Faculty Bibliography

OBJECTIVE: To document the array of diagnostic modalities, the variety of errant diagnoses and treatments. and the time from initial presentation to ultimate diagnosis in girls with an ectopic single-system ureter draining an ectopic hypoplastic and/or dysplastic kidney. PATIENTS AND METHODS: Between 1990 and 1997, seven females were identified who had an ectopic hypoplastic and/or dysplastic kidney with an ectopically draining ureter, and who were treated at our institutions, either initially or upon referral. The nature and number of all diagnostic evaluations, previous diagnoses and treatments, and the time from presentation to definitive diagnosis were recorded. RESULTS: All seven females had a classical history of successful toilet training, a normal voiding pattern and continuous urinary incontinence. Typically, a solitary kidney was noted on the initial diagnostic evaluation by ultrasonography and/or intravenous urography. The mean (range) age at initial presentation was 3.2 (2-6) years. Additionally, voiding cysto-urethrography, urodynamics, radionuclide scintigraphy, computed tomography, magnetic resonance imaging and endoscopy were performed. The age at definitive diagnosis was 3-16.5 years and the mean (range) time from initial presentation to diagnosis was 5.7 (1-10) years. Nephroureterectomy was curative and all kidneys were dysplastic. CONCLUSION: Continuous urinary incontinence in females with a normal voiding pattern should prompt an evaluation for ureteric ectopia. When the initial evaluation yields the diagnosis of a solitary kidney, clinicians should be aware of the possibility of a hypoplastic and/or dysplastic, often ectopic, contralateral kidney with an ectopically draining ureter. Identification of this entity should allow curative surgical treatment

BACKGROUND: Although quantitative morphometry of benign prostatic hyperplasia (BPH) has been described, there is a paucity of information on the morphometry of the nonhyperplastic prostate. This study determines the histologic composition of prostates obtained from males, ages 2 days to 40 years, in order to provide insights into the morphometry of the 'normal' gland. METHODS: The histologic composition of 45 prostates was obtained from autopsies of males with age groups stratified to reflect the neonatal, childhood, peripubertal, adolescent, and young adult periods. Double immunoenzymatic staining and computer image analysis were used to determine the mean area densities of the smooth muscle (SM), connective tissue (CT), glandular epithelium (E), and lumen (L). RESULTS: A progressive decrease in SM area density throughout childhood, prepuberty, and puberty was seen. The density of SM significantly increased following puberty and throughout adolescence and early adulthood. There was a concomitant increase in CT from the neonatal period throughout childhood, prepuberty, and puberty, and a decrease after puberty and throughout adolescence and early adulthood. Since the changes in SM and CT were inversely related, the percent contribution of the stromal compartment to the total gland remained constant. CONCLUSIONS: The stromal to epithelial ratio remains constant from birth to age 40 in nonhyperplastic glands and is similar to the ratios in asymptomatic and symptomatic BPH tissues

Vaginal bleeding during the neonatal period is commonly related to the withdrawal of maternal estrogens. Vaginal bleeding has also been reported in female infants with congenital adrenal hyperplasia and has been proposed to be due to a treatment-induced activation of the hypothalamic-pituitary-ovarian axis. We report a female infant with the salt-losing form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, who had the onset of vaginal bleeding at 3 months of life. Adrenal steroid suppression had been achieved by 2.5 weeks of age. At the time of bleeding, imaging studies revealed an enlarged right ovary with a dominant 3-cm cyst and additional small cysts that had not been seen on the newborn sonogram. The uterus was enlarged and stimulated. Three weeks later (1 week after the cessation of bleeding), repeat ultrasound demonstrated a marked decrease in the size of the right ovary, and the dominant cyst was no longer seen. The patient had a heightened FSH response to GnRH and elevated levels of estradiol for age. At 5 months of age, no further episodes of sustained vaginal bleeding were observed. Repeat hormonal levels were prepubertal, and pelvic sonogram demonstrated no evidence of stimulation. The findings in our patient suggest that a decline in adrenal androgens after glucocorticoid treatment resulted in an increase in gonadotropin levels, which then triggered a transient and augmented end-organ response (menses). Further, we suggest that our infant's hormonal findings may reflect a delay in the timely development of the negative restraint by sex steroids on gonadotropins that is normally observed in infancy

PURPOSE: We demonstrated survival and expansion in vivo of urothelial free autografts on demucosalized seromuscular segments. MATERIALS AND METHODS: Four methods of in vivo urothelial expansion were investigated on demucosalized colonic segments in the canine model. Group 1 underwent colonic mucosal removal by manual stripping, group 2 underwent removal of colonic mucosa and submucosa, and group 3 underwent manual stripping of the colonic mucosa followed by treatment with protamine sulfate and urea. In the 3 groups urothelial autografts were then placed on the seromuscular segment and tubularized over a balloon splint. In group 4 the colonic mucosa was removed but the grafts were not tubularized. Instead the colonic segment was sutured to the parietal peritoneum. RESULTS: Group 4 grafts had no epithelial growth and shrinkage of the bowel segment. Group 1 grafts had minimal growth with no expansion and colonic mucosal regrowth. Group 2 grafts demonstrated growth and expansion, although these colonic segments had a significant inflammatory response and fibrosis. Group 3 grafts had the best growth and expansion with the least inflammatory response, and 1 colonic segment was almost completely covered with urothelium. CONCLUSIONS: We demonstrated in vivo expansion of urothelial autografts grown on seromuscular colonic segments. Preservation of the submucosa is essential to prevent fibrosis of the seromuscular colonic segment and a balloon stent is crucial to prevent graft contraction. Treatment of the demucosalized segment with protamine sulfate and urea results in better urothelial expansion and less colonic mucosal regrowth

PURPOSE: To evaluate the contractile effect of endothelin-1 (ET-1) on prostatic urethral pressure and to characterize the effect of the selective ETA receptor antagonist PD155080 on ET-1 mediated prostatic urethral pressure. MATERIALS AND METHODS: The effect of intravenous ET-1 administration on canine urethral pressure was determined in the presence and absence of PD155080. The affinity of PD155080 for endothelin-mediated contraction was determined using antagonist dissociation studies. Saturation and competition binding studies were performed using [125I] ET-1 in both human and canine prostate. RESULTS: ET-1 bolus injection elicited shallow and prolonged increases the prostatic urethral pressure. Pretreatment with PD155080 totally abolished the urethral contractile response to ET-1. Specific [125I] ET-1 binding was saturable and of high affinity. Two ET receptor subtypes (ETA receptor, ETB receptor) have been identified in human prostate. The ratio of ETA to ETB receptors was approximately 1.5:1 in both human and canine prostates. Isometric tension studies revealed that PD155080 shifted the ET-1 dose-response curves to the right and exhibited no effect on the ETB receptor selective agonist sarafotoxin dose-response curves. CONCLUSION: ET-1 mediates prostate smooth muscle tone and may play a role in the pathophysiology and treatment of benign prostatic hyperplasia (BPH)

PURPOSE: To characterize the functional effect of endothelin-1 (ET1) and endothelin-3 (ET3), immunohistochemically localize ET1-like immunoreactivity, and measure the tissue levels of immunoreactive endothelin (irET) in canine genitourinary (GU) tissues. MATERIALS AND METHODS: Canine GU tissues were characterized by measuring ET1 levels using a RIA, immunohistochemical staining of ET1 and isometric tension studies. RESULTS: Immunoreactive endothelin was present, to varying degrees, in the vas deferens, ureter, prostate, bladder and urethra. Functionally, ET1 demonstrated the typical concentration response characteristics in the canine bladder base, bladder body, and prostate. The maximal tension (Emax) measured following ET1 challenge was approximately 20-fold greater in the bladder body (0.67 +/- 0.21 g/mm.2) and bladder base (0.48 +/- 0.18 g/mm.2) as compared to the prostate 0.04 +/- 0.001 g/mm.2 The Emax of ET3 in the bladder body (0.31 +/- 0.12 g/mm.2) and bladder base (0.19 +/- 0.08 g/mm.2) was significantly lower than the corresponding Emax of ET1. No measurable contractile response was elicited by ET3 in the canine prostate. Immunohistochemical staining localized the ET-like immunoreactivity to the glandular epithelium of the prostate and the transitional epithelium of the bladder. CONCLUSIONS: Endothelins are ubiquitous in the canine lower GU tract with predominant localization to the epithelial elements. Endothelins are also functionally active in canine GU tissues, but the specific role of endothelins in the physiology and pathophysiology of GU tissues requires further investigation

OBJECTIVES: To evaluate changes in the smooth muscle and connective tissue development in the obstructed and normal fetal bladder. METHODS: The smooth muscle and connective tissue composition of 19 fetal urinary bladders, including those of 9 fetuses with anatomic obstruction and 10 controls free of urologic disease, were analyzed by light microscopy and computer-assisted color image analysis. RESULTS: The bladder wall thickness was markedly increased in obstructed fetuses throughout gestation as compared with that in controls. The disparity in bladder wall thickness increased rapidly during gestation. The percent area density of smooth muscle and connective tissue as well as the ratio of smooth muscle to connective tissue remained the same in the obstructed and normal control fetal bladders. CONCLUSIONS: Although bladder outlet obstruction is associated with a marked increase in bladder wall thickness, the percent of smooth muscle and connective tissue comprising the mural histology remains relatively constant as compared with that of normal fetal controls. This study suggests that bladder outlet obstruction in the fetus is not associated with excess collagen deposition but rather with an increased amount of bladder with normal cellular content and a concomitant increase in smooth muscle development

Purpose: The quality and efficiency of any health care system depend on an appropriate level of manpower. The manpower issues of tomorrow will be influenced by the number of physicians and specialists trained today. The objectives of this manpower survey of pediatric urologists in the United States were to determine anticipated manpower requirements and provide caveats related to the practice of pediatric urology. Materials and Methods: A manpower questionnaire was distributed to pediatric urologists at the American Urological Association meeting in Las Vegas, Nevada in April 1995. Of the 234 distributed questionnaires 204 (87%) were completed and entered into a computer program. Results: Of responding pediatric urologists 70% were younger than 50 years, 81% practiced full-time pediatric urology and 45% were university based. The rates of respondents indicating that their present workload was too busy, appropriate or not busy enough were 10, 70 and 20%, respectively. A total of 71% of respondents indicated that they would discourage a newly trained individual from setting up a practice in their area. Of practicing pediatric urologists 26% intended to retire within the next 10 years. In April 1995, 80 respondents (39%) representing 67 practices were considering adding an associate within the next 10 years. By the end of 1995 only 56 practices will remain that will add an associate within the next 10 years. A total of 82% of respondents believed that there was an excess number of pediatric urology training programs. Conclusions: The pediatric urology community presently trains 10 to 15 pediatric fellows per year. Based on the 1995 manpower survey, if this trend continues an excess of 40 to 90 pediatric urologists will be trained in the next 10 years. The conclusion that there is an overabundance of pediatric urologists in training is supported by the general consensus of practicing pediatric urologists. Policies related to the training of pediatric urology fellows and urology residents should depend, not on the manpower needs at individual medical centers, but on the collective needs of our specialty and the patients whom we serve