Low-dose Human Chorionic Gonadotropin Stimulation Test as a Prognostic Incontinent Indicator in Boys With Bladder Exstrophy-epispadias Complex.

OBJECTIVE: To investigate the effect of low-dose human chorionic gonadotropin (HCG) administration on structural changes in the lower urinary tract in boys with urinary incontinence in the setting of bladder exstrophy-epispadias complex (BEEC). PATIENTS AND METHODS: We prospectively evaluated 30 patients (median age 7.5 years) with BEEC and randomly divided them into 2 groups. Patients in the HCG group were administered 250 IU HCG intramuscularly 3 times per week during a 4-week period. The other 15 patients served as the control group. The patients were followed up for a mean duration of 4 years. Incontinence rate, hormonal changes, penile length, prostate size, and bladder capacity were evaluated using 3D sonography or pelvic magnetic resonance imaging and uroflowmetry studies before and after HCG administration. RESULTS: The incontinence score improvement was significantly higher in the HCG group (P = .01). A significant increase was detected in the health-related quality of life score of both patients and parents at the final follow-up (P < .001). The total prostate size (P < .0001) and bladder capacity (P < .0001) increased significantly in all patients of the HCG group. Basal serum testosterone level increased significantly after the first (P = .001) and last (P < .001) injections with no significant increase 3 months after the last injection (P > .05). No major side effect was found following the administration of HCG, with no need for open surgical bladder neck reconstruction. CONCLUSION: Our preliminary results suggest the role of low-dose HCG in boys with BEEC suffering from urinary incontinence. The data also reveal the role of prostate enlargement in the improvement of urinary incontinence. Chronic treatment with HCG increases bladder capacity that may facilitate future reconstructive surgery.

Drainage-related ultrasonography (DRUS): a novel technique for discriminating obstructive and nonobstructive hydroureters in children.

BACKGROUND: Despite advances in urologic imaging, the paucity of an optimal technique that accurately clarifies obstructive and nonobstructive hydroureter exists. OBJECTIVE: This study was conducted to introduce a novel and modified ultrasonographic technique, known as drainage-related ultrasonography (DRUS), discriminating obstructive and nonobstructive, nonrefluxing hydroureter. MATERIALS AND METHODS: A total of 358 children (mean age, 3.7 years) with 418 nonrefluxing hydroureter were included. These children were composed of two groups of obstructive nonrefluxing (141 children with 157 dilated ureters) and nonobstructive, nonrefluxing (217 children with 261 hydroureter). The definite diagnosis regarding the subtype of hydroureter was derived from appropriate investigation. The maximum diameter of the dilated ureter, which was observed on ultrasonography, was recorded before and after 3 h of catheterization, as D1 and D2, respectively. To assess the D ratio, a formula was developed, that is, [(|D1 - D2|)/D1] × 100. Values were recorded and cutoff points were set to discriminate between subtypes. RESULTS: Obstructive versus nonobstructive subtypes of nonrefluxing hydroureter were clarified with 78.5 % sensitivity and 83.4 % specificity, by setting a cutoff point of 22 % for the D ratio. Regardless of the cutoff point assigned to the reduction in D (D2 compared with D1), DRUS revealed 93.9 % sensitivity, 80.6 % specificity, 63.2 % positive predictive value, and 97.4 % negative predictive value in discriminating upper from lower obstruction. CONCLUSION: DRUS affords favorable results in terms of differentiating between obstructive and nonobstructive, nonrefluxing hydroureter, as well as between upper and lower obstruction in obstructive cases. It has the potential to become an efficient imaging modality in the diagnostic algorithm of hydroureter.

Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach.

INTRODUCTION: This study aimed evaluate the safety and feasibility of endoscopic potassium titanyl phosphate (KTP) laser application in the management of patients with radiation-induced hemorrhagic cystitis (RHC). TECHNICAL CONSIDERATIONS: We retrospectively reviewed the records of 20 patients with RHC who underwent endoscopic KTP laser ablation of telangiectatic bladder vessels between October 2005 and January 2013. After initial cystoscopy, KTP laser was used to ablate the submucosal vasculature while preserving the overlying mucosa. The surgical outcome was evaluated by duration of hematuria-free interval, number of episodes of hematuria, and number of required medical and/or surgical interventions after initial treatment. Overall, 20 patients underwent 26 sessions of KTP laser ablation of bladder vessels. The procedure was able to stop bleeding 92% of the time and the average hematuria-free interval after ablation was 11.8 months, with a range of 1-37 months. In 13 patients (65%) hematuria resolved after 1 session of KTP laser treatment, whereas 5 patients (25%) required multiple sessions. Two patients (10%) with severe hematuria continued to have bleeding after laser treatment, which necessitated proximal diversion of urine with percutaneous nephrostomy tubes to control bleeding. CONCLUSION: This study suggests that KTP laser, with its unique photoselectivity property, is a safe, effective, and durable treatment with minimal side effects for ablation of submucosal bladder vessels in patients with RHC.

The application of tissue-engineered preputial matrix and fibrin sealant for urethral reconstruction in rabbit model.

BACKGROUND: To introduce the role of fibrin sealant and preputial acellular matrix (PAM) as a new source of inert collagen matrix for urethral reconstruction. METHODS: A ventral urethral segmental defect was created in 24 male rabbits divided into four groups. In group 1 (G1), urethrotomy was closed in layers. In group 2 (G2), closure was followed by applying fibrin sealant. In groups 3 (G3) and 4 (G4), urethroplasty was performed with a patch graft of PAM, and in G4, fibrin sealant was also applied. Serial urethrography was performed before and after the operation. Then, the animals were euthanized, and their urethra was excised 1, 3, and 9 months postoperatively for further electron microscopic examination, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, and immunohistochemical (IHC) staining with CD34, CD31, desmin, SMA, and α-actin. RESULTS: In G1 and G2, the fistula repair failed in all the time points. In G3 and G4, serial urethrography confirmed the maintenance of a wide urethral caliber without signs of strictures or extravasations. Satisfactory vascularity was observed in G3 and G4 during the whole study, which was more significant in G4 after 9 months of follow-up. The presence of a complete transitional cell layer was confirmed over the graft in G3 and G4 in all time points. IHC staining confirmed the effectiveness of fistula repair in G3 and G4, 3 months postoperatively. CONCLUSION: This rabbit model showed that PAM combined with fibrin sealant may herald a reliable option for repairing segmental urethral defects.

Anal sphincter repair with muscle progenitor cell transplantation: serial assessment with iron oxide-enhanced MRI.

OBJECTIVE: The purpose of this study was to assess homing of ultrasmall superparamagnetic iron oxide (USPIO)-labeled muscle progenitor cells in an experimental rabbit model of anal sphincter repair using MRI. MATERIALS AND METHODS: Twelve rabbits underwent external anal sphincterotomy and randomly received injection of either autologous muscle progenitor cells labeled with USPIO at a concentration of 4 mg/10(6) cells (experimental group) or saline (control group) at the site of sphincter damage. In vivo MRI, electromyography, and manometry were performed before, 1 hour after, and 1, 2, and 4 weeks after the injection. At the end time point, anal sphincter sections were obtained for histologic analysis. Semiquantitative analysis of fibrosis, desmin, iron, CD3, and CD68 was performed using two microscopic fields in two distinct regions of the sphincter according to either presence (zone I) or absence (zone II) of signal loss on the corresponding MR images. RESULTS: Labeling efficiency was 88.67% and did not influence cell viability. On follow-up images of the cell-transplanted rabbits, significant influence was reported at 1 hour, 1 and 2 weeks after transplantation. The maximum signal loss was detected at 1 hour (75.7%). Regenerating myofibers stained positively for desmin and mainly correlated to zone I on MR images. Clusters of iron-positive particles were detectable in the myofibers located mainly at the site of injection, which correlated well to zone I. Significant signal loss and Perls Prussian blue-positive area were not detected in the control group. Functional studies showed significant improvement in sphincter pressure and electrical activity in the experimental group after 4 weeks (p<0.001). CONCLUSION: Our results support the potential of iron oxide-enhanced MRI for serial monitoring of transplanted cells in an animal model of anal sphincter repair.

Na(+)-H+ exchange inhibition attenuates ischemic injury in rat random pattern skin flap: the role of mitochondrial ATP-sensitive potassium channels.

Necrosis of distal portion of skin flaps due to ischemia still remains a problem in plastic surgery. Following ischemia, a cascade of deleterious events including over-activity of Na(+)-H(+) Exchanger (NHE) takes place. In present study we evaluated the effect of the potent NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) on ischemic tissue injury in a skin flap model, and investigated the role of mitochondrial ATP-sensitive K(+) channels (K(ATP)) in this phenomenon. Seventy-eight rats were randomly divided into thirteen treatment groups (6 rats each). Four groups received different doses of EIPA in the flap. EIPA/GLY group received an effective dose of a K(ATP) channel blocker, glibenclamide (GLY, 0.3mg/kg) intraperitoneally (i.p.) 30 min before raising the flap, and a local effective dose of EIPA (0.1mM) immediately after raising the flap. EIPA/diazoxide group (EIPA/DIA) received a sub-effective dose of diazoxide (7.5mg/kg i.p.) 30 min before raising the flap and a local sub-effective dose of EIPA (0.075 mM). EIPA 0.1 and 0.2mM significantly increased flap survival area compared to control group (56.01 ± 6.1%, P<0.001). The protective effect of EIPA (0.1mM) was abolished by administration of glibenclamide (0.3mg/kg i.p.). Co-administration of a sub-effective dose of EIPA (0.075 mM), with a sub-effective dose of diazoxide (7.5mg/kg i.p.) significantly improved flap survival (P<0.05). We demonstrated that the NHE inhibitor, EIPA can increase random pattern skin flap survival. Administration of diazoxide potentiates this effect, while glibenclamide abolishes that, implicating that the protective effect of EIPA is mediated through mitochondrial-K(ATP) channels.

Prostate cancer imaging: what the urologist wants to know.

No consensus exists at present regarding the use of imaging for the evaluation of prostate cancer. Ultrasonography is mainly used for biopsy guidance and magnetic resonance imaging is the mainstay in evaluating the extent of local tumor. Computed tomography and radionuclide bone scanning are mainly reserved for assessment of advanced disease. Positron emission tomography is gaining acceptance in the evaluation of treatment response and recurrence. The combination of anatomic, functional, and metabolic imaging modalities has promise to improve treatment. This article reviews current imaging techniques and touches on the evolving technologies being used for detection and follow-up of prostate cancer.

Incidental findings at initial imaging workup of patients with prostate cancer: clinical significance and outcomes.

OBJECTIVE: The purpose of this article is to evaluate the frequency and clinical relevance of incidental findings in patients with prostate cancer who underwent abdominopelvic contrast-enhanced CT examination for initial staging workup. MATERIALS AND METHODS: We retrospectively reviewed 355 initial staging abdominopelvic contrast-enhanced CT examinations conducted from January 2000 to December 2010 in patients with prostate cancer for incidental findings that were not related to prostate cancer. A finding was judged to be potentially significant if therapeutic intervention, additional imaging, or tissue sampling was deemed advisable. The rate of incidental findings was correlated to patients' age and stratified prostate cancer risk groups. RESULTS: We found 779 incidental finding in 292 patients (82.3%), of which 75 findings in 73 patients (20.6%) were potentially significant. Indeterminate masses were the most prevalent significant finding (n = 62). Synchronous malignancy was detected in 21 patients (5.9%). Kidney cancer (n = 7 [1.97%]) was the most common malignancy, followed by lymphoma (n = 4 [1.13%]). Staging of the cancers revealed that 15 patients, including all of those with renal cancer, had N0M0 disease. Significant vascular abnormalities were reported in six cases. Additionally, significant findings, synchronous malignancies in particular, were identified at a higher rate in patients older than 65 years. However, no significant differences were noticed between the different prostate cancer risk groups. CONCLUSION: Abdominal contrast-enhanced CT for initial staging of prostate cancer shows a considerable prevalence of incidental vascular events and synchronous cancers, with kidney cancers being the most common. Notably, 71.5% of these malignancies were at early stage. Our results show an incremental value of CT in prostate cancer staging, with an emphasis on focused evaluation of the kidneys.

Office evaluation of male patients with lower urinary tract symptoms.

Lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) are one of the most common urologic disorders in men. Accurate history-taking and focused physical examination allows us to diagnose the majority of cases. A better understanding of risk factors helps us tailor our treatment and predict outcomes more accurately. Population studies are crucial in our understanding of LUTS/BPH natural history. Temporary prostatic urethral stents that are used for the management of urinary retention may also be used for evaluation of patients with detrusor hypo-contractility. The use of ultrasound to measure intravesical prostatic protrusion (IPP) and the Doppler study for prostate capsular artery resistive index are promising. Near-infrared spectroscopy (NIRS) examines the tissue oxygenation that may be affected by bladder outlet obstruction. The mathematical algorithm needs some fine-tuning, and its reproducibility is debatable. Serum and urinary biomarkers may help us to diagnose the disorder, and more effectively monitor patients' response to therapy. Among all, IPP is clinically more applicable at this time.

Protective effects of acute lithium preconditioning against renal ischemia/reperfusion injury in rat: role of nitric oxide and cyclooxygenase systems.

Delayed graft function secondary to ischemia/reperfusion injury has been shown to be associated with increased rate of allograft failure following kidney transplantation. Previously, we have shown that chronic lithium pretreatment protects kidney against ischemia/reperfusion injury. In the present study we aimed to examine the effects of acute lithium administration on the renal ischemia/reperfusion injury in rat. Ischemia/reperfusion injury was induced by clamping left renal pedicle for 60 min, two weeks after right nephrectomy. The mechanism of lithium-mediated renoprotection was explored by combined use of lithium and nitro-l-arginine methyl ester (L-NAME) (non-selective nitric oxide synthase inhibitor) and/or indomethacin (non-selective cyclooxygenase pathway inhibitor). Lithium-treated animals were given 40 mg/kg lithium chloride intraperitoneally, 30 min before ischemia. To investigate the role of nitric oxide and cyclooxygenase pathways in renoprotective effect of lithium, L-NAME and/or indomethacin were administered before lithium injection. Serum creatinine, blood urea nitrogen, and renal histology were assessed after 24h of reperfusion. Lithium preconditioning significantly reduced creatinine and blood urea nitrogen (P<0.001) and improved renal histology. Administration of L-NAME completely reversed renoprotective effect of lithium. In contrast indomethacin significantly potentiated the lithium renoprotection. Moreover, co-administration of L-NAME and indomethacin completely abolished the protective effects of lithium. The results show that a single dose of lithium significantly improves renal function following ischemia/reperfusion injury. In conclusion, the ability of lithium to enhance renal tissue tolerance against ischemia/reperfusion injury suggests a potential clinical application in the setting of kidney transplantation. However, more detailed investigations are required before any definite conclusion.

Safety, efficacy and health related quality of life of autologous myoblast transplantation for treatment of urinary incontinence in children with bladder exstrophy-epispadias complex.

PURPOSE: Children with bladder exstrophy-epispadias complex undergoing endourethral autologous myoblast transplantation to treat urinary incontinence were evaluated at 4 years of followup regarding the safety, efficacy and durability of the procedure, and health related quality of life. MATERIALS AND METHODS: Seven boys underwent autologous myoblast transplantation between May and December 2006. All patients had persistent urinary incontinence after bladder neck reconstruction and bulking agent injection. Patients were followed for 4 years after autologous myoblast transplantation regarding clinical outcomes and cystometric, urodynamic, uroflowmetric and urethrocystoscopic evaluations. Health related quality of life was also measured before treatment and at final followup. RESULTS: No evidence of urinary obstruction was observed. Five children (71%) were completely continent and 2 (29%) were socially dry with complete daytime dryness at final followup. Health related quality of life was improved significantly. Urodynamic studies revealed a progressive increase in bladder capacity (p <0.001). Mean detrusor leak point pressure showed a 27 cm H(2)O (158%) increase during 4-year followup. Uroflowmetry parameters of voided volume and average maximum flow rate were improved significantly (p <0.001). CONCLUSIONS: The 4-year outcomes demonstrate that autologous myoblast transplantation for urinary incontinence in children with bladder exstrophy-epispadias complex is relatively reliable, reproducible, safe and effective with minimal morbidity. This novel treatment represents a promising therapeutic approach in patients with urinary incontinence. Further randomized trials with larger numbers of patients and longer followup are needed.

In-vivo autologous bladder muscular wall regeneration: application of tissue-engineered pericardium in a model of bladder as a bioreactor.

PURPOSE: Tissue-engineered pericardium (TEP) is a collagen-rich matrix that has previously been shown to promote in vivo and in vitro tissue regeneration. We evaluated the potential of TEP as a source for the in-vivo creation of bladder muscular wall grafts. We used bladder wall as a bioreactor to create a natural environment for cellular growth and differentiation. MATERIALS AND METHODS: Sixteen rabbits were divided into four groups. A control group underwent classical bladder autoaugmentation. Other groups underwent insertion of TEP between bladder mucosa and muscular layer: group 2 with insertion of TEP, group 3 with TEP over autologous bladder muscular wall fragments, and group 4 with autologous bladder smooth muscle cells (SMCs) seeded on TEP. After 4 and 8 weeks, grafts were biopsied for histopathological evaluations. RESULTS: Frames from groups 3 and 4 demonstrated more organized muscular wall generation with a significantly higher number of CD34 + endothelial progenitor cells and CD31 + microvessels, and maintenance of α-smooth muscle actin expression through immunohistochemistry. Group 4 showed significant enhancement of SMC penetration to TEP. Although the fragment-seeded group required a simpler procedure, the cell-seeded group showed superior organization of the muscular layer on histopathology. We found a semi-organized muscular layer and new vessels in the margins of TEP in group 3, while there was a homogeneous pattern of SMCs and new vessels in both the margins and center of TEP in group 4. CONCLUSIONS: This preliminary work has important functional and clinical implications, as it indicates that use of the autologous SMC seeding method may enhance the properties of TEP in terms of bladder wall regeneration.

Miniature pyeloplasty as a minimally invasive surgery with less than 1 day admission in infants.

PURPOSE: Open dismembered pyeloplasty is usually performed through flank, anterior subcostal or posterior lumbotomy incisions. These incisions are cosmetically less acceptable and may produce significant postoperative pain. We present the smallest incision for open pyeloplasty, called a 'miniature pyeloplasty'. The aim of this study was to reduce hospital stay and postoperative pain, along with enhanced cosmetic results. PATIENTS AND METHOD: 373 infants (mean age 4 months) with hugely dilated pelvises underwent the miniature pyeloplasty. The exact site of incision was determined by intraoperative renal ultrasonography and palpation. A muscle-splitting incision was made in the most dependent part of the lower quadrant. After meticulous dissection of the ureteropelvic junction component, the affected section was pulled out and underwent classic dismembered pyeloplasty without renal pelvis reduction. All children had long-duration stented anastomoses. Surgical incision size, operative time, hospital stay, postoperative analgesic use and complication rate were recorded. RESULTS: The operation was successful in all patients. The mean operative time was 53 min (range 43-75) and patients were discharged after 18 ± 3 (mean ± SD) h. Incision size ranged from 11 to 15 mm (mean 13). No narcotic analgesic was required postoperatively and there were no major complications during follow up. CONCLUSIONS: Miniature pyeloplasty is a safe and successful technique for ureteropelvic junction obstruction that avoids long operative time with negligible postoperative pain compared to the classic open pyeloplasty in infants. The exact incision site must be reconfirmed intraoperatively by physical examination or renal ultrasonography.

Precise delineation of ureterocele anatomy: virtual magnetic resonance cystoscopy.

PURPOSE: To evaluate the application of virtual magnetic resonance cystoscopy (VMRC) in precise detection of ureterocele extension compared with conventional cystoscopy (as the gold standard) and other imaging modalities. MATERIALS AND METHODS: Medical records of 55 patients, with confirmed diagnosis of ureterocele during endoscopic surgery, were reviewed retrospectively. Thirty-two of them (14 girls and 18 boys, age range: 4-22 months) whom underwent investigation with magnetic resonance urography, voiding cystourethrography, and ultrasonography were included. Images were obtained using T1-scanner with pulse sequences (TR = 30-50 ms, TE = 2-8 ms, echo train length = 8 moderate, filip angel = 40°). Using multiplanar reformation from source images, the bladder was evaluated to determine ureterocele anatomy. Virtual findings were compared with other imaging studies. RESULTS: Cystoscopy confirmed 3(9%) bilateral and 9(28%) unilateral intravesical ureteroceles, and 20(63%) ectopic type. VMRC was the most sensitive method in detection of ureterocele anatomy and its extension (detection rate: 94%) It detected one case of bilateral intravesical and three ectopic types, which were not detected in other imaging modalities. CONCLUSION: VMRC is a promising non-invasive technique in exact detection of ureterocele extension prior to endoscopic operation. It permits evaluation of concurrent genitourinary abnormalities and facilitates preoperative planning especially in complex ectopic ureteroceles. It may be indicated as a clinical routine, when conventional cystoscopy is contraindicated.

Use of biodegradable plates and screws for approximation of symphysis pubis in bladder exstrophy: applications and outcomes.

OBJECTIVES: To investigate the feasibility of biodegradable plate and screws for the tension-free internal fixation of the symphysis pubis in patients with bladder exstrophy, with a particular emphasis on pelvic bone changes as seen on 3-dimensional computed tomography. METHODS: A total of 11 children with bladder exstrophy underwent surgical repair with biodegradable plate and screw fixation (mean age 4.13 years). Of the 11 patients, 6 had a history of failed bladder closures and pelvic osteotomies, 1 had failed bladder closure, and 4 had no such history. All 11 children underwent single-stage classic bladder closure. Subsequently, the symphysis pubis was fixed by placing a biodegradable miniplate and screws. The patients remained in leg bandages for 2 weeks. The follow-up period was 6-50 months (average 30.1). Three-dimensional pelvic bone computed tomography was performed initially and at 6 months postoperatively. RESULTS: All 11 children had an uneventful postoperative period, except for a superficial infection at the site of the suprapubic tube in 1 patient. The mean hospital stay was 13.4 days. The plate remained in situ, and no further surgery was needed to remove it. Pelvic 3-dimensional computed tomography revealed a 35.48 ± 1.50 mm, 20.06 ± 1.97 mm, and 10.73° ± 0.84° decrease in pubic diastasis, intertriradiate distance, and iliac wing angle at 6 months postoperatively, respectively. Significant improvement was seen in the patients' urinary continence and gait compared with the preoperative values. At the final follow-up visit, 6 patients were socially dry. CONCLUSIONS: Internal fixation of the pubic arch using biodegradable plates as a biocompatible alternative to current metal fixation system offers intriguing potential for early exstrophy management. This adds a layer of security to the pubic closure, in addition to the current surgical armamentarium for bladder exstrophy.

Chronic lithium treatment protects the rat kidney against ischemia/reperfusion injury: the role of nitric oxide and cyclooxygenase pathways.

Ischemia/reperfusion injury is a major problem in renal transplantation. Several evidences represent lithium preconditioning effect against ischemia/reperfusion injury in various tissues. In this study our aim was to investigate the protective effect of chronic lithium administration on renal ischemia/reperfusion injury in rats. Ischemia/reperfusion injury was induced by clamping left renal pedicle for 60 min, 2 weeks after right nephrectomy. Lithium-treated animals received lithium-chloride in drinking water for 30days. In order to investigate the role of nitric oxide (NO) and cyclooxygenase (COX) pathways in renoprotective effect of lithium, N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME, NO synthase inhibitor) and indomethacin (COX inhibitor) were used, respectively. Serum creatinine, blood urea nitrogen and renal histology were assessed 24h after inducing ischemia/reperfusion injury. Dimercaptosuccinic acid scan was also performed 48 h following operation. Chronic lithium treatment in ischemia/reperfusion injury groups significantly decreased creatinine (1.09±0.16 mg/dl), blood urea nitrogen (59.0±13.38 mg/dl), histological damage (7.83%±4.02%) and improved cortical function compared with non-lithium treated animals (4.45±0.44, 176.66±12.24 mg/dl and 83.5%±3.5%, respectively) (P<0.001). Either L-NAME or indomethacin administration partially reversed the protective effect of lithium, while simultaneous blockade of NO and COX pathways completely abolished lithium renoprotective effect. Our results indicate that lithium ameliorates renal ischemia/reperfusion injury through NO and/or COX pathways. We propose that lithium pre-treatment as a simple and practical intervention to boost the renal viability and function after ischemia/reperfusion injury may be promising in the setting of transplantation.

Functional external anal sphincter reconstruction for treatment of anal incontinence using muscle progenitor cell auto grafting.

PURPOSE: This study aimed to investigate the feasibility of autologous muscle progenitor cell transplantation for anal sphincter regeneration in a rabbit model of anal incontinence. We examined the serial changes in structure, with particular emphasis on histology and functional properties of the anal sphincter. METHODS: External anal sphincterotomy was performed in 21 rabbits; these rabbits were randomly assigned to 2 groups. In group I (n = 9), autologous muscle progenitor cells were isolated from quadriceps myofiber explants, labeled with PKH-26, and injected into sphincter 3 weeks after sphincterotomy. In group II (n = 12), saline buffer was injected at the site of damage. Sphincter electromyography and manometry were performed immediately before sphincterotomy and 14, 28, and 60 days after injection in 3 animals in each group at every interval and the findings were correlated with histomorphological studies. In addition, electromyography and manometry were performed in the remaining 3 rabbits in group II after 6 months. RESULTS: In group II, a flaccid sphincter persisted during the 6 months of follow-up. In group I, muscle progenitor autografting accelerated sphincter myofiber repair and improvement in functional capacity of the damaged sphincter. Fluorescently labeled cells were detected in all of the grafted sphincters; regenerated myotubes were detectable at the injection site as evidenced by the presence of desmin. We also observed a significant decrease in interstitial fibrosis in the 4th week and strikingly higher amounts of Ki-67-positive cells in group I. Manometry and electromyography showed a significant improvement in the mean resting anal canal pressure and sphincteric electrical activity 4 weeks after cell injection, respectively. CONCLUSION: Transplanting muscle progenitor cells showed the potential for recapitulation of a myogenic program when injected into deficient rabbit anal sphincter. Objective anal measures of resting and stimulated pressures and electromyographic profile improved. Stem cell-mediated anal myoplasty warrants additional investigation as a new method to treat anal incontinence before attempting this modality in the clinical setting.

Three-dimensional anatomy of the pelvic bone in bladder exstrophy: comparison between patients managed with osteotomy and pubic symphysis internal fixation using metal plates.

OBJECTIVES: To compare intrapelvic osseous dimensions in classic bladder exstrophy patients who underwent pelvic osteotomy and pubic symphysis internal fixation, using metal plates without osteotomy by defining intrapelvic angles and distances using three-dimensional computed tomography scan (3D-CT). METHODS: Fourteen exstrophy patients who were operated with osteotomy (OST) and 19 patients who had undergone pubic approximation using metal plates (PLT) were enrolled in this study. 3D-CT was performed to measure 8 intrapelvic angles and 9 distances. In addition, a 3D-CT image of control group of 14 age- and sex-matched patients and the preoperative data of 12 cases (6 patients in each group) were considered to compare the bony aspects of exstrophy patients before and 6 months after surgery. RESULTS: Sacroiliac joint angle, pubococcygeal angle, ischiopubic angle, pubic diastasis, and inter-triradiate distance were different from controls in both techniques. Iliac wing angle, however, was at near normal values in PLT group. The result of before-after comparison revealed significant changes in iliac wing angle, sacroiliac joint angle, and pubic diastasis in both groups. CONCLUSIONS: Our study suggests that internal fixation of pubic arch using metal plates in bladder exstrophy may be as effective as the currently accepted osteotomy-containing techniques from the standpoint of intrapelvic osseous dimensions and angles. Modification of our new pubic approximation technique is essential to better recapitulate the anatomy of the normal bony pelvis.

Voltage-dependent calcium channel and NMDA receptor antagonists augment anticonvulsant effects of lithium chloride on pentylenetetrazole-induced clonic seizures in mice.

Although lithium is still a mainstay in the treatment of bipolar disorder, its underlying mechanisms of action have not been completely elucidated. Several studies have shown that lithium can also modulate seizure susceptibility in a variety of models. In the present study, using a model of clonic seizures induced with pentylenetetrazole (PTZ) in male Swiss mice, we investigated whether there is any interaction between lithium and either calcium channel blockers (CCBs: nifedipine, verapamil, and diltiazem) or N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine and MK-801) in modulating seizure threshold. Acute lithium administration (5-100mg/kg, ip) significantly (P<0.01) increased seizure threshold. CCBs and NMDA receptor antagonists also exerted dose-dependent anticonvulsant effects on PTZ-induced seizures. Noneffective doses of CCBs (5mg/kg, ip), when combined with a noneffective dose of lithium (5mg/kg, ip), exerted significant anticonvulsant effects. Moreover, co-administration of a noneffective dose of either MK-801 (0.05mg/kg, ip) or ketamine (5mg/kg, ip) with a noneffective dose of lithium (5mg/kg, ip) significantly increased seizure threshold. Our findings demonstrate that lithium increases the clonic seizure threshold induced by PTZ in mice and interacts with either CCBs or NMDA receptor antagonists in exerting this effect, suggesting a role for Ca(2+) signaling in the anticonvulsant effects of lithium in the PTZ model of clonic seizures in mice.

Genitourinary involvement in epidermolysis bullosa: clinical presentations and therapeutic challenges.

OBJECTIVES: To present our experience of children with epidermolysis bullosa (EB; a rare bullous disorder of the skin) with genitourinary involvement. PATIENTS AND METHODS: The medical records of eight children diagnosed with EB (six junctional and two dystrophic type) with genitourinary involvement were reviewed retrospectively. The data collected included age, clinical presentation, ultrasonographic findings, voiding cystourethrography, urodynamic and uroflowmetry studies, and the treatment challenges. The outcomes of the interventions were evaluated every 6 months. RESULTS: The mean age was 2.3 years (range 1 day to 7 years). The most common clinical presentations were urinary retention and voiding difficulty. Meatomy was performed in two of three boys followed by diminution of urological complaints. In children with vesico-ureteric reflux, subureteric injections of bulking agent and ureteric stenting were satisfactory. Detrusor instability and bladder compliance improved after α-blocker therapy. The mean (range) follow-up was 62.6 (11-120) months except for two who died in early infancy. CONCLUSIONS: Considering the potential urological involvement in every child with EB it is essential to provide patients with early appropriate treatment. Management of urological problems should preferably be in a way to entail minimal interventions and if required be performed using small sized instruments. Medical therapy seems promising for voiding dysfunction in this subset of patients.