241
242
ANTI-
BLADDER RECONSTITUTION WITH BONE MARROW DERIVED STEM CELLS SEEDED ON ACELLULAR SCAFFOLD SHOWS I M P R O V E D M O R P H O L O G I C AND M O L E C U L A R C O M P O S I T I O N
Imperial College, London, Reproductive Science and Medicine, London, Ulaited Kingdom, 2Royal Hallamsbire Hospital, Urology. Sheffield, United Kingdom, 3Heron Evidence Development Ltd., Systellaatie Review, Letchworth, United Kingdom, 4Pfizer, Outcomes Research, Tadworth, United Kingdom
C h u n g S. 1, Krivorov N), Rausei V.2, Thomas L 3, Frantzen M.3, Landsittel D.4, Kang Y), Ng C.1, Fuchs G.1
INTRODUCTION & OBJECTIVES: Tbe International Contthence Society states that quality of llfe (QoL) measures should he included in every study evaluating lower urinary tract dysfunction. A systematic review was cond~lcted to determine whether this information was routinely being collected and reported in studies of OAB.
~Cedars-Sinai Medical Center, Minimally Invasive Urology Institute, Los Angeles, United States, 2Cedars-Sinai Medical Center, Department of Pathology, Los Angeles, United States, 3Cedars-Sinai Medical Center, Department of Medicine, Los Angeles, United States, 4University of Pittsburgh, Biostatistics, Pittsburgh, United States
QUALITY
OF
LIFE
MEASUREMENT
IN
TRIALS
OF
MUSCARINIC THERAPIES FOR OVERACTIVE BLADDER Khu0ar __V.1, Chapple C. 2, Gabriel Z.3, Dooley J.A. 4
MATERIAL & METHODS: A systematic review of published randemised controlled trials of antimuscarinic treatments for overactive bladder and/or urinary incontinence was carried out. Eligible studies published between 1966 and August 20O4 were included. RESULTS: Of 56 trials included in the review, 25 reported QoL findings. The most commonly employed instruments were the IIQ, KHQ, SF-36, Oaudenz Appraisal Questionnaire and UDL Statistically significant differences in QoL compared to placebo were reported for tolteredine IR (immediate release) and ER (extended release), trospium, solifenacin, propiverine and oxybutynin TDS (transdermal system) (Table 1). These data were limited by inconsistency in the instruments used, a small number of assessed patients and few reported domains. A pooled analysis of three RCTs presented QoL data for darifenacin, but this paper did not meet the inclusion criteria of the review. Tolterodine ER was the only intervention that was found to have a significant effect versus placebo for two or more trials that used the stone QoL instrument. Table 1: Statistically significant differences between antimusearinie treatments and placebo in QoL (as reported by included trials)
QoL Instrument
Anfimuscarinic Treatments DarifeOxybuty- Oxybutynaein nin 1R nin TDS
Propiverine
Confilife
Solifenaein Tolter~ dine IR
~/6 I33
Gaudenz
Tolterodine ER
Trospium
~/8 240 3 9/11 2190 1
I/8 523
11/6 75
~/2 93
IIQ 495
V,HQ
1 7/1I 989
UDI
/3 238
1/3
240
BasleSubjeeave "WM1-BeillgSurvey
I 98 Notes to Table 1. Where cells are empty statistically significant differences between treatment and placebo were not reported. For cells with data, the top row represents the number of studies reporting statistically significant differences between treatment and placebo, the middle row shows the number of statistieally significant domains compared to placebo out of the total number of domains e.g. 5 from 6 is shown as 5/6 and the bottom row the number of assessed patients. 2. Contilith Quality of Life Assessment Questionnaire Concerning Urinary Incontinence, Gaudenz-Gaudenz Appraisal Questionnaire, nQ-lncontinence Impact Questionnaire, KHQ-KJngs Health Questionnaire, UDI-Urogenital Distress Inventory. CONCLUSIONS: There is evidence indicating that antimuscarinics have a significant beneficial effect on Q o L The most extensive and conclusive data is for tulterodine ER versus placebo due to a more consistent use of instrument, larger patient numbers and the greatest number of QoL domains reported.
& OBJECTIVES: Tissue engineering has been used for bladder augmentations with various acellular scaffolds. Although favourable short-term outcomes have been reported, long-term followup has been poor. Recently, scaffolds seeded with smooth muscle and urothelial cells have shown favourable results. We investigate novel tissue engineering with stem cells and evaluate morphologic and genetic composition of reconstructed bladders. INTRODUCTION
MATERIAL & METHODS: Thirty-three Lewis rats were used to investigate bladder
augmentations with 4-layer small intestinal submucosa (SIS) in the following groups: control (CG, sham operation), partial cystectomy with oversewn defect (OG), augmentation with unseeded SIS (USG), and augmentation with stem cell seeded SIS (SSG). Bladders from 4 rats in each group were harvested at 1 and 3 month(s) post-surgery. Morphologic analyses were performed using Masson trichrome and immunohistochemical staining (cytokeratin AE1/AE3, smooth muscle c~-actin, S100), and gene expression was evaluated using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for collagens I and III, cytokeratins 8 and 19, and smooth muscle myosin heavy chain (MHC). RESULTS: At 1 month post-surgery, Massun trichrome staining revealed collagen admixed with indiscrete cells and morphology similar to controls in USG and SSG groups, respectively. Discrete smooth muscles fascicles and S100 staining were found in all groups except in USG. Organized urothelium with increased basal cell layer staining was present in eonlrols and SSG only. At 3 months follow-up, trichrome staining showed increased collagen formation in both OG and USG. Immunostaining showed hyperplasia of the urothelittm with increased staining of the basal cell layer, discrete muscle fascicles, and positive nerve staining in all groups. Using quantitative RT-PCR, expression levels in SSG were more improved than USG, especially for collagens I and III and MHC. At 3 months, collagens I and III were over expressed in OG and USG but not in CG and SSG. Furthermore, quantitative evaluation showed cytokeratins 8 and 19 and MHC to have greater expression levels in SSG than seen in USG. CONCLUSIONS: Morphologic and molecular reconstitution of bladders occurs more rapidly using stem cell seeded SIS. Although USG and SSG appear to develop all three cellular constituents by 3 months, only SSG had gone expression levels similar to controls. Seeding SIS with stem cells may provide a novel method for urological tissue engineering.
243 I M M U N O C Y T O C H E M I C A L I N V E S T I G A T I O N OF N E R V E - M U S C L E C O M M U N I C A T I O N IN B L A D D E R E X S T R O P H Y PATIENTS
244 C H I L D R E N W I T H A C U T E URINARY R E T E N T I O N
As~ari S.A., Falahatkar S., Mokhtari G., Ghanei M. Makedonsky I., LyzogubovV. Gums, Urology, Rasht, Iran Dnipropetrovsk Children's Hospital #3, Urology, Dnipropetrovsk, Ukraine The anatomical, histological and biochemical properties of the exstrophied bladder are poorly understood. In normal urinary bladder detrusor smooth muscle is endowed principally with M2 and M3 muscarinic receptors with the former predominating in number. Recently was shown that exstrophied bladders present pathological changes in distribution and quantity of MAch-M2 and Mach-M3 receptors. Collagen type IV (CIV) and Her2neu molecules play role in maturation of nerve-muscle communication. No data known about localization of CIV and Her2neu in exstropied bladders. The aim of this work was immunochistochemicaly detect localization and distribution collagen type IV and Her2neu in normal bladder and bladder exstrophy patients. INTRODUCTION
& OBJECTIVES:
M A T E R I A L & M E T H O D S : Tissue samples were obtained during primary
closure from the bladder wall of 18 children with bladder exstrophy. Control biopsies from 6 healthy bladders of an age-compatible group were subjected to the same examination. Indirect immunocytochemistry for MAch-M2 and Mach-M3 receptors, CIV and Her2neu was performed on 5-micron paraffin sections. RESULTS: We found CIV in great amount around smooth muscles cells of the detrusor (SMD) and vessels (SMV) and in zone of basal membrane of the epithelium of normal bladders. We discover that muscle cells of SMV and SMD also contain Her2neu in their cytoplasm. Exstrophy bladders had decreased (up to full absence) both CIV and Her2neu only in SMD. The quantity of those markers in SMV was equal to control. Decreasing of CIV and Her2neu correlate with low level of MAch-M2 and Mach-M3 receptors in cells of SMD. C O N C L U S I O N S : Our studies suggest that exstrophied bladders present pathological changes in nerve and muscle maturation. Defects of collagen IV type and her2neu expression in bladder exstrophy may lead to arrest of detrusor smooth muscle maturation and muscarinic receptors abnormality.
I N T R O D U C T I O N & OBJECTIVES: Acute urinary retention in children is a
relatively rare entity. There are a variety of causes that are poorly defined in the literature. In this study we investigated to identify the common causes of urinary retention in the paediatric population. M A T E R I A L & M E T H O D S : Between 1996 and 2001, children (up to 14 years
old) referred due to acute urinary retention are examined. All children underwent a through case history questionnaire, careful physical examination, and conducted laboratory examination and radiographic procedures. Cystoureteroscopic and urodynamic procedures carried out according to patient's conditions. All cases resulting postoperatively and believed secondary to surgical dissection, narcotic use, trauma, immobility and children previously diagnosed with chronic neurological disorders and voiding dysfunction or with reduced mental status were excluded from study. RESULTS: We identified 42 children meeting these criteria, including 34 (80.9%) boys 1 month to 14 years old and 8 girls (19.1%) 4 days to 14 years old. Etiologies included lower urinary tract stone in 40.4%, urinary tract infection in 11.2%, posterior urethral valve in 11.2%, ureterocele in 9.5%, turnout (including Rhabdomyosarcoma and teratoma ) in 7.1%, constipation 4.7%, large prostate utriele 2.7%, and finally pararurethral cyst, prune - belly syndrome, hinmans syndrome and hydrocolpus each one case (2.2%). CONCLUSIONS: Acute urinary retention in children is a relatively infrequent condition. In our study, the most common cause of acute urinary retention was urethral stone. Moreover, it appears that in infant male and female patients the common causes for acute urinary retention were posterior urethral vave and ureterocele, respectively.
European Urology Supplements 4 (2005) No. 3, pp. 63