Sarah D. Blaschko

Molecular mechanisms of external genitalia development.

External genitalia development occurs through a combination of hormone independent, hormone dependent, and endocrine pathways. Perturbation of these pathways can lead to abnormal external genitalia development. We review human and animal mechanisms of normal and abnormal external genitalia development, and we evaluate abnormal mechanisms that lead to hypospadias. We also discuss recent laboratory findings that further our understanding of animal models of hypospadias.

Urology Resident Publication Output and Its Relationship to Future Academic Achievement

PURPOSE Scholarly research is considered by many to be an important component of residency training but little is known about the quantity and types of publications produced by urology residents. To our knowledge whether publication efforts during residency predict future academic publication performance is also unknown. We evaluated resident productivity, as measured by peer reviewed publication output, and determined its relation to future publication output as junior faculty. MATERIALS AND METHODS We assembled a list of graduating residents from 2002 to 2004 who were affiliated with the top 50 urology hospitals, as ranked in 2009 by U.S. News&World Report. PubMed® was queried to determine the publication total in the last 3 years of residency of each individual and during years 2 to 4 after residency graduation. Resident publication output was stratified by research time and fellowship training. The relationship between resident productivity and future achievement was assessed. RESULTS We assessed the publication output of 251 urologists from a total of 34 training programs affiliated with the top 50 urology hospitals. Subjects published a mean total of 3.5 and a mean of 2.0 first author papers during training. Greater research time during residency was associated with increased productivity during and after residency. Publication during training correlated with publication during the early academic career. CONCLUSIONS Publication output correlated with increasing dedicated research time and was associated with the pursuit of fellowship training and an academic career. Publication during residency predicted future academic achievement.

De novo erectile dysfunction after anterior urethroplasty: a systematic review and meta‐analysis

Erectile dysfunction has been associated with urethroplasty operations, but the incidence of erectile dysfunction after anterior urethroplasty operations is largely unknown. A 1% incidence of de novo erectile dysfunction after anterior urethropathy was found with systematic review and meta analysis of 36 studies with 2323 patients. In most cases the erectile dysfunction was transient and resolved within six to twelve months.

A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs. Micro X-ray absorption near edge spectroscopy (μXANES) synchrotron analyses revealed high enrichment of zinc in the Drosophila equivalent of kidney stones, which was also observed in human kidney stones and Randall’s plaques (early calcifications seen in human kidneys thought to be the precursor for renal stones). To further test the role of zinc in driving mineralization, we inhibited zinc transporter genes in the ZnT family and observed suppression of Drosophila stone formation. Taken together, genetic, dietary, and pharmacologic interventions to lower zinc confirm a critical role for zinc in driving the process of heterogeneous nucleation that eventually leads to stone formation. Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches.

Repeat Urethroplasty After Failed Urethral Reconstruction: Outcome Analysis of 130 Patients

PURPOSE Male urethral stricture disease accounts for a significant number of hospital admissions and health care expenditures. Although much research has been completed on treatment for urethral strictures, fewer studies have addressed the treatment of strictures in men with recurrent stricture disease after failed prior urethroplasty. We examined outcome results for repeat urethroplasty. MATERIALS AND METHODS A prospectively collected, single surgeon urethroplasty database was queried from 1977 to 2011 for patients treated with repeat urethroplasty after failed prior urethral reconstruction. Stricture length and location, and repeat urethroplasty intervention and failure were evaluated with descriptive statistics, and univariate and multivariate logistic regression. RESULTS Of 1,156 cases 168 patients underwent repeat urethroplasty after at least 1 failed prior urethroplasty. Of these patients 130 had a followup of 6 months or more and were included in analysis. Median patient age was 44 years (range 11 to 75). Median followup was 55 months (range 6 months to 20.75 years). Overall, 102 of 130 patients (78%) were successfully treated. For patients with failure median time to failure was 17 months (range 7 months to 16.8 years). Two or more failed prior urethroplasties and comorbidities associated with urethral stricture disease were associated with an increased risk of repeat urethroplasty failure. CONCLUSIONS Repeat urethroplasty is a successful treatment option. Patients in whom treatment failed had longer strictures and more complex repairs.

Pubic Hair Grooming Injuries Presenting to U.S. Emergency Departments

OBJECTIVE To describe the demographics and mechanism of genitourinary (GU) injuries related to pubic hair grooming in patients who present to U.S. emergency departments (EDs). MATERIALS AND METHODS The National Electronic Injury Surveillance System contains prospectively collected data from patients who present to EDs with consumer product-related injuries. The National Electronic Injury Surveillance System is a stratified probability sample, validated to provide national estimates of all patients who present to U.S. EDs with an injury. We reviewed the National Electronic Injury Surveillance System to identify incidents of GU injury related to pubic hair grooming for 2002-2010. The variables reviewed included age, race, gender, injury type, location (organ) of injury, hospital disposition, and grooming product. RESULTS From 2002 to 2010, an observed 335 actual ED visits for GU injury related to grooming products provided an estimated 11,704 incidents (95% confidence interval 8430-15,004). The number of incidents increased fivefold during that period, amounting to an estimated increase of 247 incidents annually (95% confidence interval 110-384, P = .001). Of the cohort, 56.7% were women. The mean age was 30.8 years (95% confidence interval 28.8-32.9). Shaving razors were implicated in 83% of the injuries. Laceration was the most common type of injury (36.6%). The most common site of injury was the external female genitalia (36.0%). Most injuries (97.3%) were treated within the ED, with subsequent patient discharge. CONCLUSION Most GU injuries that result from the use of grooming products are minor and involve the use of razors. The demographics of patients with GU injuries from grooming products largely paralleled observations about cultural grooming trends in the United States.

Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol‐Treated mice

Because both androgens and estrogens have been implicated in penile morphogenesis, we evaluated penile morphology in transgenic mice with known imbalance of androgen and estrogen signaling using scanning electron microscopy (SEM), histology, and immunohistochemistry of androgen and estrogen receptors α/β. Penises of adult wild‐type, estrogen receptor‐α knockout (αERKO), estrogen receptor‐β knockout (βERKO), aromatase knockout (Arom‐KO), and aromatase overexpression (Arom+) mice were evaluated, as well as adult mice treated with diethylstilbestrol (DES) from birth to day 10. Adult penises were examined because the adult pattern is the endpoint of development. The urethral orifice is formed by fusion of the MUMP (male urogenital mating protuberance) with the MUMP ridge, which consists of several processes fused to each other and to the MUMP. Similarly, the internal prepuce is completed ventrally by fusion of a ventral cleft. In adult murine penises the stromal processes that form the MUMP ridge are separated from their neighbors by clefts. αERKO, βERKO, and Arom‐KO mice have penises with a MUMP ridge clefting pattern similar to that of wild‐type mice. In contrast, Arom+ mice and neonatally DES‐treated mice exhibit profound malformations of the MUMP, MUMP ridge clefting pattern, and internal prepuce. Abnormalities observed in Arom+ and neonatally DES‐treated mice correlate with the expression of estrogen receptor‐beta (ERβ) in the affected structures. This study demonstrates that formation of the urethal orifice and internal prepuce is due to fusion of separate epithelial‐surfaced mesenchymal elements, a process dependent upon both androgen and estrogen signaling, in which ERβ signaling is strongly implicated. Anat Rec, 296:1127–1141, 2013.

The Impact of Serial Prostate Biopsies on Sexual Function in Men on Active Surveillance for Prostate Cancer

PURPOSE NCCN Guidelines® recommend annual prostate biopsies for men with low risk prostate cancer on active surveillance. We determined whether erectile function decreases with the number of biopsies experienced. MATERIALS AND METHODS During a median 3.2-year followup after prostate cancer diagnosis in 2003 to 2010 at our institution 427 men on active surveillance underwent a total of 1,197 biopsies and provided 1,398 erectile function evaluations via the Sexual Health Inventory for Men questionnaire. For analysis we decomposed the 25-point questionnaire responses into a 5-point erectile function score and a 3-level sexual activity status. We used separate models adjusted for patient characteristics to determine whether either outcome varied with biopsy exposure. RESULTS At diagnosis the median age was 61 years and median prostate specific antigen was 5.3 ng/ml. Of the cases 70% were clinical stage cT1 and 93% were Gleason score less than 7. Of biopsies followed by evaluations 40% were the first undergone by the patient and 9% were the fifth to ninth. At the first erectile function evaluation 15% of men were inactive, 8% engage in stimulation and 77% engaged in intercourse. Sexual activity level changed in greater than 20% of respondents between evaluations. Adjusted erectile function scores were not associated with biopsy exposure cross-sectionally or longitudinally but they corresponded with the 50th, 63rd and 80th percentiles of erectile function by increasing sexual activity level. Similarly, sexual activity was not associated with biopsy exposure. Separated outcomes were more accurate and informative than Sexual Health Inventory for Men scores. CONCLUSIONS Our study had high power to detect erectile function-biopsy associations but it estimated that the effects were negligible. We recommend erectile function scores over Sexual Health Inventory for Men scores to avoid biased assessment of erectile function.

National Incidence and Impact of Noninfectious Urethral Catheter Related Complications on the Surgical Care Improvement Project

PURPOSE We defined the incidence and health outcomes related impact of noninfectious urethral catheter related complications for the 7 surgical procedures monitored by the Joint Commission as part of the Surgical Care Improvement Project. MATERIALS AND METHODS We performed a cross-sectional analysis of the 2007 National Inpatient Sample (a 20% stratified sampling of nonfederal United States hospitals) using ICD-9-CM procedure and diagnostic codes to identify the incidence of catheter related complications for coronary artery bypass graft, and noncoronary artery bypass graft cardiac surgery, hysterectomy, colon, hip, knee and major vascular surgery. Univariate and multivariate analysis (with a significance level of less than 0.05) was performed to determine if these complications were associated with length of stay, urinary tract infections and/or deaths. RESULTS A total of 1,420 cases of catheter related complications were identified nationally. The incidence of catheter related complications varied by surgical procedure (average 1 in 528 men and 1 in 5,217 women for all procedures). Univariate analysis revealed that in the presence of catheter related complications, mean length of stay (6 of 7 procedures, range 1.5 to 3.0 days, p <0.05) and urinary tract infection (5 of 7 procedures, absolute range 6.9% to 11.8%, p <0.05) were statistically increased for most procedures. Multivariate analysis demonstrated a significant association between catheter related complications, and increased length of stay (range 1.5 to 3.5 days, p <0.05) and urinary tract infection (OR 2.4-6.8, p <0.05) for 5 and 6 of 7 procedure types, respectively, but not mortality rate (0 of 7 procedures). CONCLUSIONS Catheter related complications are reported rarely, but are associated with increased length of stay and urinary tract infection rates for patients in the Surgical Care Improvement Project.

Sexual differentiation in the male and female mouse from days 0 to 21: A detailed and novel morphometric description

PURPOSE We hypothesized that a significant portion of sexual differentiation of mouse external genitalia occurs postnatally. To establish a baseline of normal development to which genital abnormalities could be compared, we determined morphometric measurements and morphological descriptions of the postnatal period of sexual differentiation in mice from birth to 21 days postnatally. MATERIALS AND METHODS The external genitalia of male and female CD-1® mice were serially sectioned for histological staining. Mice were studied by age group, including ages 0 to 1, 2 to 3, 4 to 5, 10 and 21 days. Three-dimensional reconstructions were created to visually compare differences. Morphometric measurements were made of the distal mouse external genitalia and compared across age groups, and between males and females. RESULTS The morphology of male and female mouse external genitalia is similar at 0 to 1 days but undergoes dramatic changes during 21 days. The changes include the development of mesenchymal extensions, which in males form the male urogenital mating protuberance and erectile bodies, as well as comparable structures in females. Differences in morphometric measurements in homologous males and females became pronounced during 0 to 21 days, serving as a baseline for recognizing the genesis of malformations of the mouse external genitalia. CONCLUSIONS Male and female mouse external genitalia are similar morphologically and morphometrically at birth but achieve dramatic differences by age 21 days, suggesting that a significant portion of sexual differentiation in the mouse occurs after birth. We described these changes using novel, accurate morphometric measurements and 3-dimensional reconstruction. These results will be useful for studying abnormal sexual development of the mouse external genitalia.