Home About us Contact
|
Home About us Contact | ||
|
|
||
Hypospadias
Kinds of Hypospadias Terms modified by Hypospadias Selected AbstractsHOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endotheliaDEVELOPMENTAL DYNAMICS, Issue 4 2007Carley A. Shaut Abstract Hypospadias, a common defect affecting the growth and closure of the external genitalia, is often accompanied by gross enlargements of the genital tubercle (GT) vasculature. Because Hoxa13 homozygous mutant mice also exhibit hypospadias and GT vessel expansion, we examined whether genes playing a role in angiogenesis exhibit reduced expression in the GT. From this analysis, reductions in EphA6 and EphA7 were detected. Characterization of EphA6 and EphA7 expression in the GT confirmed colocalization with HOXA13 in the GT vascular endothelia. Analysis of the EphA6 and EphA7 promoter regions revealed a series of highly conserved cis -regulatory elements bound by HOXA13 with high affinity. GT chromatin immunoprecipitation confirmed that HOXA13 binds these gene-regulatory elements in vivo. In vitro, HOXA13 activates gene expression through the EphA6 and EphA7 gene-regulatory elements. Together these findings indicate that HOXA13 directly regulates EphA6 and EphA7 in the developing GT and identifies the GT vascular endothelia as a novel site for HOXA13-dependent expression of EphA6 and EphA7. Developmental Dynamics 236:951,960, 2007. © 2007 Wiley-Liss, Inc. [source] Teratogenic Effects of Antiepileptic Drugs: Use of an International Database on Malformations and Drug Exposure (MADRE)EPILEPSIA, Issue 11 2000Carla Arpino Summary: Purpose: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations. Methods: Information on all malformed infants (1990,1996) with maternal first-trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries. Results: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs. Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid. Conclusions: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports. [source] Hypospadias repair: an overviewINTERNATIONAL JOURNAL OF UROLOGICAL NURSING, Issue 1 2010Michael Pfeil Hypospadias is a birth defect in boys where the meatus is not placed at the tip of the glans of the penis. This article reviews the rapidly developing international literature surrounding hypospadias and hypospadias repairs paying specific attention to important aspects of nursing care, including preparing for surgery, use of dressings, stents and catheters as well as medication. It concludes by considering the long-term impact of hypospadias and its surgical correction on the patient's life. Hypospadias is treated surgically, normally during the second 6 months of the boy's life. Hospitalization periods vary from day case surgery to several days. The success of the hypospadias repair can be measured according to functional results and cosmetic appearance of the penis. The post-operative use of dressings as well as urinary catheters or stents is common but not uniform. Complication rates for hypospadias surgery vary from below 10% in boys with distal hypospadias to above 50% in children with a proximal meatus. The most common complications are urethral fistulas, strictures and stenoses. The continuing efforts by paediatric urologists focus on further optimizing the cosmetic and functional results. [source] Ventral based dartos flap for the prevention of the urethrocutaneous fistula urethroplastyINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2007Yutaro Hayashi Background: Urethrocutaneous fistula is a common complication of urethroplasty for hypospadias even when a microsurgical technique is applied. Methods: From January 1999 to November 2006, we applied the ventral based dartos flap wrapping technique to prevent the occurrence of urethrocutaneous fistula in 34 patients with hypospadias. Results: Hypospadias was repaired without fistula formation in 31 patients while three patients developed a tiny fistula, which was later closed successfully by a simple procedure. Conclusion: We conclude that the ventral based dartos flap wrapping technique could be an alternative to the dorsal dartos flap for covering the neourethra with a vascularized flap because the procedure is very simple, and complications rarely occur. [source] Hypospadias and maternal exposures to cigarette smokePAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 6 2005Suzan L. Carmichael Summary The few previous studies of hypospadias and smoking have suggested either no association or a reduced risk. This study, which uses data from the National Birth Defects Prevention Study, a multi-state, population-based case,control study, includes data on males born with severe hypospadias (i.e. the urethra opens at the penile shaft, scrotum or perineum) from 1997 to 2000. Non-malformed, liveborn male controls were selected randomly from birth certificates or from birth hospitals. Maternal interviews were completed by telephone with 453 case mothers and 1267 control mothers. Maternal smoking was not associated with hypospadias risk. For example, during the third month of pregnancy, smoking < 0.5 pack/day had an odds ratio (OR) of 1.1 [95% CI 0.6, 1.9]; 0.5 pack/day, 0.6 [0.4, 1.1]; and ,,1 pack/day, 0.8 [0.4, 1.6]. Exposure to any secondhand smoke at home during the third month of pregnancy showed an OR of 0.6 [95% CI 0.4, 1.0], and exposure at work or school, an OR of 0.7 [0.5, 1.1]. Similar risks were observed for other months during the periconceptional period, and adjustment for several potential confounders did not substantially alter results. This analysis does not confirm a recent report suggesting that maternal smoking is associated with a reduced risk of having offspring with hypospadias. [source] Molecular epidemiology of hypospadias: Review of genetic and environmental risk factorsBIRTH DEFECTS RESEARCH, Issue 10 2003Jeanne M. Manson Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 125 live male births. It is characterized by altered development of the urethra, foreskin, and ventral surface of the penis. In this review, the embryology, epidemiology, risk factors, genetic predisposition, and likely candidate genes for hypospadias are described. Recent reports have identified increases in the birth prevalence of mild and severe forms of hypospadias in the United States from the 1960s to the present. Studies in consanguineous families and small case series have identified allelic variants in genes controlling androgen action and metabolism that cause hypospadias, but the relevance of these findings to the general population is unknown. Concern has also focused on whether exposure to endocrine disrupting chemicals (EDC) with antiandrogenic activity is the cause of this increase. Hypospadias is believed to have a multifactorial etiology in which allelic variants in genes controlling androgen action and metabolism predispose individuals to develop this condition. When genetic susceptibility is combined with exposure to antiandrogenic agents, a threshold is surpassed, resulting in the manifestation of this birth defect. A clear role for exposure to antiandrogenic environmental chemicals has yet to be established in the etiology of hypospadias, although results from laboratory animal models indicate that a number of environmental chemicals could be implicated. Molecular epidemiology studies that simultaneously examine the roles of allelic variants in genes controlling androgen action and metabolism, and environmental exposures are needed to elucidate the risk factors for these anomalies and the causes of the increased rate of hypospadias. Birth Defects Research (Part A), 2003. © 2003 Wiley-Liss, Inc. [source] Hypospadias: risk factor patterns and different phenotypesBJU INTERNATIONAL, Issue 2 2010Marijn M. Brouwers Study Type , Aetiologic (case-referent) Level of Evidence 2a OBJECTIVE To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes. PATIENTS AND METHODS Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTS Low birth weight, being a twin or triplet, mother being a diethylstilbestrol-daughter, fertility treatments, paternal subfertility, obesity, prescriptive drug use, and familial occurrence of hypospadias or testicular cancer were associated with hypospadias in general. For familial occurrence of hypospadias, there were high risk estimates for the distal and middle phenotypes with an OR (95%CI) of 10.4 (4.5,24.1) and 9.0 (3.1,26.0), but not for the proximal type at 1.8 (0.2,14.9). By contrast, the association with low birth weight (a proxy for placental dysfunction) seemed much stronger for proximal hypospadias with an OR (95%CI) of 9.1 (3.4,24.2) compared with distal and middle hypospadias at 2.6 (1.4,5.0) and 2.3 (0.8,6.5). There were similar estimates for pre-eclampsia. CONCLUSION These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development. [source] Hypospadias surgery: when, what and by whom?BJU INTERNATIONAL, Issue 8 2004Gianantonio Manzoni Summary Hypospadias is repaired by paediatric surgeons, paediatric urologists, adult reconstructive urologists and plastic surgeons. This review is unique in representing all four specialities, to provide a unified policy on the management of hypospadias. The surgeon of whichever speciality should have a dedicated interest in this challenging work, ideally having an annual volume of at least 40,50 cases. The ideal time for primary repair is at 6,12 months old, although when this is not practicable there is another opportunity at 3,4 years old. A surgical protocol is presented which emphasises both functional and cosmetic refinement. Using a logical progression of a very few related procedures allows the reliable correction of almost any hypospadias deformity. A one-stage repair is used when the urethral plate does not require transection and its axial integrity can be maintained. Occasionally, when the plate is of adequate width and depth, it can be tubularized directly using the second stage of the two-stage repair. When (usually) the urethral plate is not adequately developed and requires augmentation before it can be tubularized, then that second-stage procedure is modified by adding a dorsal releasing incision ± a graft (alias Snodgrass and ,Snodgraft' procedures). The two-stage repair offers the most reliable and refined solution for those patients who require transection of the urethral plate and a full circumferential substitution urethroplasty. From available evidence this protocol combines excellent function and cosmesis with optimum reliability. Nevertheless, it would be complacent to assume that these gratifying results will be maintained into adult life. We therefore recommend that there is still a need for active follow-up through to genital maturity. [source] HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endotheliaDEVELOPMENTAL DYNAMICS, Issue 4 2007Carley A. Shaut Abstract Hypospadias, a common defect affecting the growth and closure of the external genitalia, is often accompanied by gross enlargements of the genital tubercle (GT) vasculature. Because Hoxa13 homozygous mutant mice also exhibit hypospadias and GT vessel expansion, we examined whether genes playing a role in angiogenesis exhibit reduced expression in the GT. From this analysis, reductions in EphA6 and EphA7 were detected. Characterization of EphA6 and EphA7 expression in the GT confirmed colocalization with HOXA13 in the GT vascular endothelia. Analysis of the EphA6 and EphA7 promoter regions revealed a series of highly conserved cis -regulatory elements bound by HOXA13 with high affinity. GT chromatin immunoprecipitation confirmed that HOXA13 binds these gene-regulatory elements in vivo. In vitro, HOXA13 activates gene expression through the EphA6 and EphA7 gene-regulatory elements. Together these findings indicate that HOXA13 directly regulates EphA6 and EphA7 in the developing GT and identifies the GT vascular endothelia as a novel site for HOXA13-dependent expression of EphA6 and EphA7. Developmental Dynamics 236:951,960, 2007. © 2007 Wiley-Liss, Inc. [source] Cumulative effects of in utero administration of mixtures of reproductive toxicants that disrupt common target tissues via diverse mechanisms of toxicityINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010C. V. Rider Summary Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act required the US Environmental Protection Agency to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures of chemicals to elucidate mechanisms of joint action at the systemic level with the goal of providing a framework for assessing the cumulative effects of reproductive toxicants. Previous mixture studies conducted with antiandrogenic chemicals are reviewed briefly and two new studies are described. In all binary mixture studies, rats were dosed during pregnancy with chemicals, singly or in pairs, at dosage levels equivalent to approximately one-half of the ED50 for hypospadias or epididymal agenesis. The binary mixtures included androgen receptor (AR) antagonists (vinclozolin plus procymidone), phthalate esters [di(n-butyl) phthalate (DBP) plus benzyl n-butyl phthalate (BBP) and diethyl hexyl phthalate (DEHP) plus DBP], a phthalate ester plus an AR antagonist (DBP plus procymidone), a mixed mechanism androgen signalling disruptor (linuron) plus BBP, and two chemicals which disrupt epididymal differentiation through entirely different toxicity pathways: DBP (AR pathway) plus 2,3,7,8 TCDD (AhR pathway). We also conducted multi-component mixture studies combining several ,antiandrogens'. In the first study, seven chemicals (four pesticides and three phthalates) that elicit antiandrogenic effects at two different sites in the androgen signalling pathway (i.e. AR antagonist or inhibition of androgen synthesis) were combined. In the second study, three additional phthalates were added to make a 10 chemical mixture. In both the binary mixture studies and the multi-component mixture studies, chemicals that targeted male reproductive tract development displayed cumulative effects that exceeded predictions based on a response-addition model and most often were in accordance with predictions based on dose-addition models. In summary, our results indicate that compounds that act by disparate mechanisms of toxicity to disrupt the dynamic interactions among the interconnected signalling pathways in differentiating tissues produce cumulative dose-additive effects, regardless of the mechanism or mode of action of the individual mixture component. [source] The hypothalamus-pituitary-testis axis in boys during the first six months of life: a comparison of cryptorchidism and hypospadias cases with controlsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2009Frank H. Pierik Summary It is inconclusive whether the feedback mechanisms of the hypothalamus-pituitary-testis (HTP) axis are already established in the first 6 months of life, partly due to the dramatic changes in HPT-axis hormone levels over this period. Moreover, it is unclear whether these hormone levels are aberrant in boys with cryptorchidism or hypospadias, and therefore predictive for future fertility. We studied the regulation mechanisms of the HTP axis, and the effect of age, in boys 1,6 months of age. Secondly, we studied testicular function - as reflected by HPT hormones - in newborns with cryptorchidism or hypospadias. Sera from a population sample of infants with cryptorchidism (n = 43), hypospadias (n = 41) and controls (n = 113) were analyzed for inhibin B, anti-Müllerian hormone (AMH), testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG). LH, testosterone, non-shbg-bound testosterone (NSBT), and AHM levels showed significant age-related trends. After age-correction, a negative correlation between FSH and inhibin B was observed (r = ,0.43). The only significant group-differences were lower testosterone and NSBT levels in cryptorchidism cases, with a mean testosterone of 1.8 and 2.6 nmol/L and a mean NSBT of 0.48 and 0.70 nmol/L for cryptorchidism cases and controls, respectively. The higher levels of LH, testosterone, and NSBT in boys born pre-term or with a low birthweight indicate that abnormal prenatal development may determine postnatal testis function. Our results support the hypothesis that the inhibin B , FSH feedback loop is already functional before puberty. The lower testosterone and NSBT levels indicate that disturbed Leydig cell function can already be detected early after birth in cryptorchid boys. [source] Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the ratINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2008S. Christiansen Summary The incidence of hypospadias is increasing in young boys, but it remains unclear whether human exposure to endocrine disrupting chemicals plays a role. Risk assessment is based on estimation of no-observed-adverse-effect levels for single compounds, although humans are exposed to combinations of several anti-androgenic chemicals. In a mixture (MIX) study with three androgen receptor antagonists, vinclozolin, flutamide and procymidone, rats were gavaged during gestation and lactation with several doses of a MIX of the three chemicals or the chemicals alone. External malformations of the male reproductive organs were assessed on PND 47 using a score from 0 to 3 (normal to marked) for hypospadias. Markedly increased frequencies were observed after exposure to a MIX of the three chemicals compared to administration of the three chemicals alone. Anogenital distance at PND 1, nipple retention at PND 13, and dysgenesis score at PND 16 were highly correlated with the occurrence of hypospadias, and MIX effects were seen at doses where each of the individual chemicals caused no observable effects. Therefore, the results indicate that doses of anti-androgens, which appear to induce no hypospadias when judged on their own, may induce a very high frequency of hypospadias when they interact in concert with other anti-androgens. [source] A mixture of seven antiandrogens induces reproductive malformations in ratsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2008Cynthia V. Rider Summary To date, regulatory agencies have not considered conducting cumulative risk assessments for mixtures of chemicals with diverse mechanisms of toxicity because it is assumed that the chemicals will act independently and the individual chemical doses are not additive. However, this assumption is not supported by new research addressing the joint effects of chemicals that disrupt reproductive tract development in the male rat by disrupting the androgen signalling pathway via diverse mechanisms of toxicity [i.e. androgen receptor (AR) antagonism in the reproductive tract vs. inhibition of androgen synthesis in the foetal testis]. In this study, pregnant rats were exposed to four dilutions of a mixture containing vinclozolin, procymidone, linuron, prochloraz, benzyl butyl phthalate, dibutyl phthalate and diethylhexyl phthalate during the period of sexual differentiation and male offspring were assessed for effects on hormone sensitive endpoints including: anogenital distance, infant areolae retention and reproductive tract tissue weights and malformations. The ratio of the chemicals in the mixture was based upon each chemical's ED50 for inducing reproductive tract malformations (hypospadias or epididymal agenesis). The observed responses from the mixture were compared with predicted responses generated with a toxic equivalency approach and models of dose addition, response addition or integrated addition. As hypothesized, we found that the mixture of chemicals that alter the androgen signalling pathway via diverse mechanisms disrupted male rat reproductive tract differentiation and induced malformations in a cumulative, dose-additive manner. The toxic equivalency and dose addition models provided the best fit to observed responses even though the chemicals do not act via a common cellular mechanism of action. The current regulatory framework for conducting cumulative risk assessments needs to consider the results, including those presented herein, which indicate that chemicals that disrupt foetal tissues during sexual differentiation act in a cumulative, dose-additive manner irrespective of the specific cellular mechanism of toxicity. [source] The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case,control study in rural SicilyINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2007P. Carbone Abstract This was an open case,control study of the possible association between parental occupational and domestic exposures to potential endocrine disrupting chemicals (EDC) assessed by questionnaire and cryptorchidism and hypospadias in their offspring in the agricultural area of Ragusa. Cases of infants born between 1998 and 2002 with either of these two malformations (n = 90), and controls (n = 203), were recruited through the paediatric services (for cases) and a random sample of healthy infants attending the same services born in the same period of time (for controls). Data on occupational and environmental exposures of parents prior to and during the index case (or control), were collected through interviews with both parents. Concerning occupational exposures, we did not find a statistically significant increase in risk among parents directly involved in agricultural work. We did find a non-statistically significant increase in risk for cryptorchidism in mothers employed in agriculture [adjusted odds ratios (OR) 2.97; 95% confidence interval (CI) 0.77,11.47] and with probable exposure to pesticides (adjusted OR 2.74; 95% CI 0.72,10.42). Fathers who had indirect contact with agricultural products (transport and retail) had an increased risk (not statistically significant) for cryptorchidism (adjusted OR 2.45; 95% CI 0.63,9.59) and hypospadias and cryptorchidism combined (adjusted OR 2.24; 95% CI 0.67,7.48). Increases in risk of the two malformations pooled were also observed in relation to the mother's age below 25 (adjusted OR 1.99; 95% CI 0.97,4.09), to the presence of genital disease of the father (adjusted OR 2.41; 95%C I0.94,6.17), and the mother (adjusted OR 3.47;95% CI1.34,8.99), to low birth weight of the infant (adjusted OR 4.49; 95% CI 1.23,16.31). Increased risk was also observed for mothers consuming alcohol during pregnancy (adjusted OR 3.09; 95% CI 0.98,9.66), and for couples who conceived while using condoms (adjusted OR 2.12; 95% CI 1.02,4.41). The study therefore provides only limited support to the hypothesis of a possible association between the risk of cryptorchidism and hypospadias and the occupational exposure to EDC and agricultural work. [source] The ,oestrogen hypothesis', where do we stand now?,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2003Richard M. Sharpe Summary The original ,oestrogen hypothesis' postulated that the apparent increase in human male reproductive developmental disorders (testis cancer, cryptorchidism, hypospadias, low sperm counts) might have occurred because of increased oestrogen exposure of the human foetus/neonate; five potential routes of exposure were considered. This review revisits this hypothesis in the light of the data to have emerged since 1993. It addresses whether there is a secular increasing trend in the listed disorders and highlights the limitations of available data and how these are being addressed. It considers whether new data has emerged to support the suggestion that increased oestrogen exposure could cause these abnormalities and reviews new data on potential routes via which such increased exposure could have occurred. Secular trends: The disorders listed above are now considered to represent a syndrome of disorders (testicular dysgenesis syndrome, TDS) with a common origin in foetal life. Testicular cancer has increased in incidence in Caucasian men worldwide and lifetime risk is 0.3,0.8%. Secular trends in cryptorchidism are unclear but it is by far the commonest (2,4% at birth) congenital abnormality in either sex. Secular trends for hypospadias are not robust, although most studies suggest a progressive increase; registry data probably under-estimates incidence, but based on this data hypospadias is the second most common (0.3,0.7% at birth) congenital malformation. Retrospective analyses of sperm count data show a global downward trend but this is inconclusive , prospective studies using standardized methodology show significant differences between countries and very low sperm counts in the youngest cohort of men. For all disorders, other then testis cancer, standardized prospective studies are the best way forward and are in progress across Europe. Oestrogen effects: Evidence that foetal exposure to oestrogens can induce the above disorders has strengthened. New pathways via which such changes could be induced have been identified, including suppression of testosterone production by the foetal testis, suppression of androgen receptor expression and suppression of insulin-like factor-3 (InsL3) production by foetal Leydig cells. Other evidence suggests that the balance between androgen and oestrogen action may be important in induction of reproductive tract abnormalities. Oestrogen exposure: Although many new environmental oestrogens have been identified, their uniformly weak oestrogenicity excludes the possibility that they could induce the above disorders. However, emerging data implicates various environmental chemicals in being able to alter endogenous levels of androgens (certain phthalates) and oestrogens (polychlorinated biphenyls, polyhalogenated hydrocarbons), and the former have been shown to induce a similar collection of disorders to TDS. Other mechanisms via which increased fetal exposure to pregnancy oestrogens might occur (increasing trend in obesity, dietary changes) are also discussed. [source] Endocrine disruptors and male reproductive function , a short reviewINTERNATIONAL JOURNAL OF ANDROLOGY, Issue S2 2000Sin-Eng Chia Semen quality has decline in many countries over the last few decades. There has been an increase in the incidence of testicular cancer world-wide. The incidences of cryptorchidism and hypospadias have also increased in many countries. A biological plausible hypothesis has suggested that man-made chemicals act as endocrine disruptors resulting in altered development of the reproductive tract causing the observed effects. Endocrine disruptors include natural products, pharmaceuticals, industrial products and environmental pollutants. There are limitations in the current in vivo and in vitro assays for the assessment of endocrine disruptors. Epidemiological human studies are necessary to fill in the gap of knowledge. Based on the current knowledge, the impact of endocrine disruptors on the male reproductive function remain to be appreciated. [source] Hypospadias repair: an overviewINTERNATIONAL JOURNAL OF UROLOGICAL NURSING, Issue 1 2010Michael Pfeil Hypospadias is a birth defect in boys where the meatus is not placed at the tip of the glans of the penis. This article reviews the rapidly developing international literature surrounding hypospadias and hypospadias repairs paying specific attention to important aspects of nursing care, including preparing for surgery, use of dressings, stents and catheters as well as medication. It concludes by considering the long-term impact of hypospadias and its surgical correction on the patient's life. Hypospadias is treated surgically, normally during the second 6 months of the boy's life. Hospitalization periods vary from day case surgery to several days. The success of the hypospadias repair can be measured according to functional results and cosmetic appearance of the penis. The post-operative use of dressings as well as urinary catheters or stents is common but not uniform. Complication rates for hypospadias surgery vary from below 10% in boys with distal hypospadias to above 50% in children with a proximal meatus. The most common complications are urethral fistulas, strictures and stenoses. The continuing efforts by paediatric urologists focus on further optimizing the cosmetic and functional results. [source] Current concepts in hypospadias surgeryINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2008Yutaro Hayashi Abstract: Anatomical anomalies in hypospadias are an abnormal ventral opening of the urethral meatus, abnormal ventral curvature of the penis and abnormal distribution of the foreskin around the glans with a ventrally deficient hooded foreskin. The techniques of hypospadias surgery continue to evolve. The current standard of care for hypospadias repair includes not only a functional penis adequate for sexual intercourse and urethral reconstruction offering the ability to stand to urinate, but also a satisfactory cosmetic result. Tubularized incised plate repair has been the mainstay for distal hypospadias. In cases of proximal hypospadias, one-stage repairs such as the Duckett repair or the Koyanagi repair have been well established, while two-stage repairs remain important alternatives. Whether dorsal plication or ventral lengthening should be used to correct penile curvature is still controversial, and long-term results are required. Efforts have been made in this decade to improve cosmetic appearance, constructing a slit-like meatus or performing foreskin reconstruction, and to prevent onerous complications. [source] Achieving a natural glanular meatus for distal hypospadias with a narrow and shallow plate: Tubularized incised plate versus modified Barcat repairINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2008Yutaro Hayashi Objectives: Although the tubularized incised plate (TIP) repair has become the most popular surgical procedure for distal hypospadias, some authors suggest that this is not suitable for hypospadias with a narrow plate or shallow groove. Methods: The configuration and position of the reconstructed meatus were postoperatively analyzed in patients with distal hypospadias whose preoperative urethral plates were shallow or narrow. The findings were compared between six patients undergoing TIP repair and seven patients undergoing modified Barcat (BAVIS) repair. Results: Among those undergoing the TIP procedure, a slit-like meatus at the tip of the glans was achieved in one patient, a slit-like meatus at the mid portion of the glans in four patients and a round meatus at the mid portion of the glans in one patient. In those repaired by the BAVIS procedure, a slit-like meatus at the tip of glans was achieved in three patients, a round or irregularly shaped meatus at the tip of the glans in two patients, an irregularly shaped meatus at the mid portion of the glans in one patient and neourethral dehiscence in one patient. Conclusions: The present study confirms that a higher rate of achieving slit-like meatus but a lower rate of locating in the glans tip can be attained after TIP repair. On the other hand, there is a higher rate of locating the meatus in the glans tip but a lower rate of achieving a slit-like meatus after BAVIS repair. [source] Modified foreskin reconstruction for distal hypospadias and chordee without hypospadiasINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2008Yutaro Hayashi Abstract: Although foreskin reconstruction was established for hypospadias surgery in Europe two decades ago, it appears to introduce an extra risk of postoperative complications. We modified foreskin reconstruction in order to reduce the complications caused by its use. After correction of penile curvature and urethroplasty, the inner mucosal layer of the foreskin was separated from the outer skin layer. The approximation of each layer in the midline was limited and transverse adaptation was added to the remaining portion. We carried out the modified foreskin reconstruction for 11 patients and no patients developed postoperative complications. After the foreskin reconstruction, the glans, which was concealed by the reconstructed foreskin, was easily exposed by retracting the foreskin. [source] Ventral based dartos flap for the prevention of the urethrocutaneous fistula urethroplastyINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2007Yutaro Hayashi Background: Urethrocutaneous fistula is a common complication of urethroplasty for hypospadias even when a microsurgical technique is applied. Methods: From January 1999 to November 2006, we applied the ventral based dartos flap wrapping technique to prevent the occurrence of urethrocutaneous fistula in 34 patients with hypospadias. Results: Hypospadias was repaired without fistula formation in 31 patients while three patients developed a tiny fistula, which was later closed successfully by a simple procedure. Conclusion: We conclude that the ventral based dartos flap wrapping technique could be an alternative to the dorsal dartos flap for covering the neourethra with a vascularized flap because the procedure is very simple, and complications rarely occur. [source] Use of bladder mucosal graft for urethral reconstructionINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2000ar Özgök Background: The ideal tissue for complex urethral reconstruction has yet to be determined, especially in patients with deficient preputium. The use of bladder mucosa as a free graft could be an alternative in these problem cases. Methods: Bladder mucosa graft urethroplasty was performed on 14 patients with penoscrotal or scrotal hypospadias. The mean age of the patients was 18.7 (range 14,23) years. Ten cases were subjected to primary urethral reconstruction while four cases had previous hypospadias repair. Results: Complete urethral replacement by the bladder mucosa tube was performed in six patients. Meatal problems occurred in two (33.33%) patients and proximal fistula formed in one (16.67%) patient. A bladder mucosa graft was combined with preputial or tunica vaginalis grafts distally in eight cases, and one patient in the tunica vaginalis group developed fistula at the anastomosis of the bladder mucosa and tunica vaginalis grafts. The overall complication rate was 28.6%. Conclusions: Our initial results showed that bladder mucosa grafts can be used successfully for urethral reconstruction especially when combined with preputial or tunica vaginalis grafts distally. [source] Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndromeMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2008Valérie Schumacher Abstract Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1,+,KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial,spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as ,testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1,+,KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line. Mol. Reprod. Dev. 75: 1484,1494, 2008. © 2008 Wiley-Liss, Inc. [source] First report of overactive detrusor in association with hypospadias detected by urodynamic screeningNEUROUROLOGY AND URODYNAMICS, Issue 1 2005Cuneyd Ozkurkcugil Abstract Aims The purpose of this study was to determine urodynamic features in hypospadic patients. Methods Thirty-seven patients with hypospadias (distal: 31, proximal: 6) underwent preoperative urodynamic study according to International Continence Society (ICS) recommendations. Statistical analysis were done for comparison between urethral obstruction and non-obstruction in patients with detrusor overactivity (DO) plus the relationship of DO with localization of hipospadias. Results Nearly 45.9% of the patients showed overactive detrusor. Urethral obstruction was found in 60.8% of the patients. The rate of DO was higher in proximal hipospadias, and urethral obstruction than distal type, and non-obstructed patients (P,>,0.005). The means overall cystometric capacity, maximum voiding detrusor pressure and maximal urinary flow measured were 132.6,± 111.14 ml (range 21,610), 72,±,53 cmH2O (range 12,181), and 7.9,±,7.1 ml/sec (range 2,30 ml/sec), respectively. Conclusions To the best of our knowledge, this is the first study ever to show that overactive detrusor is an accompanying entity in the hypospadic patients. © 2004 Wiley-Liss, Inc. [source] Hypospadias and maternal exposures to cigarette smokePAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 6 2005Suzan L. Carmichael Summary The few previous studies of hypospadias and smoking have suggested either no association or a reduced risk. This study, which uses data from the National Birth Defects Prevention Study, a multi-state, population-based case,control study, includes data on males born with severe hypospadias (i.e. the urethra opens at the penile shaft, scrotum or perineum) from 1997 to 2000. Non-malformed, liveborn male controls were selected randomly from birth certificates or from birth hospitals. Maternal interviews were completed by telephone with 453 case mothers and 1267 control mothers. Maternal smoking was not associated with hypospadias risk. For example, during the third month of pregnancy, smoking < 0.5 pack/day had an odds ratio (OR) of 1.1 [95% CI 0.6, 1.9]; 0.5 pack/day, 0.6 [0.4, 1.1]; and ,,1 pack/day, 0.8 [0.4, 1.6]. Exposure to any secondhand smoke at home during the third month of pregnancy showed an OR of 0.6 [95% CI 0.4, 1.0], and exposure at work or school, an OR of 0.7 [0.5, 1.1]. Similar risks were observed for other months during the periconceptional period, and adjustment for several potential confounders did not substantially alter results. This analysis does not confirm a recent report suggesting that maternal smoking is associated with a reduced risk of having offspring with hypospadias. [source] Prenatal diagnosis of jumping translocation involving chromosome 22 with ultrasonographic findingsPRENATAL DIAGNOSIS, Issue 11 2005Halil Aslan Abstract We report on the prenatal diagnosis and ultrasonographic findings of a second-trimester fetus with jumping translocation involving chromosome 22. A 28-year-old gravida 2, partus 1, Turkish woman was referred for genetic counselling and ultrasonographic examination at 18 weeks' gestation because of a high risk of trisomy 21 in triple test. Prenatal ultrasonography showed tetralogy of Fallot with a diverticular dilatation of the pulmonary artery, flattened brow, complete absence of the right upper limb, hypospadias, oligodactyly (three digits) in left hand and in both feet, and hyperechogenic abdominal foci. Amniocentesis revealed a karyotype of 46,XY[4]/46,XY,,8,+ der(8),t(8;22)(q24.3;q11.21)[2]/45, XY,,22,,8,+ der(8)t(8;22)(q24.3;q11.21)[22]/45,XY,,22,,5,+ der(5)t(5;22)(q35.3;q11.21)[44]. A C-banding and FISH study with a specific centromeric probe (D14Z1/D22Z1) for chromosome 22 was made. In our case, partial monosomy for the regions 22q11.21,22pter, 8q24.3,8qter and 5q35.3,5qter may partially explain the fetal malformations. Copyright © 2005 John Wiley & Sons, Ltd. [source] Y chromosome haplogroups: A correlation with testicular dysgenesis syndrome?APMIS, Issue 1 2003KEN McELREAVEY Testicular dysgenesis syndrome encompasses low sperm quality, hypospadias, cryptorchidism and testicular cancer. Epidemiological studies and genetic data from familial cases suggest that testicular dysgenesis syndrome has a common etiology. The Y chromosome is known to encode genes that are involved in germ cell development or maintenance. We have therefore investigated if different classes of Y chromosomes in the general population (Y chromosome haplogroups) are associated with aspects of the testicular dysgenesis syndrome. We defined the Y chromosome haplogroups in individuals from different European counties who presented with either (i) oligo- or azoospermia associated with a Y chromosome microdeletion, (ii) unexplained reduced sperm counts (<20×106/ml) or (iii) testicular cancer. We failed to find Y chromosome haplotype associations with either microdeletion formation or testicular cancer. However, in a study of the Danish population, we found that a specific Y chromosome haplogroup (hg26) is significantly overrepresented in men with unexplained reduced sperm counts compared with a Danish control population. The factors encoded by genes on this class of Y chromosome may be particularly susceptible to environmental influences that cause testicular dysgenesis syndrome. Our current data highlight the need for further analyses of clinically well-defined patient groups from a wide range of ethnic and geographic origins. [source] The birth rate of hypospadias in the Turku area in Finland,APMIS, Issue 2 2001H. E. VIRTANEN Reports based on national registers of congenital malformations have suggested that the birth rate of hypospadias has increased during the last few decades. Register-based information may, however, have pitfalls because of changes in diagnostics, reporting accuracy and registration system. The aim of this study was to determine the current birth rate of hypospadias in Turku University Central Hospital (TUCH) in Finland. This was a prospective study on live-born boys born in TUCH from 1997 to 1999. In the total birth cohort (n=5,798) as well as in a special subcohort group (n=1,505) 0.3% of boys had hypospadias. Only one scrotal hypospadias was found in a boy who had a chromosomal anomaly. Other hypospadias were glandular or coronal. No increase was found in the birth rate of hypospadias when comparing our result with register-based data of boys born in Finland during the years 1970 to 1986 and surgically treated for hypospadias by the age of 8 years. No difference was found either from malformation register-based data concerning the nationwide birth rate of hypospadias during the years 1993 to 1998. Due to differences in national registration systems between countries, prospective studies with equal assessment criteria are needed in order to make reliable international comparisons. [source] Secular trends of hypospadias prevalence and factors associated with it in southeast China during 1993,2005BIRTH DEFECTS RESEARCH, Issue 6 2010Lei Jin Abstract BACKGROUND The aim of this study is to describe the prevalence of hypospadias and its time trends during 1993,2005 in southeast China, and to explore the potential risk factors. METHODS The study population included all male live and still births (at least 20 weeks of gestation) in 11 cities and counties in Jiangsu and Zhejiang Provinces in Southeast China born during January 1, 1993, through December 31, 2005. RESULTS Overall prevalence of hypospadias was 5.8 per 10,000 male births and presented an increasing trend during 1993,2005 (with , of 3.94, p = 0.047). Prevalence of coronal hypospadias and those with unknown sites increased from 1.7 and 0.3 per 10,000 male births in 1993 to 3.6 and 1.4 per 10,000 male births in 2005, respectively (with , of 7.29 and 9.05, p = 0.007 and p = 0.002, respectively), but prevalence of perineal hypospadias decreased (with , of 7.13, p = 0.008). Maternal fever during first trimester, birth of twins or more children, and year of birth were independent risk factors for hypospadias, with odds ratios of 4.14 (95% CI, 1.32,12.83), 3.37 (95% CI, 1.73,6.58), and 1.04 (95% CI, 1.00,1.08), respectively, after adjusting for confounding factors with multivariable logistic regression analysis. CONCLUSIONS Prevalence of hypospadias increased during 1993,2005 in the two provinces in southeast China. Maternal fever in the first trimester and birth of twins or more children are associated with the risk for hypospadias. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc. [source] Congenital malformations in infants born after in vitro fertilization in SwedenBIRTH DEFECTS RESEARCH, Issue 3 2010Bengt Källén Abstract BACKGROUND: The risk for congenital malformations is increased in infants born after in vitro fertilization (IVF). Some specific malformations appear to be more affected than others. METHODS: The presence of congenital malformations in 15,570 infants born after IVF with an embryo transfer between April 1, 2001, and the end of 2006 were compared with all infants born in Sweden during 2001 to 2007 (n = 689,157). Risk estimates were made after adjusting for year of birth, maternal age, parity, smoking, and body mass index. The risks of specific malformations were compared with data from a previous study (1982 to March 31, 2001) of 16,280 infants born after IVF. Different IVF methods were compared to respect to malformation risk. RESULTS: Increased risks of a similar magnitude were found for most cardiovascular malformations and limb reduction defects for both study periods. For neural tube defects, cardiac septal defects, and esophageal atresia, there was still an increased risk, but it was lower during the second than during the first period. For small bowel atresia, anal atresia, and hypospadias, the risk increase observed during the first study period had disappeared during the second period. An increased risk was seen for some syndromes that have been associated with imprinting errors. No difference in malformation risk according to IVF method was apparent. CONCLUSIONS: A slightly increased risk for congenital malformations after IVF persists. A decreasing risk is seen for some specific malformations, either true or the result of multiple testing. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||