.

PubMed

Majerus, Steve J A; Garverick, Steven L; Suster, Michael A; Fletter, Paul C; Damaser, Margot S

2012-06-01

The wireless implantable/intracavity micromanometer (WIMM) system was designed to fulfill the unmet need for a chronic bladder pressure sensing device in urological fields such as urodynamics for diagnosis and neuromodulation for bladder control. Neuromodulation in particular would benefit from a wireless bladder pressure sensor which could provide real-time pressure feedback to an implanted stimulator, resulting in greater bladder capacity while using less power. The WIMM uses custom integrated circuitry, a MEMS transducer, and a wireless antenna to transmit pressure telemetry at a rate of 10 Hz. Aggressive power management techniques yield an average current draw of 9 μ A from a 3.6-Volt micro-battery, which minimizes the implant size. Automatic pressure offset cancellation circuits maximize the sensing dynamic range to account for drifting pressure offset due to environmental factors, and a custom telemetry protocol allows transmission with minimum overhead. Wireless operation of the WIMM has demonstrated that the external receiver can receive the telemetry packets, and the low power consumption allows for at least 24 hours of operation with a 4-hour wireless recharge session.

rs1495741 as a tag single nucleotide polymorphism of N-acetyltransferase 2 acetylator phenotype associates bladder cancer risk and interacts with smoking: A systematic review and meta-analysis.

PubMed

Ma, Chong; Gu, Liyan; Yang, Mingyuan; Zhang, Zhensheng; Zeng, Shuxiong; Song, Ruixiang; Xu, Chuanliang; Sun, Yinghao

2016-08-01

Rs1495741 has been identified to infer N-acetyltransferase 2 (NAT2) acetylator phenotype, and to decrease the risk of bladder cancer. However, a number of studies conducted in various regions showed controversial results. To quantify the association between rs1495741 and the risk of bladder cancer and to estimate the interaction effect of this genetic variant with smoking, we performed a systematic literature review and meta-analysis involving 14,815 cases and 58,282 controls from 29 studies. Our results indicates rs1495741 significantly associated with bladder cancer risk (OR = 0.85, 95% CI = 0.82-0.89, test for heterogeneity P = 0.36, I = 7.0%). And we verified this association in populations from Europe, America, and Asia. Further, our stratified meta-analysis showed rs1495741's role is typically evident only in ever smokers, which suggests its interaction with smoking. This study may provide new insight into gene-environment study on bladder cancer.

Wireless, Ultra-Low-Power Implantable Sensor for Chronic Bladder Pressure Monitoring

PubMed Central

MAJERUS, STEVE J. A.; GARVERICK, STEVEN L.; SUSTER, MICHAEL A.; FLETTER, PAUL C.; DAMASER, MARGOT S.

2015-01-01

The wireless implantable/intracavity micromanometer (WIMM) system was designed to fulfill the unmet need for a chronic bladder pressure sensing device in urological fields such as urodynamics for diagnosis and neuromodulation for bladder control. Neuromodulation in particular would benefit from a wireless bladder pressure sensor which could provide real-time pressure feedback to an implanted stimulator, resulting in greater bladder capacity while using less power. The WIMM uses custom integrated circuitry, a MEMS transducer, and a wireless antenna to transmit pressure telemetry at a rate of 10 Hz. Aggressive power management techniques yield an average current draw of 9 μA from a 3.6-Volt micro-battery, which minimizes the implant size. Automatic pressure offset cancellation circuits maximize the sensing dynamic range to account for drifting pressure offset due to environmental factors, and a custom telemetry protocol allows transmission with minimum overhead. Wireless operation of the WIMM has demonstrated that the external receiver can receive the telemetry packets, and the low power consumption allows for at least 24 hours of operation with a 4-hour wireless recharge session. PMID:26778926

Urinary incontinence

MedlinePlus

Loss of bladder control; Uncontrollable urination; Urination - uncontrollable; Incontinence - urinary ... have diabetes, keep your blood sugar under good control. For urine leaks, wear absorbent pads or undergarments. ...

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

PubMed Central

Ogawa, Teruyuki; Miyazato, Minoru; Kitta, Takeya; Furuta, Akira; Chancellor, Michael B.; Tyagi, Pradeep

2014-01-01

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed. PMID:24578802

Stress and coping of parents of young children diagnosed with bladder exstrophy.

PubMed

Mednick, Lauren; Gargollo, Patricio; Oliva, Melisa; Grant, Rosemary; Borer, Joseph

2009-03-01

Previous studies have examined the psychological impact that living with bladder exstrophy has on patients. However, little is known about how parents of children diagnosed with this condition are affected. We examine how parents caring for children diagnosed with bladder exstrophy are impacted. An increased understanding of the stressors these parents face may lead to the development of appropriate parenting interventions, which may ultimately affect psychosocial and health outcomes in the child. All parents of children 10 years and younger treated for bladder exstrophy at our institution were selected from a centralized database. A total of 20 parents (65% of the eligible population) completed standardized questionnaires assessing pediatric specific parenting stress (Pediatric Inventory for Parents) and coping (Ways of Coping Questionnaire). Parents identified several common stressors (eg worrying about the long-term impact of the illness, helping the child with his/her hygiene needs) and overall reported using adaptive ways of coping (ie planful problem solving, seeking social support, positive reappraisal). However, when they experienced increased stress they reported using more nonadaptive ways of coping (ie escape/avoidance and distancing). Overall the findings of our study suggest that parents of children diagnosed with bladder exstrophy experience a significant amount of stress. In fact, parents in our study indicated experiencing similar frequency and difficulty of stress compared to parents of the same aged children diagnosed with type 1 diabetes. Increased stress can have negative consequences for parents and children. Future directions and implications of these findings are discussed.

Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease

PubMed Central

2017-01-01

Pathogens often inhabit the body asymptomatically, emerging to cause disease in response to unknown triggers. In the bladder, latent intracellular Escherichia coli reservoirs are regarded as likely origins of recurrent urinary tract infection (rUTI), a problem affecting millions of women worldwide. However, clinically plausible triggers that activate these reservoirs are unknown. Clinical studies suggest that the composition of a woman’s vaginal microbiota influences her susceptibility to rUTI, but the mechanisms behind these associations are unclear. Several lines of evidence suggest that the urinary tract is routinely exposed to vaginal bacteria, including Gardnerella vaginalis, a dominant member of the vaginal microbiota in some women. Using a mouse model, we show that bladder exposure to G. vaginalis triggers E. coli egress from latent bladder reservoirs and enhances the potential for life-threatening outcomes of the resulting E. coli rUTI. Transient G. vaginalis exposures were sufficient to cause bladder epithelial apoptosis and exfoliation and interleukin-1-receptor-mediated kidney injury, which persisted after G. vaginalis clearance from the urinary tract. These results support a broader view of UTI pathogenesis in which disease can be driven by short-lived but powerful urinary tract exposures to vaginal bacteria that are themselves not “uropathogenic” in the classic sense. This “covert pathogenesis” paradigm may apply to other latent infections, (e.g., tuberculosis), or for diseases currently defined as noninfectious because routine culture fails to detect microbes of recognized significance. PMID:28358889

Basal and stress-activated hypothalamic pituitary adrenal axis function in postmenopausal women with overactive bladder.

PubMed

Smith, Ariana L; Hantsoo, Liisa; Malykhina, Anna P; File, Daniel W; Valentino, Rita; Wein, Alan J; Sammel, Mary D; Epperson, C Neill

2016-09-01

The aim of this study was to measure physiologic and psychologic stress reactivity in women with overactive bladder (OAB). There is growing evidence in preclinical models that central nervous system dysregulation, particularly in response to psychological stress, may contribute to lower urinary tract symptoms in women with OAB. Postmenopausal women with OAB and healthy controls underwent Structured Clinical Interview for DSM-IV Axis I disorders (SCID) to identify those without identifiable psychiatric disease. Eligible participants underwent physiologic measures including basal (cortisol-awakening response; CAR) and stress-activated salivary cortisol levels, heart rate (HR), urinary metanephrines and neurotrophins, as well as validated symptom assessment for stress, anxiety, depression, and bladder dysfunction at baseline and during, and following an acute laboratory stressor, the Trier Social Stress Test (TSST). Baseline measures of cortisol reactivity measured by CAR showed blunted response among women with OAB (p = 0.015), while cortisol response to the TSST was greater in the OAB group (p = 0.019). Among OAB patients, bladder urgency as measured by visual analog scale (VAS) increased from pre- to post-TSST (p = 0.04). There was a main effect of TSST on HR (p < 0.001), but no group interaction. Preliminary findings suggest that women with OAB have greater physiologic and psychologic stress reactivity than healthy controls. Importantly for women with OAB, acute stress appears to exacerbate bladder urgency. Evaluation of the markers of stress response may suggest targets for potential diagnostic and therapeutic interventions.

[Effects of gap junction blocking on the oxygen partial pressure in acupoints of the bladder meridian].

PubMed

Wang, Qi; Yu, Wei-Chang; Jiang, Hong-Zhi; Chen, Sheng-Li; Zhang, Ming-Min; Kong, E-Sheng; Huang, Guang-Ying

2010-12-01

To explore the relation between gap junction and meridian phenomenon. The oxygen partial pressure in acupoints [see text for formula] and in their corresponding non-acupoints of the Bladder Meridian was observed with the needle-type tissue oxygen tension sensor in the gap junction blocking goats by 1-Heptanol injection and the Connexin 43 (Cx43) gene knockout mice. (1) The oxygen partial pressure in acupoints of Bladder Meridian on goats was higher than that in non-acupoints after 1-Heptanol injection with significant differences between them (both P < 0.01). (2) The oxygen partial pressure in acupoints of Bladder Meridian on goats increased significantly after injecting 1-Heptanol as compare with that either injecting normal saline or injecting nothing with significant differences between them (all P < 0.01). (3) The oxygen partial pressure in acupoints of the Bladder Meridian was significantly higher than that in the non-acupoint controls in Cx43 wild type (WT) mice (all P < 0.01). In Cx43 heterozygote (HT) mice, the oxygen partial pressure between acupoints and non-acupoint controls showed no significant differences (all P > 0.05). (4) In acupoints, the oxygen partial pressure in Cx43 WT mice was significantly higher than that in Cx43 HT mice (all P < 0.05), while in the corresponding non-acupoints, this difference had no statistically significant (all P > 0.05). Gap junction maybe the essential factor in signal transduction of acupuncture.

Nocturnal enuresis in a longitudinal perspective. A primary problem of maturity and/or a secondary environmental reaction?

PubMed

Klackenberg, G

1981-07-01

The study is part of a prospective longitudinal investigation, involving annual somatic, psychological and social check-ups in a random sample of 212 children. Data are presented on the gradual achievement of bladder control, with relapses into wetting. Information is provided on relationships with training, with behavioural variables, with emotional maturity (Rorschach) and with sleep. It seems probable that primary enuresis usually ceases by the age of 8 at the latest and that enuresis in older children is a secondary emotional disorder which may, however, have started at an earlier age. The 6-year-old enuretic shows signs of delayed emotional maturity. The relation with somnambulism is ambiguous. Enuresis is not significantly related to training. None of the data obtained in this study conflict with the theory that primary enuresis is chiefly a maturity problem, the nature of which can be emotional. The neurophysiological aspect has not been investigated.

COMBINED USE OF α-ADRENERGIC AND MUSCARINIC ANTAGONISTS FOR THE TREATMENT OF VOIDING DYSFUNCTION

PubMed Central

RUGGIERI, MICHAEL R.; BRAVERMAN, ALAN S.; PONTARI, MICHEL A.

2012-01-01

Purpose We provide an overview of the medical literature supporting the combined use of muscarinic and α-adrenergic antagonist therapy for the treatment of voiding dysfunction. Materials and Methods The MEDLINE database (1966 to 2004) of the United States National Library of Medicine was searched for pertinent studies. Results Although the mechanism of action of α-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M2 receptor mediates hypertrophied bladder contractions and there is evidence for an M2 component to the suprasacral control of voiding. Conclusions Based on the physiology of α-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome. PMID:16217275

Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis.

PubMed

Liang, Simin; Li, Jie; Gou, Xin; Chen, Daihui

2016-01-01

Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E-binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats. The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis. © The Author(s) 2016.

Risk factors for urinary bladder cancer in Baluchistan.

PubMed

Ahmad, Muhammad Riaz; Pervaiz, Muhammad Khalid; Chawala, Javed Akhtar

2012-01-01

Urinary Bladder cancer is a life threatening and aggressive disease. This retrospective study was conducted in Baluchistan for assessing the risk factors for urinary bladder cancer. A questionnaire was developed in order to collect the requisite information about the characteristics like age, drinking habits, smoking history, family history of cancer and others factors. Interview method was used to obtain the information from 50 cases and 100 controls from two hospitals of the province. Binary logistic regression model was run to study the odds ratios and 95% confidence intervals. The odds ratios and 95% confidence intervals for cigarette smoking, fluid consumption and higher use of fruits were [26.064; 7.645-88.856], [0.161; 0.059-0.441], and [0.206; 0.059-0.725] respectively. The higher risk of urinary bladder cancer was observed in smokers as compared to non-smokers. Higher consumption of fluid and fruits are protective factors against the disease.

A novel automatic regulatory device for continuous bladder irrigation based on wireless sensor in patients after transurethral resection of the prostate: A prospective investigation.

PubMed

Ding, Aimin; Cao, Huling; Wang, Lihua; Chen, Jiangang; Wang, Jian; He, Bosheng

2016-12-01

Benign prostatic hyperplasia is a common progressive disease in aging men, which leads to a significant impact on daily lives of patients. Continuous bladder irrigation (CBI) is a supplementary option for preventing the adverse events following transurethral resection of the prostate (TURP). Regulation of the flow rate based on the color of drainage bag is significant to prevent the clot formation and retention, which is controlled manually at present. To achieve a better control of flow rate and reduce inappropriate flow rate-related adverse effects, we designed an automatic flow rate controller for CBI applied with wireless sensor and evaluated its clinical efficacy. The therapeutic efficacy was evaluated in patients receiving the novel automatic bladder irrigation post-TURP in the experimental group compared with controls receiving traditional bladder irrigation in the control group. A total of 146 patients were randomly divided into 2 groups-the experimental group (n = 76) and the control group (n = 70). The mean irrigation volume of the experimental group (24.2 ± 3.8 L) was significantly lower than that of the controls (54.6 ± 5.4 L) (P < 0.05). Patients treated with automatic irrigation device had significantly decreased incidence of clot retention (8/76) and cystospasm (12/76) compared to controls (21/70; 39/70, P < 0.05). There was no significant difference between the 2 groups with regard to irrigation time (28.6 ± 2.7 vs 29.5 ± 3.4 hours, P = 0.077). The study suggests that the automatic regulating device applied with wireless sensor for CBI is safe and effective for patients after TURP. However, studies with a large population of patients and a long-term follow-up should be conducted to validate our findings.

A novel automatic regulatory device for continuous bladder irrigation based on wireless sensor in patients after transurethral resection of the prostate

PubMed Central

Ding, Aimin; Cao, Huling; Wang, Lihua; Chen, Jiangang; Wang, Jian; He, Bosheng

2016-01-01

Abstract Background: Benign prostatic hyperplasia is a common progressive disease in aging men, which leads to a significant impact on daily lives of patients. Continuous bladder irrigation (CBI) is a supplementary option for preventing the adverse events following transurethral resection of the prostate (TURP). Regulation of the flow rate based on the color of drainage bag is significant to prevent the clot formation and retention, which is controlled manually at present. To achieve a better control of flow rate and reduce inappropriate flow rate–related adverse effects, we designed an automatic flow rate controller for CBI applied with wireless sensor and evaluated its clinical efficacy. Methods: The therapeutic efficacy was evaluated in patients receiving the novel automatic bladder irrigation post-TURP in the experimental group compared with controls receiving traditional bladder irrigation in the control group. Results: A total of 146 patients were randomly divided into 2 groups—the experimental group (n = 76) and the control group (n = 70). The mean irrigation volume of the experimental group (24.2 ± 3.8 L) was significantly lower than that of the controls (54.6 ± 5.4 L) (P < 0.05). Patients treated with automatic irrigation device had significantly decreased incidence of clot retention (8/76) and cystospasm (12/76) compared to controls (21/70; 39/70, P < 0.05). There was no significant difference between the 2 groups with regard to irrigation time (28.6 ± 2.7 vs 29.5 ± 3.4 hours, P = 0.077). Conclusion: The study suggests that the automatic regulating device applied with wireless sensor for CBI is safe and effective for patients after TURP. However, studies with a large population of patients and a long-term follow-up should be conducted to validate our findings. PMID:28033276

Validation of deformable image registration algorithms on CT images of ex vivo porcine bladders with fiducial markers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wognum, S., E-mail: s.wognum@gmail.com; Heethuis, S. E.; Bel, A.

2014-07-15

Purpose: The spatial accuracy of deformable image registration (DIR) is important in the implementation of image guided adaptive radiotherapy techniques for cancer in the pelvic region. Validation of algorithms is best performed on phantoms with fiducial markers undergoing controlled large deformations. Excised porcine bladders, exhibiting similar filling and voiding behavior as human bladders, provide such an environment. The aim of this study was to determine the spatial accuracy of different DIR algorithms on CT images ofex vivo porcine bladders with radiopaque fiducial markers applied to the outer surface, for a range of bladder volumes, using various accuracy metrics. Methods: Fivemore » excised porcine bladders with a grid of 30–40 radiopaque fiducial markers attached to the outer wall were suspended inside a water-filled phantom. The bladder was filled with a controlled amount of water with added contrast medium for a range of filling volumes (100–400 ml in steps of 50 ml) using a luer lock syringe, and CT scans were acquired at each filling volume. DIR was performed for each data set, with the 100 ml bladder as the reference image. Six intensity-based algorithms (optical flow or demons-based) implemented in theMATLAB platform DIRART, a b-spline algorithm implemented in the commercial software package VelocityAI, and a structure-based algorithm (Symmetric Thin Plate Spline Robust Point Matching) were validated, using adequate parameter settings according to values previously published. The resulting deformation vector field from each registration was applied to the contoured bladder structures and to the marker coordinates for spatial error calculation. The quality of the algorithms was assessed by comparing the different error metrics across the different algorithms, and by comparing the effect of deformation magnitude (bladder volume difference) per algorithm, using the Independent Samples Kruskal-Wallis test. Results: The authors found good structure accuracy without dependency on bladder volume difference for all but one algorithm, and with the best result for the structure-based algorithm. Spatial accuracy as assessed from marker errors was disappointing for all algorithms, especially for large volume differences, implying that the deformations described by the registration did not represent anatomically correct deformations. The structure-based algorithm performed the best in terms of marker error for the large volume difference (100–400 ml). In general, for the small volume difference (100–150 ml) the algorithms performed relatively similarly. The structure-based algorithm exhibited the best balance in performance between small and large volume differences, and among the intensity-based algorithms, the algorithm implemented in VelocityAI exhibited the best balance. Conclusions: Validation of multiple DIR algorithms on a novel physiological bladder phantom revealed that the structure accuracy was good for most algorithms, but that the spatial accuracy as assessed from markers was low for all algorithms, especially for large deformations. Hence, many of the available algorithms exhibit sufficient accuracy for contour propagation purposes, but possibly not for accurate dose accumulation.« less

Probiotics for preventing urinary tract infection in people with neuropathic bladder.

PubMed

Toh, Swee-Ling; Boswell-Ruys, Claire L; Lee, Bon San B; Simpson, Judy M; Clezy, Kate R

2017-09-08

Neuropathic or neurogenic bladder describes a process of dysfunctional voiding as the result of injury in the brain, spinal cord or nerves innervating the bladder. People with neuropathic bladder, such as from spinal cord injury (SCI), are at significant risk of morbidity from urinary tract infections (UTI). Effective methods to prevent UTI in people with SCI have been sought for many years. Probiotics (micro-organisms that exert beneficial health effects in the host) have been recommended for bacterial interference of the urological tract to reduce colonisation by uropathogen and to manage the dual problems of infection and antibiotic resistance. This review looked at the benefits and harms of probiotics in preventing symptomatic UTI in people with neuropathic bladder compared with placebo, no therapy, or non-antibiotic prophylaxis (cranberry juice, methenamine hippurate, topical oestrogen). We searched the Cochrane Kidney and Transplant Specialised Register up to 10 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. All randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs looking at the use of probiotics for the prophylaxis of UTI in people with neuropathic bladders was considered for inclusion. Men, women and children of all ages with neuropathic bladders from neurological injury such as suprapontine, supra sacral and sacral aetiologies was included. All bladder management types, including reflex voiding, time voiding, indwelling and intermittent catheterization were eligible for this review.Studies comparing probiotics to placebo, no treatment or other non-antibiotic prophylaxis was included. Studies comparing probiotics with antibiotics or in combination with antibiotics were excluded. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI were planned for continuous outcomes. This review includes a total of three studies (one cross-over and two parallel RCTs) which involved 110 participants. All three studies looked at intravesical instillation of a low virulent Escherichia coli (E. coli) strain in reducing the risk of symptomatic UTI in participants with neuropathic bladder, predominantly from SCI. Two studies used the E. coli 83972 strain and one study used the E. coli HU2117 strain.We did not find any RCTs involving other probiotics or other routes of administration for preventing UTI in people with neuropathic bladder.There was consistency in definition of symptomatic UTI in all three studies. Symptoms that all studies considered were relevant to diagnose UTI were adequately defined. All three studies defined microbiological diagnosis of symptomatic UTI.Asymptomatic bacteriuria was not considered an outcome measure in any of the included studies; however it was defined in two studies to establish successful inoculation.It is uncertain if the risk of symptomatic UTI is reduced with bladder inoculation using E. coli because the certainty of the evidence is very low (3 studies, 110 participants: RR 0.32, 95% CI 0.08 to 1.19; I 2 = 82%).Two studies reported adverse events. One study reported one episode of autonomic dysreflexia. One study reported three symptomatic UTI occurring in two patients, and two studies mentioned the absence of septicaemia and pyelonephritis. Intravesical instillation was reported as "generally safe". One study reported high attrition rates in participants due to the need to adhere to strict instillation protocols.The overall quality of the studies was poor. All three studies had high risk of attrition bias due to failure of an intention-to-treat analysis which undermines the randomisation process and weakened the results of the studies. All three studies also had high risk of reporting bias. In this review, there were no studies identified addressing oral probiotics in preventing UTI in people with neuropathic bladder. It is uncertain if the risk of symptomatic UTI is reduced in people with neuropathic bladders via intravesical instillation of non-pathogenic E. coli as data were derived from small studies with high risk of bias.Although very minimal levels of harm was reported with this procedure, due to variable success rates, the need for strict adherence to instillation protocols together with high attrition rates in these studies, it is doubtful bladder instillation will be a widely accepted intervention in its current form.It is recommended that further appropriately powered RCTs with more robust methodological reporting be carried out.

"But You Look So Good!": Managing Specific Issues

MedlinePlus

... and resources about handling bladder or bowel problems. Self-esteem “I think the most difficult thing to cope ... feel. It’s understandable then that MS can impact self-esteem and confidence. “It’s difficult to feel powerful, competent, ...

Association Between N-acetyltransferase 2 Polymorphism and Bladder Cancer Risk: Results From Studies of the Past Decade and a Meta-Analysis.

PubMed

Wu, Haoran; Wang, Xugang; Zhang, Liang; Mo, Naixin; Lv, Zhong

2016-04-01

Numerous studies have identified that the slow acetylation status of N-acetyltransferase 2 (NAT2) is associated with an elevated bladder cancer risk. However, the results remain inconclusive. The aim of our study was to evaluate the effect of NAT2 acetylation status in patients with bladder cancer. Electronic databases were searched to retrieve related studies published in the past decade. The pooled odds ratio (OR) with its 95% confidence interval (CI) was used to calculate the strength of this relationship. Overall, a total of 18 studies were selected for the analysis, which included 4473 bladder cancer cases and 7204 matched controls. Our result showed that the NAT2 slow acetylation phenotypes were significantly associated with an increased risk of bladder cancer compared with the rapid phenotypes (OR, 1.56; 95% CI, 1.33-1.82; P < .00001) in a random-effect model. This significant association was also found in a subgroup analysis of ethnicity (P < .05). Furthermore, the NAT2 slow phenotypes also significantly increased the risk of bladder cancer in smokers (OR, 0.75; 95% CI, 0.62-0.90; P = .002). However, no correlation was found between the combined effect of NAT2 slow phenotypes and gender with bladder cancer risk (OR, 0.89; 95% CI, 0.28-2.78; P = .84). In conclusion, our results suggest that the NAT2 slow acetylator, in particular, the NAT2 slow acetylator combined with smoking, are associated with an increased bladder cancer risk. Future well-designed studies with large populations and more ethnicities are needed to clarify this association further. Copyright © 2016 Elsevier Inc. All rights reserved.

Social stress in mice induces voiding dysfunction and bladder wall remodeling

PubMed Central

Chang, Andy; Butler, Stephan; Sliwoski, Joanna; Valentino, Rita; Canning, Douglas

2009-01-01

Several studies have anecdotally reported the occurrence of altered urinary voiding patterns in rodents exposed to social stress. A recent study characterized the urodynamic and central changes in a rat model of social defeat. Here, we describe a similar voiding phenotype induced in mice by social stress and in addition we describe potential molecular mechanisms underlying the resulting bladder wall remodeling. The mechanism leading to the altered voiding habits and underlying bladder phenotype may be relevant to the human syndrome of dysfunctional voiding which is thought to have a psychological component. To better characterize and investigate social stress-induced bladder wall hypertrophy, FVB mice (6 wk old) were randomized to either social stress or control manipulation. The stress involved repeated cycles of a 1-h direct exposure to a larger aggressive C57Bl6 breeder mouse followed by a 23-h period of barrier separation over 4 wk. Social stress resulted in altered urinary voiding patterns suggestive of urinary retention and increased bladder mass. In vivo cystometry revealed an increased volume at micturition with no change in the voiding pressure. Examination of these bladders revealed increased nuclear expression of the transcription factors MEF-2 and NFAT, as well as increased expression of the myosin heavy chain B isoform mRNA. BrdU uptake was increased within the urothelium and lamina propria layers in the social stress group. We conclude that social stress induces urinary retention that ultimately leads to shifts in transcription factors, alterations in myosin heavy chain isoform expression, and increases in DNA synthesis that mediate bladder wall remodeling. Social stress-induced bladder dysfunction in rodents may provide insight into the underlying mechanisms and potential treatment of dysfunctional voiding in humans. PMID:19587139

COMPREHENSIVE ANALYSES OF DNA REPAIR PATHWAYS, SMOKING, AND BLADDER CANCER RISK IN LOS ANGELES AND SHANGHAI

PubMed Central

Corral, Roman; Lewinger, Juan Pablo; Berg, David Van Den; Joshi, Amit D.; Yuan, Jian-Min; Gago-Dominguez, Manuela; Cortessis, Victoria K.; Pike, Malcolm C.; Conti, David V.; Thomas, Duncan C.; Edlund, Christopher K.; Gao, Yu-Tang; Xiang, Yong-Bing; Zhang, Wei; Su, Yu-Chen; Stern, Mariana C.

2014-01-01

Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1,004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repai, nucleotide excision repair (NER), non-homologous end-joining (NHEJ), and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT, and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and POLB rs7832529 (BER) (pACT = 0.003; ppathway = 0.021) among all, and SNPs in XPC (NER) and OGG1 (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER p = 0.034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (Smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (POLB, OGG1) and NER genes (XPC). A SNP that tags both the XRCC6 and SREBF2 genes strongly modifies the association between bladder cancer risk and smoking. PMID:24382701

Effects of streptozotocin-induced diabetes on bladder and erectile (dys)function in the same rat in vivo.

PubMed

Christ, George J; Hsieh, Yi; Zhao, Weixin; Schenk, Gregory; Venkateswarlu, Karicheti; Wang, Hong-Zhan; Tar, Moses T; Melman, Arnold

2006-05-01

To establish the methods, feasibility and utility of evaluating the impact of diabetes on bladder and erectile function in the same rat, as more than half of diabetic patients have bladder dysfunction, and half of diabetic men have erectile dysfunction, but the severity of coincident disease has not been rigorously assessed. In all, 16 F-344 rats had diabetes induced by streptozotocin (STZ), and were divided into insulin-treated (five) and untreated (11), and compared with age-matched controls (10), all assessed in parallel. All STZ rats were diabetic for 8-11 weeks. Cystometric studies were conducted on all rats, with cavernosometric studies conducted on a subset of rats. There were insulin-reversible increases in the following cystometric variables; bladder weight, bladder capacity, micturition volume, residual volume, micturition pressure and spontaneous activity (P < 0.05, in all, one-way analysis of variance, anova). Cavernosometry showed a diabetes-related, insulin-reversible decline in the cavernosal nerve-stimulated intracavernosal pressure (ICP) response at all levels of current stimulation (P < 0.05, in all one-way anova). Plotting erectile capacity (i.e. ICP) against bladder capacity showed no correlation between the extent of the decline in erectile capacity and the magnitude of the increase in bladder capacity. These studies extend previous work to indicate that the extent of diabetes-related bladder and erectile dysfunction can vary in the same rat. As such, these findings highlight the importance of evaluating the impact of diabetes on multiple organ systems in the lower urinary tract. Future studies using this model system should lead to a better understanding of the initiation, development, progression and coincidence of these common diabetic complications.

Outlines on nanotechnologies applied to bladder tissue engineering.

PubMed

Alberti, C

2012-01-01

Tissue engineering technologies are more and more expanding as consequence of recent developments in the field of biomaterial science and nanotechnology research. An important issue in designing scaffold materials is that of recreating the ECM (extra-cellular matrix) functional features - particularly ECM-derived complex molecule signalling - to mimic its capability of directing cell-growth and neotissue morphogenesis. In this way the nanotechnology may offer intriguing chances, biomaterial nanoscale-based scaffold geometry behaving as nanomechanotransducer complex interacting with different cell nanosize proteins, especially with those of cell surface mechanoreceptors. To fabricate 3D-scaffold complex architectures, endowed with controlled geometry and functional properties, bottom-up approaches, based on molecular self-assembling of small building polymer units, are used, sometimes functionalizing them by incorporation of bioactive peptide sequences such as RDG (arginine - glycine - aspartic acid, a cell-integrin binding domain of fibronectin), whereas the top-down approaches are useful to fabricate micro/nanoscale structures, such as a microvasculature within an existing complex bioarchitecture. Synthetic polymer-based nanofibers, produced by electrospinning process, may be used to create fibrous scaffolds that can facilitate, given their nanostructured geometry and surface roughness, cell adhesion and growth. Also bladder tissue engineering may benefit by nanotechnology advances to achieve a better reliability of the bladder engineered tissue. Particularly, bladder smooth muscle cell adhesion to nanostructured polymeric surfaces is significantly enhanced in comparison with that to conventional biomaterials. Moreover nanostructured surfaces of bladder engineered tissue show a decreased calcium stone production. In a bladder tumor animal model, the dispersion of carbon nanofibers in a polymeric scaffold-based tissue engineered replacement neobladder, appears to inhibit a carcinogenic relapse in bladder prosthetic material. Facing the future, a full success of bladder tissue engineering will mainly depend on the progress of both biomaterial nanotechnologies and stem cell biology research.

Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer.

PubMed

James, Nicholas D; Hussain, Syed A; Hall, Emma; Jenkins, Peter; Tremlett, Jean; Rawlings, Christine; Crundwell, Malcolm; Sizer, Bruce; Sreenivasan, Thiagarajan; Hendron, Carey; Lewis, Rebecca; Waters, Rachel; Huddart, Robert A

2012-04-19

Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemoradiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone. In this multicenter, phase 3 trial, we randomly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy. The regimen consisted of fluorouracil (500 mg per square meter of body-surface area per day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C (12 mg per square meter) on day 1. Patients were also randomly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy (in which the volume of bladder receiving full-dose radiotherapy was reduced) in a partial 2-by-2 factorial design (results not reported here). The primary end point was survival free of locoregional disease. Secondary end points included overall survival and toxic effects. At 2 years, rates of locoregional disease-free survival were 67% (95% confidence interval [CI], 59 to 74) in the chemoradiotherapy group and 54% (95% CI, 46 to 62) in the radiotherapy group. With a median follow-up of 69.9 months, the hazard ratio in the chemoradiotherapy group was 0.68 (95% CI, 0.48 to 0.96; P=0.03). Five-year rates of overall survival were 48% (95% CI, 40 to 55) in the chemoradiotherapy group and 35% (95% CI, 28 to 43) in the radiotherapy group (hazard ratio, 0.82; 95% CI, 0.63 to 1.09; P=0.16). Grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group during treatment (36.0% vs. 27.5%, P=0.07) but not during follow-up (8.3% vs. 15.7%, P=0.07). Synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer, as compared with radiotherapy alone, with no significant increase in adverse events. (Funded by Cancer Research U.K.; BC2001 Current Controlled Trials number, ISRCTN68324339.).

[Clinical experience on the use of total parenteral nutrition in patients subjected to radical cystectomy intervention for infiltrating neoplasms of the bladder].

PubMed

Del Boca, C; Furiosi, D; Bolis, C; Ferrari, C

1989-03-01

The Authors report their 7 year follow-up on the use of T.P.N. in 28 patients treated surgically for infiltrating cancer of the bladder. They consider the pathogenetic mechanisms that influence the organism's adaptation to surgical stress with particular reference to the multiple neuroendocrinal and biochemical interconnections. The procedures to define the nutritional/metabolic levels, of the patients undergoing operation are exposed. The T.P.N. is given according to the personal requirements of each patient and is a function of the "performance status", caloric need and to the presence of sepsis. Problems concerning the radical cistectomy such as: time of surgery, extention of exeresis, uroentheroanastomosis, metabolic variations, sepsis, etc., are evaluated. Considering the positive results obtained with this nutritional procedure, the Authors underline the importance of a systematic use of T.P.N. wich should be included, in their opinion, in a multidisciplinar treatment of advanced bladder neoplasms.

Magnetic spheres as foreign body into the bladder.

PubMed

Graziottin, Tulio M; de Freitas G Soares, Daniel; Da Ros, Carlos T; Sogari, Paulo R; Telöken, Cláudio; Laste, Paulo Roberto

2013-10-01

A great variety of foreign bodies in the lower urinary tract have been described; many of them are self-inflicted by the patient with masturbatory purposes. Depending on the nature of the foreign body the diagnostic and management might be challenging. We report a case of an unusual magnetic self-inserted foreign body into the bladder for autoerotism and briefly discuss the diagnostic and therapeutic implications in this challenging situation. We describe all the steps we have used to adequately diagnose the problem, describe the foreign body and treatments for the patient. Related articles were found by utilizing the PubMed database and are summarized in this study.   The management approach must be planned according to the nature of the foreign body and should minimize bladder and urethral trauma. However, most of cases can be managed endoscopically. Removal of magnetic foreign body may be quite challenging, requiring high-level surgical skills and minimally invasive techniques resulting in fast recovery and low complication rate. © 2012 International Society for Sexual Medicine.

Voiding school as a treatment of daytime incontinence or enuresis: Children's experiences of the intervention.

PubMed

Saarikoski, A; Koppeli, R; Salanterä, S; Taskinen, S; Axelin, A

2018-02-01

Daytime incontinence and enuresis are common problems in otherwise healthy children, and negatively influence their social lives and self-esteem. Motivation for treatment is often a real clinical problem. Children's experiences of their incontinence treatments have not been previously described. The aim of this study was to describe children's experiences of the Voiding School intervention as a treatment for their incontinence. A qualitative, descriptive focus-group study with a purposive sample was conducted at a Finish university hospital in 2014. Children aged 6-12 years participated in the Voiding School at an outpatient clinic. The intervention included two 1-day group visits 2 months apart. The educational content was based on the International Children Continence Society's standards for urotherapy. The education was delivered with child-oriented teaching methods. At the end of the second visit, 19 children were interviewed in five groups. Data were analysed with inductive content analysis. The children described incontinence as an embarrassing problem, which they had to hide at any cost. They had experienced bullying and social isolation because of it. Normal outpatient visits emphasized adult-to-adult communication, which made the children feel like outsiders. The children perceived the Voiding School as a nice and child-oriented experience. Making new friends was especially important to younger boys who felt that the Voiding School day was too long and issue-oriented. In the Voiding School, videos and 'learning by doing' helped the children to understand the basis of given advice, and they were able to learn new habits, which gave them control over the incontinence; this helped them to become 'the boss of the bladder'. Sharing experiences and improvements in their incontinence with their peers supported the children's self-esteem and encouraged them to do new things, such as staying overnight with friends. These experiences helped them to acquire control over the problem (Summary Figure). According to the children's experiences, normal outpatient visits were only appointments for adults, and not very useful for children. In the Voiding School, they were respected as being the main person, and their views were listened to. The results underlined the importance of a child-oriented approach to patient education with regard to children, and provided encouragement to further develop the intervention. Child orientation, peer support, learning by doing, and understanding the cause and effect helped children to gain control over their bladders. Based on the children's experiences, this could be achieved by a voiding school. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

PubMed Central

Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E.; Lenz, Petra; Figueroa, Jonine D.; Tang, Wei; Porter-Gill, Patricia; Chatterjee, Nilanjan; Scott-Johnson, Alexandra; Garcia-Closas, Montserrat; Muchmore, Brian; Baris, Dalsu; Paquin, Ashley; Ylaya, Kris; Schwenn, Molly; Apolo, Andrea B.; Karagas, Margaret R.; Tarway, McAnthony; Johnson, Alison; Mumy, Adam; Schned, Alan; Guedez, Liliana; Jones, Michael A.; Kida, Masatoshi; Monawar Hosain, GM; Malats, Nuria; Kogevinas, Manolis; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; Garcia-Closas, Reina; Lloreta, Josep; Wu, Xifeng; Purdue, Mark; Andriole, Gerald L.; Grubb, Robert L.; Black, Amanda; Landi, Maria T.; Caporaso, Neil E.; Vineis, Paolo; Siddiq, Afshan; Bueno-de-Mesquita, H. Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Severi, Gianluca; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Prescott, Jennifer; Chen, Constance; De Vivo, Immaculata; Govannucci, Edward; Hunter, David; Kraft, Peter; Lindstrom, Sara; Gapstur, Susan M.; Jacobs, Eric J.; Diver, W. Ryan; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Kooperberg, Charles; Hohensee, Chancellor; Rodabough, Rebecca J.; Cortessis, Victoria K.; Conti, David V.; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Haiman, Christopher A.; Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Porru, Stefano; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Grossman, H. Barton; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Fraumeni, Joseph; Chanock, Stephen J.; Hewitt, Stephen M.; Silverman, Debra T.; Rothman, Nathaniel; Prokunina-Olsson, Ludmila

2014-01-01

A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell cycle protein. We performed genetic fine mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r2≥0.7) associated with increased bladder cancer risk. From this group we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWAS, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele odds ratio (OR) =1.18 (95%CI=1.09-1.27, p=4.67×10−5 vs. OR =1.01 (95%CI=0.93-1.10, p=0.79) for non-aggressive disease, with p=0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (p=0.013) and, independently, with each rs7257330-A risk allele (ptrend=0.024). Over-expression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E over-expression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. PMID:25320178

A Murine Model of Inflammatory Bladder Disease: Cathelicidin Peptide Induced Bladder Inflammation and Treatment With Sulfated Polysaccharides

PubMed Central

Oottamasathien, Siam; Jia, Wanjian; McCoard, Lindsi; Slack, Sean; Zhang, Jianxing; Skardal, Aleksander; Job, Kathleen; Kennedy, Thomas P.; Dull, Randal O.; Prestwich, Glenn D.

2013-01-01

Purpose Studies show that LL-37 is a naturally occurring urinary defensin peptide that is up-regulated during urinary tract infections. Although normal urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may trigger bladder inflammation. We further suggest that anti-inflammatory sulfated polysaccharides known as semi-synthetic glycosaminoglycan ether compounds can treat/prevent LL-37 mediated bladder inflammation. Materials and Methods C57BL/6 mice were catheterized/instilled with LL-37 (320 μM at 150 μl) for 45 minutes. Animals were sacrificed at 12 and 24 hours, and tissues were examined using hematoxylin and eosin. Separate experiments were performed for myeloperoxidase to quantify inflammation. GM-1111 semi-synthetic glycosaminoglycan ether treatments involved instillation of 10 mg/ml for 45 minutes directly before or after LL-37. Tissues were harvested at 24 hours. To compare semi-synthetic glycosaminoglycan ether efficacy experiments were performed using 10 mg/ml heparin. Finally, tissue localization of semi-synthetic glycosaminoglycan ether was examined using a fluorescent GM-1111-Alexa Fluor® 633 conjugate. Results Profound bladder inflammation developed after LL-37. Greater tissue inflammation occurred after 24 hours compared to that at 12 hours. Myeloperoxidase assays revealed a 21 and 61-fold increase at 12 and 24 hours, respectively. Semi-synthetic glycosaminoglycan ether treatment after LL-37 showed mild attenuation of inflammation with myeloperoxidase 2.5-fold below that of untreated bladders. Semi-synthetic glycosaminoglycan ether treatment before LL-37 demonstrated almost complete attenuation of inflammation. Myeloperoxidase results mirrored those in controls. In heparin treated bladders minimal attenuation of inflammation occurred. Finally, instillation of GM-1111-Alexa Fluor 633 revealed urothelial coating, significant tissue penetration and binding to endovasculature. Conclusions We developed what is to our knowledge a new model of inflammatory bladder disease by challenge with the naturally occurring urinary peptide LL-37. We also noted that a new class of anti-inflammatory sulfated polysaccharides prevents and mitigates bladder inflammation. PMID:21855919

Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

ClinicalTrials.gov

2018-03-20

Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

Dynamic Expression of Serotonin Receptor 5-HT3A in Developing Sensory Innervation of the Lower Urinary Tract

PubMed Central

Ritter, K. Elaine; Southard-Smith, E. Michelle

2017-01-01

Sensory afferent signaling is required for normal function of the lower urinary tract (LUT). Despite the wide prevalence of bladder dysfunction and pelvic pain syndromes, few effective treatment options are available. Serotonin receptor 5-HT3A is a known mediator of visceral afferent signaling and has been implicated in bladder function. However, basic expression patterns for this gene and others among developing bladder sensory afferents that could be used to inform regenerative efforts aimed at treating deficiencies in pelvic innervation are lacking. To gain greater insight into the molecular characteristics of bladder sensory innervation, we conducted a thorough characterization of Htr3a expression in developing and adult bladder-projecting lumbosacral dorsal root ganglia (DRG) neurons. Using a transgenic Htr3a-EGFP reporter mouse line, we identified 5-HT3A expression at 10 days post coitus (dpc) in neural crest derivatives and in 12 dpc lumbosacral DRG. Using immunohistochemical co-localization we observed Htr3a-EGFP expression in developing lumbosacral DRG that partially coincides with neuropeptides CGRP and Substance P and capsaicin receptor TRPV1. A majority of Htr3a-EGFP+ DRG neurons also express a marker of myelinated Aδ neurons, NF200. There was no co-localization of 5-HT3A with the TRPV4 receptor. We employed retrograde tracing in adult Htr3a-EGFP mice to quantify the contribution of 5-HT3A+ DRG neurons to bladder afferent innervation. We found that 5-HT3A is expressed in a substantial proportion of retrograde traced DRG neurons in both rostral (L1, L2) and caudal (L6, S1) axial levels that supply bladder innervation. Most bladder-projecting Htr3a-EGFP+ neurons that co-express CGRP, Substance P, or TRPV1 are found in L1, L2 DRG, whereas Htr3a-EGFP+, NF200+ bladder-projecting neurons are from the L6, S1 axial levels. Our findings contribute much needed information regarding the development of LUT innervation and highlight the 5-HT3A serotonin receptor as a candidate for future studies of neurally mediated bladder control. PMID:28111539

Clinical significance of CDH13 promoter methylation as a biomarker for bladder cancer: a meta-analysis.

PubMed

Chen, Feng; Huang, Tao; Ren, Yu; Wei, Junjun; Lou, Zhongguan; Wang, Xue; Fan, Xiaoxiao; Chen, Yirun; Weng, Guobin; Yao, Xuping

2016-08-30

Methylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers. However, the clinical effect of the CDH13 methylation status of patients with bladder cancer remains to be clarified. A systematic literature search was performed to identify eligible studies in the PubMed, Embase, EBSCO, CKNI and Wanfang databases. The pooled odds ratio (OR) and the corresponding 95 % confidence interval (95 % CI) was calculated and summarized. Nine eligible studies were included in the present meta-analysis consisting of a total of 1017 bladder cancer patients and 265 non-tumor controls. A significant association was found between CDH13 methylation levels and bladder cancer (OR = 21.71, P < 0.001). The results of subgroup analyses based on sample type suggested that CDH13 methylation was significantly associated with bladder cancer risk in both the tissue and the urine (OR = 53.94, P < 0.001; OR = 7.71, P < 0.001; respectively). A subgroup analysis based on ethnic population showed that the OR value of methylated CDH13 was higher in Asians than in Caucasians (OR = 35.18, P < 0.001; OR = 8.86, P < 0.001; respectively). The relationships between CDH13 methylation and clinicopathological features were also analyzed. A significant association was not observed between CDH13 methylation status and gender (P = 0.053). Our results revealed that CDH13 methylation was significantly associated with high-grade bladder cancer, multiple bladder cancer and muscle invasive bladder cancer (OR = 2.22, P < 0.001; OR = 1.45, P = 0.032; OR = 3.42, P < 0.001; respectively). Our study indicates that CDH13 methylation may play an important role in the carcinogenesis, development and progression of bladder cancer. In addition, CDH13 methylation has the potential to be a useful biomarker for bladder cancer screening in urine samples and to be a prognostic biomarker in the clinic.

In vitro and in vivo effects of CpG-Oligodeoxynucleotides (CpG-ODN) on murine transitional cell carcinoma and on the native murine urinary bladder wall.

PubMed

Olbert, Peter Jochen; Schrader, Andres Jan; Simon, Corinna; Dalpke, Alexander; Barth, Peter; Hofmann, Rainer; Hegele, Axel

2009-06-01

Intravesical BCG instillation is established and efficient in the prophylaxis of recurrent transitional cell carcinoma. A Th-1 biased immune response is postulated. Recent work has proven the efficacy of synthetic CpG-Oligodeoxynucleotides (ODN) as inducers and adjuvants for a strong Th1-response and there is evidence for a direct and/or adjuvant anti-neoplastic effect. The purpose of this study was to examine the local effects of CpG-ODN on the murine bladder wall after intravesical instillation and the effects on cytokine expression in an orthotopic murine bladder cancer model. Histopathology, immunohistochemistry and fluorescence microscopy were performed after different instillation schedules of stimulatory, non-stimulatory biotinylized and FITC-labelled CpG-ODN into the murine bladder. MB-49 murine bladder cancer cells were tested for TLR-9 expression to exclude a potential direct responsiveness to CpG-ODN. Furthermore induction of apoptosis was tested by annexin V staining and FACS analysis of CpG-ODN stimulated tumor cells. In an orthotopic C57/Bl6 murine bladder cancer model, the expressions of IL-12, IFNgamma, IL-10 and TGF-beta were evaluated after repeated CpG-ODN treatment. Single and repeated instillation of CpG-ODN induced subepithelial and urothelial lymphocytic infiltrations with consecutive apoptoses. PBS and non-stimulative ODN induced no visible reaction. Bladder submucosa stained positive for biotin. Controls showed no endogenic biotin staining. FITC-labelled ODN adhered to the bladder mucosa and penetration of the mucosal barrier was not detected. MB-49 TCC cells did not express TLR-9 and CpG-ODN did not induce apoptosis in these cells. Repeated intravesical instillations of CpG-ODN in orthotopic murine tumor bearing urinary bladders resulted in significant up-regulation of both Th-1 and Th-2 cytokines. CpG-ODNs have promising anti-neoplastic potential. They exert a pronounced immunological response both in the native murine urinary bladder and in murine TCC. The mechanisms of action appear to be mediated immunologically, There was no direct effect of CpG-ODN on the tumor cells in this model.

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murthy, Vedang, E-mail: vmurthy@actrec.gov.in; Masodkar, Renuka; Kalyani, Nikhil

Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gymore » in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.« less

Midstream clean-catch urine collection in newborns: a randomized controlled study.

PubMed

Altuntas, Nilgun; Tayfur, Asli Celebi; Kocak, Mesut; Razi, Hasan Cem; Akkurt, Serpil

2015-05-01

We aimed to evaluate a recently defined technique based on bladder stimulation and paravertebral lumbar massage maneuvers in collecting a midstream clean-catch urine sample in newborns. A total of 127 term newborns were randomly assigned either to the experimental group or the control group. Twenty-five minutes after feeding, the genital and perineal areas of the babies were cleaned. The babies were held under the armpits with legs dangling. Bladder stimulation and lumbar paravertebral massage maneuvers were only applied to the babies in the experimental group. Success was defined as collection of a urine sample within 5 min of starting the stimulation maneuvers in the experimental group and of holding under the armpits in the control group. The success rate of urine collection was significantly higher in the experimental group (78%) than in the control group (33%; p < 0.001). The median time (interquartile range) for sample collection was 60 s (64.5 s) in the experimental group and 300 s (95 s) in the control group (p < 0.0001). Contamination rates were similar in both groups (p = 0.770). We suggest that bladder stimulation and lumbar paravertebral massage is a safe, quick, and effective way of collecting midstream clean-catch urine in newborns.

The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies

PubMed Central

Aggio, Raphael B. M.; de Lacy Costello, Ben; White, Paul; Khalid, Tanzeela; Ratcliffe, Norman M.; Persad, Raj; Probert, Chris S. J.

2016-01-01

Prostate cancer is one of the most common cancers. Serum prostate-specific antigen (PSA) is used to aid the selection of men undergoing biopsies. Its use remains controversial. We propose a GC-sensor algorithm system for classifying urine samples from patients with urological symptoms. This pilot study includes 155 men presenting to urology clinics, 58 were diagnosed with prostate cancer, 24 with bladder cancer and 73 with haematuria and or poor stream, without cancer. Principal component analysis (PCA) was applied to assess the discrimination achieved, while linear discriminant analysis (LDA) and support vector machine (SVM) were used as statistical models for sample classification. Leave-one-out cross-validation (LOOCV), repeated 10-fold cross-validation (10FoldCV), repeated double cross-validation (DoubleCV) and Monte Carlo permutations were applied to assess performance. Significant separation was found between prostate cancer and control samples, bladder cancer and controls and between bladder and prostate cancer samples. For prostate cancer diagnosis, the GC/SVM system classified samples with 95% sensitivity and 96% specificity after LOOCV. For bladder cancer diagnosis, the SVM reported 96% sensitivity and 100% specificity after LOOCV, while the DoubleCV reported 87% sensitivity and 99% specificity, with SVM showing 78% and 98% sensitivity between prostate and bladder cancer samples. Evaluation of the results of the Monte Carlo permutation of class labels obtained chance-like accuracy values around 50% suggesting the observed results for bladder cancer and prostate cancer detection are not due to over fitting. The results of the pilot study presented here indicate that the GC system is able to successfully identify patterns that allow classification of urine samples from patients with urological cancers. An accurate diagnosis based on urine samples would reduce the number of negative prostate biopsies performed, and the frequency of surveillance cystoscopy for bladder cancer patients. Larger cohort studies are planned to investigate the potential of this system. Future work may lead to non-invasive breath analyses for diagnosing urological conditions. PMID:26865331

Thyroid disrupting effects of halogenated and next generation chemicals on the swim bladder development of zebrafish.

PubMed

Godfrey, Amy; Hooser, Blair; Abdelmoneim, Ahmed; Horzmann, Katharine A; Freemanc, Jennifer L; Sepúlveda, Maria S

2017-12-01

Endocrine disrupting chemicals (EDCs) can alter thyroid function and adversely affect growth and development. Halogenated compounds, such as perfluorinated chemicals commonly used in food packaging, and brominated flame retardants used in a broad range of products from clothing to electronics, can act as thyroid disruptors. Due to the adverse effects of these compounds, there is a need for the development of safer next generation chemicals. The objective of this study was to test the thyroid disruption potential of old use and next generation halogenated chemicals. Zebrafish embryos were exposed to three old use compounds, perfluorooctanoic acid (PFOA), tetrabromobisphenol A (TBBPA) and tris (1,3-dichloro-2-propyl) phosphate (TDCPP) and two next generation chemicals, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxdie (DOPO) and perfluorobutyric acid (PFBA). Sub-chronic (0-6days post fertilization (dpf)) and chronic (0-28dpf) exposures were conducted at 1% of the concentration known to kill 50% (LC 50 ) of the population. Changes in the surface area of the swim bladder as well as in expression levels of genes involved in the thyroid control of swim bladder inflation were measured. At 6dpf, zebrafish exposed to all halogenated chemicals, both old use and next generation, had smaller posterior swim bladder and increased expression in the gene encoding thyroid peroxidase, tpo and the genes encoding two swim bladder surfactant proteins, sp-a and sp-c. These results mirrored the effects of thyroid hormone-exposed positive controls. Fish exposed to a TPO inhibitor (methimazole, MMI) had a decrease in tpo expression levels at 28dpf. Effects on the anterior swim bladder at 28dpf, after exposure to MMI as well as both old and new halogenated chemicals, were the same, i.e., absence of SB in ∼50% of fish, which were also of smaller body size. Overall, our results suggest thyroid disruption by the halogenated compounds tested via the swim bladder surfactant system. However, with the exception of TBBPA and TDCPP, the concentrations tested (∼5-137ppm) are not likely to be found in the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Tetrachloroethylene Exposure and Bladder Cancer Risk: A Meta-Analysis of Dry-Cleaning-Worker Studies

PubMed Central

Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima; Blair, Aaron; Hansen, Johnni; Lynge, Elsebeth; Charbotel, Barbara; Loomis, Dana; Kauppinen, Timo; Kyyronen, Pentti; Pukkala, Eero; Weiderpass, Elisabete

2014-01-01

Background: In 2012, the International Agency for Research on Cancer classified tetrachloroethylene, used in the production of chemicals and the primary solvent used in dry cleaning, as “probably carcinogenic to humans” based on limited evidence of an increased risk of bladder cancer in dry cleaners. Objectives: We assessed the epidemiological evidence for the association between tetrachloroethylene exposure and bladder cancer from published studies estimating occupational exposure to tetrachloroethylene or in workers in the dry-cleaning industry. Methods: Random-effects meta-analyses were carried out separately for occupational exposure to tetrachloroethylene and employment as a dry cleaner. We qualitatively summarized exposure–response data because of the limited number of studies available. Results: The meta-relative risk (mRR) among tetrachloroethylene-exposed workers was 1.08 (95% CI: 0.82, 1.42; three studies; 463 exposed cases). For employment as a dry cleaner, the overall mRR was 1.47 (95% CI: 1.16, 1.85; seven studies; 139 exposed cases), and for smoking-adjusted studies, the mRR was 1.50 (95% CI: 0.80, 2.84; 4 case–control studies). Conclusions: Our meta-analysis demonstrates an increased risk of bladder cancer in dry cleaners, reported in both cohort and case–control studies, and some evidence for an exposure–response relationship. Although dry cleaners incur mixed exposures, tetrachloroethylene could be responsible for the excess risk of bladder cancer because it is the primary solvent used and it is the only chemical commonly used by dry cleaners that is currently identified as a potential bladder carcinogen. Relatively crude approaches in exposure assessment in the studies of “tetrachloroethylene-exposed workers” may have attenuated the relative risks. Citation: Vlaanderen J, Straif K, Ruder A, Blair A, Hansen J, Lynge E, Charbotel B, Loomis D, Kauppinen T, Kyyronen P, Pukkala E, Weiderpass E, Guha N. 2014. Tetrachloroethylene exposure and bladder cancer risk: a meta-analysis of dry-cleaning-worker studies. Environ Health Perspect 122:661–666; http://dx.doi.org/10.1289/ehp.1307055 PMID:24659585

Opium and bladder cancer: A systematic review and meta-analysis of the odds ratios for opium use and the risk of bladder cancer

PubMed Central

Afshari, Mahdi; Janbabaei, Ghasem; Bahrami, Mohammad Amin

2017-01-01

Objective The association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis. Methods The study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3. Results We included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05–4.87) and 5.7 (1.9–16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6–7.7). Conclusion This meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It is therefore expected to be a risk factor for other cancers. PMID:28586371

Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using Low Energy Shock Waves.

PubMed

Chuang, Yao-Chi; Huang, Tung-Liang; Tyagi, Pradeep; Huang, Chao-Cheng

2016-08-01

We investigated the feasibility of using low energy shock waves for intravesical botulinum toxin A delivery. We also evaluated its efficacy for acetic acid induced bladder hyperactivity in rats. In study 1 magnetic resonance imaging with intravesical administration of Gd-DTPA (Gd-diethylenetriamine pentaacetic acid) contrast medium was performed to visualize increased bladder urothelial permeability after low energy shock waves. In study 2 saline (1 ml) or botulinum toxin A (20 U/1 ml saline) was administered in the bladder with or without low energy shock waves (300 pulses at 0.12 mJ/mm(2)) and retained for 1 hour on day 1. Continuous cystometrograms were performed on day 8 by filling the bladder with saline followed by 0.3% acetic acid. The bladder was harvested for histology, and SNAP-25, SNAP-23 and COX-2 expression by Western blot or immunostaining. Magnetic resonance imaging established bladder urothelial leakage of Gd-DTPA after low energy shock waves, which was not seen in controls. The intercontraction interval was decreased 71.9%, 72.6% and 70.6% after intravesical instillation of acetic acid in saline, saline plus low energy shock wave and botulinum toxin A pretreated rats, respectively. However, rats that received botulinum toxin A plus low energy shock waves showed a significantly reduced response (48.6% decreased intercontraction interval) to acetic acid instillation without compromising voiding function. Rats pretreated with botulinum toxin A plus low energy shock waves showed a decreased inflammatory reaction (p <0.05), and decreased expression of SNAP-23 (p <0.05), SNAP-25 (p = 0.061) and COX-2 (p <0.05) compared with the control group. Low energy shock waves increased urothelial permeability, facilitated intravesical botulinum toxin A delivery and blocked acetic acid induced hyperactive bladder. These results support low energy shock waves as a promising method to deliver botulinum toxin A without the need for injection. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Reducing aluminum: an occupation possibly associated with bladder cancer.

PubMed Central

Thériault, G; De Guire, L; Cordier, S

1981-01-01

A case-control study, undertaken to identify reasons for the exceptionally high incidence of bladder cancer among men in the Chicoutimi census division of the province of Quebec, revealed an increased risk associated with employment in the electrolysis department of an aluminum reduction plant. The estimated relative risk was 2.83 (95% confidence interval; 1.06 to 7.54). An interaction was found between such employment and cigarette smoking, resulting in a combined relative risk of 5.70 (95% confidence interval: 2.00 to 12.30). These findings suggest that employment in an aluminum reduction plant accounts for part of the excess of bladder cancer in the region studied. PMID:7214271

Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.

PubMed

Michiels, Stefan; Laplanche, Agnès; Boulet, Thomas; Dessen, Philippe; Guillonneau, Bertrand; Méjean, Arnaud; Desgrandchamps, François; Lathrop, Mark; Sarasin, Alain; Benhamou, Simone

2009-05-01

Several defense mechanisms have been developed and maintained during the evolution to protect human cells against damage produced from exogenous or endogenous sources. We examined the associations between bladder cancer and a panel of 652 polymorphisms from 85 genes involved in maintenance of genetic stability [base excision repair, nucleotide excision repair, double-strand break repair (DSBR) and mismatch repair, as well as DNA synthesis and cell cycle regulation pathways] in 201 incident bladder cancer cases and 326 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model. To account for multiple testing, we associated to each P-value the expected proportion of false discoveries (q-value). Haplotype analysis revealed significant associations (P < 0.01) between bladder cancer and two genes (POLB and FANCA) with an associated q-value of 24%. A permutation test was also used to determine whether, in each pathway analyzed, there are more variants whose allelic frequencies are different between cases and controls as compared with what would be expected by chance. Differences were found for cell cycle regulation (P = 0.02) and to a lesser extent for DSBR (P = 0.05) pathways. These results hint to a few potential candidate genes; however, our study was limited by the small sample size and therefore low statistical power to detect associations. It is anticipated that genome-wide association studies will open new perspectives for interpretation of the results of extensive candidate gene studies such as ours.

Neuromodulation of the neural circuits controlling the lower urinary tract

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Gerasimenko, Yury P.; Taccola, Giuliano; Edgerton, V. Reggie

2017-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. PMID:27381425

Real-time measurement of oxyhemoglobin concentration changes in the frontal micturition area: an fNIRS study.

PubMed

Sakakibara, Ryuji; Tsunoyama, Kuniko; Takahashi, Osamu; Sugiyama, Megumi; Kishi, Masahiko; Ogawa, Emina; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori; Awa, Yusuke; Yamaguchi, Chiharu

2010-06-01

To explore brain activity in the frontal micturition area during natural bladder behavior. Five control subjects (one man and four women; mean age 61 years [38-70]) and four subjects with detrusor overactivity (all men; mean age 55 years [33-65]) were enrolled in the study. We performed real-time measurements of oxyhemoglobin concentration (oxy-Hb) changes in the frontal micturition area using functional near-infrared spectroscopy (fNIRS) in response to quasi-natural, continuous bladder filling, and voiding in a sitting position. In the control group the following results were obtained: (1) a slight increase of oxy-Hb before first sensation occurred, (2) there was a continuous increase of oxy-Hb during bladder filling to the point just after voiding began, (3) there was a continuous decrease of oxy-Hb after voiding, (4) in subjects who were unable to urinate, oxy-Hb also decreased after attempting to void, and (5) the area activated was the bilateral lateral prefrontal area, particularly Brodmann's areas 8, 10, and 46. In the detrusor overactivity group, (6) an increase of oxy-Hb before first sensation was rare and frontal cortical activation was weak, (7) at the moment detrusor overactivity appeared, fNIRS brain activity in the frontal cortex did not change significantly; and otherwise the results were almost the same as those in the control group. This study shows that the frontal micturition area is activated during natural bladder filling and voiding using fNIRS. (c) 2010 Wiley-Liss, Inc.

[The ice water test and bladder cooling reflex. Physiology, pathophysiology and clinical importance].

PubMed

Hüsch, T; Neuerburg, T; Reitz, A; Haferkamp, A

2016-04-01

Urodynamic studies are utilised for identification and follow-up of functional disorders of the lower urinary tract. Provocation tests are used to determine disorders which could not be revealed in standard cystometry. The ice water test is a simple test to identify neurogenic bladder dysfunction and to screen the integrity of the upper motor neuron in neurogenic bladder dysfunction. Development and significance of the ice water test is presented in this review against the background of physiology and pathophysiology of the lower urinary tract. A systematic review of PubMed and ScienceDirect databases was performed in April 2015. No language or time limitation was applied. The following key words and Medical Subject Heading terms were used to identify relevant studies: "ice water test", "bladder cooling reflex", "micturition" and "neuronal control". Review articles and bibliographies of other relevant studies identified were hand searched to find additional studies. The ice water test is performed by rapid instillation of 4-8 °C cold fluid into the urinary bladder. Hereby, afferent C fibers are activated by cold receptors in the bladder leading to the bladder cooling reflex. It is a spinal reflex which causes an involuntarily contraction of the urinary bladder. The test is normally positive in young infants during the first 4 years of life and become negative with maturation of the central nervous system afterwards by inhibition of the reflex. The damage of the upper motor neuron causes the recurrence of the reflex in the adulthood and indicates spinal and cerebral lesions. The ice water test is utilised to identify lesions of the upper motor neuron. However, in the case of detrusor acontractility the test will always be negative and can not be utilized to distinguish between neurogenic or muscular causes. Furthermore, the test is also positive in a small percentage of cases of non-neurogenic diseases, e.g. in prostate-related bladder outlet obstruction or idiopathic overactive bladder. Although no clear explanation exists, a positive ice water test could be the first sign of an otherwise asymptomatic neurological disease. Due to the simple procedure, the ice water test is a reliable possibility to identify neurologic bladder hyperactivity subsequent to standard cystometry.

Contouring and Constraining Bowel on a Full-Bladder Computed Tomography Scan May Not Reflect Treatment Bowel Position and Dose Certainty in Gynecologic External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yaparpalvi, Ravindra, E-mail: ryaparpa@montefiore.org; Mehta, Keyur J.; Bernstein, Michael B.

Purpose: To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials: Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined.more » Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results: Average (±SD) planned bladder volume was 299.7 ± 68.5 cm{sup 3}. Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm{sup 3} (range, 74.3-251.4 cm{sup 3}). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm{sup 3}; P=.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions: Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV{sub B}owel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient.« less

Transcutaneous electrical nerve stimulation (TENS) improves the diabetic cytopathy (DCP) via up-regulation of CGRP and cAMP.

PubMed

Ding, Liucheng; Song, Tao; Yi, Chaoran; Huang, Yi; Yu, Wen; Ling, Lin; Dai, Yutian; Wei, Zhongqing

2013-01-01

The objective of this study was to investigate the effects and mechanism of Transcutaneous Electrical Nerve Stimulation (TENS) on the diabetic cytopathy (DCP) in the diabetic bladder. A total of 45 rats were randomly divided into diabetes mellitus (DM)/TENS group (n=15), DM group (n=15) and control group (n=15). The rats in the DM/TENS and TENS groups were electronically stimulated (stimulating parameters: intensity-31 V, frequency-31 Hz, and duration of stimulation of 15 min) for three weeks. Bladder histology, urodynamics and contractile responses to field stimulation and carbachol were determined. The expression of calcitonin gene-related peptide (CGRP) was analyzed by RT-PCR and Western blotting. The results showed that contractile responses of the DM rats were ameliorated after 3 weeks of TENS. Furthermore, TENS significantly increased bladder wet weight, volume threshold for micturition and reduced PVR, V% and cAMP content of the bladder. The mRNA and protein levels of CGRP in dorsal root ganglion (DRG) in the DM/TENS group were higher than those in the DM group. TENS also significantly up-regulated the cAMP content in the bladder body and base compared with diabetic rats. We conclude that TENS can significantly improve the urine contractility and ameliorate the feeling of bladder fullness in DM rats possibly via up-regulation of cAMP and CGRP in DRG.

Personal use of hair dyes and the risk of bladder cancer: results of a meta-analysis.

PubMed Central

Huncharek, Michael; Kupelnick, Bruce

2005-01-01

OBJECTIVE: This study examined the methodology of observational studies that explored an association between personal use of hair dye products and the risk of bladder cancer. METHODS: Data were pooled from epidemiological studies using a general variance-based meta-analytic method that employed confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of bladder cancer development associated with use of hair dye products vs. non-use. Sensitivity analyses were performed to explain any observed statistical heterogeneity and to explore the influence of specific study characteristics of the summary estimate of effect. RESULTS: Initially combining homogenous data from six case-control and one cohort study yielded a non-significant RR of 1.01 (0.92, 1.11), suggesting no association between hair dye use and bladder cancer development. Sensitivity analyses examining the influence of hair dye type, color, and study design on this suspected association showed that uncontrolled confounding and design limitations contributed to a spurious non-significant summary RR. The sensitivity analyses yielded statistically significant RRs ranging from 1.22 (1.11, 1.51) to 1.50 (1.30, 1.98), indicating that personal use of hair dye products increases bladder cancer risk by 22% to 50% vs. non-use. CONCLUSION: The available epidemiological data suggest an association between personal use of hair dye products and increased risk of bladder cancer. PMID:15736329

Impaired swim bladder inflation in early-life stage fathead ...

EPA Pesticide Factsheets

The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). In the first study, fathead minnow (Pimephales promelas) embryos were exposed to 0.6, 1.9, or 6.0 mg IOP/L or control water in a flow-through system until reaching 6 days post-fertilization (dpf) at which time posterior swim bladder inflation was assessed. To examine effects on anterior swim bladder inflation, a second study was conducted with 6 dpf larvae exposed to the same IOP concentrations until reaching 21 dpf. Fish from both studies were sampled for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, incidence and length of inflated posterior swim bladders were significantly reduced in the 6.0 mg/L treatment at 6 dpf. Incidence of inflation and length of anterior swim bladder in larval fish were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole body T4 concentrations were significantly increased and T3 concentrations were significantly decreased in all IOP treatments. Consistent with hypothesized compensatory responses, sig

Ultrasonographic evaluation of abdominal distension in 52 camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-08-01

The purpose of this study was to assess the diagnostic value of ultrasonography in the evaluation of abdominal distension in 52 camels (Camelus dromedarius). The conditions included trypanosomiasis (n=35), intestinal obstruction (n=12) and ruptured urinary bladder (n=5). Fifteen clinically normal camels were included as controls. Transabdominal and transrectal ultrasonography was carried out on all camels. In animals with trypanosomiasis, ultrasonographic findings included accumulation of massive amounts of hypoechoic abdominal fluids where liver, intestine, kidney, spleen and urinary bladder were imaged floating. Except in two cases of bile duct calcification and one of hepatic abscessation, no detectable abnormal sonographic lesions were detected while imaging the hepatic and renal parenchyma, and the heart and its valves and major blood vessels. In camels with intestinal obstruction, ultrasonographic findings included distended intestinal loops with markedly reduced or absent motility. In one camel, the intestinal lumen contained localised hyperechoic material that was consistent with a foreign body. Hypoechoic fluid with or without fibrin was seen between intestinal loops. In camels with ruptured urinary bladder, ultrasonographic findings included collapsed and perforated bladder, echogenic blood clots within the urinary bladder and peritoneal cavity, increased thickness of the bladder wall, floating intestines in hypoechogenic fluid and echogenic calculi within the urethra. Ultrasonography was considered a useful tool for the evaluation of dromedary camels with abdominal distension. Copyright © 2011 Elsevier Ltd. All rights reserved.

Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

PubMed

de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

2007-10-01

The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse.

PubMed

Becknell, Brian; Mohamed, Ahmad Z; Li, Birong; Wilhide, Michael E; Ingraham, Susan E

2015-01-01

Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI. Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice. Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys. CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice.

Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse

PubMed Central

Becknell, Brian; Mohamed, Ahmad Z.; Li, Birong; Wilhide, Michael E.; Ingraham, Susan E.

2015-01-01

Purpose Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI. Methods Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice. Results Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys. Conclusions CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice. PMID:26401845

Hem-o-lok clip: a neglected cause of severe bladder neck contracture and consequent urinary incontinence after robot-assisted laparoscopic radical prostatectomy.

PubMed

Cormio, Luigi; Massenio, Paolo; Lucarelli, Giuseppe; Di Fino, Giuseppe; Selvaggio, Oscar; Micali, Salvatore; Carrieri, Giuseppe

2014-02-20

Hem-o-lok clips are widely used during robot-assisted and laparoscopic radical prostatectomy to control the lateral pedicles. There are a few reports of hem-o-lok clip migration into the bladder or vesico-urethral anastomosis and only four cases of hem-o-lok clip migration resulting into bladder neck contracture. Herein, we describe the first case, to our knowledge, of hem-o-lok clip migration leading to severe bladder neck contracture and subsequent stress urinary incontinence. A 62-year-old Caucasian man underwent robot-assisted laparoscopic radical prostatectomy for a T1c Gleason 8 prostate cancer. One month after surgery the patient was fully continent; however, three months later, he presented with acute urinary retention requiring suprapubic drainage. Urethroscopy showed a hem-o-lok clip strongly attached to the area between the vesico-urethral anastomosis and the urethral sphincter and a severe bladder neck contracture behind it. Following cold-knife urethral incision and clip removal, the bladder neck contracture was widely resected. At 3-month follow-up, the patient voided spontaneously with a peak flow rate of 9.5 ml/sec and absence of post-void residual urine, but leaked 240 ml urine at the 24-hour pad test. To date, at 1-year follow-up, his voiding situation remains unchanged. The present report provides further evidence for the risk of hem-o-lok clip migration causing bladder neck contracture, and is the first to demonstrate the potential of such complication to result into stress urinary incontinence.

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

PubMed

Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

2011-01-01

Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

Serum Paraoxonase-1 Concentration as a Potential Predictor of Urinary Bladder Cancer Recurrence. A Five Year Follow-Up Study.

PubMed

Iftimie, Simona; García-Heredia, Anabel; Pujol-Bosch, Francesc; Pont-Salvadó, Antoni; López-Azcona, Ana Felisa; Hernández-Aguilera, Anna; Cabré, Noemí; Luciano-Mateo, Fedra; Fort-Gallifa, Isabel; Castro, Antoni; Camps, Jordi; Joven, Jorge

2018-04-23

This study provides preliminary information on the usefulness of measuring serum paraoxonase-1 (PON1) concentration and activity (and other inflammatory markers) to predict tumor recurrence in patients with urinary bladder cancer. We studied a total of 39 hospitalized patients in whom the diagnosis of urinary bladder cancer was confirmed by transurethral resection. After five years of follow-up, 29 patients presented with tumor recurrence. As control subjects, we also studied 61 healthy subjects and a further 132 hospitalized patients who had a urinary catheter-related infection due to causes other than cancer. Results showed that urinary bladder patients had lower serum PON1 concentration and activity, and higher chemokine (C-C motif) ligand 2, C-reactive protein, and procalcitonin concentrations than the control individuals. Patients with tumor recurrence had significantly lower serum PON1 concentration than patients without tumor recurrence. The mean area under the curve of the receiver operating characteristics plot for serum PON1 concentration in discriminating patients with and those without tumor recurrence was 0.755 and the best combination of sensitivity and specificity was obtained at PON1 = 100 mg/L (0.72 and 0.80, respectively). Establishing this value as a cut-off, positive predictive value was = 0.91, and negative predictive value was = 0.50. These results suggest that the measurement of serum PON1 concentration may be a high-sensitivity marker of tumor recurrence in urinary bladder cancer patients. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

Bladder cancer biomarker discovery using global metabolomic profiling of urine.

PubMed

Wittmann, Bryan M; Stirdivant, Steven M; Mitchell, Matthew W; Wulff, Jacob E; McDunn, Jonathan E; Li, Zhen; Dennis-Barrie, Aphrihl; Neri, Bruce P; Milburn, Michael V; Lotan, Yair; Wolfert, Robert L

2014-01-01

Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence after initial diagnosis and treatment. As a result, recurrent surveillance, primarily involving repeated cystoscopies, is a critical component of post diagnosis patient management. Since cystoscopy is invasive, expensive and a possible deterrent to patient compliance with regular follow-up screening, new non-invasive technologies to aid in the detection of recurrent and/or primary bladder cancer are strongly needed. In this study, mass spectrometry based metabolomics was employed to identify biochemical signatures in human urine that differentiate bladder cancer from non-cancer controls. Over 1000 distinct compounds were measured including 587 named compounds of known chemical identity. Initial biomarker identification was conducted using a 332 subject sample set of retrospective urine samples (cohort 1), which included 66 BCa positive samples. A set of 25 candidate biomarkers was selected based on statistical significance, fold difference and metabolic pathway coverage. The 25 candidate biomarkers were tested against an independent urine sample set (cohort 2) using random forest analysis, with palmitoyl sphingomyelin, lactate, adenosine and succinate providing the strongest predictive power for differentiating cohort 2 cancer from non-cancer urines. Cohort 2 metabolite profiling revealed additional metabolites, including arachidonate, that were higher in cohort 2 cancer vs. non-cancer controls, but were below quantitation limits in the cohort 1 profiling. Metabolites related to lipid metabolism may be especially interesting biomarkers. The results suggest that urine metabolites may provide a much needed non-invasive adjunct diagnostic to cystoscopy for detection of bladder cancer and recurrent disease management.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer.

PubMed

Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R; Guterres, Silvia S; Collares, Tiago; Seixas, Fabiana Kömmling

2017-01-01

Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

PubMed Central

Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R.; Guterres, Silvia S.; Collares, Tiago; Seixas, Fabiana Kömmling

2018-01-01

Mycobacterium bovis bacillus Calmette–Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer. PMID:29379438

Lifetime carcinogenicity study of 1- and 2-naphthylamine in dogs.

PubMed Central

Purchase, I. F.; Kalinowski, A. E.; Ishmael, J.; Wilson, J.; Gore, C. W.; Chart, I. S.

1981-01-01

Groups of male and female beagle dogs were given daily doses of 400 mg of various mixtures of naphthylamines for up to 109 months. Survivors were killed at 128 months. A variety of pathological conditions was diagnosed, but the only effect related to treatment was the induction of bladder neoplasms. All dogs which received pure 2-naphthylamine developed transitional-cell carcinomas of the bladder within 34 months. Two of 8 dogs receiving 6% 2-naphthylamine in 1-naphthylamine developed early carcinoma and 2/8 dogs receiving 0.5% 2-naphthylamine in 1-naphthylamine developed haemangioma of the bladder. Some of the dogs receiving 1-naphthylamine (total dose 950 g) and the controls had focal cystitis or hyperplasia, but no neoplasia of the bladder. These results confirm the carcinogenicity of 2-naphthylamine to dogs. No carcinogenic effect of 1-naphthylamine was observed, indicating that it is at least 200 times less potent as a carcinogen than 2-naphthylamine. The incidence of bladder cancer in dogs fed mixtures of both naphthylamines explains why previous experimental and epidemiological studies of impure 1-naphthylamine have revealed carcinogenicity. Images Fig. 1 Fig. 2 PMID:7326199

Effect of spinal anaesthesia on the lower urinary tract in continent women.

PubMed

Haeusler, G; Sam, C; Chiari, A; Tempfer, C; Hanzal, E; Koelbl, H

1998-01-01

To evaluate the effect of spinal anaesthesia on the bladder neck position and the urethral closure function in the resting state and during clinical stress test in healthy, continent women. Controlled clinical trial. Department of Gynaecology and Obstetrics, Vienna University Medical School. Fourteen continent women, of which seven were nulliparous and seven parous, underwent minor gynaecological procedures under spinal anaesthesia. Urodynamics and ultrasound investigations were performed before and during spinal anaesthesia. Changes in the bladder neck position and the urethral closure function before and during spinal anaesthesia. Bladder neck position was found to be lower and more posterior during spinal anaesthesia as compared with pre-operative assessment. The posterior urethrovesical angle increased significantly both at rest and during maximum straining. We observed a significant increase in bladder compliance, and all parameters of the urethral pressure profile decreased significantly. While none of the nulliparous women had a positive clinical stress test during spinal anaesthesia, 4/7 parous women demonstrated leakage (Fisher's exact test, P = 0.003). Blockage of nerve supply to the pelvic floor muscles in continent women is associated with a significant loss of support of the bladder neck region confirming the theory of an active mechanism of muscular elements providing continence.

Leech in urinary bladder causing hematuria.

PubMed

Alam, Shadrul; Das Choudhary, Mrigen Kumar; Islam, Kabirul

2008-02-01

To estimate efficacy of normal saline in the management of hematuria caused by accidental entry of a leech per urethra into the urinary bladder. An intervention study was carried out in the Department of Pediatric Surgery of Sylhet MAG Osmani Medical College between January 1998 and December 2003. A total of 43 boys (mean age 8 years, SD+/-2.6) were enrolled. In all cases, a leech had entered the urinary bladder through the urethra causing hematuria. All patients were equipped with a self-retaining Foley catheter. They were managed by infusing 50ml of normal saline into the urinary bladder through the catheter that was then clamped for 3h. After removing the catheter, in all cases the whole leech was spontaneously expelled intact, dead or alive, within 2-24h during the subsequent act of micturition. Hematuria gradually diminished to a clear flow within the next 6h in 27 cases, 12h in 14 cases and 24h in two cases. All patients were followed up for 2 weeks, and none developed recurrent hematuria. Catheterization and irrigation of the urinary bladder with normal saline is a relatively simple, safe and inexpensive method of removing the leech and controlling hematuria.

Chemotherapeutic potential of quercetin on human bladder cancer cells.

PubMed

Oršolić, Nada; Karač, Ivo; Sirovina, Damir; Kukolj, Marina; Kunštić, Martina; Gajski, Goran; Garaj-Vrhovac, Vera; Štajcar, Damir

2016-07-28

In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection.

CT Urography: Segmentation of Urinary Bladder using CLASS with Local Contour Refinement

PubMed Central

Cha, Kenny; Hadjiiski, Lubomir; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Zhou, Chuan

2016-01-01

Purpose We are developing a computerized system for bladder segmentation on CT urography (CTU), as a critical component for computer-aided detection of bladder cancer. Methods The presence of regions filled with intravenous contrast and without contrast presents a challenge for bladder segmentation. Previously, we proposed a Conjoint Level set Analysis and Segmentation System (CLASS). In case the bladder is partially filled with contrast, CLASS segments the non-contrast (NC) region and the contrast-filled (C) region separately and automatically conjoins the NC and C region contours; however, inaccuracies in the NC and C region contours may cause the conjoint contour to exclude portions of the bladder. To alleviate this problem, we implemented a local contour refinement (LCR) method that exploits model-guided refinement (MGR) and energy-driven wavefront propagation (EDWP). MGR propagates the C region contours if the level set propagation in the C region stops prematurely due to substantial non-uniformity of the contrast. EDWP with regularized energies further propagates the conjoint contours to the correct bladder boundary. EDWP uses changes in energies, smoothness criteria of the contour, and previous slice contour to determine when to stop the propagation, following decision rules derived from training. A data set of 173 cases was collected for this study: 81 cases in the training set (42 lesions, 21 wall thickenings, 18 normal bladders) and 92 cases in the test set (43 lesions, 36 wall thickenings, 13 normal bladders). For all cases, 3D hand segmented contours were obtained as reference standard and used for the evaluation of the computerized segmentation accuracy. Results For CLASS with LCR, the average volume intersection ratio, average volume error, absolute average volume error, average minimum distance and Jaccard index were 84.2±11.4%, 8.2±17.4%, 13.0±14.1%, 3.5±1.9 mm, 78.8±11.6%, respectively, for the training set and 78.0±14.7%, 16.4±16.9%, 18.2±15.0%, 3.8±2.3 mm, 73.8±13.4% respectively, for the test set. With CLASS only, the corresponding values were 75.1±13.2%, 18.7±19.5%, 22.5±14.9%, 4.3±2.2 mm, 71.0±12.6%, respectively, for the training set and 67.3±14.3%, 29.3±15.9%, 29.4±15.6%, 4.9±2.6 mm, 65.0±13.3%, respectively, for the test set. The differences between the two methods for all five measures were statistically significant (p<0.001) for both the training and test sets. Conclusions The results demonstrate the potential of CLASS with LCR for segmentation of the bladder. PMID:24801066

Quality of Life in Non-Muscle-Invasive Bladder Cancer Survivors: A Systematic Review.

PubMed

Jung, Ahrang; Nielsen, Matthew E; Crandell, Jamie L; Palmer, Mary H; Bryant, Ashley Leak; Smith, Sophia K; Mayer, Deborah K

2018-06-01

Non-muscle-invasive bladder cancer (NMIBC) represents approximately 75% of newly diagnosed patients with bladder cancer. Non-muscle-invasive bladder cancer survivors have unique chronic burdens including frequent recurrences, repeated surveillance cystoscopies and treatments, and the highest lifetime medical cost per person among all cancers. The purpose of this study was to summarize studies assessing quality of life (QOL) in NMIBC survivors. The literature from January 2005 to March 2017 found in PubMed, CINAHL, and PsycINFO databases was reviewed systematically. Inclusion criteria were as follows: (1) research about NMIBC survivors, (2) outcomes included QOL, (3) original research article published in peer-reviewed journals, and (4) published in English. A total of 15 studies were included: 14 quantitative studies and 1 mixed-methods study. Non-muscle-invasive bladder cancer survivors had significantly lower QOL compared with the general population, especially in fatigue, physical and role functioning, and mental health. Repeated transurethral resections and intravesical treatments were associated with impaired physical function and mental health. Most NMIBC survivors had concerns of urinary and bowel problems and sexual function. Despite a good prognosis, NMIBC and its treatment have a significant impact on QOL in survivors. The findings showed large burdens in NMIBC survivors and suggest that further research is needed to better understand potential opportunities to improve QOL in this population. Oncology nurses are in the critical position for assessing symptoms and concerns. Oncology nurses should pay special attention to NMIBC survivors who have unique symptoms and burden with the aim of improving survivors' QOL.

COMPARISON OF BASELINE UROLOGIC SYMPTOMS IN MEN AND WOMEN IN THE MULTIDISCIPLINARY APPROACH TO THE STUDY OF CHRONIC PELVIC PAIN (MAPP) RESEARCH COHORT

PubMed Central

Clemens, J. Quentin; Clauw, Daniel J.; Kreder, Karl; Krieger, John N.; Kusek, John W.; Lai, H. Henry; Rodriguez, Larissa; Williams, David A.; Hou, Xiaoling; Stephens, Alisa; Landis, J Richard

2015-01-01

INTRODUCTION The clinical features of interstitial cystitis/ bladder pain syndrome (IC/BPS) are similar to those of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have directly compared the characteristics of these syndromes in men and women. METHODS The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network recruited 191 men and 233 women with IC/BPS or CP/CPPS. Baseline data included demographics, the Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), the Genitourinary Pain Index (GUPI), the American Urological Association Symptom Index (AUASI), Likert scales to assess urinary urgency, frequency, pain and overall symptom severity, and a single question about the most bothersome pelvic symptom. RESULTS After adjustment for age, income and symptom duration, measures of pain severity were similar across genders. Mean scores for the ICSI, ICPI and AUASI were significantly higher in women than men, reflecting more bladder-focused symptoms in women. The most bothersome single symptom in both men and women was pain in the pubic/bladder area (34% of men, 58% of women). The characteristics of the men and women in the MAPP cohort were similar to those reported in other research cohorts of IC/BPS and CP/CPPS. CONCLUSIONS Our findings indicate that pain severity is similar in both sexes, and that bladder-focused symptoms (urgency, suprapubic pain, frequency) are more common in women. However, a substantial proportion of men also report these types of bladder symptoms. PMID:25463989

Development and Validation of the Actionable Bladder Symptom Screening Tool for Multiple Sclerosis Patients

PubMed Central

Chancellor, Michael; Bates, David; Denys, Pierre; MacDiarmid, Scott; Nitti, Victor; Globe, Denise; Signori, Manuel; Hudgens, Stacie; Odderson, Ib; Panicker, Jalesh; Ross, Amy Perrin

2013-01-01

Bladder symptoms such as urinary urgency, frequency, and incontinence are common in people with multiple sclerosis (MS). These symptoms, which often result from neurogenic detrusor overactivity (NDO), can have a major impact on patients' day-to-day lives. However, in many cases they are over-looked in the clinical management of MS. The objective of this study was to develop and validate a reliable, sensitive, and specific screening tool for patients with bladder problems related to MS. We performed a literature review and then conducted a content validation study followed by a multisite observational study of a new screening tool, the Actionable Bladder Symptom Screening Tool (ABSST). All ABSST domains as well as the total score met the threshold for good internal consistency (Cronbach α ≥ 0.70), with a Cronbach α value of 0.95 for the total score and values ranging from 0.85 to 0.90 for the three domains. The validity of the ABSST was demonstrated by high correlation of the domains and total score with the Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity and Total Health-Related Quality of Life (HRQOL) scores (Spearman correlation coefficient ≥ 0.782). The predictive validity of the ABSST total score to identify patients who might receive a recommendation to see a urologist was strong. This new instrument, which was developed with input from clinicians as well as MS patients, meets the current content validity and psychometric testing thresholds established by the US Food and Drug Administration, with high sensitivity and specificity. PMID:24453782

[Is bacteriological testing of bladder urine informative in acute obstructive pyelo- nephritis?

PubMed

Kogan, M I; Naboka, Yu L; Bedzhanyan, S K; Mitusova, E V; Gudima, I A; Morgun, P P; Vasileva, L I

2017-07-01

The problem of the etiology and pathogenesis of acute obstructive pyelonephritis (OOP) remains one of the challenging issues of modern urology. Etiological agents of pyelonephritis can be both gram-negative and gram-positive opportunistic bacteria mostly belonging to the normal flora in humans. The generally accepted diagnostic work-up involves a bacteriological testing of not pelvic urine, but of bladder urine collected by a transurethral catheter or midstream specimens of urine collected from the patients. The aim of our study was to compare the microbiota of bladder and pelvic urine in patients with OOP. The study comprised 72 sequentially selected patients (12 men and 60 women) with OOP associated with ureteral stones. Mean age of patients was 53.7+/-0.5 years. All patients underwent bacteriological examination of the bladder urine collected by a transurethral catheter and pelvic urine obtained after relieving stone-related ureteral obstruction. Urinary diversion was performed using j-j stent and PCN in 64 and 8 patients, respectively. Preoperative prophylactic antibiotics were administered routinely. Bacteriological testing of urine was carried out using an extended set (9-10) of culture media. Empirical antibiotic therapy was initiated only after the restoration of urine outflow from the kidney and continued for 5-6 days until the availability of bacteriological testing results. Levels of bacteriuria with Enterobacteria, gram-positive pathogens and NAB in two urine samples did not differ significantly (p>0.05). There was a wide range of bacteriuria from 101 to 106 CFU/ml of most microorganisms except @Proteus spp., S. aureus. In bladder urine, the rates of bacteriuria of more or equal 104 CFU/ml for E. coli, Klebsiella spp. and Proteus spp. were 90.9%, 72.7% and 100.0%, respectively. For the remaining microorganisms, predominant bacteriuria was less or equal 103 CFU/ml. In pelvic urine, the rates of bacteriuria of more or equal 104 CFU/ml for E. coli, Klebsiella spp. and Proteus spp. was 71.8%, 40.0% and 66.7%, respectively. Other uropathogens in the pelvic urine mainly had a bacterial count of less or equal 103 CFU/ml. Only the concentration of Corynebacterium spp. in the pelvic urine significantly (p=0.023) differed from that of the bladder urine. There were no significant differences between microbiota of bladder and pelvic urine depending on duration of OOP except higher rates of Corynebacterium spp. in the bladder urine.

ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

EPA Science Inventory

ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). Rece...

ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVIE OXYGEN SPECIES

EPA Science Inventory

ARSENIC SPECIES. CAUSE RELEASE OF IRON , FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). R...

Athletes with Disabilities. Removing Medical Barriers.

ERIC Educational Resources Information Center

Peck, David M.; McKeag, Douglas B.

1994-01-01

Disability-related conditions such as bladder problems or pressure sores need not keep people from activity. Although active individuals with disabilities require some specialized management, they mainly need medical care for sports-related cuts, sprains, and strains. Physicians can help remove medical barriers to participation for active…

PubMed Central

Schick, Erik; Tessier, Jocelyne

1991-01-01

Urodynamics has profoundly changed our understanding of the physiopathology of urinary incontinence which is, first and foremost, a functional problem. The urodynamic study is the only diagnostic tool which makes it possible to explore the functioning of the urethra and bladder. As such, it constitutes the cornerstone of our therapeutic strategy. PMID:21229029

Optimization of Neuromodulation for Bladder Control in a Rat Cystitis Model.

PubMed

Su, Xin; Nickles, Angela; Nelson, Dwight E

2016-01-01

In a bladder overactivity model of cystitis induced by intravesical infusion of acetic acid (a.a.), several parameters of spinal nerve stimulation (SNS) were optimized using continuous infusion cystometry. The optimal stimulation was further characterized through measurements of urodynamic function using single-fill cystometry. In anesthetized male rats, a cannula was placed into the bladder dome for saline or 0.3% a.a. infusion and intravesical pressure monitoring. For SNS, two teflon-coated stainless steel electrodes were placed bilaterally under each of the L6 spinal nerves, and current stimulation was controlled independently using two Grass stimulators. Stimulation of 1 Hz or 50 Hz at motor threshold (Tmot ) was ineffective for altering bladder activities, but 10-Hz SNS increased the infused volume (IV) in a stimulation intensity-dependent fashion (P < 0.01, mixed model repeated analysis). Pairwise comparisons of IV differences to each stimulation intensity show that IV during 1 × Tmot stimulation was significantly larger than 0 × Tmot (no stim, P = 0.001), while the IV during 2 × Tmot stimulation was significantly larger than other intensities tested (P < 0.01). The mean IV (±SEM) during 0 × Tmot (no stim), 0.5 × Tmot , 1 × Tmot , and 2 × Tmot were 0.23 ± 0.04 mL, 0.25 ± 0.03 mL, 0.26 ± 0.03 mL, and 0.40 ± 0.04 mL, respectively. In single-fill cystometry, 10-Hz SNS at 1 × Tmot and 2 × Tmot stimulation increased the IV, or voiding duration and threshold pressure. SNS did not produce significant effects on basal pressure and micturition pressure. SNS significantly attenuates hypersensitive micturition reflex; 10 Hz and high-intensity stimulation are mostly effective. Acute peripheral nerve activation increases the functional bladder capacity, which may be via mechanisms on the afferent arm of the bladder micturition reflex. © 2015 International Neuromodulation Society.

Surveillance of nasal and bladder cancer to locate sources of exposure to occupational carcinogens.

PubMed Central

Teschke, K; Morgan, M S; Checkoway, H; Franklin, G; Spinelli, J J; van Belle, G; Weiss, N S

1997-01-01

OBJECTIVE: To locate sources of occupational exposure to nasal and bladder carcinogens for surveillance follow up in British Columbia, Canada. METHODS: Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population based controls (n = 159) matched for sex and age, were interviewed about their jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57 occupational groups with stratified exact methods to control for age, sex, and smoking. RESULTS: Occupational groups at increased risk of nasal cancer included: textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases, OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR 3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not increased in occupations exposed to wood dust, possibly due to low exposures in local wood industries. Strongly increased risks of bladder cancer were found for sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations originally considered at risk, the following had increased risks of bladder cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3); chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR 1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups with increased risks and three or more cases with similar duties were selected for surveillance follow up. For nasal cancer, these included textile workers (five were garment makers) and pulp and paper workers (three performed maintenance tasks likely to entail stainless steel welding). For bladder cancer, these included miners (12 worked underground), machinists (five worked in traditional machining), hairdressers (three had applied hair dyes), and laundry workers (three were drycleaners). PMID:9245952

Combined Chemoradiation Therapy With Twice-Weekly Gemcitabine and Cisplatin for Organ Preservation in Muscle-Invasive Bladder Cancer: Long-Term Results of a Phase 1 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Azria, David, E-mail: david.azria@icm.unicancer.fr; INSERM, U896, IRCM, Montpellier; Riou, Olivier

2014-03-15

Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabinemore » twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.« less

Elevated Bladder Cancer in Northern New England: The Role of Drinking Water and Arsenic

PubMed Central

Waddell, Richard; Beane Freeman, Laura E.; Schwenn, Molly; Colt, Joanne S.; Ayotte, Joseph D.; Ward, Mary H.; Nuckols, John; Schned, Alan; Jackson, Brian; Clerkin, Castine; Rothman, Nathaniel; Moore, Lee E.; Taylor, Anne; Robinson, Gilpin; Hosain, GM Monawar; Armenti, Karla R.; McCoy, Richard; Samanic, Claudine; Hoover, Robert N.; Fraumeni, Joseph F.; Johnson, Alison; Karagas, Margaret R.

2016-01-01

Abstract Background: Bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than the United States overall. We explored reasons for this excess, focusing on arsenic in drinking water from private wells, which are particularly prevalent in the region. Methods: In a population-based case-control study in these three states, 1213 bladder cancer case patients and 1418 control subjects provided information on suspected risk factors. Log transformed arsenic concentrations were estimated by linear regression based on measurements in water samples from current and past homes. All statistical tests were two-sided. Results: Bladder cancer risk increased with increasing water intake ( Ptrend = .003). This trend was statistically significant among participants with a history of private well use ( Ptrend = .01). Among private well users, this trend was apparent if well water was derived exclusively from shallow dug wells (which are vulnerable to contamination from manmade sources, Ptrend = .002) but not if well water was supplied only by deeper drilled wells ( Ptrend = .48). If dug wells were used pre-1960, when arsenical pesticides were widely used in the region, heavier water consumers (>2.2 L/day) had double the risk of light users (<1.1 L/day, Ptrend = .01). Among all participants, cumulative arsenic exposure from all water sources, lagged 40 years, yielded a positive risk gradient ( Ptrend = .004); among the highest-exposed participants (97.5th percentile), risk was twice that of the lowest-exposure quartile (odds ratio = 2.24, 95% confidence interval = 1.29 to 3.89). Conclusions: Our findings support an association between low-to-moderate levels of arsenic in drinking water and bladder cancer risk in New England. In addition, historical consumption of water from private wells, particularly dug wells in an era when arsenical pesticides were widely used, was associated with increased bladder cancer risk and may have contributed to the New England excess. PMID:27140955

Elevated bladder cancer in northern New England: The role of drinking water and arsenic

USGS Publications Warehouse

Baris, Dalsu; Wadell, Richard; Freeman, Laura; Schwenn, Molly; Colt, Joanne; Ayotte, Joseph; Ward, Mary; Nuckols, John; Schned, Alan; Jackson, Brian; Clerkin, Castine; Rothman, Nathanial; Moore, Lee; Taylor, Anne; Robinson, Gilpin; Hosain, Monawar G.; Armenti, Carla; McCoy, Richard; Samanic, Claudine; Hoover, Robert; Fraumeni, Joseph; Johnson, Alison; Karagas, Margaret; Silverman, Debra

2016-01-01

Background: Bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than the United States overall. We explored reasons for this excess, focusing on arsenic in drinking water from private wells, which are particularly prevalent in the region.Methods: In a population-based case-control study in these three states, 1213 bladder cancer case patients and 1418 control subjects provided information on suspected risk factors. Log transformed arsenic concentrations were estimated by linear regression based on measurements in water samples from current and past homes. All statistical tests were two-sided.Results: Bladder cancer risk increased with increasing water intake ( Ptrend = .003). This trend was statistically significant among participants with a history of private well use ( Ptrend = .01). Among private well users, this trend was apparent if well water was derived exclusively from shallow dug wells (which are vulnerable to contamination from manmade sources, Ptrend = .002) but not if well water was supplied only by deeper drilled wells ( Ptrend = .48). If dug wells were used pre-1960, when arsenical pesticides were widely used in the region, heavier water consumers (>2.2 L/day) had double the risk of light users (<1.1 L/day, Ptrend = .01). Among all participants, cumulative arsenic exposure from all water sources, lagged 40 years, yielded a positive risk gradient ( Ptrend = .004); among the highest-exposed participants (97.5th percentile), risk was twice that of the lowest-exposure quartile (odds ratio = 2.24, 95% confidence interval = 1.29 to 3.89).Conclusions: Our findings support an association between low-to-moderate levels of arsenic in drinking water and bladder cancer risk in New England. In addition, historical consumption of water from private wells, particularly dug wells in an era when arsenical pesticides were widely used, was associated with increased bladder cancer risk and may have contributed to the New England excess.

Adenoviral mediated interferon-alpha 2b gene therapy suppresses the pro-angiogenic effect of vascular endothelial growth factor in superficial bladder cancer.

PubMed

Adam, Liana; Black, Peter C; Kassouf, Wassim; Eve, Beryl; McConkey, David; Munsell, Mark F; Benedict, William F; Dinney, Colin P N

2007-05-01

Intravesical adenovirus mediated interferon-alpha gene transfer has a potent therapeutic effect against superficial human bladder carcinoma xenografts growing in the bladder of athymic nude mice. We determined whether the inhibition of angiogenesis might contribute to the antitumor effect. We treated several human urothelial carcinoma cells with adenovirus mediated interferon-alpha 2b and monitored its effects on the production of angiogenic factors using real-time reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemical analysis and a gel shift based transcription factor array. To assess the role of adenovirus mediated interferon 2b in angiogenic activity we used in vitro invasion assays and evaluated the anti-angiogenic effects of adenovirus mediated interferon gene therapy in an orthotopic murine model of human superficial bladder cancer. In adenovirus mediated interferon-alpha infected 253J B-V cells vascular endothelial growth factor was decreased and anti-angiogenic interferon-gamma inducible protein 10 was up-regulated. In contrast, the addition of as much as 100,000 IU recombinant interferon had no apparent effect on vascular endothelial growth factor production. Conditioned medium derived from adenovirus mediated interferon 2b infected 253J B-V cells greatly decreased the invasive potential of human endothelial cells and down-regulated their matrix metalloproteinase 2 expression compared to controls. Furthermore, adenovirus mediated interferon 2b blocked pro-angiogenic nuclear signals, such as the transcription factors activating protein-1 and 2, stimulating protein-1, nuclear factor kappaB and c-myb. In vivo experiments revealed significant vascular endothelial growth factor down-regulation and decreased tumor vessel density in the adenovirus mediated interferon 2b treated group compared to controls. Treatment with adenovirus mediated interferon 2b increases the angiostatic activity of the bladder cancer microenvironment. This inhibition may prove beneficial for treating superficial bladder cancer with adenovirus mediated interferon-alpha and hopefully contribute to a decreased recurrence rate of this neoplasm.

Phenoxybenzamine

MedlinePlus

... of high blood pressure and sweating related to pheochromocytoma.This medication is sometimes prescribed for other uses; ... by your doctor.Phenoxybenzamine controls symptoms related to pheochromocytoma and controls bladder symptoms but does not cure ...

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

PubMed Central

Figueroa, Jonine D.; Middlebrooks, Candace D.; Banday, A. Rouf; Ye, Yuanqing; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Koutros, Stella; Kiemeney, Lambertus A.; Rafnar, Thorunn; Bishop, Timothy; Furberg, Helena; Matullo, Giuseppe; Golka, Klaus; Gago-Dominguez, Manuela; Taylor, Jack A.; Fletcher, Tony; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark P.; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Chung, Charles C.; Vermeulen, Sita H.; Aben, Katja K.; Galesloot, Tessel E.; Thorleifsson, Gudmar; Sulem, Patrick; Stefansson, Kari; Kiltie, Anne E.; Harland, Mark; Teo, Mark; Offit, Kenneth; Vijai, Joseph; Bajorin, Dean; Kopp, Ryan; Fiorito, Giovanni; Guarrera, Simonetta; Sacerdote, Carlotta; Selinski, Silvia; Hengstler, Jan G.; Gerullis, Holger; Ovsiannikov, Daniel; Blaszkewicz, Meinolf; Castelao, Jose Esteban; Calaza, Manuel; Martinez, Maria Elena; Cordeiro, Patricia; Xu, Zongli; Panduri, Vijayalakshmi; Kumar, Rajiv; Gurzau, Eugene; Koppova, Kvetoslava; Bueno-De-Mesquita, H. Bas; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Stern, Marianna C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Jeppson, Rebecca P.; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Turman, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Zhang, Liren; Gong, Yilei; Pu, Xia; Hutchinson, Amy; Burdett, Laurie; Wheeler, William A.; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Monawar Hosain, G. M.; Schwenn, Molly; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Andriole, Gerald; Grubb, Robert; Black, Amanda; Diver, W. Ryan; Gapstur, Susan M.; Weinstein, Stephanie; Virtamo, Jarmo; Haiman, Christopher A.; Landi, Maria Teresa; Caporaso, Neil E.; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Chanock, Stephen J.; Silverman, Debra T.; Prokunina-Olsson, Ludmila; Rothman, Nathaniel

2016-01-01

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer. PMID:26732427

Intake of α-linolenic acid and other fatty acids in relation to the risk of bladder cancer: results from the New Hampshire case-control study.

PubMed

Brinkman, Maree T; Karagas, Margaret R; Zens, Michael S; Schned, Alan R; Reulen, Raoul C; Zeegers, Maurice P

2011-10-01

The role of dietary fat in bladder cancer aetiology is currently unclear due to few studies, equivocal findings and a lack of information on important dietary fatty acids. The aim of the present study was to investigate the association between the intake of major dietary fats and fatty acids and the risk of bladder cancer. A case-control study was conducted in New Hampshire, USA. Dietary data were collected from 322 cases and 239 controls, and OR and 95 % CI were calculated using unconditional logistic regression. Adjustment was made for potential confounders: sex, age, smoking status, pack-years smoked, cholesterol and energy intake. Statistically significant reduced odds of bladder cancer were observed for high intakes (highest quartile v. lowest quartile) of α-linolenic acid (ALA) (OR 0·26, 95 % CI 0·10, 0·65; P for trend = 0·01) and vegetable fat (OR 0·39, 95 % CI 0·18, 0·86; P for trend = 0·03). Borderline statistically significant reduced odds were detected for polyunsaturated fat (OR 0·43, 95 % CI 0·19, 0·98; P for trend = 0·07) and linoleic acid (OR 0·43, 95 % CI 0·19, 0·96; P for trend = 0·06). These fats and fatty acids were highly correlated and following adjustment for each other, the only potential inverse association to remain was for ALA. The present findings suggest that ALA may have a protective role against developing bladder cancer; however, further investigation and replication in other epidemiological studies are required. Future research should focus on the type, source and quantities of different dietary fatty acids consumed.

LncRNA AWPPH inhibits SMAD4 via EZH2 to regulate bladder cancer progression.

PubMed

Zhu, Feng; Zhang, Xinjun; Yu, Qinnan; Han, Guangye; Diao, Fengxia; Wu, Chunlei; Zhang, Yan

2018-06-01

This study aimed to investigate the effect and underlying mechanism of lncRNA AWPPH in bladder cancer (BC). A total of 20 Ta-T1 stage BC tissues, 20 T2-T4 stage BC tissues, and 20 normal bladder tissues, as well as human bladder epithelial cell line SV-HUC-1, human BC cell lines RT4, and T24 were obtained to detect the levels of AWPPH, enhancer of zeste homolog 2 (EZH2) and SMAD4 using RT-qPCR or Western blotting. RT4 cells were transfected with pc-AWPPH, pc-EZH2, or pc-control and T24 cells were transfected with si-AWPPH, si-EZH2, si-control, or pc-AWPPH + pc-SMAD4, respectively. Then, cell proliferation, apoptosis, autophagy, and migration, were detected using MTT assay, colony formation assay, Annexin V-FITC/PI method, Western blotting, and Transwell analysis, respectively. The relationship of AWPPH and EZH2 or SMAD4 was evaluated by RNA immunoprecipitation (RIP) assay or Chromatin immunoprecipitation (ChIP) assay. Compared with normal bladder tissues or cells, the levels of AWPPH and EZH2 were overexpressed, while SMAD4 was down-regulated in BC tissues or cells (all P < 0.01). Cell viability, colony number, and migration were significantly increased, while cell apoptosis ratio was reduced in cells with pc-AWPPH compared with cells with pc-control (all P < 0.05), meanwhile, these effects were reversed by the treatment of pc-SMAD4. Then, RIP assay revealed that AWPPH could bind to EZH2 and ChIP assay showed SMAD4 was regulated by EZH2. LncRNA AWPPH can promote cell proliferation, autophagy, and migration, as well as inhibit cell apoptosis in BC by inhibiting SMAD4 via EZH2. © 2017 Wiley Periodicals, Inc.

Exploring relationships of catheter-associated urinary tract infection and blockage in people with long-term indwelling urinary catheters.

PubMed

Wilde, Mary H; McMahon, James M; Crean, Hugh F; Brasch, Judith

2017-09-01

To describe and explore relationships among catheter problems in long-term indwelling urinary catheter users, including excess healthcare use for treating catheter problems. Long-term urinary catheter users experience repeated problems with catheter-related urinary tract infection and blockage of the device, yet little has been reported of the patterns and relationships among relevant catheter variables. Secondary data analysis was conducted from a sample in a randomised clinical trial, using data from the entire sample of 202 persons over 12 months' participation. Descriptive statistics were used to characterise the sample over time. Zero-inflated negative binomial models were employed for logistic regressions to evaluate predictor variables of the presence/absence and frequencies of catheter-related urinary tract infection and blockage. Catheter-related urinary tract infection was marginally associated with catheter blockage. Problems reported at least once per person in the 12 months were as follows: catheter-related urinary tract infection 57%, blockage 34%, accidental dislodgment 28%, sediment 87%, leakage (bypassing) 67%, bladder spasms 59%, kinks/twists 42% and catheter pain 49%. Regression analysis demonstrated that bladder spasms were significantly related to catheter-related urinary tract infection and sediment amount, and catheter leakages were marginally significantly and positively related to catheter-related urinary tract infection. Frequencies of higher levels of sediment and catheter leakage were significantly associated with higher levels of blockage, and being female was associated with fewer blockages. Persons who need help with eating (more disabled) were also more likely to have blockages. Catheter-related urinary tract infection and blockage appear to be related and both are associated with additional healthcare expenditures. More research is needed to better understand how to prevent adverse catheter outcomes and patterns of problems in subgroups. Nurses can develop care management strategies to identify catheter blockage prior to its occurrence by tracking the amount of sediment and frequency of leakage. Bladder spasms could be an early warning of catheter-related urinary tract infection. © 2016 John Wiley & Sons Ltd.

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

ClinicalTrials.gov

2017-06-23

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

Activation of P2Y6 Receptors Facilitates Nonneuronal Adenosine Triphosphate and Acetylcholine Release from Urothelium with the Lamina Propria of Men with Bladder Outlet Obstruction.

PubMed

Silva, Isabel; Ferreirinha, Fátima; Magalhães-Cardoso, Maria Teresa; Silva-Ramos, Miguel; Correia-de-Sá, Paulo

2015-10-01

Deregulation of purinergic bladder signaling may contribute to persistent detrusor overactivity in patients with bladder outlet obstruction. Activation of uridine diphosphate sensitive P2Y6 receptors increases voiding frequency in rats indirectly by releasing adenosine triphosphate from the urothelium. To our knowledge this mechanism has never been tested in the human bladder. We examined the role of the uridine diphosphate sensitive P2Y6 receptor on tetrodotoxin insensitive nonneuronal adenosine triphosphate and [(3)H]acetylcholine release from the human urothelium with the lamina propria of control organ donors and patients with benign prostatic hyperplasia. The adenosine triphosphate-to-[(3)H]acetylcholine ratio was fivefold higher in mucosal urothelium/lamina propria strips from benign prostatic hyperplasia patients than control men. The selective P2Y6 receptor agonist PSB0474 (100 nM) augmented by a similar amount adenosine triphosphate and [(3)H]acetylcholine release from mucosal urothelium/lamina propria strips from both groups of individuals. The facilitatory effect of PSB0474 was prevented by MRS2578 (50 nM) and by carbenoxolone (10 μM), which block P2Y6 receptor and pannexin-1 hemichannels, respectively. Blockade of P2X3 (and/or P2X2/3) receptors with A317491 (100 nM) also attenuated release facilitation by PSB0474 in control men but not in patients with benign prostatic hyperplasia. Immunolocalization studies showed that P2Y6, P2X2 and P2X3 receptors were present in choline acetyltransferase positive urothelial cells. In contrast to P2Y6 staining, choline acetyltransferase, P2X2 and P2X3 immunoreactivity decreased in the urothelium of benign prostatic hyperplasia patients. Activation of P2Y6 receptor amplifies mucosal adenosine triphosphate release underlying bladder overactivity in patients with benign prostatic hyperplasia. Therefore, we propose selective P2Y6 receptor blockade as a novel therapeutic strategy to control persistent storage symptoms in obstructed patients. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Epidemiologic survey of bladder cancer in greater New Orleans.

PubMed

Sullivan, J W

1982-08-01

Primary ancestry of the patients and controls in this study was not statistically different but the Jewish population had a significantly increased incidence of bladder cancer. Over-all, a significantly greater number of patients smoked filtered cigarettes, began drinking artificially sweetened beverages at an earlier age, drank artificially sweetened beverages for a greater number of years, consumed a greater number of glasses of artificially sweetened beverages weekly and related a history of urinary tract infections. A significantly increased incidence of bladder cancer was noted in individuals employed by certain types of companies, by certain job titles and by certain job material handled. Analysis of the data failed to show any significant difference in years of consumption of coffee, amount of various types of coffee or tea consumed, consumption of various nonalcoholic and alcoholic beverages, including source of drinking water, use of hair dye, incidence of diabetes mellitus, family history of urinary cancer and a history of pelvic irradiation or bladder stones.

Morphological modification of female bladder after prolonged use of soy-based diets.

PubMed

da Silva Faria, Tatiane; Soares, Lavínia Leal; Medeiros, Jorge L; Boaventura, Gilson T; Sampaio, Francisco J B; da Fonte Ramos, Cristiane

2009-01-20

The aim of this study was to compare the effects of a prolonged use of organic and transgenic soy upon the lipid profile and the collagen/muscle ratio of the detrusor muscle of the bladder. Wistar rats were fed three different diets from weaning until sacrifice (15 months old): control group (CG) casein-based diet; organic soy group (OSG) organic soy-based diet; genetically modified soy group (GMSG) transgenic soy-based diet. There was no difference in the food consumption or in the diet isoflavone components among the groups. Comparing to CG, both OSG and GMSG groups presented a significant (p<0.05) reduction in the body weight, triglycerides, cholesterol and the smooth muscle of the detrusor and a significant (p<0.05) increase of collagen fibers number of the detrusor muscle. These findings call into question that, the prolonged use of soy-based diets can be deleterious to the bladder by altering the collagen/muscle ratio what can cause bladder dysfunctions similar with that occurring during menopause.

Rehabilitation R&D Progress Reports 1995, Volume 33, June 1996

DTIC Science & Technology

1996-06-01

Stimulation 72 Rehabilitation of the Colon after Spinal Cord Injury: A Pilot Study 73 Electrical Control of Bladder and Bowel following Spinal Cord Injury...A. General 130 Design of New Toilet Prototypes for Elderly and Disabled Veterans 131 Design of a New Bowel Care/Shower Chair for SCI Veterans...and Rehabilitation 292 Functional Restoration of Grasp: A Pilot Study 293 High-Frequency Magnetic Stimulation of the Bladder and Bowel 294 Treatment

Robotic Y-V Plasty for Recalcitrant Bladder Neck Contracture.

PubMed

Granieri, Michael A; Weinberg, Aaron C; Sun, Jeffrey Y; Stifleman, Michael; Zhao, Lee

2018-07-01

To demonstrate the technique and the outcomes of robot assisted Y-V plasty bladder neck reconstruction (RYVBNR). We present our technique for treatment of recalcitrant bladder neck contracture (BNC) in 7 patients who underwent RYVBNR at our institution between March 2016 and September 2017. Indication for the procedure was incomplete emptying, recurrent urinary tract infections, and dysuria. On follow-up, patients were assessed for clinical success by absence of infections, symptoms, and cystoscopic evaluation. Robotic assisted dissection is performed to open the space of Retzius and mobilize the bladder. The cystoscope is passed to the level of the BNC, and Firefly technology is used to localize the BNC. The BNC is incised anteriorly, and a V-shaped bladder flap is advanced into the BNC in a Y-V plasty fashion. We place a perioperative closed suction drain, which is removed before discharge, and a 22 Fr catheter, which that will be removed in the office at approximately 2 weeks. Six men developed recalcitrant BNCs and 1 developed a recalcitrant vesicourethral anastomotic stenosis. All patients had previously undergone an endoscopic procedure. Median time for last attempt at endoscopic management to robot-assisted bladder neck repair was 4.7 months. The average number of prior attempts at endoscopic management was 2. All patients underwent RYVBNR without conversion to open surgery. The median operative time was 240 minutes, estimated blood loss was 67 mL, and length of stay was 1 day. There were no intraoperative complications. Catheters were removed in the office at a median time of 15 days. At a median follow-up of 8 months, all cases were successful with no evidence of recurrence. Only 2 patients had persistent urinary incontinence at 1 pad per day. RYVBNR with a Y-V plasty is a feasible and effective technique for managing a difficult reconstructive problem. Copyright © 2018 Elsevier Inc. All rights reserved.

Time course and host responses to Escherichia coli urinary tract infection in genetically distinct mouse strains.

PubMed

Hopkins, W J; Gendron-Fitzpatrick, A; Balish, E; Uehling, D T

1998-06-01

Recurrent urinary tract infections (UTIs) are a significant clinical problem for many women; however, host susceptibility factors have not been completely defined. The mouse model of induced UTI provides an experimental environment in which to identify specific host characteristics that are important in initial bacterial colonization of the urinary tract and in resolution of an infection. This study examined initial susceptibility, bacterial clearance, and host defense mechanisms during induction and resolution of Escherichia coli UTIs in genetically distinct strains of mice. Of the ten inbred strains tested, six (BALB/c, C3H/HeN, C57BL/6, DBA.1, DBA.2, and AKR) showed progressive resolution of bladder infections over a 14-day period. A constant, low-level bladder infection was observed in SWR and SJL mice. High bladder infection levels persisted over the 14-day study period in C3H/HeJ and C3H/OuJ mice. Kidney infection levels generally correlated with bladder infection levels, especially in C3H/HeJ and C3H/OuJ mice, the two most susceptible strains, in which infections became more severe with time after challenge. The degree of inflammation in bladder and kidneys, as well as antibody-forming cell responses, positively correlated with infection intensity in all strains except C3H/HeJ, which had minimal inflammation despite high infection levels. These results demonstrate two important aspects of host defense against UTI. First, the innate immune response to an infection in the bladder or kidneys consists primarily of local inflammation, which is followed by an adaptive response characterized in part by an antibody response to the infecting bacteria. Second, a UTI will be spontaneously resolved in most cases; however, in mice with specific genetic backgrounds, a UTI can persist for an extended length of time. The latter result strongly suggests that the presence or absence of specific host genes will determine how effectively an E. coli UTI will be resolved.

MEMS fluidic actuator

DOEpatents

Kholwadwala, Deepesh K [Albuquerque, NM; Johnston, Gabriel A [Trophy Club, TX; Rohrer, Brandon R [Albuquerque, NM; Galambos, Paul C [Albuquerque, NM; Okandan, Murat [Albuquerque, NM

2007-07-24

The present invention comprises a novel, lightweight, massively parallel device comprising microelectromechanical (MEMS) fluidic actuators, to reconfigure the profile, of a surface. Each microfluidic actuator comprises an independent bladder that can act as both a sensor and an actuator. A MEMS sensor, and a MEMS valve within each microfluidic actuator, operate cooperatively to monitor the fluid within each bladder, and regulate the flow of the fluid entering and exiting each bladder. When adjacently spaced in a array, microfluidic actuators can create arbitrary surface profiles in response to a change in the operating environment of the surface. In an embodiment of the invention, the profile of an airfoil is controlled by independent extension and contraction of a plurality of actuators, that operate to displace a compliant cover.

Medical Concerns among Wheelchair Road Racers.

ERIC Educational Resources Information Center

Martinez, Santos F.

1989-01-01

Results of a questionnaire administered to 43 wheelchair road racers suggest that their medical problems may lead to complications while training or racing. The study looked at the effects of training, injuries, bladder management, medications, and spasms. Sports medicine professionals are provided with information on handling disabled athletes.…

Case-control study of urinary bladder cancer in metropolitan Nagoya.

PubMed

Ohno, Y; Aoki, K; Obata, K; Morrison, A S

1985-12-01

We conducted a population-based case-control study of patients with bladder cancer and of controls drawn randomly from the general population of Metropolitan Nagoya and interviewed both groups. The incidence rates of bladder cancer were 2.42 and 7.05/100,000 for females and males, respectively. The analysis, based on 293 patients and 589 controls who were frequency matched for age, sex, and residence, provided the following major findings. Age-adjusted relative risks of 1.89 (1.15-3.10) and 3.53 (1.71-7.27) were found in male and female cigarette smokers, respectively. Significant relative risk was also found in males who drank cocoa. Elevated risk with a dose-response relationship was observed among women who used hair dye and who smoke, but this risk was insignificant, with the disappearance of a dose-response relationship, when it was adjusted for smoking. Age- and smoking-adjusted relative risk of coffee drinking was insignificant with no dose-response relationship. Relative risk of artificial sweetener use was below 1 with adjustment for age and smoking. Intake of alcoholic beverages and cola was insignificantly associated. Reduced risk of significance was suggested for the intake of black tea and matcha (powdered green tea) in females and of fruit juice in males.

Systematic reviews of bladder training and voiding programmes in adults: a synopsis of findings from data analysis and outcomes using metastudy techniques.

PubMed

Roe, Brenda; Ostaszkiewicz, Joan; Milne, Jill; Wallace, Sheila

2007-01-01

This paper reports a comparison of the data analysis and outcomes from four Cochrane systematic reviews on bladder training and voiding programmes for the management of urinary incontinence using metastudy descriptive techniques to inform clinical practice, generate new ideas and identify future research directions. Bladder training is used for cognitively and physically able adults to regain continence by increasing the time interval between voids. Prompted voiding, habit retraining and timed voiding, collectively known as voiding programmes, are generally used for people with cognitive and physical impairments in institutional settings. Bladder training and voiding programmes feature as common clinical practice for the management of urinary incontinence. A synopsis of four Cochrane systematic reviews that included randomized controlled trials on bladder training, prompted voiding, habit retraining and timed voiding was undertaken using metastudy techniques for the synthesis of qualitative research, and has provided a discursive comparison and contrast of the meta-data analysis and outcomes of these reviews. Frequency of incontinence was the most common and constant outcome measure of effectiveness in the reviews. Limited data were available on other health outcomes, change in dependency status, quality of life and cost-effectiveness. The systematic review on bladder training included different types of urinary incontinence, whereas those on voiding programmes did not differentiate the type of incontinence. There is evidence on the effectiveness of bladder training but long-term follow up studies are needed. Evidence on the effectiveness of voiding programmes is limited and not available for many outcomes. Future research needs to consider the theory underpinning interventions for bladder training and voiding programmes for urinary incontinence and should incorporate recognized 'quality' research designs, established outcomes and long-term follow up. It is unclear whether health outcomes for people with comorbidities, cognitive and physical impairments will improve if extensive diagnostic and assessment investigations are undertaken.

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition

PubMed Central

Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Introduction Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Methods Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Results Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Conclusion Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families. PMID:29494684

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition.

PubMed

Costa Monteiro, Lucia Maria; Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families.

Effect of Botox injection at the bladder neck in boys with bladder dysfunction after valve ablation.

PubMed

Mokhless, Ibrahim; Zahran, Abdel-Rahman; Saad, Ashraf; Yehia, Mohamed; Youssif, Mohamed E

2014-10-01

After posterior urethral valve ablation, some boys are still have a hostile bladder. We conducted a prospective randomized study to determine if Botox injection at the bladder neck will help improve vesical dysfunction in this subgroup of boys or not. Twenty boys with history of posterior urethral valve ablation and severe bladder dysfunction with a mean age of 16 months were studied. Cases were further randomized into two groups. Group I (study group) had endoscopic injection of a single dose of 100 IU of Botox into the hypertrophied bladder neck at 3, 6, and 9 o'clock. Group II (control group) patients with the same parameters had urethroscopy to exclude residual valves. Both groups had the standard conservative treatment. Cases were followed after 6 months of initiating the management protocol. This includes laboratory studies (urine culture and sensitivity, blood urea nitrogen, serum creatinine), ultrasound of the urinary tract. Voiding cysto-urethrogram and urodynamic study (pressure flow study). There was no statistical difference in both groups regarding rate of urinary tract infection, improvement of hydronephrosis, resolution of vesico-ureteral reflux, creatinine level at the start or at the end of the study. Urodynamic parameters revealed an increase in cystometric capacity in both groups at the end of the study but without statistical difference. The mean voiding pressure reduced significantly in both groups but without statistical difference. Temporarily abolishing the effect of bladder neck by Botox injection does not seem to improve the outcome of those boys who had a severe voiding dysfunction after valve ablation. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder.

PubMed

Gevaert, Thomas; Ridder, Dirk De; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Aa, Frank Van Der; Pintelon, Isabel; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Neuhaus, Jochen

2017-06-01

The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT + ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody-related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin-1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT + cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT + ICC are present in bladder. In this perspective, functional concepts of KIT + ICC being involved in sensory and/or motor aspects of bladder physiology should be revised. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.