Current understanding of hypospadias: relevance of animal models

Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies

Tratamento cirúrgico da otite média com efusão: tubo de ventilação versus aplicação tópica de mitomicina C Surgical treatment of otitis media with effusion: ventilation tube versus topical application of mitomycin C

O uso do tubo de ventilação (TV) da orelha média, tratamento cirúrgico eleito da otite média com efusão (OME), não é isento de complicações, promovendo ainda limitação social pela necessidade de abandono dos banhos de imersão. A mitomicina C (MMC) é um antineoblástico, cuja aplicação tópica retarda a fibrose e previne a estenose cicatricial. Em cobaias, retardou o fechamento de timpanotomias, permitindo maior tempo de aeração da orelha média, à semelhança dos tubos de ventilação. FORMA DE ESTUDO: Clínico prospectivo. OBJETIVO: Comparar a eficácia entre timpanotomia, aspirado da efusão e inserção de tubo de ventilação (grupo TV) versus timpanotomia, aspirado da efusão e aplicação tópica de mitomicina C (grupo MMC). Comparar o tempo de manutenção da timpanotomia e a incidência de complicações nos dois grupos. RESULTADOS: O grupo MMC apresentou eficácia significativamente menor (52% versus 80%) que o grupo TV (p= 0,34). A presença de timpanometria tipo "B" e a ausência de comprometimento do óstio faríngeo tubário pelo tecido adenóide no pré-operatório representaram fatores de mau prognóstico. A aplicação tópica de MMC nas bordas da timpanotomia proporcionou um tempo de abertura da membrana timpânica por duas a três semanas. No grupo TV, a otorréia foi observada em 13,3% dos pacientes. No grupo MMC, apesar da menor eficácia, nenhum paciente apresentou complicações nem sofreu prolongada proibição dos banhos de imersão. CONCLUSÃO: Apesar de concluirmos que o TV apresenta maior eficácia, novos estudos utilizando maior concentração, maior tempo de aplicação ou o uso seriado de MMC no tratamento da otite média com efusão devem ser realizados.<br>The insertion of the ventilation tube (VT), which is the surgical treatment for otitis media with effusion (OME), is not free from complications and also limits social life because of the need of abandoning immersion baths. Mitomycin C is an antineoblastic that delays fibrosis and avoids stenosis in scars by its topical use. It permitted a longer ventilation of the middle ear in guinea pigs by delaying tympanostomies closure similarly to the ventilation tubes. STUDY DESIGN: Prospective clinical trial. AIM: Observe and compare the efficacy of tympanostomy, effusion suction and insertion of the ventilation tube (VT group) versus results of tympanostomy, effusion suction and topic application of mitomycin C(MMC group), and also the duration of tympanotomy and incidence of complications in both groups. RESULTS: MMC group showed a significant lower efficacy (52% versus 80%) than that of VT group (p=0,34). The occurrence of type B curve in the tympanometry and tube pharyngeal ostium free from adenoid tissue in the preoperative period represent poor prognosis factors. The topic application of mitomycin on the tympanostomy permitted a patency period of two to three weeks. On the VT group, otorrhea was observed in 13,3 % of the patients. On the MMC group, despite its smaller efficacy, there were no complications or need of missing immersion baths. CONCLUSION: We concluded that VT showed better efficacy than mitomycin on this trial. However more study is needed specially focusing on higher mitomycin C concentrations, longer periods of application or its serial use, for the treatment of otitis media with effusion