Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism.

Background: Copy number variation (CNV) is a potential contributing factor to many genetic diseases. Here we investigated the potential association of CNV with nonsyndromic cryptorchidism, the most common male congenital genitourinary defect, in a Caucasian population.

Methods: Genome wide genotyping were performed in 559 cases and 1772 controls (Group 1) using Illumina HumanHap550 v1, HumanHap550 v3 or Human610-Quad platforms and in 353 cases and 1149 controls (Group 2) using the Illumina Human OmniExpress 12v1 or Human OmniExpress 12v1-1.

Pathway analysis supports association of nonsyndromic cryptorchidism with genetic loci linked to cytoskeleton-dependent functions.

Study Question: What are the genetic loci that increase susceptibility to nonsyndromic cryptorchidism, or undescended testis?

Summary Answer: A genome-wide association study (GWAS) suggests that susceptibility to cryptorchidism is heterogeneous, with a subset of suggestive signals linked to cytoskeleton-dependent functions and syndromic forms of the disease.

What Is Known Already: Population studies suggest moderate genetic risk of cryptorchidism and possible maternal and environmental contributions to risk. Previous candidate gene analyses have failed to identify a major associated locus, although variants in insulin-like 3 (INSL3), relaxin/insulin-like family peptide receptor 2 (RXFP2) and other hormonal pathway genes may increase risk in a small percentage of patients.

Phenotype specific association of the TGFBR3 locus with nonsyndromic cryptorchidism.

Purpose: Based on a genome-wide association study of testicular dysgenesis syndrome showing a possible association with TGFBR3, we analyzed data from a larger, phenotypically restricted cryptorchidism population for potential replication of this signal.

Materials And Methods: We excluded samples based on strict quality control criteria, leaving 844 cases and 2,718 controls of European ancestry that were analyzed in 2 separate groups based on genotyping platform (ie Illumina® HumanHap550, version 1 or 3, or Human610-Quad, version 1 BeadChip in group 1 and Human OmniExpress 12, version 1 BeadChip platform in group 2). Analyses included genotype imputation at the TGFBR3 locus, association analysis of imputed data with correction for population substructure, subsequent meta-analysis of data for groups 1 and 2, and selective genotyping of independent cases (330) and controls (324) for replication.

IL-18 neutralization ameliorates obstruction-induced epithelial-mesenchymal transition and renal fibrosis.

Ureteral obstruction results in renal fibrosis in part due to inflammatory injury. The role of interleukin-18 (IL-18), an important mediator of inflammation, in the genesis of renal fibrosis was studied using transgenic mice overexpressing human IL-18-binding protein. In addition, HK-2 cells were analyzed following direct exposure to IL-18 compared to control media.

Tap water irrigation and additives to optimize success with the Malone antegrade continence enema: the Indiana University algorithm.

Purpose: We report the long-term effectiveness of standard tap water for Malone antegrade continence enema irrigation as well as our algorithm for managing refractory constipation/fecal incontinence in a large single institution experience.

Materials And Methods: We retrospectively reviewed the charts of 256 Malone antegrade continence enema procedures performed for chronic constipation and/or incontinence due to neuropathic bowel. Continence, type of fluid used to irrigate the colon, volume of flushes and the need for additives were recorded and a database was created.

The Malone antegrade continence enema: single institutional review.

Purpose: We report the long-term outcome of the Malone antegrade continence enema procedure in the treatment of chronic constipation and fecal incontinence in children with neuropathic bowel.

Materials And Methods: We performed a retrospective chart review of 256 Malone antegrade continence enema procedures. Patient age at surgery, bowel segment used, location of stoma, number and type of revisions required, and fecal continence were documented and a database was created.

The JNK inhibitor SP600129 enhances apoptosis of HCC cells induced by the tumor suppressor WWOX.

Background/aims: The FRA16D fragile site gene WWOX is a tumor suppressor that participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1 interacts with WWOX and inhibits apoptosis. We investigated the function of WWOX in human hepatocellular carcinoma (HCC) and the effect of JNK inhibition on WWOX-mediated apoptosis.

Cytokines in epithelial-mesenchymal transition: a new insight into obstructive nephropathy.

Purpose: Tubulointerstitial fibrosis is the final common pathway to end stage renal disease. The pathophysiology of renal fibrosis involves fibroblast proliferation, macrophage infiltration, the elaboration of cytokines and other proinflammatory mediators, and an imbalance in extracellular matrix deposition and degradation. Although the exact origin of activated fibroblasts remains uncertain, emerging evidence indicates that mature tubular epithelial cells are capable of transforming into myofibroblasts under pathological conditions, a process that is called epithelial-mesenchymal transition.

Management of nephrolithiasis after Cohen cross-trigonal and Glenn-Anderson advancement ureteroneocystostomy.

Purpose: Ureteroneocystotomy is frequently performed for ureteral injury or vesicoureteral reflux. The Glenn-Anderson technique advances the ureteral orifice distal to its native position, while the Cohen technique crosses the orifice to the opposite trigone. Each treatment can alter access to the upper genitourinary tracts.

Specimen extraction with a surgical glove during laparoscopic radical prostatectomy.

Introduction And Objective: Cost containment during techniques of laparoscopic radical prostatectomy remains an ongoing concern. We present a cost-effective alternative technique of specimen extraction using a surgical glove.

Materials And Methods: We describe an alternative technique of prostate removal using a surgical glove in seven patients who underwent laparoscopic radical prostatectomy using a robotic-assisted technique.

Neuromodulation in pediatrics.

Several neuromodulatory options are available for selected children who have voiding dysfunction resistant to conventional therapy. Integral to all types of treatment is an educated team that reinforces progress rather than cure and encourages long-term behavioral changes.

Associations with contralateral recurrence following nephrectomy for renal cell carcinoma using a cohort of 2,352 patients.

Purpose: We determined the incidence of and factors associated with the development of renal cell carcinoma (RCC) in the contralateral kidney after nephrectomy for localized RCC.

Materials And Methods: Between 1970 and 2000, 2,352 patients with sporadic, localized unilateral RCC and a normal contralateral kidney underwent nephrectomy for RCC. Cancer specific survival rates were estimated using the Kaplan-Meier method.

Urinary matrix calculi: our experience at a single institution.

Purpose: Matrix stones are an uncommon form of urinary calculi and may be mistaken for tumors involving the renal collecting system, thereby presenting a diagnostic and therapeutic dilemma to the practicing urologist.

Materials And Methods: From 1980 to 2003 we identified 5 patients with urinary matrix stones referred to our tertiary medical center for evaluation and treatment.

Results: All 5 cases had complex clinical and radiographic features at presentation.