Faculty Bibliography

BACKGROUND: Approximately 15% of recipients of live attenuated varicella vaccine may develop mild breakthrough varicella months to years after immunization. Although some vaccinees will develop zoster, it is less common in recipients of vaccine than in those who have had natural varicella. OBJECTIVE: To determine the varicella-zoster virus (VZV) strain responsible for breakthrough varicella and zoster in recipients of varicella vaccine. METHODS: A PCR assay capable of distinguishing wild-type from vaccine strain VZV was performed on samples from skin lesions from vaccinees with breakthrough varicella and zoster. RESULTS: All of 57 vaccinees with breakthrough varicella, clinically diagnosed on the basis of a generalized maculopapular or vesicular rash, in which there was amplifiable DNA [corrected], had wild-type VZV infection based on analysis of viral DNA. The Oka vaccine strain of VZV was not identified in any of these cases. In contrast, in 32 patients with zosteriform rashes, the vaccine strain was identified in 22 samples, and the wild-type strain was identified in 10 samples. CONCLUSIONS: Wild-type virus was identified in all generalized rashes occurring after the immediate 6-week postvaccination period. When reactivation of vaccine strain occurred, it presented as typical zoster. We find no evidence that reactivation of vaccine virus occurs with the clinical picture of generalized rash

PURPOSE/OBJECTIVE:We investigated the role of peptide growth factors and androgens in the developing human prostate. MATERIALS AND METHODS/METHODS:We performed immunohistochemical staining of prostate tissue sections from human fetuses 9.5, 11.5, 13, 16.5, 18 and 20 weeks in gestation. RESULTS:The temporal and spatial expression of these growth factors was related to the gestational androgen surge. Before the androgen surge (9.5 to 11.5 weeks) transforming growth factor (TGF)-alpha, TGF-beta1 and TGF-beta3 but not TGF-beta2 were present in the mesenchyme. The epithelium exhibited no detectable staining for any of the growth factors. During the androgen peak (13 to 16.5 weeks) TGF-beta1 decreased and TGF-beta2 increased in the mesenchyme, and TGF-alpha, TGF-beta1 and TGF-beta3 increased in the epithelium. With declining androgen levels TGF-alpha, TGF-beta2 and TGF-beta3 remained unchanged but TGF-beta1 increased in the mesenchyme with no change in the tested peptide growth factor levels in the epithelium. CONCLUSIONS:These data suggest that androgens regulate the differential expression of TGF-alpha and TGF-beta, and support a role for peptide growth factors as the direct mediators of androgen action on the mesenchymal and epithelial interactions responsible for prostate development.

PURPOSE: To our knowledge the pathogenesis of malignancy associated with ileal cystoplasty, ureterosigmoidostomy and ileal conduits is currently unknown. To gain further insights into the mechanism of neoplastic transformation we studied histological changes in a canine augmentation cystoplasty model. MATERIALS AND METHODS: Enterocystoplasty and gastrocystoplasty were performed using a 5 to 7 cm. patch of ileum in 8 dogs and gastric antrum in 6. Specimens were harvested 4 months postoperatively. Representative 3 microm sections of the enterovesical and gastrovesical junctions were stained with hematoxylin and eosin. Uroplakin expression was assessed using an indirect peroxidase method subjected to double staining with alcian blue and periodic acid-Schiffreagent. RESULTS: The bladder portion of the augmentation cystoplasty had 3 to 4 stratified cell layers covered with a distinctive umbrella cell layer. Strong uroplakin staining was visible in all cell layers except the basal layer. At the enterovesical and gastrovesical junctions 6 to 10 layers of hyperplastic, urothelial appearing cells covered the glandular epithelium of the ileal and gastric segments. These cells expressed uroplakins. At this junction zone there was a marked decrease of underlying enteric glands, which had atrophied in proportion to the degree of urothelial hyperplasia. Double staining of uroplakin stained sections with alcian blue and periodic acid-Schiff reagent revealed mucosubstances in hyperplastic urothelial cells covering the enteral segments, indicating that the cells co-expressed uroplakins and mucins. CONCLUSIONS: Histological changes in this experimental canine model of augmentation cystoplasty indicated that the overgrowth of hyperplastic transitional epithelium develops at the enterovesical and gastrovesical junctions. These cells express not only uroplakins, but also mucosubstances. Our results suggest that the migrated hyperplastic urothelial cells have undergone changes characteristic of the enteric and gastric epithelium, which may have important implications in the pathogenesis of malignancy in bladder augmentations

Although many genetic alterations are known to be associated with human transitional cell carcinoma (TCC) of the urinary bladder, relatively little is known about the roles of these molecular defects, singular or in combination, in bladder tumorigenesis. We have developed a transgenic mouse model of bladder tumorigenesis using a 3.6-kb promoter of uroplakin II gene to drive the urotheliums-specific expression of oncogenes. In this study, we demonstrate that transgenic mice bearing a low copy number of SV40T transgene developed bladder carcinoma in situ (CIS), whereas those bearing high copies developed CIS as well as invasive and metastatic TCCs. These results indicate that the SV40T inactivation of p53 and retinoblastoma gene products, defects frequently found in human bladder CIS and invasive TCCs, can cause the aggressive form of TCC. Our results also provide experimental proof that CIS is a precursor of invasive TCCs, thus supporting the concept of two distinct pathways of bladder tumorigenesis (papillary versus CIS/invasive TCC). This transgenic system can be used for the systematic dissection of the roles of individual or combinations of specific molecular events in bladder tumorigenesis

PURPOSE: Prenatal sonography has evolved through advancements in imaging technology and observer experience. This review focuses on our current knowledge of the sonographic appearance of normal and abnormal fetal genitalia. MATERIALS AND METHODS: A MEDLINE computerized reference and manual bibliography reviews were performed to find pertinent peer-reviewed articles on the sonographic appearance of normal and abnormal fetal genitalia. RESULTS: The sonographic appearance of the normal fetal genitalia has been defined. The male phallus can be visualized as early as 10 to 11 weeks of gestation, while testicular descent is not seen before 26 weeks. Hydroceles are commonly detected. In the female subject the labia majora and labia minora are visible by 15 weeks. Hydrometrocolpos due to uterovaginal anomalies can be seen as early as 26 weeks. CONCLUSIONS: Advances in prenatal sonography enable one to diagnose late first trimester gender. Sonography of the fetal genitalia complements fetal sex determination in cases of intersex, X-linked disorders or gender specific fetal anomalies, and is an important tool with increasing indications in prenatal medicine

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

Recurrent urinary tract infections (UTIs) and vesicoureteral reflux are common diagnosis' in infants and children who are referred to a urologist. Recurrent UTIs in these patients can be challenging, especially when radiographic evaluation reveals no structural abnormality. Prophylaxis and correction of voiding and bowel dysfunction are important treatment strategies. Febrile UTIs are commonly associated with reflux and should be treated aggressively to avoid renal scarring and its sequelae. Based on a comprehensive survey of the literature, long-term treatment strategies for children with reflux are now available