Angela M. Arlen

TGF-β1, -β2 and -β3 cooperate to facilitate tubulogenesis in the explanted quail heart

Background: Transforming growth factor-β (TGF-β) isoforms have been implicated as both pro- and anti-angiogenic modulators. In this study we addressed the roles of TGF-β isoforms on coronary tubulogenesis. Methods: Embryonic (E6) quail ventricular specimens were explanted onto collagen gels allowing endothelial cells to migrate and form vascular tubes. Growth factors and/or neutralizing growth factor antibodies were added to the cultures. Endothelial cells were identified using a quail endothelial cell marker, QH1. Image analysis was used to quantify aggregate tube length. Results: Addition of any isoform (TGF-β1, TGF-β2 or TGF-β3) virtually prevented tubulogenesis (>95% inhibition), while stimulation of tubulogenesis occurred by adding neutralizing antibodies to TGF-β3, but not to TGF-β1 or -β2. When all three isoforms were added, tubulogenesis was enhanced, indicating the key role of TGF-β3. Documentation of the inhibitory effect of TGF-β isoforms on tubulogenesis is further supported by our experiments in which the marked enhancement of tube formation by bFGF and VEGF was negated when exogenous TGF-β1, -β2, or -β3 were added to the cultures. Conclusions: (1) TGF-β1, -β2 and -β3 each inhibits angiogenesis; (2) cooperation between the three TGF-β isoforms and other angiogenic factors is essential for the regulation of normal tubulogenesis and (3) the stimulatory effect of VEGF or bFGF on tubulogenesis is negated by exogenous TGB-βs.

Asymptomatic chronic partial obstruction of a normal ureter following dextranomer/hyaluronic acid copolymer (Deflux ) injection for grade I vesicoureteral reflux

Endoscopic management of vesicoureteral reflux with dextranomer/hyaluronic copolymer (Deflux(®), Oceana Therapeutics, Inc., Edison, NJ, USA) has gained widespread acceptance with increasing success rates and minimal morbidity. Formation of a pseudocapsule and calcification are known histologic changes at the injection site. Postoperative ureteral obstruction has been reported in cases of severe voiding dysfunction, neurogenic bladder and abnormal ureteral anatomy. We present a case of chronic asymptomatic obstruction in a normal ureter following injection of 0.7 ml Deflux.

Safety and efficacy of spica casts for immobilization following initial bladder closure in classic bladder exstrophy.

OBJECTIVESnPelvic immobilization constitutes a necessary component of successful bladder exstrophy closure. The efficacy of spica cast immobilization has been reported as markedly inferior to external fixation, with success rates below 25%. We reviewed our experience with spica cast immobilization following bladder closure.nnnPATIENTS AND METHODSnWe retrospectively reviewed classic bladder exstrophy patients undergoing bladder closure with spica cast immobilization. Success of bladder closure and complications related to immobilization were noted, as were age, type of closure, use of osteotomy, duration of immobilization, and number of cast changes.nnnRESULTSnFifteen patients underwent bladder closure (10 staged, 5 complete repair) at a median age of 4 days (range 1-6) and 14 were immobilized with spica casts. Initial closures were successful in 11 (73%). Success rates were higher in patients undergoing osteotomies (6/7, 86%) compared to those without osteotomies (5/8, 63%). No patients immobilized with spica casts developed serious complications related to their immobilization. Minor skin breakdown occurred in 3/14 patients (21%). Median time of immobilization was 39 days (range 22-48).nnnCONCLUSIONSnSpica casts are a safe, effective method of postoperative immobilization and are associated with a low risk of cast-related complications.

Controversies in the Management of Vesicoureteral Reflux

Vesicoureteral reflux (VUR) is the abnormal retrograde flow of urine from the bladder into the upper urinary tract. Diagnosis and subsequent management of VUR have become increasingly controversial, with differing opinions over which children should be evaluated for reflux, and when detected, who should undergo treatment. Management goals include prevention of recurrent febrile urinary tract infection (fUTI) and renal injury while minimizing the morbidity of treatment and follow-up. Management options include observation with or without continuous antibiotic prophylaxis and surgical correction via endoscopic, open or laparoscopic/robotic approaches. Management should be individualized and based on patient age, health, risk of subsequent renal injury, clinical course, renal function, and parental preference.

The prognostic impact of an abnormal initial renal ultrasound on early reflux resolution

OBJECTIVEnIn a group of children diagnosed with vesicoureteral reflux (VUR) we evaluated renal ultrasound findings, associated findings on renal scan, and prognostic impact on VUR resolution.nnnMETHODSnMedical records were reviewed for children with primary reflux and no history of antenatal hydronephrosis who underwent an initial renal ultrasound. Abnormal renal ultrasound was defined as hydronephrosis or relative difference in renal size ≥1 cm. Reflux resolution was evaluated at 2 years post diagnosis.nnnRESULTSnIn 129 children with VUR (111 girls, 18 boys), 39 (30%) had an abnormal renal ultrasound. Two-year VUR resolution in the abnormal renal ultrasound group was 21% versus 46% in the group with normal renal ultrasound (P = 0.01). Combining grade II and III reflux, an abnormal ultrasound was associated with a statistically significantly lower resolution rate (grade II-III 23% vs 47%, P = 0.049). For children with moderate hydronephrosis, 8/9 (89%) had abnormal initial renal scans and all failed to achieve resolution of reflux at 2 years.nnnCONCLUSIONSnIn this cohort of children with VUR, 30% had abnormalities on renal ultrasound. The presence of moderate hydronephrosis on ultrasound may indicate a high likelihood of abnormality on renal scan and failure to achieve early resolution of VUR.

Buccal mucosal graft urethroplasty in the treatment of urethral strictures: experience using the two-surgeon technique.

At our institution, the majority of buccal mucosal graft urethroplasties are performed using a two-team approach with an otolaryngologic surgeon. We report our two-surgeon experience with buccal mucosal grafting for reconstruction of all anterior urethral strictures. Twenty-four men underwent autologous buccal mucosal graft urethroplasty between October 2001 and September 2008 for recurrent urethral stricture disease. Twenty-two underwent a single-stage repair and two underwent a two-stage repair. Medical charts were retrospectively reviewed for demographics, comorbidities, etiology, location and length of stricture, and prior interventions in order to identify predictors of buccal urethroplasty success, defined as no evidence of stricture recurrence. All patients underwent retrograde urethrogram and cystoscopy. Operative and anesthesia times were evaluated. We determined an overall success rate of 83.3% (20 of 24 cases). Mean anesthesia time for single-stage urethroplasty was 155 min and mean operative time was 123 min. One of the two two-stage urethroplasties experienced stricture recurrence (50%). The single-stage buccal graft success rate was 86.4% (19 of 22 cases). Two of the four who developed recurrent stricture disease that required intervention had undergone a previous mesh urethroplasty. Complications developed in four of 24 patients (16.6%), including superficial wound infection (one), superficial wound dehiscence (two), and abscess/fistula formation requiring reoperation (one). The buccal mucosa is an ideal tissue for both single- and two-stage substitution urethroplasty for patients with recurrent stricture disease. Our two-surgeon technique minimizes anesthesia and operative times, and contributes to the overall high success rate and relatively low complication rate.

School nurse perceptions and knowledge of pediatric toileting

OBJECTIVEnWe surveyed school nurses on toileting conditions in schools, their level of understanding related to normal toileting patterns in school-age children, and whether they are in need of additional resources to promote healthy toilet habits for their students.nnnMATERIALS AND METHODSnAn Institutional Review Board approved web-based survey with 34 questions was employed; 562 nurses completed the survey and 97% were currently employed as school nurses. Participants were invited via email blasts through national school nursing associations and the Iowa Department of Education.nnnRESULTSnOnly 48% and 33% of respondents suspected an underlying health problem in children with frequent urination and bladder or bowel accidents, respectively. Despite 61% reporting never receiving information about childrens normal elimination patterns, 43% had been asked to provide such information to teachers. Only 42% felt they had adequate resources to respond to such requests. School nurses requested information about treatment of dysfunctional elimination (67%), health effects of childhood toileting habits (65%), fluid intake guidelines (44%) and improvement of bathroom facilities (39%); 70% were unaware of local providers specially trained to treat children with these problems.nnnCONCLUSIONSnOur survey results suggest that school nurses need additional information and resources in order to promote healthy elimination patterns in school children.

Urological Manifestations of Duchenne Muscular Dystrophy

PURPOSEnDuchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date.nnnMATERIALS AND METHODSnWe reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup.nnnRESULTSnOf 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology.nnnCONCLUSIONSnAs these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists.

Sacral Neuromodulation for Refractory Urge Incontinence Is Less Effective Following Spinal Surgery

Patients with neurogenic disorders and voiding dysfunction have been reported to respond poorly to sacral neuromodulation. We report on our experience in treating voiding symptoms with sacral neuromodulation after spinal surgery. The medical charts of patients evaluated for sacral neuromodulation from 2000–2008 were retrospectively reviewed. Indications, need for explantation, and clinical success (>50% symptom improvement) were recorded. The cohort of patients who had undergone prior spinal surgery was compared to patients with no history of spinal surgery or neurological disease. Thirty-two patients with a history of spinal surgery and 136 with no history of neurologic disease underwent sacral neuromodulation testing. Twenty men and women (62.5%) from the spinal surgery group ultimately underwent permanent implantation. Seventeen of the 32 patients were diagnosed with urge incontinence, of whom 52.9% reported a successful outcome at a mean of 2.3 years of follow-up, compared to an 80.3% success rate in patients with no history of spinal surgery (p = 0.018). Sixteen of 32 carried a diagnosis of urgency/frequency with 62.5% success at last follow-up, compared 73.9% (p = 0.35) of those without a history of spinal surgery or neurological disease. Thirteen of 32 patients diagnosed with urinary retention experienced a 61.5% long-term success rate, compared with 63.6% for those without spinal surgery and urinary retention. Six of 20 (30.0%) in the spinal surgery group were explanted at a mean time of 2.9 years, compared with 27 of 102 (26.5%) of the non-neurologic patients. Clinical success can be achieved using sacral neuromodulation in patients with voiding dysfunction and a history of spinal surgery; however, those with urge incontinence are less likely to report significant improvement.

The Iowa Voiding Improvement Partnership experience: Early observations with a collaborative pediatric uro-psychologic clinic

INTRODUCTIONnBladder and bowel dysfunction (BBD) are common problems in children presenting for pediatric urology referral. Psychiatric issues may be present in these children, making their treatment difficult. In 2013, the University of Iowa Voiding Improvement Partnership (VIP) Clinic was established for the treatment of these patients.nnnSTUDY OBJECTIVEnThis study sought to evaluate early experience with this specialized clinic, to determine the pre-existing urologic and psychologic conditions seen in these clinic patients, and to evaluate the clinical outcomes after VIP treatment.nnnSTUDY DESIGNnA retrospective, Institutional Review Board-approved review of all patients seen in the VIP Clinic was performed. The following were evaluated: patient demographics, underlying urologic and psychologic diagnosis, and treatment decisions. All patients were asked to complete the University of Iowa Pediatric Bladder and Bowel Dysfunction questionnaire at each visit. Questionnaire scores from the patients first and most recent clinic visits were compared.nnnRESULTSnTo date, 66 patients have been evaluated at the VIP Clinic, accounting for 112 clinic visits. The mean age of the VIP patients was 8.5 years (range, 4-16) and 59% of the patients were female. Pre-existing urological conditions and psychological conditions are shown in the Summary Table. A large number (62%) of patients required further psychological evaluation, secondary to concern for an undiagnosed psychiatric issue. In addition, the clinic had improved patients BBD symptoms over time. When first evaluated in clinic, patients had an average Iowa BBD Questionnaire score of 31 (range, 47-13), which improved to an average score of 25 (range, 47-7) (Pxa0=xa00.03). In addition, 23% of the patients improved to where they could be discharged from uro-psychologic care.nnnCONCLUSIONSnIt was feasible to establish the present multidisciplinary uro-psychology clinic. Such a clinic may unearth undiagnosed psychological issues, and improve bowel and bladder dysfunction in these difficult-to-treat patients.