Gene expression change study in hypospadias by microarray / 中华泌尿外科杂志

Objective To detect the gene expression changes between urethra plates from hypospadias patients and foreskins from non-hypospadias patients by microarray and to investigate the underlying mechanisms of hypospadias.Methods Twelve hypospadias patients,aged 6-12 months (mean,8 months),were enrolled as the test group,including 5 moderate and 7 severe hypospadias patients.Six age-matched patients underwent circumcision were enrolled as controls.Samples from hypospaidas patient's urethra plates during hypospadias repair and samples from the foreskins during circumcision were obtained and processed into Tri-Reagent immediately for RNA extraction.Oligonucleotide expression microarrays were used to detect genes expression changes in tissues from patients with and without hypospadias.This microarray analysis incorporated 22 000 genes.The intensity of all genes present was analyzed by one-way ANOVA (P＜0.01) and Tukey's test.Four estrogen responsive genes,CYR61,CTGF,ATF3 and GADD45β,were tested by RT-PCR in 8 controls,8 moderate hypospadias and 8 severe hypospadias as well.Results Ninty-four genes were detected differentially expressed in hypospadias patients compared with phimosis patients.There were 47 genes upregulated in moderate hypospadias compared with controls(P＜0.01),68 genes up-regulated in severe hypospadias compared with controls(P＜0.001),17 genes up-regulated in severe hypospadias compared with moderate hypospadias(P＞0.05).These genes were involved in different cell functions such as growth regulation and signal transduction.CYR61,CTGF,ATF3 and GADD45β,known to be estrogen responsive or to interact with estrogen receptor were found up-regulated in microarray and the up-regulations were confirmed by RT-PCR.Conclusions The up-regulated genes contribute to the development of hypospadias.Up-regulation of estrogen responsive genes may play important roles in the development of hypospadias.

Prenatal intervention for urinary obstruction and myelomeningocele

Widespread use of ultrasonography has resulted in an increase in the recognition of fetal hydronephrosis. The enthusiasm that accompanied early interventions has been tempered by the experience and results obtained over the past 2 decades. The goal has remained the same: to identify patients with serious prenatal obstruction and to identify those which may benefit from intervention. Myelomeningocele remains a devastating congenital anomaly. Fetal and experimental studies suggested that patients with myelomeningocele could benefit from prenatal intervention. Advances in technology and perinatal management have made intervention for more complex malformations such as myelomeningocele possible. This article will review current knowledge and will detail rational management for the management of prenatal hydronephrosis. The current state of antenatal myelomeningocele repair and the urologic implications will be described as well.

Surgical management of the neurogenic bladder and bowel

Spina bifida and myelodysplasia are associated with neurogenic abnormalities of the bladder and bowel function. All children with myelodysplasia require an evaluation of their urinary tract with ultrasound and urodynamics to confirm normal bladder and kidney function. Patients with anatomical and functional abnormalities require treatment, the mainstay being intermittent catheterization and anticholinergic medication. The treatment goals for patients with a neurogenic bladder are the preservation of the upper urinary tract, bladder and bowel continence, independence, autonomy, and facilitation of self-esteem. A minority of children will not respond to conservative therapy and will ultimately require surgical intervention. This review will discuss the surgical options for bladder augmentation, bladder neck reconstruction and closure, as well as the methods for the creation of continent catheterizable stomas. The timing, indications, and description for each procedure will be addressed. Finally, the antegrade continence enema procedure will be described for the management of refractory fecal incontinence