Rita Gobet
University of Zurich, Switzerland, Childrens Hospital, Faculty Member
The article “Swiss consensus recommendations on urinary tract infections in children”
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The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the... more
The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended. Conclusion: Based ...
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Prenatal myelomeningocele (MMC) repair has been proven to significantly reduce the need for hydrocephalus shunting and improve lower-extremity motor outcomes. The aim of this study was to evaluate the effect of prenatal MMC repair on the... more
Prenatal myelomeningocele (MMC) repair has been proven to significantly reduce the need for hydrocephalus shunting and improve lower-extremity motor outcomes. The aim of this study was to evaluate the effect of prenatal MMC repair on the urological outcome. All patients who underwent fetal MMC repair at our institution are followed prospectively. Assessments include medical history, renal and bladder ultrasound, voiding cystourethrogram and urodynamic study, need for clean intermittent catheterization (CIC) and anticholinergics, and the occurrence of urinary tract infections (UTI). Of the 30 patients who underwent prenatal MMC closure from December 2010 to December 2015, eight patients with a postnatal follow-up of at least 2 years were included in this study and compared with eight patients after postnatal MMC repair. The level of the bony spinal defect was similar in both groups. Urological evaluation at 2 years revealed normal bladder function in 50% after prenatal repair. Neurogenic bladder dysfunction requiring CIC and anticholinergic therapy was seen in 50% in the prenatal and in 100% in the postnatal group. Significant bladder wall thickening was found in 37.5% and 87.5%, respectively. Febrile UTIs occurred in 37.5% in the prenatal and 62.5% in the postnatal group during the observation period. Our data suggest a positive effect of prenatal MMC closure on lower urinary tract function. The long-term significance of these results remains unclear. Therefore, continued close monitoring of renal and bladder function are mandatory.
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We describe the long-term psychosocial and sexual outcomes of patients born with bladder exstrophy treated with ureterosigmoidostomy at our institution. Of 42 patients born with bladder exstrophy between 1937 and 1968, 28 were located, of... more
We describe the long-term psychosocial and sexual outcomes of patients born with bladder exstrophy treated with ureterosigmoidostomy at our institution. Of 42 patients born with bladder exstrophy between 1937 and 1968, 28 were located, of whom 25 agreed to participate in this study. Evaluation consisted of studying pediatric and adult medical records, medical examination, and reports of sexual and social history. Four female and 21 male patients with a mean age of 50 years (range 39 to 67) were evaluated. Of the patients 21 (84%) were married or lived in a stable relationship, 6 (24%) had several children after normal conception and an additional 2 (8%) became parents with assisted reproductive technology. Nine patients (36%) reported no sexual activity or were unable to engage in sexual intercourse. All patients except 2 are professionally and socially successful. The long-term followup of this study of 37 to 68 years provides valuable information on patients who live with bladder exstrophy during a long period. Most followed patients who were born with bladder exstrophy and treated with ureterosigmoidostomy were able to lead satisfactory lives socially and professionally. However, at least 36% of the patients are severely restricted in their sexual lives.
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Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a... more
Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a novel electrospun biomaterial based on degradable polyesterurethane (PEU) (DegraPol(®) ) was investigated for potential use for bladder engineering in vitro and in vivo. Hybrid microfibrous PEU and PLGA scaffolds were produced by direct electrospinning of the polymer onto a bladder acellular matrix. The scaffold morphology of the scaffold was analyzed, and the biological performance was tested in vitro and in vivo using a rat cystoplasty model. Anatomical and functional outcomes after implantation were analyzed macroscopically, histologically and by cystometry, respectively. Scanning electron microscopy analysis showed that PEU samples had a lower porosity (p < 0.001) and were slightly thinner (p = 0.009) than the PGLA samples. Proliferation and survival of the seeded smooth muscle cells in vitro were comparable on PEU and PLGA scaffolds. After 8 weeks in vivo, the PEU scaffolds exhibited no shrinkage. However, cystometry of the reconstructed bladders exhibited a slightly greater functional bladder capacity in the PLGA group. Morphometric analyses revealed significantly better tissue healing (p < 0.05) and, in particular, better smooth muscle regeneration, as well as a lower rate of inflammatory responses at 8 weeks in the PEU group. Collectively, the results indicated that PEU-hybrid scaffolds promote bladder tissue formation with excellent tissue integration and a low inflammatory reaction in vivo. PEU is a promising biomaterial, particularly with regard to functional tissue engineering of the bladder and other hollow organs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
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On behalf of the European Society of Paediatric Urology (ESPU), a prospective study was designed with the aim of defining the actual number of babies born with bladder exstrophy, cloacal exstrophy, and epispadias in Europe over a 12-month... more
On behalf of the European Society of Paediatric Urology (ESPU), a prospective study was designed with the aim of defining the actual number of babies born with bladder exstrophy, cloacal exstrophy, and epispadias in Europe over a 12-month period, and verifying the distribution of the exstrophy patients born during the study period among the different paediatric urology centres in Europe. The study was structured with a chief investigator and one national investigator for each country enrolled in the study. The national investigators nominated one local investigator for each European centre of paediatric surgery/paediatric urology and urology where the exstrophy complex could potentially be treated. The local investigators were responsible for reporting babies treated in their institutions for bladder/cloacal exstrophy and/or epispadias. During 2010, every 3 months, an electronic survey (Figure) was e-mailed to the local investigators asking them to report babies treated or referred for treatment during the previous 3 months. One-hundred and sixteen centres in 27 European counties were enrolled in the study. The overall response rate for the four online surveys was 79%. Two-hundred and thirty-eight babies were reported to be born with a condition within the bladder exstrophy epispadias complex (BEEC): 71 primary epispadias (66 males), 146 classic bladder exstrophy (97 males) of which two were female bladder exstrophy variant, and 21 cloacal exstrophy (17 males). Two of 67 (3%) male epispadias, 24/146 (16.4%) bladder exstrophy, and 6/21 (28%) cloacal exstrophy were antenatally diagnosed. Associated anomalies were reported in 2/71 (2.8%) epispadias patients, 8/146 (5.5%) bladder exstrophy patients, and 15/21 (71.4%) cloacal exstrophy patients. One-hundred and forty-seven (62%) of the 238 babies born in Europe with a condition within the exstrophy spectrum during 2010 were transferred from other institutions for treatment (36 male epispadias, 97 bladder exstrophy, and 14 cloacal exstrophy). Only 12 centres treated six or more exstrophy and or epispadias patients during the study period; 52 treated between one and five patients, of which 22 treated only one case in 12 months. This study provides a contemporary incidence of the BEEC in Europe. It demonstrates also that only a minority (19%) of the European centres involved in the treatment of exstrophy can be considered "high volume" exstrophy centres. There is a case for proposing a rationalisation of the treatment of this group of conditions in a small number of exstrophy units around Europe.
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Congenital anomalies of the kidney and urinary tract are common findings on fetal ultrasound. The aim of this prospective observational study was to describe outcome and risk factors in 115 patients born 1995-2001. All prenatally... more
Congenital anomalies of the kidney and urinary tract are common findings on fetal ultrasound. The aim of this prospective observational study was to describe outcome and risk factors in 115 patients born 1995-2001. All prenatally diagnosed children were stratified into low- and high-risk group and followed postnatally clinically and by imaging at defined endpoints. Risk factors were evaluated using odds ratios. Neonatal diagnosis included pelvi-ureteric junction obstruction (n = 33), vesicoureteral reflux (n = 27), solitary mild pelvic dilatation (postnatal anteroposterior diameter 5-10 mm; n = 25), and further diagnosis as primary obstructive megaureter, unilateral multicystic dysplastic kidney, renal dysplasia and posterior urethral valves. In 38 children with prenatal isolated hydronephrosis, ultrasound normalized at median age of 1.2 years (range 0.1-9). Surgery was performed in 34 children at median age of 0.4 years (0.1-10.8). Persistent renal anomalies without surgery were present in 43 children and followed in 36 for median time of 16 years (12.2-18). Oligohydramnios and postnatal bilateral anomalies were significantly associated with surgery and impaired renal function. The majority of children had a favourable postnatal outcome, in particular children with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis. Oligohydramnios and postnatal bilateral anomalies were risk factors for non-favourable outcome. What is Known: • In congenital anomalies of the kidney and urinary tract significantly poorer outcome is known in patients with bilateral renal hypoplasia or solitary kidney associated with posterior urethral valves. • Other factors as proteinuria and vesicoureteral reflux were associated with a higher risk of progression to chronic renal failure in these patients. What is New: • Unlike other studies giving us above-mentioned information, we included all patients with any kind of prenatally diagnosed congenital anomalies of the kidney and urinary tract. Our study shows long-term follow up (median 16 years, range 12.2-18 years), especially in patients not needing surgery, but with persistent anomalies. • During postnatal long-term follow up (median 2.2 years, range 0.1-18 years) one third each showed normalization, need of surgery or persistence of anomalies without need of surgery. Our study revealed a good prognosis in the majority of these children, in particular with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis, and revealed oligohydramnios and postnatal bilateral anomalies as risk factors for a non-favourable outcome, defined as need of surgery, persistent anomalies with impaired renal function, end stage renal failure or death.
Research Interests: Kidney diseases, Prospective studies, Pregnancy, Humans, Kidney, and 15 moreFemale, Male, Follow-up studies, Switzerland, Incidence, Risk factors, Newborn Infant, Urinary Tract, Adult, Public health systems and services research, Prenatal Diagnosis, Risk Factors, Chronic Kidney Failure, Cause of death, and Paediatrics and reproductive medicine
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Men with corrected hypospadias often suffer from sexual inhibition and fear of being ridiculed by others because of their penile appearance. However, no investigation has thus far been made of the perception of hypospadias-affected... more
Men with corrected hypospadias often suffer from sexual inhibition and fear of being ridiculed by others because of their penile appearance. However, no investigation has thus far been made of the perception of hypospadias-affected surgically repaired genitals by laypersons unacquainted with hypospadias. Therefore, the aim of this study was to find out whether laypersons notice a difference between genitals of men with corrected hypospadias in comparison with circumcised genitals. Furthermore, the most relevant predictors of laypersons' perception of hypospadias-affected genitals were examined. A cross-sectional study was performed in which a questionnaire with 10 standardized photographs of non-erect hypospadias-affected genitals and 10 circumcised genitals was presented to laypersons unacquainted with hypospadias to measure how they rated these genitals. Laypersons were 105 women and 70 men of three different age groups (age ranges 16-20, 25-30, and 40-45 years). Furthermore, laypersons were asked about demographic characteristics, their sexuality and their genital self-perception. The results showed that genitals with distal forms of hypospadias were rated similarly to circumcised genitals. In contrast, genitals with more proximal types were perceived as significantly less positive than circumcised genitals. However, the effect size was small. Higher age, being in an intimate relationship, higher socio-economic status, and a higher sexual interest predicted a better layperson's perception of hypospadias-affected genitals. These findings do not support the fear of some men with corrected hypospadias of being ridiculed by others because of their penile appearance. The results indicate that laypersons do not notice a difference between corrected distal types of hypospadias (which represent the majority of hypospadias) and circumcised genitals. Although the findings showed that laypersons perceive more proximal forms of hypospadias less positively than circumcised genitals, the difference does not appear to be clinically relevant as the effect size was small. A major strength of this study is its comprehensive study design. However, the low response rate of hypospadias patients and control individuals for photo documentation and of laypersons who rated these photosets is a limitation of the study. Therefore, generalization from the results must be made carefully. The results are relevant for patient counseling. Knowing that the penile appearance would not trouble laypersons may prevent the development of a negative genital self-perception and feelings of shame. The findings also suggest that hypospadias-affected genitals seem to be rated more positively when laypersons know more about the "normal" variation of penile appearance (e.g. with increasing sexual experience at a higher age).
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... Robotic Surgery for Ureteral Anomalies in Children Rita Gobet and Craig A. Peters 50.1 Introduction ... c. For all ureteral procedures (Table 50.1) d. Sutures: Monocryl 5-0 for closure of any mucosal defects Vicryl 3-0 for the hitch... more
... Robotic Surgery for Ureteral Anomalies in Children Rita Gobet and Craig A. Peters 50.1 Introduction ... c. For all ureteral procedures (Table 50.1) d. Sutures: Monocryl 5-0 for closure of any mucosal defects Vicryl 3-0 for the hitch stitch and 4-0 for the closure of the detrusor tunnel ...
To determine the clinical significance of routine postoperative voiding cystourethrography (VCUG) and renal functional studies in the postoperative management of children after a transtrigonal ureteric reimplantation. A retrospective... more
To determine the clinical significance of routine postoperative voiding cystourethrography (VCUG) and renal functional studies in the postoperative management of children after a transtrigonal ureteric reimplantation. A retrospective record review of 126 consecutive patients undergoing transtrigonal ureteric reimplantation. Inclusion criteria included primary reflux and >5 years of follow-up. Follow-up imaging studies consisted of serial renal ultrasounds (US) and one VCUG and intravenous urogram (IVU) each. Of 126 patients, 2 required a reoperation for contralateral reflux and pyelonephritis. In all other patients the results of the VCUG did not alter management. Dilatation seen in IVU was always visible in the renal US as well and always resolved spontaneously. No new dilatation was observed after 1 year of follow-up. Routine postoperative VCUG and renal functional studies are not warranted in asymptomatic patients after transtrigonal reimplantation. Only in patients with postoperative pyelonephritis did the imaging studies alter the treatment. In the majority of patients, follow-up with an early and 1-year renal US may suffice. Elimination of routine VCUG and functional studies will decrease morbidity and cost after ureteric reimplantation.
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This is a report on 31 children with operated extradural hematoma. The aim of the study was to elucidate the characteristics of extradural hematoma in childhood and the different clinical pattern and outcome compared to adults. For that... more
This is a report on 31 children with operated extradural hematoma. The aim of the study was to elucidate the characteristics of extradural hematoma in childhood and the different clinical pattern and outcome compared to adults. For that reason the charts of the patients seen at the Department of Surgery of the Children's University Hospital Zurich between 1972 and 1990 have been revised. Follow-up criteria were recorded according to the Glasgow Outcome Scale. Most hematomas have been provoked by minor injuries and almost all children presented with at least one typical clinical sign. Associated intracranial injuries have been found in four patients, while two were polytraumatised. 30 of the 31 patients survived. One patient died of malignant brain edema. The mean range of follow-up was seven years. 28 patients had a "good recovery", "moderate disability" and "severe disability" was found in a patient one each. Our results demonstrate that the long-term outcome in children with extradural hematoma is far better than in adults regarding survival as well as quality of life. The causes may be minor traumas with fewer associated lesions and presentation with typical clinical findings and therefore early diagnosis and treatment.
Research Interests: Adolescent, Humans, Child, Female, Glasgow Coma Scale, and 3 moreInfant, Follow-up studies, and Prognosis
Recent long-time outcome studies of patients with bladder exstrophy treated with primary urinary diversions or primary reconstruction force pediatric urologists to reassess the place of alternative management options in the armamentarium... more
Recent long-time outcome studies of patients with bladder exstrophy treated with primary urinary diversions or primary reconstruction force pediatric urologists to reassess the place of alternative management options in the armamentarium of bladder exstrophy treatment. After classic ureterosigmoidostomy (USS) or Mainz II pouch, continence rates are very high even in the long-term follow-up with a mean of 50 years. In contrast, multiple procedures including bladder neck repair (BNR) were needed in the majority of patients after complete primary repair of bladder exstrophy (CPRE) to achieve normal voiding and to provide cosmetically acceptable and functional genitalia. After multiple staged repair of bladder exstrophy (MSRE), the requirements of multiple procedures including bladder augmentation to achieve urinary continence, not normal voiding, is well known. The augmentation rates published in the literature range form 0 to 82%. There is increasing concern that the risk for tumor formation might be the same for any type of inclusion of intestinal tissue in the urinary tract even without the direct exposure to the fecal stream. The hope of providing normal voiding with a single operation (CPRE) might not be fulfilled even in the most skilled hands. This means that existing concerns after reconstructive techniques in bladder exstrophy regarding risk of tumor formation and BNR not standing the test of time remain important. Long-term psychosocial and sexual outcomes, including fertility of patients after reconstruction or primary diversion, will need to be taken into consideration.
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Between 1982 and 1992, 22 patients were treated with colonic strictures in the course of necrotizing enterocolitis (NEC). Fourteen newborns in whom a primary enterostomy and, when necessary, resection of necrotic bowel was performed... more
Between 1982 and 1992, 22 patients were treated with colonic strictures in the course of necrotizing enterocolitis (NEC). Fourteen newborns in whom a primary enterostomy and, when necessary, resection of necrotic bowel was performed developed strictures in the diverted colon. The strictures were detected by colon contrast enema study performed on average 3 months after the first intervention. Eight additional children suffered from an ileus due to primary strictures after conservatively treated NEC, which was surgically managed by enterostomy. Closure of the enterostomy and resection of the stenotic part of the colon was performed thereafter in all 22 children as a single stage procedure. There was no insufficiency of the anastomosis nor any late stricture at follow-up 2.7 years after NEC in our patients. It is concluded therefore that reanastomosis of the enterostomy and resection of an intestinal stricture can be performed as a single stage procedure without any risk after an interval of 3 months between onset of acute NEC and reevaluation. During this interval, a close monitoring and an appropriate management of adequate supplement of electrolytes and bicarbonates is necessary. Most of our babies could be nursed at home and showed a good weight gain during this period, despite the enterostomy.
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Boys with hypospadias can suffer from specific psychological stress as a result of genital surgery and a cosmetically and/or functionally impaired penis. During recent decades intensive efforts have been made to improve the surgical... more
Boys with hypospadias can suffer from specific psychological stress as a result of genital surgery and a cosmetically and/or functionally impaired penis. During recent decades intensive efforts have been made to improve the surgical techniques; yet the psychosocial and psychosexual development of children and adolescents after hypospadias surgery has only rarely been investigated. While the results of the few studies are altogether very contradictory, they also indicate that hypospadias patients suffer from specific problems like a negative perception of genital appearance. Therefore, they should be offered long-term follow-ups and psychosocial support until they reach young adulthood. For future research, it is necessary to systematically investigate the boys' quality of life and development in methodologically sound studies.
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Abstract Objective. The aim of this study was to characterize and differentiate adipose-derived stem cells (ADSCs) to functional smooth muscle cells (SMCs) as an alternative cell source for bladder engineering. Materials and methods. Rat... more
Abstract Objective. The aim of this study was to characterize and differentiate adipose-derived stem cells (ADSCs) to functional smooth muscle cells (SMCs) as an alternative cell source for bladder engineering. Materials and methods. Rat ADSCs were differentiated into SMCs for 1-6 weeks using induction medium. The changes in contractile genes and protein expression were investigated by real-time polymerase chain reaction, fluorescence-activated cell sorting and Western blot at different time-points. Spontaneous and carbachol-induced contractions of engineered SMC tissue at different stages were investigated to define the optimal duration of induction. Results. ADSCs differentiated into SMCs lost their capacity for expansion and their contractile phenotype, changing to a synthetic phenotype over time. Highest levels of calponin, smoothelin and MyH11 expression were observed in ADSCs induced for 3 weeks. Cells acquired typical SMC morphology when contractile proteins were expressed. However, SMC morphology was lost with reduction of contractile proteins, especially smoothelin and MyH11. The maximal spontaneous and carbachol-induced contraction of differentiated ADSCs was after 3 weeks. Conclusions. This study demonstrates that ADCSs are a suitable cell source for engineering tissues that require functional and contractile SMCs. An induction time of 3 weeks appears to be sufficient for ADSC differentiation to contractile SMCs suitable for urological tissue engineering.
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To evaluate contrast agent-enhanced harmonic ultrasonographic (US) imaging and Doppler hemodynamics during acute urinary obstruction. In 12 piglets, the distal ureter was obstructed for 60 minutes, followed by intravenous injection of... more
To evaluate contrast agent-enhanced harmonic ultrasonographic (US) imaging and Doppler hemodynamics during acute urinary obstruction. In 12 piglets, the distal ureter was obstructed for 60 minutes, followed by intravenous injection of furosemide. In six piglets, ureteral pressure was further elevated to mean arterial pressure, and in six other piglets ureteral obstruction was released. Contrast-enhanced harmonic imaging was performed, and interlobar resistive index (RI) and renal blood flow were determined at baseline and during each experimental condition. A bolus injection curve was constructed by plotting mean pixel intensity versus time, and the area under this normalized curve was compared with renal blood flow values. Ureteral obstruction and high ureteral pressure reduced cortical renal blood flow to 88% and 66%, respectively, of baseline values. Administration of contrast agent resulted in marked homogeneous enhancement of the renal cortex. The area under the curve diminished during ureteral obstruction and correlated well with mean cortical blood flow. RI correlated well with renal perfusion pressure but poorly with changes in renal blood flow. Contrast-enhanced harmonic US imaging depicts changes in renal blood flow during acute obstruction. Interlobar RI is a good predictor of renal perfusion pressure but not of changes in renal blood flow.
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To evaluate the efficacy of intradetrusor injection of Botulinum-A toxin (BoNT/A) in children with neuropathic bladder dysfunction and poor bladder compliance, due to meningomyelocele. We retrospectively reviewed the charts of 11 children... more
To evaluate the efficacy of intradetrusor injection of Botulinum-A toxin (BoNT/A) in children with neuropathic bladder dysfunction and poor bladder compliance, due to meningomyelocele. We retrospectively reviewed the charts of 11 children (mean age 6.7 ± 5.3 years) with neuropathic bladder and poor bladder compliance (mean 7 ml/cmH(2) O) treated with intradetrusor injection of BoNT/A. After urodynamic evaluation a standardized injection was performed. The authors describe their results in 11 children after the first (5×) or repeated (6×) BoNT/A injections. Re-evaluation was performed 3 and 12 months after each injection. Three months after injection detrusor pressure decreased by 17% and bladder capacity increased by 33%. In all but 1 patient bladder compliance stayed poor. Twelve months after treatment patients still had an effect but the values were already reverting towards preoperative levels. With repeated injections we achieved a similar effect on capacity and detrusor pressure as after the first injection. Overall, bladder compliance normalized (>20 cmH(2) O) in only 1 patient. The results confirmed the positive temporary effect of BoNT/A on detrusor pressure and bladder capacity in children with myelomeningocele, even after repeated injections. Nevertheless, bladder compliance stayed severely pathological. Whether an earlier treatment may prevent poor bladder compliance is a yet unanswered question.
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We describe the long-term psychosocial and sexual outcomes of patients born with bladder exstrophy treated with ureterosigmoidostomy at our institution. Of 42 patients born with bladder exstrophy between 1937 and 1968, 28 were located, of... more
We describe the long-term psychosocial and sexual outcomes of patients born with bladder exstrophy treated with ureterosigmoidostomy at our institution. Of 42 patients born with bladder exstrophy between 1937 and 1968, 28 were located, of whom 25 agreed to participate in this study. Evaluation consisted of studying pediatric and adult medical records, medical examination, and reports of sexual and social history. Four female and 21 male patients with a mean age of 50 years (range 39 to 67) were evaluated. Of the patients 21 (84%) were married or lived in a stable relationship, 6 (24%) had several children after normal conception and an additional 2 (8%) became parents with assisted reproductive technology. Nine patients (36%) reported no sexual activity or were unable to engage in sexual intercourse. All patients except 2 are professionally and socially successful. The long-term followup of this study of 37 to 68 years provides valuable information on patients who live with bladder exstrophy during a long period. Most followed patients who were born with bladder exstrophy and treated with ureterosigmoidostomy were able to lead satisfactory lives socially and professionally. However, at least 36% of the patients are severely restricted in their sexual lives.
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Impaired concentrating capacity has been demonstrated in human refluxing kidneys and in kidneys of growing animals with experimental congenital vesicoureteral reflux. Aquaporin water channel proteins are the principal mediators of water... more
Impaired concentrating capacity has been demonstrated in human refluxing kidneys and in kidneys of growing animals with experimental congenital vesicoureteral reflux. Aquaporin water channel proteins are the principal mediators of water homeostasis in the kidney. We examined the impact of experimental congenital vesicoureteral reflux on renal aquaporin protein expression. Vesicoureteral reflux was surgically induced bilaterally in male fetal sheep at 95 days of gestation (term 140 days). Following birth animals received antibiotic prophylaxis, and reflux grades were assessed by fluoroscopic voiding cystogram. After sacrifice at age 6 months 1 kidney of each animal (5 refluxing kidneys, and 3 from normal age and sex matched controls) was retrieved, frozen in liquid nitrogen and used for immunoblotting. The second kidney was perfusion fixed and processed for immunohistochemical analysis. Semiquantitative immunoblotting of inner medulla showed that vesicoureteral reflux was associated with a marked down-regulation in expression of aquaporin 1 (arbitrary units 7.0 +/- 4.3 vs 22.5 +/- 2.8, p <0.05) and aquaporin 2 (5.7 +/- 5.1 vs 24.8 +/- 3.8, p <0.05), which was confirmed by immunocytochemical analysis. Dot blot analysis revealed a homogeneous down-regulation of aquaporin 2 expression throughout the refluxing kidney to 0.029 vs 0.1 in normal kidneys (p = 0.026). Progressively impaired renal concentrating capacity induced by experimental fetal reflux is associated with decreased levels of renal aquaporin 1 and 2 expression. This long-term down-regulation of aquaporin 1 and 2 provides important molecular evidence for a defect in resorptive capacity of water induced by vesicoureteral reflux.
Research Interests: Urology, Aquaporins (AQP), Kidney, Sheep, Animals, and 7 moreMale, The, Clinical Sciences, Aquaporin, PBS, Vesicoureteral Reflux, and Serum albumin
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Severe spinal cord injury leads to neurogenic bladder dysfunction. We recently developed a multisystem neuroprosthetic training program that promotes plastic changes capable of restoring refined locomotion in rats with severe spinal cord... more
Severe spinal cord injury leads to neurogenic bladder dysfunction. We recently developed a multisystem neuroprosthetic training program that promotes plastic changes capable of restoring refined locomotion in rats with severe spinal cord injury. We investigated whether multisystem neuroprosthetic training would influence the development of posttraumatic bladder dysfunction. Eight and 4 adult rats were randomly assigned to a spinal cord injury and an intact control group, respectively. Spinal cord injury consisted of 2 opposite lateral hemisections (T7 and T11), thus, interrupting all direct supraspinal input. After spinal cord injury 4 rats were subjected to a multisystem neuroprosthetic training program and 4 were not trained. At 8 weeks we performed urodynamics and evaluated kidney function using creatinine and cystatin C. Bladder investigation included morphological, histological and immunohistochemical evaluations. Bladder capacity increased threefold in trained and sevenfold in nontrained rats compared to intact rats. During filling we found a mean ± SEM of 2.7 ± 1.1 vs 12.6 ± 5.2 nonvoiding contractions in trained vs nontrained rats. Bladder morphology was similar in trained and intact rats. Nontrained rats showed detrusor hypertrophy, characterized by increased detrusor thickness and a decreased connective tissue-to-smooth muscle ratio. As labeled with protein gene product 9.5, general nerve density was significantly increased in trained and significantly decreased in nontrained rats. The relative proportion of neurofilament 200 positive afferent nerves was significantly lower in trained than in intact and nontrained rats. Neuropeptide Y positive fibers showed significantly lower density in nontrained rats. Multisystem neuroprosthetic training effectively counteracts the formation of neurogenic bladder dysfunction after severe spinal cord injury and might contribute to preserving bladder function and preventing long-term complications in patients with severe spinal cord injury.