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This study investigated the degree of consensus between stakeholders regarding the most important employment outcome expectations for community-based rehabilitation programs (CRPs) as well as optimal time frames for determining such outcomes. Opinions of matched sets of CRP providers, funding agents, and consumers were surveyed to determine the degree of consensus that existed regarding employment outcome expectancies. In total, 42 sets of all three were analyzed. This analysis found that 63 of the 66 variables studied did not show a significant difference. The study also revealed that the top concerns among all three groups were related to quality of employment, quality of services, and opportunity for informed choice. [ABSTRACT FROM AUTHOR]

Objective: To develop a robust sterile, fully demucosalized and vascularized seromuscular patch for use as an adjunct to novel bioengineering techniques aimed at augmenting, reconstructing, or replacing the bladder because of endstage disease. To eliminate deep colonic epithelial crypts to prevent the possibility of colonocyte regrowth. To maintain sterility by excluding the possibility of contamination from the bowel contents., Methods: Pilot studies were performed on euthanized pigs to optimize the technique, with tissue samples examined by immunohistochemistry. In vivo, vascularized seromuscular colonic flaps were created from the bowel exterior in 7 large white hybrid pigs. The dissection was facilitated by placing an inflated Foley catheter within the colonic lumen. The seromuscular ends were approximated with 5/0 Vicryl sutures and excess mucosa intussuscepted within the lumen. Demucosalized flaps were used to augment the bladder by composite cystoplasty and were examined immunohistochemically at 3 months., Results: Pilot studies showed that the technique was successful in creating seromuscular segments with no epithelial remnants. When applied surgically, the seromuscular flaps survived and showed no evidence of colonocyte regrowth at 3 months., Conclusion: Extraluminal dissection creates robust seromuscular flaps and prevents both regrowth by colonic epithelial cells and contamination of the tissue by exposure to the bowel contents. This technique should find application in a range of bladder reconstruction techniques, including composite cystoplasty and autoaugmentation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The term 'regenerative medicine' encompasses strategies for restoring or renewing tissue or organ function by: (i) in vivo tissue repair by in-growth of host cells into an acellular natural or synthetic biomaterial, (ii) implantation of tissue 'engineered'in vitro by seeding cultured cells into a biomaterial scaffold, and (iii) therapeutic cloning and stem cell-based tissue regeneration. In this article, we review recent developments underpinning the emerging science of regenerative medicine and critically assess where successful implementation of novel regenerative medicine approaches into urology practice might genuinely transform the quality of life of affected individuals. We advocate the need for an evidence-based approach supported by strong science and clinical objectivity., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: • To document the outcome of ureterocalicostomy in children., Patients and Methods: • The outcomes of 13 children who had undergone ureterocalicostomy consecutively under the care of two paediatric urologists between 1997 and 2009 were evaluated retrospectively. • Ureterocalicostomy was performed as the primary procedure in four children with horseshoe kidney and four children presenting with gross pelvi-ureteric junction (PUJ) obstruction. • In the remaining five children, it was performed as a secondary procedure for recurrent PUJ obstruction after previous pyeloplasty. • An open approach was employed in 12 patients, whereas, in one patient, it was performed by a laparoscopically-assisted technique., Results: • Mean age at operation was 9.3 years and the mean (range) duration of follow-up was 2.6 (0.3-7.0) years. Twelve children (92%) experienced a good functional outcome following ureterocalicostomy, as defined by reduced dilatation and improved drainage on postoperative ultrasonography and/or isotope imaging. • However one child (8%) developed symptomatic anastomotic obstruction 5 months after primary ureterocalicostomy for obstruction in a horseshoe kidney. Surgical revision was successful, with good drainage, preservation of differential function and relief of symptoms on further follow-up to 3 years., Conclusions: • Ureterocalicostomy provides a versatile and reliable means of relieving obstruction for a variety of indications, including horseshoe kidney, recurrent PUJ obstruction and gross PUJ obstruction with unfavourable anatomy. • Approximation of ureteric and caliceal urothelium and excision of renal parenchyma in the proximity to the anastomosis are the key steps for securing a satisfactory outcome., (© 2010 BJU INTERNATIONAL. NO CLAIM TO ORIGINAL US GOVERNMENT WORKS.)

4-Nitrophenyl sulfenyl chloride was used as a new precursor for the formation of densely packed aromatic SAMs on gold. The adsorption involves the reductive dissociation of the S-Cl bond. A well-ordered row structure corresponding to a √3 × 4 phase with a molecular area of 27.8 Å(2) is obtained., (This journal is © The Royal Society of Chemistry 2011)

Background: Enterocystoplasty is associated with serious complications resulting from the chronic interaction between intestinal epithelium and urine. Composite cystoplasty is proposed as a means of overcoming these complications by substituting intestinal epithelium with tissue-engineered autologous urothelium., Objective: To develop a robust surgical procedure for composite cystoplasty and to determine if outcome is improved by transplantation of a differentiated urothelium., Design, Setting, and Participants: Bladder augmentation with in vitro-generated autologous tissues was performed in 11 female Large-White hybrid pigs in a well-equipped biomedical centre with operating facilities. Participants were a team comprising scientists, urologists, a veterinary surgeon, and a histopathologist., Measurements: Urothelium harvested by open biopsy was expanded in culture and used to develop sheets of nondifferentiated or differentiated urothelium. The sheets were transplanted onto a vascularised, de-epithelialised, seromuscular colonic segment at the time of bladder augmentation. After removal of catheters and balloon at two weeks, voiding behaviour was monitored and animals were sacrificed at 3 months for immunohistology., Results and Limitations: Eleven pigs underwent augmentation, but four were lost to complications. Voiding behaviour was normal in the remainder. At autopsy, reconstructed bladders were healthy, lined by confluent urothelium, and showed no fibrosis, mucus, calculi, or colonic regrowth. Urothelial morphology was transitional with variable columnar attributes consistent between native and augmented segments. Bladders reconstructed with differentiated cell sheets had fewer lymphocytes infiltrating the lamina propria, indicating more effective urinary barrier function., Conclusions: The study endorses the potential for composite cystoplasty by (1) successfully developing reliable techniques for transplanting urothelium onto a prepared, vascularised, smooth muscle segment and (2) creating a functional urothelium-lined augmentation to overcome the complications of conventional enterocystoplasty., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

In this work, we have directly grown three-dimensional nanoporous Au networks onto a Ti substrate using the hydrothermal technique. This newly designed material with a large surface area was used as a supporting matrix for immobilizing a redox protein, hemoglobin (Hb), to develop a high-performance hydrogen peroxide biosensor. Scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray (EDX) spectroscopy were employed to characterize the morphology and composition of the fabricated nanoporous Au network. Cyclic voltammetry (CV) and amperometry were used to study and to optimize the performance of the fabricated electrochemical biosensor. Our CV studies show the direct electron transfer of Hb immobilized on the nanoporous Au network. In addition, amperometric H(2)O(2) sensing experiments revealed that the nanoporous Au-network based biosensor exhibits fast response, long linearity, a low detection limit, high stability and very good reproducibility. Under the optimized conditions, the linearity of the developed biosensor for the detection of H(2)O(2) spans from 5 x 10(-8) to 2 x 10(-4)M with a detection limit of 2 x 10(-8)M (based on S/N=3)., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Although prenatal diagnosis has been a prominent feature of Paediatric Urology for more than two decades the published literature has been largely characterized by studies reporting short to medium-term follow up. This deficiency is now being addressed by the growing availability of published and unpublished long-term outcome data for a range of prenatally detected anomalies. This review analyses the evidence on long-term outcomes which is provided by studies with mean or median follow- up exceeding 5 years, with particular emphasis on the small number of studies reporting follow -up at 10 years and beyond. The natural history and outcome of conservatively managed uropathies is considered in conjunction with an appraisal of evidence- based indications for surgical intervention. This review evaluates the relative benefits and drawbacks of prenatal diagnosis for children and their parents and also considers the impact of prenatal diagnosis on the delivery of Paediatric Urological services and specialist training., (Copyright (c) 2010. Published by Elsevier Ltd.)

Background: Urothelium is generally considered to be impermeable to water and constituents of urine. The possibility that human urothelium expresses aquaporin (AQP) water channels as the basis for water and solute transport has not previously been investigated., Objective: To investigate the expression of AQP water channels by human urothelium in situ, in proliferating urothelial cell cultures and in differentiated tissue constructs., Design, Setting, and Participants: AQP expression by human urothelium in situ and cultured urothelial cells was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunolabelling. Expression screening was carried out on samples of freshly isolated urothelia from multiple surgical (bladder and ureteric) specimens and on proliferating and differentiated normal human urothelial (NHU) cells in culture. Urothelial tissue constructs were established and investigated for expression of urothelial differentiation markers and AQPs., Measurements: Qualitative study., Results and Limitations: Transcripts for AQP3, AQP4, AQP7, AQP9, and AQP11 were expressed consistently by freshly isolated urothelia as well as by cultured NHU cells. AQP0, AQP1, AQP2, AQP5, AQP6, AQP8, AQP10, and AQP12 were not expressed. Immunochemistry confirmed expression of AQP3, AQP4, AQP7, and AQP9 at the protein level. AQP3 was shown to be intensely expressed at cell borders in the basal and intermediate layers in both urothelium in situ and differentiated tissue constructs in vitro., Conclusions: This is the first study to demonstrate that AQPs are expressed by human urothelium, suggesting a potential role in transurothelial water and solute transport. Our findings challenge the traditional concept of the urinary tract as an impermeable transit and storage unit and provide a versatile platform for further investigations into the biological and clinical relevance of AQPs in human urothelium.

Background: The primary function of urothelium is to serve as a physical urinary barrier. This function is dependent on features expressed at the molecular level that are acquired during cytodifferentiation. Urothelial cells lose differentiated and functional characteristics when propagated in vitro., Objective: To investigate methods of inducing molecular and functional differentiation of normal porcine urothelial (NPU) cells in vitro., Design and Measurements: NPU cells were isolated from normal porcine bladders and propagated in a low-calcium keratinocyte serum-free medium. Effects of 5% fetal bovine serum (FBS) and exogenous calcium were investigated. Molecular differentiation was assessed by immunolabelling for urothelial differentiation-associated proteins (UPIIIa, CK20, ZO-1), and barrier function was assessed by measurement of transepithelial electrical resistance (TER)., Results: NPU cell cultures grew as monolayers in low-calcium, serum-free medium. Supplementation with 5% FBS and/or physiological calcium resulted in stratification into basal, intermediate, and superficial cell zones. Superficial cells were positive for UPIIIa, CK20, and ZO-1. TER measurement showed that NPU cells grown with FBS had significantly enhanced barrier function (6,720 ohms.cm(2)+/-1312 SD) compared with cells grown without FBS (102 ohms.cm(2)+/-34 SD; p<0.001)., Limitations: Importantly, our study demonstrates that expression of differentiation-associated immunohistochemical markers by cultured urothelial cells can be regarded as evidence of only morphological differentiation and does not represent a surrogate marker of function., Conclusions: We have shown that normal porcine bladder urothelium has many cell biological properties equivalent to normal human urothelium, making it an excellent research substitute for difficult-to-obtain tissue. A differentiated, functional barrier urothelium has been produced from porcine bladder urothelial cells propagated in vitro and displays molecular and functional properties equivalent to native urothelium. This tissue has application in developing tissue-engineered bladders with urinary barrier properties and as a research tool for understanding the relationship between molecular and functional tissue differentiation.

A novel nanostructure of a PtAu catalyst, alloyed PtAu nanodendrites, has been synthesized via a reproducible single-step hydrothermal co-reduction of Pt and Au inorganic precursors and shows exceptionally high catalytic activity towards the electrooxidation of formic acid.

Objective: To document the functional outcome of patients with prenatally detected posterior urethral valves (PUV) in the second decade of life, and to evaluate the possible impact of prenatal diagnosis on the long-term outcome of this condition., Patients and Methods: We analysed the functional outcome of 25 patients with prenatally detected PUV born between 1984 and 1996, whose mean (range) age at follow-up was 17.7 (10-23) years. The findings were compared with those in 17 patients (mean age 16.1 years) who had presented clinically to our unit during the same period. The duration of follow-up in both groups was >or=10 years. Late outcomes were also compared with published data for PUV. Outcome measures included; death, incidence of end-stage renal failure (ESRF), age at transplantation and the most the recently available plasma creatinine level in untransplanted patients. We also examined any possible association between functional outcome and early predictors, including nadir plasma creatinine level at <1 year and vesico-ureteric reflux (VUR)., Results: Three patients died (12%), two as neonates and one aged 3 years. Of five patients who had been shunted in utero, four died or developed early-onset renal failure. In the 23 prenatally detected patients who survived the neonatal period, four (17%) had a renal transplant at a mean (range) age of 6.5 (3.0-12.0) years. Of 19 patients with prenatally detected PUV who had not been transplanted in the first 12 years of life, only one (5%) developed new-onset ESRF at 10.0-23.4 years whilst 11 (58%) of these patients had normal creatinine values. In the untransplanted patients there was a statistically significant correlation between age and plasma creatinine level, but no correlation between late functional outcome and nadir creatinine in the first year of life, or bilateral VUR., Conclusions: Prenatal diagnosis had little impact on mortality or ESRF in the first decade of life. This appears to be largely predetermined by renal dysplasia and the severity of intrauterine obstruction. However, the functional outcome of patients with prenatally detected PUV aged 10-23 years was considerably better than published long-term data and the outcome of clinically presenting patients in our study. These findings suggest that the long-term prognosis of PUV of intermediate severity might be improved by prenatal diagnosis.

The long-term outcomes of prenatally detected uropathies are poorly documented. Limited data on fetal intervention show a possible reduction in early mortality from pulmonary hypoplasia, but no beneficial effect on long-term prognosis for renal function. Prenatally detected vesicoureteric reflux (VUR) is characterised by males with high-grade primary reflux, who are at long-term risk of renal impairment. Prenatal diagnosis and surgical intervention have contributed to a reduction in long-term morbidity in children with pelviureteric junction (PUJ) obstruction. By the same token, many children have almost certainly undergone unnecessary early pyeloplasty for an obstruction that would have resolved spontaneously. Multicystic dysplastic kidney (MCDK) carries a low (1%) risk of hypertension in childhood. The limited evidence on the long-term outcome of mild dilatation (pelvicaliectasis) indicates this is a largely innocent finding, which carries no increased risk of morbidity.

We report on a novel and facile approach for the direct growth of F-doped flower-like TiO(2) nanostructures on the surface of Ti in HF solutions under low-temperature hydrothermal conditions. The influence of the experimental parameters such as temperature, reaction duration, and the HF concentration on the morphology and photoelectrocatalytic activity of the formed F-doped flower-like TiO(2) nanostructures was systematically studied. The presence of HF and the reaction time play an important role in the formation of the F-doped flower-like TiO(2) nanostructures. The synthesized novel F-doped TiO(2) flower-like nanomaterials possess good crystallinity and exhibit high photoelectrochemical activity for water-splitting and photodegradation of organic pollutants compared with P-25, which is currently considered to be one of the best commercial TiO(2) photocatalysts. The approach described in this study provides a simple and novel method to synthesize F-doped TiO(2) nanostructured materials that are ready for practical applications such as the photodegradation of wastewater.

Here, we report on a novel nonenzymatic amperometric glucose sensor based on three-dimensional PtPb networks directly grown on Ti substrates using a reproducible one-step hydrothermal method. The surface morphology and bimetallic composition of the synthesized nanoporous PtPb materials were characterized using scanning electron microscopy and energy-dispersive X-ray spectrometry, respectively. Voltammetry and amperometric methods were used to evaluate the electrocatalytic activities of the synthesized electrodes toward nonenzymatic glucose oxidation in neutral media in the absence and in the presence of chloride ions. The synthesized nanoporous PtPb electrodes have strong and sensitive current responses to glucose. Their amperometric sensitivities increase in the order of Pt-Pb (0%) < Pt-Pb (30%) < Pt-Pb (70%) < Pt-Pb (50%). These nanoporous PtPb electrodes are also highly resistant toward poisoning by chloride ions and capable of sensing glucose amperometrically at a very low potential, -80 mV (Ag/AgCl), where the interference from the oxidation of common interfering species such as ascorbic acid, acetamidophenol, and uric acid is effectively avoided.

Background: Uroplakin (UP) proteins cover urothelial apical surfaces. Mice lacking UPIIIa have elevated urothelial permeability and congenital renal tract anomalies, and UPIIIa mutations have been reported in children with kidney and ureter malformations. Mice with null mutation of another UP family member, UPII, are often born with congenital hydronephrosis. We hypothesized that UPII mutations may be present in humans with renal tract malformations., Methods: Mutations were sought, using direct sequencing of the five UPII exons, in 42 children with diverse renal tract anomalies., Results: No UPII abnormalities were detected in 41 patients, whereas one index case had a heterozygous frameshift change which, if expressed, would generate a truncated protein. This Caucasian child presented with vesicoureteric reflux (VUR), bilateral nephropathy and renal failure. The genetic change was also found in the index case's mother who had normal renal ultrasonography, but it was absent in 150 healthy Caucasian control individuals (96 assessed by direct sequencing and another 54 assessed by restriction digests). UPII was immunolocalized in urothelium of the normal human embryonic renal pelvis in a pattern similar to UPIIIa., Conclusion: This study offers no definitive support for UPII mutations causing human renal tract malformations. In rare patients, UPII variants might be implicated in pathogenesis when acting in conjunction with other yet-to-be-defined, genetic or environmental modifying factors.

Objective: The strong familial basis of vesicoureteric reflux (VUR) is well recognised, however little progress has been made in identifying the causative genes. In this study we have investigated whether human vesicoureteric reflux (VUR) is associated with the aberrant expression of urothelial differentiation-associated antigens in view of the VUR phenotype of the Uroplakin IIIa (UPIIIa) "knockout" mouse., Methods: Samples of urothelium were collected from 13 children with primary VUR, four children with secondary VUR and from seven children with non-refluxing disorders of the urinary tract. Immunohistochemistry was used to assess the expression of five uroplakin (UP) and cytokeratin (CK) differentiation-restricted antigens, UPIa, UPIb, UPIIIa, CK13 and CK20. Samples were ranked blind according to immunohistochemical patterns relating to the differentiation-associated distributions of the five antigens and the results were analysed statistically using the Kruskal-Wallis test., Results: No objective differences in urothelial morphology or the expression of the five differentiation antigens were discernable in the urothelium of children with primary VUR, when compared with urothelium of children with a range of other pathology including VUR associated with duplication or pelvic renal ectopia, VUR secondary to outflow obstruction and non-refluxing upper tract obstruction. The p-values ranged from 0.168-0.651 and were not considered statistically significant., Conclusion: The results indicate that primary VUR is not associated with any major, collective abnormality of urothelial differentiation in man. In particular our findings provide no support for the suggestion that abnormalities of UPIIIa expression are implicated in the aetiology of human primary VUR.

A simple and facile method is described to directly synthesize TiO(2) nanostructures on titanium substrates by oxidizing Ti foil using small organic molecules as the oxygen source. The effect of reaction temperature and oxygen source on the formation of the TiO(2) nanostructures has been studied using scanning electron microscopy, x-ray diffraction, transmission electron microscopy, Raman spectroscopy and water contact angle measurement. Polycrystalline grains are formed when pure oxygen and formic acid are used as the oxygen source; elongated micro-crystals are produced when water vapour is used as the oxygen source; oriented and aligned TiO(2) nanorod arrays are synthesized when ethanol, acetaldehyde or acetone are used as the oxygen source. The growth mechanism of the TiO(2) nanostructures is discussed. The diffusion of Ti atoms to the oxide/gas interface via the network of the grain boundaries of the thin oxide layer is the determining factor for the formation of well-aligned TiO(2) nanorod arrays. The wetting properties of the TiO(2) nanostructured surfaces formed are dictated by their structure, varying from a hydrophilic surface to a strongly hydrophobic surface as the surface structure changes from polycrystalline grains to well-aligned nanorod arrays. This tunable growth of TiO(2) nanostructures is desirable for promising applications of TiO(2) nanostructures in the development of optical devices, sensors, photo-catalysts and self-cleaning coatings.

Human renal adysplasia usually occurs sporadically, and bilateral disease is the most common cause of childhood end-stage renal failure, a condition that is lethal without intervention using dialysis or transplantation. De novo heterozygous mutations in Uroplakin IIIa (UPIIIa) are reported in four of 17 children with kidney failure caused by renal adysplasia in the absence of an overt urinary tract obstruction. One girl and one boy in unrelated kindreds had a missense mutation at a CpG dinucleotide in the cytoplasmic domain of UPIIIa (Pro273Leu), both of whom had severe vesicoureteric reflux, and the girl had persistent cloaca; two other patients had de novo mutations in the 3' UTR (963 T-->G; 1003 T-->C), and they had renal adysplasia in the absence of any other anomaly. The mutations were absent in all sets of parents and in siblings, none of whom had radiologic evidence of renal adysplasia, and mutations were absent in two panels of 192 ethnically matched control chromosomes. UPIIIa was expressed in nascent urothelia in ureter and renal pelvis of human embryos, and it is suggested that perturbed urothelial differentiation may generate human kidney malformations, perhaps by altering differentiation of adjacent smooth muscle cells such that the metanephros is exposed to a functional obstruction of urine flow. With advances in renal replacement therapy, children with renal failure, who would otherwise have died, are surviving to adulthood. Therefore, although the mechanisms of action of the UPIIIa mutations have yet to be determined, these findings have important implications regarding genetic counseling of affected individuals who reach reproductive age.

Objectives: To study the outcome of composite cystoplasty using cultured urothelial cells combined with de-epithelialized colon or uterus in a porcine surgical model, using appropriate controls, and to characterize the neo-epithelium created by composite cystoplasty., Materials and Methods: Urothelial cells were isolated and propagated in vitro from open bladder biopsies taken from nine female minipigs. Cohesive sheets of confluent urothelial cells were transferred to polyglactin carrier meshes and sutured to de-epithelialized autologous colon in four animals and de-epithelialized autologous uterus in five. These composite segments were then used for augmentation cystoplasty. Conventional colocystoplasty, de-epithelialized colocystoplasty and sham operations were carried out in six control animals. After killing the animals at approximately 90 days the bladders were removed for examination and immunohistochemical analysis, using a panel of antibodies against cytokeratins and urothelial differentiation-associated antigens., Results: Macroscopically, the bladders augmented with composite segments derived from uterine muscle had no evidence of shrinkage or contracture. Histological analysis showed that in four of five composite uterocystoplasties, the neo-urothelium was stratified and had a transitional morphology, although in some areas coverage was incomplete. Immunohistochemical analysis showed evidence of squamous differentiation in both native and augmented segments. All composite and de-epithelialized colonic segments showed significant contraction with poor urothelial coverage, reflecting the unsuitability of the thin-walled porcine colon for de-epithelialization., Conclusions: The functional and macroscopic outcome of bladder augmentation with a composite derived from cultured urothelium and de-epithelialized smooth muscle of uterine origin endorses the feasibility of composite cystoplasty.

Glucosylation of xenobiotics in mammals has been observed for a limited number of drugs. Generally, these glucoside conjugates are detected as urinary excretion products with limited information on their formation. An in vitro assay is described for measuring the formation of the phenobarbital N-glucoside diasteriomers ((5R)-PBG, (5S)-PBG) using human liver microsomes. Human livers (n = 18) were screened for their ability to N-glucosylate PB. Cell viability, period of liver storage, prior drug exposure, serum bilirubin levels, age, sex and ethnicity did not appear to influence the specific activities associated with the formation of the PB N-glucosides. The average rate of formation for both PB N-glucoside was 1.42 +/- 1.04 (range 0.11-4.64) picomole/min/mg-protein with an (5S)-PBG/(5R)-PBG ratio of 6.75 +/- 1.34. The apparent kinetic constants, Km and Vmax, for PB N-glucosylation for eight of the livers ranged from 0.61-20.8 mM and 2.41-6.29 picomole/min/mg-protein, respectively. The apparent Vmax/Km ratio for PB exhibited a greater than 20 fold variation in the ability of the microsomes to form the PB N-glucosides. It would appear that the formation of these barbiturate N-glucoside conjugates in vitro are consistent with the amount of barbiturate N-glucosides formed and excreted in the urine in prior drug disposition studies.

Surgical reconstruction of the urinary bladder is performed on patients of all ages for a diverse range of conditions, including congenital abnormalities, bladder dysfunction, trauma and cancer. The most common material utilized to augment or replace the bladder during these procedures is a segment of the patient's own intestine. However, this procedure ('enterocytoplasty') is associated with significant clinical complications that arise due to the exposure of the epithelial lining of the intestine to urine. A number of alternative approaches are being actively developed to find a practical and functional substitute for native bladder tissue. These range from 'composite enterocystoplasty', where the de-epithelialized intestine wall is lined with bladder epithelial cells that have been propagated in vitro, to augmenting the urinary system with natural or synthetic biomaterials that may incorporate in vitro-propagated cells. However, if tissue-engineered products are to have therapeutic application in bladder reconstruction, a number of issues remain to be addressed; these issues are discussed briefly below.

Purpose: We document the inheritance pattern of multicystic dysplastic kidney in 3 affected families and screen first-degree relatives of a cohort of children with prenatally detected multicystic dysplastic kidney for renal anomalies. The study also afforded an opportunity to document the natural history of prenatally detected multicystic dysplastic kidney., Materials and Methods: We identified 3 families during clinical treatment of children with prenatally detected multicystic dysplastic kidneys. Other members of these families were evaluated with renal ultrasonography. For the family screening study index cases were identified from a fetal uropathy database. A total of 94 first-degree relatives (52 parents, 35 full siblings and 7 half siblings) of 29 children with prenatally detected multicystic dysplastic kidneys were studied with urinary tract ultrasonography, blood pressure measurement, urinalysis and plasma biochemistry., Results: Two families had affected sibling pairs, 1 of which also had a half sibling with vesicoureteral reflux. The third family included 3 individuals with multicystic dysplastic kidney and 1 with renal agenesis thought to have resulted from involution of multicystic dysplastic kidney. This family is consistent with autosomal dominant inheritance with variable expressivity and reduced penetrance. In the screening study ultrasonography did not demonstrate significant renal anomalies in any of the 94 first-degree relatives of the multicystic dysplastic kidney index cases. Followup assessment of prenatally detected multicystic dysplastic kidneys in index cases demonstrated total involution in 52% at a median age of 6.5 years with no multicystic dysplastic kidney related morbidity., Conclusions: Multicystic dysplastic kidney can be familial but is most commonly a sporadic anomaly. Formal screening of relatives is not recommended. Followup data on a cohort of children with prenatally detected multicystic dysplastic kidney add further support to conservative management.

The prenatal detection of urinary tract anomalies is changing paediatric practice but in many areas the impact on clinical outcome remains difficult to quantify. However it is already apparent that termination of pregnancy has reduced the numbers of infants with lethal pulmonary hypoplasia and renal dysplasia who would previously have been liveborn but destined to succumb as neonates. Similarly, referrals of major non lethal abnormalities such as bladder exstrophy are declining as parents increasingly opt for termination. Fetuses at greatest risk of early onset postnatal renal failure can now be identified with considerable accuracy on prenatal ultrasound. Termination, prompted by quality of life considerations, could result in reduced numbers of infants and young children requiring end stage renal failure treatment in the first few years of life. Pre natal detection of anomalies such as PUJ obstruction and reflux undoubtedly provides an opportunity to avert functional deterioration and minimise urinary infection. But the proportion of children who genuinely benefit has proved difficult to assess. The prenatal detection of mild dilatation is of doubtful benefit in all but a minority of cases. Clinically significant underlying pathology is rare yet this common prenatal finding often generates disproportionate parental anxiety., (Copyright 2001 John Wiley & Sons, Ltd.)

Reconstruction of the urinary bladder with bowel to restore storage capacity is associated with significant complications arising from substituting an absorptive, mucus-producing intestinal epithelium for the barrier urothelium of the bladder. To overcome these problems, we are developing a "composite enterocystoplasty" procedure to replace the epithelium of the bowel with autologous in vitro-propagated normal urothelial cells. The aims of this study were to evaluate synthetic biomaterials as delivery vehicles for the cultured urothelial cells and provide support during transfer and cell adherence to the de-epithelialized bowel wall. The surgical compliance of 12 biomaterials was evaluated, along with their ability to support urothelial cell attachment. Transfer of urothelial cells onto biomaterials as single cell suspensions or intact cell sheets was investigated. Seeding of a single cell suspension on to non-woven mesh resulted in poor cell attachment. Seeding onto woven mesh was more efficient, but the most effective transfer method involved producing an intact cell sheet that could be combined with woven, knitted and non-woven biomaterials. Transfer of the cell sheet : mesh complexes onto a de-epithelialized bladder stroma produced a stratified epithelium incorporating the strands of the mesh and expressing urothelial-associated antigens after 48 h in organ culture. Thus, we have developed and evaluated a suitable transfer method for in vitro propagated urothelial cells to be used in "composite enterocystoplasty"., (Copyright 2001 Kluwer Academic Publishers)

Objective: To document the current role of adult urologists in the care of children in the UK and to consider the future provision of urological services for children within the context of published national guidelines., Methods: A detailed postal questionnaire was sent to all 416 consultant urologists listed as full members of the British Association of Urological Surgeons and resident in the UK. The range of information sought from each urologist included details of personal paediatric training, scope of personal practice, and information about facilities and provision of urological services for children in their base National Health Service hospital., Results: The response rate was 69%; most consultant urologists (87%) in District General Hospitals (DGHs) undertake paediatric urology, mainly routine procedures of minor or intermediate complexity. Of urologists in teaching hospitals, 32% treat children but their involvement is largely collaborative. Consultants appointed within the last 10 years are less willing to undertake procedures such as ureteric reimplantation or pyeloplasty than those in post for > or = 10 years. Currently, 18% of DGH urologists hold dedicated children's outpatient clinics and 34% have dedicated paediatric day-case operating lists. Almost all urologists practise in National Health Service hospitals which meet existing national guidelines on the provision of inpatient surgical care for children., Conclusion: Urologists practising in DGHs will retain an important role as providers of routine urological services for children. However, the tendency for recently appointed consultants to limit their practice to the more routine aspects of children's urology is likely to increase. Training and intercollegiate assessment should focus on the practical management of the conditions most commonly encountered in DGH practice. The implementation of national guidelines may require greater paediatric subspecialization at DGH level to ensure that urologists treating children have a paediatric workload of sufficient volume to maintain a high degree of surgical competence.

Objective: To report experience of a broad multimodality approach to the treatment of calculi in children using extracorporeal shock wave lithotripsy (ESWL), ureteroscopy/laser lithotripsy, lithoclast and percutaneous nephrolithotomy (PCNL)., Patients and Methods: The treatment and outcome were reviewed in 43 children managed by a range of minimally invasive modalities, either singly or in combination, between 1990 and 1997. These patients represent a selected group deemed suitable for minimally invasive management during a period of developing experience with these techniques. Of this cohort, six children had previously undergone open stone surgery and contributory metabolic abnormalities were identified in seven. ESWL was the sole treatment modality in 24 children (56%). In five children (12%) ureteroscopy/laser lithotripsy was combined with ESWL, eight (18%) underwent ureteroscopy/laser lithotripsy alone, whilst three with bladder stones were treated with the lithoclast. Combined therapy including PCNL was required in three patients., Results: Of the 43 children treated, 38 (88%) were rendered stone-free. Metabolic disorders accounted for three of the five cases of residual calculi. Complications requiring intervention occurred in two children (7%) and three subsequently underwent open pyelolithotomy or ureterolithotomy after unsuccessful minimally invasive treatment., Conclusions: Used selectively, the range of minimally invasive procedures available for adults, including ureteroscopy and PCNL, can be safely and effectively extended to the treatment of urinary tract calculi in children. The role of open surgery will diminish further with the availability of specialized instruments for paediatric PCNL.

We previously showed that inhibition of the expression of CD28 (an essential immune receptor on T cells) mediated by a phosphorothioate (PS)-modified aptameric oligodeoxynucleotide (ODN) sequence, GR1, resulted in reduced T cell responses in vitro and in vivo. Using GR1 sequences differing only in the amount of terminal PS linkages (chimeric SO-ODN), the present study demonstrated that even after a substantial reduction in PS linkages, this 18-mer ODN sequence could still confer functionality in the ODN-mediated inhibition of CD28 expression. We showed that secondary structure and full retention of the ability to form a specific protein-ODN complex and to increase cellular uptake in activated Jurkat T cells were critical parameters in the determination of the magnitude of bioactivity of chimeric SO-ODN. We report that a chimeric SO-ODN with terminal PS linkages that total 9 (ICN 17221) or 12 (ICN 17263) was sufficient to inhibit CD28 expression and suppress in vivo inflammatory ear responses to contact allergen in mice with similar potency to the 17-thioate S-ODN (ICN 16064). Interestingly, all chimeric SO-ODN showed similar in vitro nuclease resistance. These data suggest alternate functional properties for PS linkages, unrelated to nuclease resistance, in enhancing the bioactivity of a G-rich aptamer.

Purpose: We document the postpubertal outcome of feminizing genitoplasty., Materials and Methods: A total of 14 girls, mean age 13.1 years, with congenital adrenal hyperplasia were assessed under anesthesia by a pediatric urologist, plastic/reconstructive surgeon and gynecologist. Of these patients 13 had previously undergone feminizing genitoplasty in early childhood at 4 different specialist centers in the United Kingdom., Results: The outcome of clitoral surgery was unsatisfactory (clitoral atrophy or prominent glans) in 6 girls, including 3 whose genitoplasty had been performed by 3 different specialist pediatric urologists. Additional vaginal surgery was necessary for normal comfortable intercourse in 13 patients. Fibrosis and scarring were most evident in those who had undergone aggressive attempts at vaginal reconstruction in infancy., Conclusions: These disappointing results, even in the hands of specialists, highlight the importance of late followup and challenge the prevailing assumption that total correction can be achieved with a single stage operation in infancy. Although simple exteriorization of a low vagina can reasonably be combined with cosmetic correction of virilized external genitalia in infancy, we now believe that in some cases it may be best to defer definitive reconstruction of the intermediate or high vagina until after puberty. The psychological issues surrounding sexuality in these patients are inadequately researched and poorly understood.

Background: This study evaluates the role of laparoscopy for managing the intra-abdominal testis., Methods: Over 30 months, 48 children (six with previous groin explorations) underwent laparoscopy for a unilateral impalpable undescended testis. The patients' age ranged from 1 to 9 years., Results: Eleven children required insertion of 'working ports' for mobilization of obscuring colon before the diagnosis could be established. Twenty-eight children had an absent testis. In nine, vas and vessels entered the internal ring. In 19, vas and vessels ended blindly above the internal ring. Twenty children had an intra-abdominal testis. Ten underwent a laparoscopic single-stage orchidopexy (eight without and two with ligation of vessels); at a minimum follow-up of 2 years, one testis in this group had atrophied, three were located in the lower half of the scrotum and six in the upper half. The remaining ten children underwent a laparoscopic two-stage Fowler-Stephens operation. At a minimum follow-up of 6 months, eight of these testes were palpable in the lower half and two in the upper half of the scrotum. CONCLUSION In the majority of cases, laparoscopy obviates the need for groin exploration. Technically a first-stage Fowler-Stephens procedure can be performed easily and effectively via the laparoscope. However, the second-stage Fowler-Stephens procedure or single-stage orchidopexy requires laparoscopic skills and may not necessarily provide sufficient length to the testicular attachment.

Objectives: To determine if the indications for cutaneous vesicostomy have changed with the advent of prenatal diagnosis and to assess if temporary vesicostomy remains an effective measure in preventing urinary infection and stabilising renal function in children with severe uropathy., Methods: Retrospective case note review., Results: Nineteen patients underwent temporary cutaneous vesicostomy over a 12-year period. Of these, 10 had a prenatally detected uropathy. Children with prenatal findings were diverted at a significantly younger age than cases presenting clinically (33 (range 10-240) vs. 182 days (range 28-425), p = 0.02). In addition, there were significantly more boys diverted in the prenatally detected group (p = 0.02). The majority of clinically presenting infants were diverted because of severe or recurrent urosepsis whereas most prenatally detected cases underwent surgery for progressive renal impairment. In both groups vesicostomy was successful in preventing further urosepsis and resulted in improved renal function. Follow-up data, however, revealed 9 (50%) of 18 patients with chronic renal failure. One patient died prior to stoma closure from septicaemia and renal disease., Conclusions: The timing and indications for vesicostomy may be changing in the light of prenatal diagnosis. Temporary vesicostomy diversion remains a simple, effective and easily reversible method of preventing urosepsis and stabilising upper tract function. The poor renal outcome on follow-up may reflect the fact vesicostomy is reserved for infants and children with severe disease.

Purpose: We established a 3-dimensional organ culture model of urinary tract tissue in which to study the effects of seeding cultured urothelial cells onto de-epithelialized urothelial stroma., Materials and Methods: Normal human urinary tract tissues were placed in organ culture or used to establish urothelial cell cultures. At passage 2 cell cultures were harvested and used to reconstitute autologous organ cultures by seeding onto de-epithelialized stroma. Organ cultures were harvested at intervals and analyzed by immunohistology with a panel of antibodies against differentiation associated antigens, cytokeratins, cell adhesion molecules, extracellular matrix components and proliferation associated antigens., Results: Human urothelial tissues were maintained in organ culture for at least 18 weeks and they retained a transitional epithelial morphology with expression of normal in situ antigenic characteristics. Within 2 weeks of reconstitution recombined organ cultures formed a stratified, polarized, transitional-like neo-epithelium that expressed many of the phenotypic and differentiated characteristics of normal tissue. Basement membrane formed at sites of direct contact between urothelial cells and stroma. After an initial stabilization period the proliferation rate of the urothelium of intact and reconstituted organ cultures decreased to the low turnover rate characteristic of normal urothelium in situ, indicating that the cells were responsive to normal growth regulatory controls., Conclusions: Normal human urothelial cells, which express a proliferative nondifferentiated phenotype in monolayer culture, retain the capacity to differentiate and reform a slow turnover, stratified transitional epithelium.

Purpose: We attempted to determine if the degree of second trimester dilatation and/or other qualitative sonographic features of the fetal urinary tract are predictive of postnatal outcome in male neonates with posterior urethral valves., Materials and Methods: We reviewed ultrasound reports and/or hard copy imaging in 17 cases of posterior urethral valves initially detected on second trimester scans (median gestation 18 weeks, range 15 to 23.5). Ultrasound appearance was categorized according to the pattern and severity of dilatation, cystic change or echogenicity of the renal cortex and presence of oligohydramnios. Outcome was reviewed at a median followup of 5.7 years (range 4.4 to 10)., Results: Of the 17 cases there was a poor outcome in 10, including death in 4 and chronic renal failure in 6. Seven patients were alive and well with normal renal function at followup. The prognosis in cases of moderate or severe upper tract dilatation was poor. Of the 9 patients with marked prenatal hydroureteronephrosis 8 (89%) were dead or had chronic renal failure at followup. In contrast, only 2 of the 8 patients (25%) with mild upper tract dilatation or dilatation limited to the bladder had chronic renal failure at review (p = 0.05). Three cases of prenatal renal parenchymal change and 3 of subsequent oligohydramnios had a poor outcome postnatally., Conclusions: The prognosis for boys with prenatally detected posterior urethral valves is closely associated with qualitative aspects of second trimester scan findings. This information may be of clinical value in the prenatal counseling of parents.