Daily use of phosphodiesterase type 5 inhibitors as prevention for recurrent priapism.

OBJECTIVE: The pathogenesis of recurrent priapism is currently being investigated based on the regulation of the phosphodiesterase 5 (PDE5) enzyme. We explored the daily use of PDE5 inhibitors to treat and prevent priapism recurrences. METHOD: We administered PDE5 inhibitors using a long-term therapeutic regimen in seven men with recurrent priapism, with a mean age of 29.2 years (range 21 to 35 years). Six men (85.7%) had idiopathic priapism recurrences and one man (24.3%) had sickle cell disease-associated priapism recurrences. Tadalafil 5 mg was administered daily. The mean follow-up was 6.6 months (range 3 to 12 months). RESULTS: Daily long-term oral PDE5 inhibitor therapy alleviated priapism recurrences in all patients. Five (71.4%) had no episodes of priapism and two (28.6%) referred decrease in their episodes of priapism. All patients referred improvement in erectile function. CONCLUSION: These findings suggest the hypothesis that PDE5 dysregulation exerts a pathogenic role for both sickle cell disease-associated priapism and for idiopathic priapism, and that it offers a molecular target for the therapeutic management of priapism. These preliminary observations suggest that continuous long-term oral PDE5 inhibitor therapy may treat and prevent recurrent priapism.

Daily use of phosphodiesterase type 5 inhibitors as prevention for recurrent priapism / Prevenção do priapismo recorrente com a utilização diária de inibidores da fosfodiesterase tipo 5

Summary Objective: The pathogenesis of recurrent priapism is currently being investigated based on the regulation of the phosphodiesterase 5 (PDE5) enzyme. We explored the daily use of PDE5 inhibitors to treat and prevent priapism recurrences. Method: We administered PDE5 inhibitors using a long-term therapeutic regimen in seven men with recurrent priapism, with a mean age of 29.2 years (range 21 to 35 years). Six men (85.7%) had idiopathic priapism recurrences and one man (24.3%) had sickle cell disease-associated priapism recurrences. Tadalafil 5 mg was administered daily. The mean follow-up was 6.6 months (range 3 to 12 months). Results: Daily long-term oral PDE5 inhibitor therapy alleviated priapism recurrences in all patients. Five (71.4%) had no episodes of priapism and two (28.6%) referred decrease in their episodes of priapism. All patients referred improvement in erectile function. Conclusion: These findings suggest the hypothesis that PDE5 dysregulation exerts a pathogenic role for both sickle cell disease-associated priapism and for idiopathic priapism, and that it offers a molecular target for the therapeutic management of priapism. These preliminary observations suggest that continuous long-term oral PDE5 inhibitor therapy may treat and prevent recurrent priapism.

Resumo Objetivo: Uma das teorias propostas para explicar a etiologia do priapismo recorrente está baseada no mecanismo de regulação da fosfodiesterase tipo 5. Estudamos o uso diário dos inibidores de fosfodiesterase tipo 5 no tratamento e na prevenção do priapismo recorrente. Método: Sete homens com diagnóstico de priapismo recorrente, com idade média de 29,5 anos (21 a 35 anos), utilizaram inibidor de fosfodiesterase tipo 5 em dose diária (tadalafila 5 mg/dia) por período prolongado. Seis homens (85,7%) apresentavam priapismo recorrente de etiologia idiopática, e um homem (24,3%), de etiologia associada à anemia falciforme. O seguimento médio foi de 6,6 meses (3 a 12 meses). Resultados: Todos os pacientes se beneficiaram com a utilização de inibidores de fosfodiesterase tipo 5. Cinco (71,4%) não apresentaram nenhum episódio de priapismo e dois (28,6%) relataram diminuição dos episódios. Todos os pacientes relataram melhora da função erétil. Conclusão: Estes achados sugerem que a hipótese do mecanismo de regulação da fosfodiesterase tipo 5 exerce papel importante na patogenia do priapismo recorrente. O uso contínuo e diário de inibidores da fosfodiesterase tipo 5 pode ser uma opção no tratamento do priapismo recorrente.

Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism.

We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing compound to correct the molecular hallmarks and pathophysiology of priapism, an important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N-nitrosoamino)-2,4-dinitrobenzene (C6') and an inactive form of the compound [1,5-bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures and penile lysates for NO release (Griess assay) and biological activity (cGMP production). The effect of local depot C6' or C6 was evaluated in mice with a priapic phenotype due to double neuronal and endothelial NO synthase deletion (dNOS(-/-)) or human sickle hemoglobin transgenic expression (Sickle). Changes in NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed by Western blot. The physiological response after C6' treatment was assessed using an established model of electrically stimulated penile erection. C6' generated NO, increased cGMP, and dose dependently increased NO metabolites. C6' treatment reversed abnormalities in key penile erection signaling molecules, including phosphodiesterase type 5, phosphorylated endothelial nitric oxide synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle mice, C6' also attenuated the increased ROS markers gp91(phox), 4-hydroxynonenal, and 3-nitrotyrosine. Finally, C6' corrected the excessive priapic erection response of dNOS(-/-) mice. Exogenous sustained NO release from C6' corrects pathological erectile signaling in mouse models of priapism and suggests novel approaches to human therapy.

Fibrotic protein expression profiles in penile tissue of patients with erectile dysfunction.

OBJECTIVE: To characterize transforming growth factor beta 1 (TGFß1) and related signaling pathway proteins in a large cohort of human penile tissue (HPT) samples. METHODS: HPT was collected from patients undergoing penile prosthesis implantation for erectile dysfunction (ED) and divided into the following 2 groups: postradical prostatectomy ED (RP-ED; n = 57) and organic ED (O-ED; n = 30). HPT from patients undergoing partial penectomy without ED was used as controls (CON; n = 6). Western blot analysis was performed to investigate the protein expressions of TGFß1, thrombospondin 1 (TSP1; an activator of TGFß1), fibronectin (an extracellular matrix glycoprotein induced by TGFß1), and a family of transcriptional factors activated by TGFß1 (Smad2, phospho-Smad2-serine-465/467 [pSmad2], Smad3, phospho-Smad3-serine-423/425 [pSmad3]). RESULTS: Expressions of TGFß1 and TSP1 were significantly higher in RP-ED (P <.05) and O-ED (P <.05) groups compared with that of the CON group and were not different between either ED groups. Expressions of Smad2, pSmad2, Smad3, pSmad3, and fibronectin were similar among all groups. Within the RP-ED group, a subgroup analysis showed that time from RP to penile prosthesis implantation was related to increased expression of pSmad2 (P <.05), and previous history of intracavernosal injection was related to increased expression of TGFß1 (P <.05). CONCLUSION: Our results demonstrate that TSP1- and TGFß1-dependent fibrotic changes occur in penile tissue in patients with ED regardless of etiology. The unchanged expression of the Smad transcriptional factors may be reconciled by a Smad-independent downstream signaling pathway transmitting TGFß1 signals.

Molecular analysis of erection regulatory factors in sickle cell disease associated priapism in the human penis.

PURPOSE: Priapism is a vasculopathy that occurs in approximately 40% of patients with sickle cell disease. Mouse models suggest that dysregulated nitric oxide synthase and RhoA/ROCK signaling as well as increased oxidative stress may contribute to the mechanisms of sickle cell disease associated priapism. We examined changes in the protein expression of nitric oxide synthase and ROCK signaling pathways, and a source of oxidative stress, NADPH oxidase, in penile erectile tissue from patients with a priapism history etiologically related and unrelated to sickle cell disease. MATERIALS AND METHODS: Human penile erectile tissue was obtained from 5 patients with sickle cell disease associated priapism and from 6 with priapism of other etiologies during nonemergent penile prosthesis surgery for erectile dysfunction or priapism management and urethroplasty. Tissue was also obtained from 5 control patients without a priapism history during penectomy for penile cancer. Samples were collected, immediately placed in cold buffer and then frozen in liquid nitrogen. The expression of phosphodiesterase 5, endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase, RhoA, ROCK1, ROCK2, p47(phox), p67(phox), gp91(phox) and ß-actin were determined by Western blot analysis. Nitric oxide was measured using the Griess reaction. RESULTS: In the sickle cell disease group phosphodiesterase 5 (p <0.05), endothelial nitric oxide synthase (p <0.01) and RhoA (p <0.01) expression was significantly decreased, while gp91(phox) expression (p <0.05) was significantly increased compared to control values. In the nonsickle cell disease group endothelial nitric oxide synthase, ROCK1 and p47(phox) expression (each p <0.05) was significantly decreased compared to control values. Total nitric oxide levels were not significantly different between the study groups. CONCLUSIONS: Mechanisms of sickle cell disease associated priapism in the human penis may involve dysfunctional nitric oxide synthase and ROCK signaling, and increased oxidative stress associated with NADPH oxidase mediated signaling.

Caso complexo Samuel

O caso Samuel é conjugado com o caso Darlene e Darnley, pois se trata de uma mesma família. São apresentados em dois momentos diferentes, por questões didáticas. Assim, o foco do caso é a abordagem familiar e o enfrentamento da violência doméstica. Dado a complexidade destes temas, os casos desafiam a equipe a um atendimento integral, focado na pessoa e no trabalho em equipe. Enfatiza a importância do vínculo e da relação profissional de saúde e pessoa. O caso Samuel apresenta a importância do registro clínico baseado em problemas e a abordagem dos problemas trazidos pelo usuário, no caso uma unha encravada, problemas sexuais e periodontais. Tem um importante destaque na necessidade da organização da prática clínica dos profissionais envolvidos, além da abordagem das doenças crônicas degenerativas, no caso a diabete melitus e obesidade. Mais uma vez o acolhimento e organização da equipe para enfrentamento da demanda espontânea é destacado como peça fundamental de acesso ao serviço, princípio da atenção primária. Objetivamente o caso trás aprofundamento teórico nos seguintes temas: - Diabete tipo 2 e neuropatias diabéticas - Obesidade e sedentarismo - Disfunção sexual masculina - Dor articular - Periodontite - Luto na família - Violência

Tumor del cuerpo carotídeo: Presentación de un caso por ecografía y resonancia magnética / Carotid body tumor: A case presentation with ultrasonography and magnetic resonance imaging

El tumor de cuerpo carotídeo, que se origina en los quimiorreceptores de dicha estructura, representa hasta el 50% de los paragangliomas de cabeza y cuello. En forma frecuente, constituye un hallazgo incidental (asintomático), aunque en algunos casos los pacientes pueden consultar por una masa indolora, ronquera, paresia lingual y/o disfagia. Sus características imagenológicas permiten una aproximación diagnóstica no invasiva con altos índices de sensibilidad y especificidad, por lo que su conocimiento facilita la conducta clínico-terapéutica. Se presenta un caso clínico que resulta particularmente elocuente para la práctica diaria, ya que la paciente tiene antecedentes quirúrgicos por patología tiroidea maligna, hecho que precisa una aproximación diagnóstica estricta para su correcto seguimiento.

The carotid body tumor, which arises from its chief cells (glomus type 1), is the most common paraganglioma of the head and neck (up to 50%). This tumor is in most cases clinically silent and is detected incidentally at imaging study during evaluation of patients with unrelated symptoms such as painless, slowly growing lateral neck mass, dysphagia, sleep apnea, and paresia or atrophy of the tongue. According to its appearance, precise non-invasive imaging techniques may allow the radiologist to reach the correct diagnosis and treatment. The following case report is particularly useful for daily practice; the patient has surgical history of tiroid neoplasm which requires a thorough diagnosis, in order to determine an accurate follow-up.

Lesiones tendinosas del tobillo en resonancia magnética: análisis retrospectivo en 548 estudios / Tendinous lesions of the ankle in MRI: retrospective review in 548 exams

Objetivo: Determinar la prevalencia de las diversas lesiones tendinosas del tobillo y sus características iconográficas típicas en los pacientes sometidos a Resonancia Magnética (RM). Material y métodos: Se efectuó un análisis descriptivo, retrospectivo y de corte transversal, de 548 estudios de RM de tobillo durante un período de 18 meses (entre enero de 2006 y junio de 2007), que contabiliza el total de los exámenes obtenidos en resonadores de campo cerrado en Diagnóstico por Imágenes Adrogué y en las sedes Hospital Fiorito de Avellaneda y Fundación Científica del Sur. Resultados: Del total de exámenes (n=548), el 40.3% fueron realizados a pacientes de sexo femenino (n=221) y el 59.7% a pacientes de sexo masculino (n=327), con una edad promedio de 47.6 ± 17 años. El 60.5% de los estudios (n=331) no reveló alteraciones en ningún grupo tendinoso del tobillo, mientras que el 39.5% (n=217) demostró la presencia de algún tipo de patología tendinosa. Asimismo, 64 estudios (11.7%) revelaron alteraciones en el tendón tibial posterior; 47 (8.6%) en el tendón de Aquiles; 34 (6.2%) en el tendón peroneo lateral corto; 27 (4.9%) a nivel del tendón del flexor propio del hallux; 26 (4.7%) en el tendón peroneo lateral largo; 10 (1.8%) en el tendón flexor común de los dedos; 6 (1.1%) en el tendón tibial anterior; y 3 (0.5%) en el tendón extensor común de los dedos. Conclusiones: La RM constituye una excelente herramienta en la valoración de las diversas patologías tendinosas debido a su capacidad multiplanar y a su alto contraste tisular.

Purpose: To determine the prevalence of several tendinous lesions of the ankle, and the MR imaging features that characterize these lesions. Materials and methods: MR images in 548 exams of ankle were retrospectively reviewed. These studies were performed during a 18-months period of time in 3 MR scanners at Hospital Fiorito (Avellaneda), Diagnóstico por Imágenes Adrogué, and Fundación Científica del Sur Avellaneda. Results: The ankle MR images (n=548) were taken from 221 women, and 327 men; median age, 47.6 years. In 60.5% studies (n=331), no pathologic images were identified. Sixty four exams (11.7%) showed some kind of tendon injury in the tibialis posterior tendon, 47 (8.6%) in the Achilles tendon, 34 (6.2%) in the peroneus brevis tendon, 27 (4.9%) in the flexor hallucis longus tendon, and 26 (4.7%) in the peroneus longus tendon. Additional findings included lesions in the flexor digitorum longus tendons (n=10), in the tibialis anterior tendon (n=6), and in the extensor digitorum longus tendons (n=3). Conclusions: The high-quality soft-tissue contrast resolution, noninvasive nature, and multiplanar capabilities of the MR images make it an excellent tool for the detection and evaluation of a variety of tendon disorders in the ankle.

Evaluación por TC y RM de tumores orbitarios: nuestra experiencia / Evaluation by TC and RM of orbitarios tumors: our experience

Objetivos: Mostrar nuestra casuística de masas ocupantes de órbita evaluadas por tomografía computada (TC) y/o resonancia magnética (RM). Mencionar los datos imageneológicos y epidemioológicos más relevantes de las mismas obtenidos de la bibliografía, basado en sus diagnósticos diferenciales. Material y métodos: En un período de 48 meses fueron evaluados 26 pacientes con tumores de órbita, 13 de sexo femenino y 13 de sexo masculino, con rango etario entre 3 y 75 años. A 17 pacientes se les realizó RM, a 8, TC, y a uno, ambos métodos. Los equipos utilizados fueron:resonadores de 0.5 y 1,5 Telsa; tomógrafos axial y helicoidal. Resultados: Del total (n=26), 7 fueron tumores benignos, 2 de comportamiento variable y 17 malignos. Los tumores benignos fueron: 2 hemangiomas cavernosos, 1 meningioma, 1 tumor epidermoide, 1 tumor dermoide, 1 lipoma y 1 varice oftálmica. Los tumores de evolución e histología variable fueron: 2 gliomas de nervio óptico. Los tumores malignos examinados resultaron: metástasis, el origen más frecuente, 3 linfomas no Hodgkin, 2 hemangiopericitomas, 2 retinoblastomas, 2 rabdomiosarcomas, 2 melanomas y 1 carcinoma de glándula lagrimal. Dentro de los pacientes con metástasis, el origen más frecuente fue la mama (n=2); otros sitios incluyeron pulmón (n=1), útero (n=1) y neuroblastoma de origen indeterminado (n=1). Conclusión: En nuestra experiencia, 3l 65,4% de los casos correspondio a tumores malignos, siendo más frecuente el secundarismo (19,2%). El 26,9% correspondió a tumores benignos, siendo más frecuente el hemangioma. Un tercer grupo (7.7%) está formado por gliomas de nervio óptico, de histología y comportamiento indeterminados.