Priapism and Sickle Cell Disease: Special Considerations in Etiology, Management, and Prevention.

Sickle cell disease (SCD) is an inherited medical condition where sickled red blood cells cause vaso-occlusive crisis. One major complication of SCD is priapism, defined as an erection of the penis lasting over four hours beyond sexual stimulation or orgasm. SCD priapism is caused by sickled erythrocytes obstructing venous outflow and can lead to permanent erectile dysfunction. This article reviews the pathology, physiology, and management of SCD priapism, including potential novel therapeutic agents.

Regimented Phosphodiesterase Type 5 Inhibitor Use Reduces Emergency Department Visits for Recurrent Ischemic Priapism.

PURPOSE: We evaluated the real-world effectiveness of regimented phosphodiesterase type 5 inhibitor dosing on recurrent ischemic priapism outcomes using emergency department visits as a proxy for therapeutic control of the disorder. MATERIALS AND METHODS: We performed a retrospective chart review of patients with recurrent ischemic priapism who were started on regimented phosphodiesterase type 5 inhibitor therapy from May 2006 to January 2020. We compared the number of emergency department visits per month during a 6-month period before treatment, during treatment and after treatment discontinuation. We extracted and categorized priapism outcomes such as priapism frequency and duration. RESULTS: Of 216 patients identified with all cause priapism 114 were diagnosed with recurrent ischemic priapism and 42 were initiated on regimented phosphodiesterase type 5 inhibitor therapy. Treatment effectiveness was analyzed for 24 evaluable patients. Priapism etiology was idiopathic in 12 patients (50%), sickle cell disease in 11 (46%) and drug-induced in 1 (4%). The median length of regimented phosphodiesterase type 5 inhibitor use was 3 months (IQR 2-7). Treatment decreased emergency department visits per month by 4.4-fold (p <0.001), priapism duration tiers (p <0.001) and priapism frequency tiers (p <0.001). Of 24 patients 22 (92%) reported improvement in priapism outcomes, 9 of whom reported resolution of recurrent ischemic priapism episodes. A subgroup analysis of 17 patients with recurrent ischemic priapism relapse after treatment discontinuation showed a significant increase in priapism duration (p <0.001) and frequency (p <0.001) but no significant change in emergency department visits per month (p=0.91). CONCLUSIONS: Regimented phosphodiesterase type 5 inhibitor therapy was an impactful treatment in managing recurrent ischemic priapism according to objective and subjective parameters. This study provides further support for the use of regimented phosphodiesterase type 5 inhibitor dosing as a preventive strategy for recurrent ischemic priapism.

[Homozygous Sickle Cell Children Treated with Hydroxyurea in Brazzaville (Congo)]. / Le devenir des enfants atteints de drépanocytose homozygote traités par hydroxyurée à Brazzaville (Congo).

The objective of this study is to reduce the morbidity of children with homozygous sickle cell disease presenting severe forms. We have conducted a longitudinal study between November 2015 and September 2017 at the Brazzaville University Hospital. Children with sickle cell disease requiring treatment with hydroxyurea were included. The variables studied were therapeutic compliance, evolutive profile of nutritional status, indications of hydroxyurea, electrophoresis of hemoglobin, blood count, and toxicity. The statistical test used was Student test with a significance threshold of less than 0.05. One thousand twenty-four children were monitored for sickle cell disease, 107 of which had received hydroxyurea (10.4%). The indications for hydroxyurea were recurrent anemic attacks (≥ 4) in 62 cases (57.9%), neurological crises 19 cases (17.8%), recurrent hyperalgesic crises in 17 cases (15.9%), priapism in 4 cases (3.7), and acute thoracic syndrome in 2 cases (1.9%). Therapeutic compliance was good in 89.5% of them. A rapid and lasting clinical improvement was noted in the majority of patients with hyperalgesic attacks (88.2%) and anemic attacks (88.7%), two recurrences for the cerebrovascular accidents, and an absence of recurrence of priapism and of the acute thoracic syndrome. From the biological point of view, there was a significant increase in fetal hemoglobin (1.2 to 16.2%; P  < 0.05), hemoglobin (7 to 8.3 g/dl; P < 0.05), mean cell volume (80.8 to 96 fl; P  < 0.05) and a significant decrease in mean white blood cell count (15,633 to 9,872/mm3; P  < 0.05) and platelets (387,002 to 324,400/mm3; P  < 0.05). The signs of toxicity observed were mainly vomiting and thrombocytopenia in two cases each, one case with headache and the other with neutropenia. Indications for use of hydroxyurea therapy in children with sickle cell disease in Brazzaville are common. These are dominated by recurrent anemic seizures, strokes, and hyperalgesic seizures. The excellent evolution of these complications under hydroxyurea represents an interesting alternative in our countries with limited resources.

Il s'agit d'une étude longitudinale réalisée entre novembre 2015 et septembre 2017 au CHU de Brazzaville. L'étude a porté sur une série hospitalière d'enfants atteints de drépanocytose homozygote et présentant des complications sévères qui imposaient le recours à l'hydroxyurée. Les variables étudiées étaient l'observance thérapeutique, l'évolution de l'état nutritionnel, des indications de l'hydroxyurée, des éléments de l'hémogramme et de l'électrophorèse de l'hémoglobine au cours du traitement, les effets secondaires et les signes de toxicité. La comparaison des moyennes des éléments hématologiques avant le traitement et la fin de l'étude a fait appel au test t de Student, avec un seuil de significativité fixé à 0,05. Sur 1 024 enfants suivis pour drépanocytose, 107 présentaient une indication de traitement par hydroxyurée, soit 10,4 %. Ces indications étaient des épisodes anémiques récurrents (≥ 4) dans 62 cas, des accidents neurovasculaires dans 19 cas, des hyperalgies récurrentes dans 17 cas, un priapisme permanent dans quatre cas et un syndrome thoracique aigu dans deux cas. L'observance thérapeutique était bonne pour 89,5 % des enfants traités. Une amélioration clinique rapide et durable était notée dans la majorité des enfants, avec 88,2 % pour les crises hyperalgiques, et 88,7 % pour les crises anémiques, deux cas de récidives de crise neurovasculaire, mais aucune pour le priapisme et le syndrome thoracique aigu. Sur le plan biologique, on a constaté une augmentation significative du taux de l'hémoglobine fœtale (1,2 à 16,2 % ; p < 0,05), de l'hémoglobine (7 à 8,3 g/dl ; p < 0,05), du volume globulaire moyen (80,8 à 96 fl ; p < 0,05), et une baisse significative du nombre de globules blancs (15 633 à 9 872/mm3 ; p < 0,05) et des plaquettes (387 002 à 324 400/mm3 ; p < 0,05). Les effets secondaires observés étaient essentiellement des vomissements et une thrombopénie dans deux cas chacun, ainsi qu'un cas de céphalée et une neutropénie. Les indications de traitement par hydroxyurée chez l'enfant atteint de drépanocytose à Brazzaville sont nombreuses. Celles-ci sont dominées par les épisodes anémiques récurrents, les accidents vasculaires cérébraux et les crises hyperalgiques. L'excellente évolution de ces complications sous hydroxyurée représente une alternative intéressante dans nos pays à ressources limitées.

Effect of lysyl oxidase (LOX) on corpus cavernous fibrosis caused by ischaemic priapism.

Penile fibrosis caused by ischemic priapism (IP) adversely affects patients' erectile function. We explored the role of lysyl oxidase (LOX) in rat and human penes after ischemic priapism (IP) to verify the effects of anti-LOX in relieving penile fibrosis and preventing erectile dysfunction caused by IP in rats. Seventy-two rats were randomly divided into six groups: control group, control + ß-aminopropionitrile (BAPN) group, 9 hrs group, 9 hrs + BAPN group, 24 hrs group, and 24 hrs + BAPN group. ß-aminopropionitrile (BAPN), a specific inhibitor of LOX, was administered in the drinking water. At 1 week and 4 weeks, half of the rats in each group were randomly selected for the experiment. Compared to the control group, the erectile function of IP rats was significantly decreased while the expression of LOX in the corpus cavernosum was significantly up-regulated in both 9 and 24 hrs group. Proliferated fibroblasts, decreased corpus cavernosum smooth muscle cells/collagen ratios, destroyed endothelial continuity, deposited abnormal collagen and disorganized fibers were observed in IP rats. The relative content of collage I and III was not obviously different among the groups. ß-aminopropionitrile (BAPN) could effectively improve the structure and erectile function of the penis, and enhance recovery. The data in this study suggests that LOX may play an important role in the fibrosis of corpus cavernosum after IP and anti-LOX may be a novel target for patients suffering with IP.

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.

Priapismo en la drepanocitosis. Diagnóstico y opciones terapéuticas / Priapism in sickle cell disease. Diagnosis and therapeutics options

El priapismo es una complicación de la anemia drepanocítica y se define como una erección prolongada, dolorosa y persistente del pene de más de 4 horas de duración sin estimulación sexual asociada. El 95 por ciento de las crisis de priapismo en estos pacientes es de tipo isquémico o de bajo flujo y constituyen una emergencia médica que, de no diagnosticarse y tratarse adecuadamente, provoca necrosis del tejido y disfunción eréctil. En este trabajo se revisan el diagnóstico y las opciones terapéuticas actuales y futuras de esta grave complicación(AU)

Priapism is a common complication of sickle cell disease and it is characterized by a prolonged, painful and persistent erection of the penis lasting more than 4 hours without associated sexual stimulation. The 95 percent of priapism crisis in these patients is ischemic type and represents a medical emergency that can provoke erectile tissue necrosis and erectile dysfunction if not treated properly. In this paper we reviewed the diagnosisand the current and perspectives therapeutic options of this severe complication(AU)

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.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism.

PURPOSE: To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. RESULTS: Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. CONCLUSIONS: The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism

ABSTRACT Purpose To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. Materials and Methods Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. Results Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. Conclusions The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

Protective effect of curcumin on priapism and ischemia-reperfusion injury in rats.

OBJECTIVE: We aimed to identify the oxidative stress effects of the ischemic priapism on cavernosal tissues and to assess the biochemical and histopathological effects of curcumin in rats. MATERIALS AND METHODS: 26 adult male Sprague Dawley rats were randomly divided into three groups. Group 1 (Control, n = 8): only penectomy was performed and 3 ml blood samples were obtained from the vena cava inferior (VCI). Group 2 (ischemia-reperfusion group; n= 8): penectomy was performed after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples were obtained from the VCI. Group III (IR + CURC group, n = 10): 200 mg/kg/day curcumin per orally before surgery for 7 days + penectomy after 1 hour ischemic priapism + 30 min reperfusion and 3 ml blood samples from the VCI. Total oxidant status (TAS), total antioxidant status (TAS) and paraoxonase (PON1) levels were measured. Tissue samples were investigated and scored histopathologically in terms of bleeding, edema and necrosis. RESULTS: TOS levels were higher (p = 0.002), and TAS levels were lower (p = 0.001) in the IR group compared to the control group. As a result of curcumin treatment, TAS levels were increased (p = 0.003), and TOS levels were decreased (p = 0.004) in the IR + CURC group compared to the IR group. In the treatment group (IR + CURC) TAS and TOS levels were similar to levels in the control group. PON1 levels were increased with ischemia-reperfusion (p = 0.21) and decreased with curcumin treatment (p = 0.53), however these changes were not statistically significant. There was no significant difference in the effects of curcumin on histopathological changes. CONCLUSIONS: This study showed that curcumin has preventive effects on oxidative stress parameters against ischemia-reperfusion injury.

Lycopene prevents experimental priapism against oxidative and nitrosative damage.

OBJECTIVE: Priapism is a persistent and often painful penile erection in the absence of sexual stimulation. It can cause progressive fibrosis, edema and drying of the erectile tissue and then it can lead to erectile dysfunction. Previous studies suggested that, neuronal nitric oxide levels increased during the priapism. High NO levels can result in the formation of reactive oxygen species (ROS) leading to oxidative stress in tissue and reproductive system. The aim of this study was to evaluate oxidative and nitrosative effects caused by priapism in cavernosal tissue and serum, and determinate beneficial effects of lycopene on ischemic priapism. MATERIALS AND METHODS: 32 rats were randomly divided into four groups and the first group being as the control. In the second group, experimental ischemic priapism was formed for an hour and then 1hour reperfusion was provided. In the third group, lycopene was intraperitoneally given at the dose of 10 mg/kg. In the fourth group, lycopene were administered to rats with experimental priapism. RESULTS: Priapism caused a significant increase in TBARS (thiobarbituric acid reactive substances) and NO levels and a significant decrease in the levels of GSH, CAT, GPx and SOD in serum and cavernosal tissue of rats. However, lycopene significantly increased GSH, CAT, GPx and SOD levels but decreased formation of TBARS production and NO in rats with priapism. CONCLUSIONS: Our findings indicated that ischemic priapism lead to significant oxidative and nitrosative damage in cavernosal tissue and serum samples of rats. However lycopene treatment eliminates these negative effects induced by priapism. For this reason, we suggested that lycopene may be used in the treatment of priapism.

Prophylactic phenylephrine for iatrogenic priapism: a pilot study with Peyronie's patients.

PURPOSE: Although penile duplex Doppler ultrasonography (PDDU) is a common and integral procedure in a Peyronie's disease workup, the intracavernosal injection of vasoactive agents can carry a serious risk of priapism. Risk factors include young age, good baseline erectile function, and no coronary artery disease. In addition, patients with Peyronie's disease undergoing PDDU in an outpatient setting are at increased risk given the inability to predict optimal dosing. The present study was conducted to provide support for a standard protocol of early administration of phenylephrine in patients with a sustained erection after diagnostic intracavernosal injection of vasoactive agents to prevent the deleterious effects of iatrogenic priapism. MATERIALS AND METHODS: This was a retrospective review of Peyronie's disease patients who received phenylephrine reversal after intracavernosal alprostadil (prostaglandin E1) administration to look at the priapism rate. Safety was determined on the basis of adverse events reported by subjects and efficacy was determined on the basis of the rate of priapism following intervention. RESULTS: Patients with Peyronie's disease only had better hemodynamic values on PDDU than did patients with Peyronie's disease and erectile dysfunction. All of the patients receiving prophylactic phenylephrine had complete detumescence of erections without adverse events, including no priapism cases. CONCLUSIONS: The reversal of erections with phenylephrine after intracavernosal injections of alprostadil to prevent iatrogenic priapism can be effective without increased adverse effects.

Priapism, an emerging complication in ß-thalassemia intermedia patients.

The increase in survival rate of ß-thalassemia (ß-thal) patients allowed for the appearance and manifestation of several complications in almost every organ system. Priapism in ß-thal patients is rarely reported in the literature. We herein report and investigate the occurrence of two cases of priapism in two young patients with ß-thal intermedia (ß-TI). The potential mechanisms are due to either a cellular mechanism involving a thrombus obstructing the efferent venules of the corpora cavernosa leading to priapism, or a recently elucidated functional mechanism that causes alteration of nitric oxide (NO) response of the penis, ultimately causing priapism. This should incite clinicians for a close follow-up and monitoring of high risk patients who are susceptible to developing priapism.

Randomized controlled trial of sildenafil for preventing recurrent ischemic priapism in sickle cell disease.

BACKGROUND: Successful preventive therapy for ischemic priapism, a disorder of penile erection with major physical and psychologic consequences, is limited. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of sildenafil by a systematic dosing protocol to prevent recurrent ischemic priapism associated with sickle cell disease. METHODS: Thirteen patients with sickle cell disease reporting priapism recurrences at least twice weekly were randomized to receive sildenafil 50 mg or placebo daily, unassociated with sleep or sexual activity, for 8 weeks, followed by open-label use of this sildenafil regimen for an additional 8 weeks. RESULTS: Priapism frequency reduction by 50% did not differ between sildenafil and placebo groups by intention-to-treat or per protocol analyses (P = 1.0). However, during open-label assessment, 5 of 8 patients (62.5%) by intention-to-treat analysis and 2 of 3 patients (66.7%) by per protocol analysis met this primary efficacy outcome. No significant differences were found between study groups in rates of adverse effects, although major priapism episodes were decreased 4-fold in patients monitored "on-treatment." CONCLUSIONS: Sildenafil use by systematic dosing may offer a strategy to prevent recurrent ischemic priapism in patients with sickle cell disease.

Prevention of recurrent ischemic priapism with ketoconazole: evolution of a treatment protocol and patient outcomes.

INTRODUCTION: The management of recurrent ischemic priapism (RIP) is not clearly defined. Ketoconazole (KTZ) is used to treat RIP and produces a temporary hypogonadal state to suppress sleep-related erections (SREs), which often evolve into episodes of ischemic priapism in this population. AIM: We review our experience to prevent RIP using KTZ and present our outcomes using a decreased dose regimen. METHODS: A retrospective chart review and phone survey of 17 patients with RIP was performed. KTZ inhibits adrenal and gonadal testosterone production with a half-life of 8 hours. By suppressing testosterone levels, SREs are interrupted. We compared our previous protocol of three times daily (TID) KTZ dosing with prednisone for 6 months with our current regimen of initiating KTZ 200 mg TID with prednisone 5 mg daily for 2 weeks and then tapering to KTZ 200 mg nightly for 6 months. MAIN OUTCOME MEASURES: The primary outcome was the prevention of RIP using KTZ. Secondary outcomes included side effects secondary to KTZ use and patient satisfaction. RESULTS: All men experienced daily or almost daily episodes of prolonged, painful erections prior to starting KTZ. The mean number of emergency room (ER) visits per patient prior to starting KTZ was 6.5. No patient required an ER visit for RIP while on KTZ. Sixteen of 17 patients (94%) had complete resolution of priapism while on KTZ with effects noted immediately after starting therapy and no reported sexual side effects attributed to KTZ. One man stopped therapy after 4 days because of nausea/vomiting. Fourteen of 16 men eventually discontinued KTZ after a median duration of 7 months. Twenty-nine percent reported no recurrent priapic episodes after discontinuing. A total of 78.6% had partial or complete resolution of symptoms persisting after KTZ was discontinued with a mean post-treatment follow-up of 36.7 months. CONCLUSION: No reliable effective preventative therapy has been identified for RIP. In our relatively sizable single-center experience, KTZ appears to be a reasonably effective, safe, and inexpensive treatment to prevent RIP while preserving sexual function. We now recommend our tapered dose regimen listed above. After 6 months, we recommend stopping the medication as we have found a majority of patients will not need to resume nightly KTZ.

[Strategies for the treatment and prevention of priapism in children].

Priapism is defined as abnormal persisting penile erection beyond or unrelated to sexual stimulation. It is rare in children and the appropriate management consensus is lacking. We have reviewed the literature on the treatment and prevention of priapism in children in the last 5 years. The following advances were reported: (1) compression or thrombin injection guided by ultrasound in nonischemic priapism prior to selective angioembolization; (2) anti-androgen therapy is the key for the prevention of nonischemic priapism occurring and reoccurring after angioembolization; (3) etiological interventions are enough to resolve some priapism in children; (4) T tunnel may be applied to the distal shunt failed cases in children. Combined with the new progress in treatment of priapism in children, we have designed the algorithm of priapism management and the algorithm of stuttering priapism prevention. The two algorithms will be helpful for clinicians dealing with the clinical challenges in children's priapism management.

Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress.

Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders.