Biomedical subjects

Laurence S Baskin

Publications and source records attributed to Laurence S Baskin.

At least 19 recordsLinked to original sources

PubMed2007

Cost-utility analysis of treatment algorithms for moderate grade vesicoureteral reflux using Markov models.

PURPOSE: The optimal treatment algorithm for vesicoureteral reflux remains controversial. Previous decision analyses have attempted to determine the best approach solely from the cost or cure perspective but have not combined the goals of minimizing treatment and disease burden. We incorporated these considerations into a contemporary, comprehensive analysis of treatment for vesicoureteral reflux. MATERIALS AND METHODS: We examined costs from the perspective of the medical institution, and utility from the perspective of parents of children with grades II and III vesicoureteral reflux. Cost-utility analysis using Markov modeling was performed to ascertain which of 5 treatment algorithms best minimized morbidity and cost. A higher utility value was based on minimizing treatment and disease burden. Measures of treatment and disease burden included duration of suppressive antibiotics, number of invasive studies, pyelonephritis episodes, endoscopic treatments and open operations. All variables were varied spanning realistic ranges during sensitivity analyses to determine threshold values. RESULTS: The protocol of no antibiotics or followup imaging yielded the best cost-utility for vesicoureteral reflux grades II and III. Sensitivity analysis of variables spanning realistic ranges demonstrated that utility penalties for invasive imaging and outpatient pyelonephritis were particularly important in determining the highest utility protocols, with threshold values ranging from -0.5 to -0.8. CONCLUSIONS: In our models of treatment for vesicoureteral reflux a noninterventional approach constitutes the highest utility and least costly treatment for moderate grade reflux. Given the relative dearth of randomized trials, these analyses provide guidelines for current management of vesicoureteral reflux.

Algorithms↗

PubMed2006

Essential role for Co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology.

Fkbp52 and Fkbp51 are tetratricopeptide repeat proteins found in steroid receptor complexes, and Fkbp51 is an androgen receptor (AR) target gene. Although in vitro studies suggest that Fkbp52 and Fkbp51 regulate hormone binding and/or subcellular trafficking of receptors, the roles of Fkbp52 and Fkbp51 in vivo have not been extensively investigated. Here, we evaluate their physiological roles in Fkbp52-deficient and Fkbp51-deficient mice. Fkbp52-deficient males developed defects in select reproductive organs (e.g. penile hypospadias and prostate dysgenesis but normal testis), pointing to a role for Fkbp52 in AR-mediated signaling and function. Surprisingly, ablation of Fkbp52 did not affect AR hormone binding or nuclear translocation in vivo and in vitro. Molecular studies in mouse embryonic fibroblast cells uncovered that Fkbp52 is critical to AR transcriptional activity. Interestingly, Fkbp51 expression was down-regulated in Fkbp52-deficient males but only in affected tissues, providing further evidence of tissue-specific loss of AR activity and suggesting that Fkbp51 is an AR target gene essential to penile and prostate development. However, Fkbp51-deficient mice were normal, showing no defects in AR-mediated reproductive function. Our work demonstrates that Fkbp52 but not Fkbp51 is essential to AR-mediated signaling and provides evidence for an unprecedented Fkbp52 function, direct control of steroid receptor transcriptional activity.

Active Transport, Cell Nucleus↗

PubMed2006

Activating transcription factor 3 is estrogen-responsive in utero and upregulated during sexual differentiation.

BACKGROUND/AIMS: Synthetic estrogens induce hypospadias, an anomaly of genital tubercle/urethral development. Activating transcription factor 3 (ATF3), which is estrogen-responsive in vitro, is upregulated in hypospadiac human tissue. We used a mouse model of steroid-dependent genital tubercle development to elucidate the ontogeny of ATF3 expression and the developmental response of ATF3 in vivo to estrogen exposure. METHODS: We used quantitative RT-PCR to assess ontogenic expression of ATF3 and its response to estrogen treatment in utero. Immunohistochemistry was used to localize the protein. RESULTS: Quantitative RT-PCR showed that ATF3 mRNA is upregulated in all estrogen-exposed fetal genital tubercles compared to controls (p = 0.024), including specifically in males exposed in utero (p = 0.049). Additionally, its expression increases significantly during the period of sexual differentiation in both sexes and significantly correlates with female development (p = 0.004), a phenomenon that appears to be attributable to higher levels at birth in females. The protein localizes in the nucleus, as expected. CONCLUSIONS: ATF3 is estrogen-responsive in vivo. The response of ATF3 to estrogenic stimulation in utero at an earlier stage may contribute to urethral abnormalities observed in estrogen-exposed male fetuses, although it is likely not the only gene involved, which supports the general understanding that hypospadias is subject to multifactorial influences. ATF3 may therefore be an appropriate gene for further investigations in an endocrine context.

Activating Transcription Factor 3↗

PubMed2006

Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice.

BACKGROUND: Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA) feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. METHODS: We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors alpha and beta, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females), we measured the lengths of the casts and performed ANOVA analysis on these data. RESULTS: Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias) and masculinizing females (longer urethras). Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen alpha and beta, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor alpha mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor alpha and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl estradiol. CONCLUSION: The results suggest that vinclozolin virilizes females and directly or indirectly affects progesterone receptor expression. It also affects estrogen receptor expression in a sex-based manner. We found no in vivo effect of vinclozolin on androgen receptor expression. We propose that vinclozolin, which has been designated an anti-androgen, may also exert its effects by involving additional steroid-signaling pathways.

Analysis of Variance↗

PubMed2006

Hypospadias: anatomy, etiology, and technique.

Hypospadias is one of the most common congenital anomalies defined by abortive development of the urethral spongiosum, the ventral prepuce and in more severe cases penile chordee. The etiology of hypospadias remains unknown with environmental exposure in the form of endocrine disruptors the most likely explanation for the worldwide increase in incidence in the last three decades. There are five sequential steps for the successful repair of hypospadias: 1) Orthoplasty or penile straightening, 2) Urethroplasty, 3) Meatoplasty and Glanuloplasty, 4) Scrotoplasty, and 5) Skin Coverage. The major technical advances in hypospadias surgery that have improved surgical outcomes are 1) Preservation of the urethral plate, 2) Incision of the urethral plate, 3) Dorsal midline plication, 4) Deepithelized urethroplasty dartos flap coverage, and 5) Two stage alternative techniques. This article reviews the pertinent embryology, anatomy and the most common hypospadias reconstructive operations to accomplish a successful repair.

Endocrine Disruptors↗

PubMed2006

Steroid receptors and mammalian penile development: an unexpected role for progesterone receptor?

PURPOSE: We investigated the role of steroid receptors in normal and abnormal genital tubercle development in males and females. We hypothesized that progesterone receptor expression might be involved in abnormal development in both sexes. MATERIALS AND METHODS: We examined the effects of medroxyprogesterone acetate on steroid receptor mRNA expression and assessed the involvement of androgen receptor in the action of medroxyprogesterone acetate on genital tubercle development using androgen receptor deficient (Tfm) mice. RESULTS: Quantitative reverse transcriptase polymerase chain reaction and morphological results demonstrated a pattern of virilized females and feminized males in medroxyprogesterone acetate exposed embryos. Progesterone receptor was the only steroid receptor examined that did not differ between medroxyprogesterone acetate treated males and vehicle treated females. At the morphological level in utero exposure to medroxyprogesterone acetate from gestational days 12 to 17 feminized male genital tubercles, producing a more proximal urethral opening. Female fetuses exposed for the same period exhibited virilized genitalia, with a more distal urethral opening. We also exposed Tfm mice to medroxyprogesterone acetate to assess the role of androgen receptor in the activity of medroxyprogesterone acetate. These medroxyprogesterone acetate exposed mice did not differ morphologically from vehicle treated Tfm mice, indicating that medroxyprogesterone acetate requires androgen receptor to elicit genital tubercle abnormalities. CONCLUSIONS: The increase of progesterone receptor mRNA expression in males and the decrease in females as a result of exposure to medroxyprogesterone acetate, which also causes urethral abnormalities in both sexes, suggests a previously unidentified role for progesterone receptor, possibly interacting with androgen receptor, in anomalous genital tubercle development.

Animals↗

PubMed2006

Foreskin preservation in penile surgery.

PURPOSE: Most hypospadias repairs performed in the United States involve the removal of any foreskin that is not used in the repair, resulting in a circumcised penis. Occasionally, the wishes of the parents or the child are for the final appearance to be that of a normal uncircumcised penis. We report our collective experience from 4 institutions in the reconstruction of the foreskin during penile surgery. MATERIALS AND METHODS: A total of 58 patients underwent penile surgery with reconstruction of the foreskin during a 6-year period. Of the patients 49 underwent hypospadias repair, 8 underwent phalloplasty for chordee correction without hypospadias and 1 underwent reconstruction of the foreskin for a dorsal hood without hypospadias or chordee. Of the 49 hypospadias repairs 46 were distal, 2 mid shaft and 1 proximal shaft. The technique for foreskin reconstruction consisted of a multilayered reapproximation of the lateral margins of the dorsal hood after completion of the urethroplasty and glanuloplasty. RESULTS: Among 49 hypospadias repairs 2 patients had dehiscence of the reconstructed foreskin, with development of a urethral fistula in 1. Of the 58 total patients undergoing penile surgery 56 had retractable foreskin, of whom 4 required postoperative steroid application. Three patients/parents requested a secondary circumcision, 2 for an unacceptable cosmetic result and 1 based on personal preference. CONCLUSIONS: Foreskin reconstruction in association with penile surgery can be performed safely and with a low complication rate in appropriately selected patients. Cases with a higher risk of complications include those involving more proximal hypospadias and those requiring complete degloving of the penile shaft. Of the reconstructions resulting in phimosis most can be salvaged with the application of steroids.

Child↗

PubMed2006

Redo ureteroneocystostomy using an extravesical approach in pediatric renal transplant patients with reflux: a retrospective analysis and description of technique.

PURPOSE: Vesicoureteral reflux and pyelonephritis following transplantation may significantly contribute to renal damage and premature graft loss. We report our retrospective experience with redo ureteral reimplantation of refluxing pediatric renal transplants and describe our surgical technique. MATERIALS AND METHODS: We identified 20 children with a diagnosis of symptomatic post-transplant vesicoureteral reflux, of whom 16 underwent redo ureteral reimplantation. Patient characteristics including etiology of end stage renal disease, presenting symptoms, serum creatinine and postoperative followup were documented. The presence or absence of lower urinary tract dysfunction was documented and values between the 2 groups were analyzed for significance. RESULTS: All 20 patients presented after assessment for a febrile urinary tract infection, and 35% had concurrent lower urinary tract dysfunction. Median interval between transplantation and vesicoureteral reflux diagnosis was 1.3 years, and mean vesicoureteral reflux grade was 3.2. Patients with lower urinary tract dysfunction presented significantly earlier and had a higher postoperative serum creatinine than those without lower urinary tract dysfunction (1.1 vs 1.7 years, p = 0.048). Redo reimplantation was performed in 94% of patients using an extravesical approach with ureteral stent placement. Seven of 16 patients underwent followup voiding cystourethrogram, with 5 demonstrating resolution and 2, both with lower urinary tract dysfunction, exhibiting persistent vesicoureteral reflux. At a mean followup of 3.6 years 25% of patients experienced recurrent pyelonephritis, while 75% were asymptomatic. One instance of anastomotic stricture occurred in a patient with lower urinary tract dysfunction. CONCLUSIONS: Effective repair of post-transplantation vesicoureteral reflux can be performed using an extravesical technique, facilitated by preoperative ureteral stent placement. Patients with lower urinary tract dysfunction are likely to present earlier after transplantation than those without lower urinary tract dysfunction, and may have an increased risk of persistent vesicoureteral reflux and renal damage despite surgical correction.

Child↗

PubMed2006

A neuroanatomical comparison of humans and spotted hyena, a natural animal model for common urogenital sinus: clinical reflections on feminizing genitoplasty.

PURPOSE: Surgical treatment of the common urogenital sinus phallus has been one of the most challenging areas in pediatric urology. To better understand the neuroanatomy of the common urogenital sinus phallus, we evaluated an animal model naturally having this condition, the spotted hyena, Crocuta crocuta. We compared the neuroanatomy of male and female humans and spotted hyenas using anatomical, immunohistochemical and 3D reconstruction techniques. We also examined the implications of the pattern of clitoral innervation for the unique challenges faced by female spotted hyenas, the only extant species of mammal that mates and gives birth through the clitoris. MATERIALS AND METHODS: Three adult male and 3 female spotted hyenas were studied. With the animals under anesthesia gross anatomical examination was performed before and after artificial erection. Histological analysis was performed on one 95-day fetal male and female spotted hyena specimens, and on 18 human male and female fetal external genitalia specimens using antibodies raised against the neuronal marker S-100. Three-dimensional computer reconstruction using serial sections allowed analysis of the neuroanatomy of the penis, clitoris and common urogenital sinus of the fetal spotted hyena and human. RESULTS: Compared to other mammals, the clitoris and penis of spotted hyenas were remarkably similar in size and configuration in the flaccid and erect states. Male and female hyenas had a single opening on the tip of the glans penis/clitoris. The basic anatomical structures of the corporeal bodies in both sexes of humans and spotted hyenas were similar. As in humans, the dorsal nerve distribution was unique in being devoid of nerves at the 12 o'clock position in the penis and clitoris of the spotted hyena. Dorsal nerves of the penis/clitoris in humans and male spotted hyenas tracked along both sides of the corporeal body to the corpus spongiosum at the 5 and 7 o'clock positions. The dorsal nerves penetrated the corporeal body and distally the glans in the hyena. In female hyenas the dorsal nerves fanned out laterally on the clitoral body. Glans morphology was different in appearance in both sexes, being wide and blunt in the female and tapered in the male. CONCLUSIONS: The neuroanatomy of the male and female external genitalia in the spotted hyena, Crocuta crocuta, although grossly similar, has distinct anatomical and functional characteristics. The clitoris of the spotted hyena is a classic example of a natural animal model of a common urogenital sinus. The neuroanatomical characteristics of the spotted hyena may be a useful model to simulate the anatomy of common urogenital sinus anomaly in humans.

Animals↗

PubMed2006

Loratadine exerts estrogen-like effects and disrupts penile development in the mouse.

PURPOSE: Hypospadias is a developmental anomaly of the penis and urethra that can be steroid mediated. It is characterized by a urethral opening occurring below the normal location at the tip of the penis. The link between loratadine, the active ingredient in a common over-the-counter antihistamine, and hypospadias, the most common congenital abnormality, has been the subject of controversy. We examined the effect of in utero exposure to an over-the-counter loratadine syrup on urethral development, and expression of androgen and estrogen receptors. MATERIALS AND METHODS: We orally gavaged pregnant dams with the equivalent of a daily dose of loratadine syrup, with 3 times that dose or with a corn oil gavage control from GD 12 through GD 17. Using gross and histological assessment and 3D reconstruction, we looked for urethral abnormalities in fetal GTs at E 19. We also used real-time quantitative PCR to characterize the expression levels of steroid receptor mRNA in the GT at E 19, a critical stage for completion of urethral and penile development in this species. RESULTS: Loratadine syrup disrupted normal urethral development in the mouse, based on gross morphology and histological assessment, and also disrupted steroid receptor expression, producing an expression profile similar to that resulting from in utero exposure to ethinyl estradiol. CONCLUSIONS: In utero exposure to over-the-counter loratadine syrup can result in hypospadias in this model, and creates changes in the steroid receptor mRNA expression profile similar to those elicited by a synthetic estrogen.

Animals↗

PubMed2006

The anatomy and embryology of posterior urethral valves.

PURPOSE: We reviewed the literature to better elucidate the history behind our understanding of the anatomy, classification and embryology of posterior urethral valves. MATERIALS AND METHODS: A directed MEDLINE literature review of the anatomy, classification and embryology of posterior urethral valves was performed. An effort was made to focus on the most frequently cited historical articles as well as those including detailed anatomical analyses of fetal specimens. Also included was the analysis of a specimen obtained at our institution in a novel manner that to our knowledge has not been previously described in the literature with respect to the anatomy of posterior urethral valves. RESULTS: The precise origins regarding the anatomy and embryology of posterior urethral valves remain undefined. However, the literature is abundant in theories regarding the origin of posterior urethral valves, based primarily on small uncontrolled series or case reports. There are a limited number of reports of the anatomy of posterior urethral valves in methodical fashion using reproducible scientific techniques such as histopathology. These reports are invaluable for providing a foundation of how to properly study and define the origins of posterior urethral valves. CONCLUSIONS: Elucidating this most fundamental feature of a congenital condition central to the practice of pediatric urology is essential. More well designed studies specifically with this goal in mind are necessary. Incorporating new reconstructive imaging modalities may assist us in pinpointing the elusive origins of the embryology and anatomy of posterior urethral valves.

Humans↗

PubMed2006

Ontogeny of androgen receptor and disruption of its mRNA expression by exogenous estrogens during morphogenesis of the genital tubercle.

PURPOSE: The ontogeny of androgen receptor expression in male and female mouse genital tubercles, and the effects of in utero ethinyl estradiol exposure on androgen receptor mRNA expression in the hypospadias model were studied. MATERIALS AND METHODS: Androgen receptor mRNA expression was measured in mouse genital tubercles from fetuses and pups collected on gestational days 12, 14, 16 and 18, and from newborns using immunohistochemistry and real-time quantitative polymerase chain reaction. Pregnant dams were exposed to ethinyl estradiol or corn oil as controls from gestational days 12 to 17. Genital tubercles of gestational day 19 fetuses were then examined by further quantitative polymerase chain reaction analysis after identification of the seam area using a dissecting microscope to diagnose hypospadias in males. RESULTS: Androgen receptor protein was detected in genital tubercles by gestational day 14. Androgen receptor mRNA expression increased gradually in each sex during normal development. However, female genital tubercles expressed a higher level of androgen receptor mRNA throughout development compared to male genital tubercles (p <0.0001). In utero ethinyl estradiol exposure led to a 5.4 and 4.5-fold increase in androgen receptor mRNA in the genital tubercles of female and male embryos (p = 0.004 and 0.001, respectively). Hypospadiac male genital tubercles showed increased androgen receptor mRNA expression compared to control males (p = 0.006). Levels in hypospadiac males did not differ from those in control females but they were less than those in ethinyl estradiol treated females (p >0.05 and 0.01, respectively). CONCLUSIONS: Androgen receptor protein is expressed abundantly in male and female genital tubercles. Androgen receptor mRNA levels are higher in female than in male genital tubercles through development and they increase in response to in utero ethinyl estradiol exposure with ethinyl estradiol treated females having the highest levels of expression, followed by ethinyl estradiol treated hypospadiac males. We infer that higher estrogen in genital tubercles results in a physiological response of increased androgen receptor mRNA expression. We found no direct association between changes in androgen receptor mRNA expression and the presence or absence of hypospadias in males, suggesting that alterations in the expression of proteins other than or in addition to androgen receptor result in anomalous urethral development. This finding supports the idea that the etiology of hypospadias is multifactorial in origin.

Animals↗

PubMed2006

Serum response factor, its cofactors, and epithelial-mesenchymal signaling in urinary bladder smooth muscle formation.

Little is known about the mechanism of bladder smooth muscle differentiation. We hypothesize that epithelial-mesenchymal signaling induces the expression of smooth muscle proteins in bladder mesenchyme resulting in smooth muscle differentiation. We confirmed that smooth muscle differentiation in the mouse urinary bladder occurs first at gestational day 14 (E14) based upon immunohistochemical localization of smooth muscle alpha-actin (SMAA). To investigate murine bladder smooth muscle differentiation and epithlelial-mesenchymal signaling in the developing bladder, we analyzed gene expression profiles of intact embryonic murine bladders and separated epithelial and mesenchymal components at embryonic days E13, E14, E15, E16, and postnatal day 1 (P1). Using cDNA microarray, we identified regulators of vascular smooth muscle differentiation in bladder mesenchyme, including serum response factor (SRF) and its cofactors, ELK1 and SRF accessory protein (SAP)1, as well as two SRF-associated pathways, angiotension receptor II and transforming growth factor- beta2. Immunohistochemistry showed diffuse expression of SRF in the bladder at E12 with localization of expression to the peripheral mesenchyme at E13 and E14. Our results suggest that bladder smooth muscle differentiation may share a similar gene expression program as occurs during vascular smooth muscle differentiation. The unique structure of the urinary bladder makes it an ideal model for studies of smooth muscle differentiation and epithelial-mesenchymal signaling.

Animals↗

PubMed2006

Gene expression profiles in mouse urethral development.

OBJECTIVE: To analyse the gene expression profiles of the mouse genital tubercle (GT) during urethral tube development at embryonic (E) days E14, E15, E16 and E17, as the aetiology of hypospadias, one of the most common congenital anomalies, remains unknown. MATERIALS AND METHODS: During GT development the urethral folds fuse to form an epithelial seam; subsequently, the epithelial seam disappears, resulting in the normal tubular urethra. Abnormalities in urethral seam formation and remodelling might explain hypospadias, and elucidating the molecular developmental mechanisms underlying normal penile development might provide the basis for understanding hypospadias. Total RNA was isolated from the genital tubercle at embryonic days E14, E15, E16, and E17. Together with reference RNA, sample RNA was labelled with Cy-3 and Cy-5 respectively and hybridized to a 16 000-mouse gene array that included the Incyte GEM2.1 and NIA 7k sets. Candidate genes were analysed by immunohistochemistry and real-time polymerase chain reaction. RESULTS: Using cDNA microarrays, we identified the up-regulation of genes involved in the transforming growth factor (TGF)-beta and Wnt-Frizzled pathways, and of thrombospondin (TSP) 4, a member of a cell-migration molecule family, all candidates for involvement in urethral tube formation. Immunohistochemistry showed TGFbeta1, TGFbeta receptor III, and Frizzled1 were expressed exclusively in E14-E17 urethral epithelium. TSP4 was expressed in the mesenchymal basal layer underlying E17 GT skin epidermis. CONCLUSIONS: Many signalling pathways are involved in late GT development, and cell migration molecules might have an important role in urethral tube formation.

Animals↗

PubMed2006

Embryonic exposure to low-dose 17beta-estradiol decreases fetal mass sex specifically in male mice and does not cause hypospadias.

BACKGROUND: Endocrine-disrupting compounds are synthetic and natural compounds in the environment that can alter endocrine-governed developmental processes. Among these are the natural estrogens genistein, a plant isoflavone, and 17beta-estradiol (E2), which is present in dietary animal products, such as eggs and meat. In addition, natural and synthetic steroids are administered to beef cattle to promote growth, and low levels of the estrogens can persist in the beef. Most previous work using E2 has involved injection; however, oral administration results in a different suite of hormone products following first-pass metabolism in the liver. METHODS: Low doses of E2 were administered orally to pregnant dams to determine embryonic effects. As end points of effects, we examined whether embryonic exposure produced hypospadias, an endocrine-linked abnormality of the male genitalia, and we assessed fetal mass. RESULTS: Male fetuses from the two highest dosage groups were significantly smaller than their control male counterparts, and males from the highest dosage group were also significantly smaller than control females. Control males were significantly larger than all females, and there was no difference in mass among control and treated females. Additionally, the E2 dose was inversely correlated with mass overall. No effect of these doses of E2 on hypospadias was seen. CONCLUSIONS: These results indicate a sex-specific fetal effect of low-dose, orally administered E2, which appears to exert androgen-inhibiting effects on mass in males.

Administration, Oral↗

PubMed2005

Identification of ectopic ureter in incontinent girl using magnetic resonance imaging.

We present the case of a 3.5-year-old girl who presented with continuous urinary leakage and a classic history suggesting an ectopic ureter, but an inconclusive physical examination and normal imaging by ultrasonography. Magnetic resonance imaging was finally able to identify an ectopic ureter draining a poorly functioning upper pole of a duplex system as the culprit. We discuss the increasing value of magnetic resonance imaging in identifying subtle pediatric genitourinary anomalies, such as in our case, and discuss the management options.

Child, Preschool↗

PubMed2005

Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration.

Urinary bladder malfunction and disorders are caused by congenital diseases, trauma, inflammation, radiation, and nerve injuries. Loss of normal bladder function results in urinary tract infection, incontinence, renal failure, and end-stage renal dysfunction. In severe cases, bladder augmentation is required using segments of the gastrointestinal tract. However, use of gastrointestinal mucosa can result in complications such as electrolyte imbalance, stone formation, urinary tract infection, mucous production, and malignancy. Recent tissue engineering techniques use acellular grafts, cultured cells combined with biodegradable scaffolds, and cell sheets. These techniques are not all currently applicable for human bladder reconstruction. However, new avenues for bladder reconstruction maybe facilitated by a better understanding of urogenital development, the cellular and molecular biology of urothelium, and cell-cell interactions, which modulate tissue repair, homeostasis, and disease progression.

Animals↗

PubMed2005

Activating transcription factor 3 is up-regulated in patients with hypospadias.

Hypospadias is a congenital anomaly of the genitalia characterized by abnormalities of the urethra and foreskin, with the urethral meatus located in an abnormal position anywhere from the distal ventral penile shaft to the perineum. Because the incidence of hypospadias is approximately 1/200-1/300 live male births, it is one of the most common congenital malformations, but its etiology is largely uncharacterized. Genomic analysis of hypospadic tissue indicated a potential role for activating transcription factor 3 (ATF3) in the development of this anomaly. ATF3 may be involved in homeostasis, wound healing, cell adhesion, or apoptosis, and normally it is expressed at a steady-state in quiescent cells. Additionally, it has been shown to be an estrogen-responsive gene, and the etiology of hypospadias may be related to in utero exposure to estrogenic or anti-androgenic compounds. We examined the expression of ATF3 in tissues from 28 children with hypospadias compared with 20 normal penile skin tissue samples from elective circumcision. Eighty-six percent of the hypospadias samples were immunohistochemically positive, compared with 13% of normal tissue samples. Seventy-five percent of hypospadias samples were positive from in situ hybridization, compared with 1% of circumcision samples. Our results indicate that ATF3 is up-regulated in the penile skin tissues of boys with hypospadias, suggesting a role for this transcription factor in the development of this abnormality. Because the etiology of hypospadias may include exposure to estrogenic compounds, the responsiveness of ATF3 to estrogen is also discussed.

Activating Transcription Factor 3↗