Effects of ketamine on penile tissues in an experimental priapism model in rats.

BACKGROUND: This study aimed to evaluate the histopathological and biochemical effects of ketamine on penile tissues following ischemia-reperfusion injury induced by priapism. METHODS: Twenty-four male rats were randomized into three groups. Group 1 served as the control group. Group 2 underwent the priapism model to induce ischemia-reperfusion injury. Group 3, the treatment group, experienced a similar ischemia-reperfusion model as Group 2; additionally, 50 mg/kg of ketamine was administered intraperitoneally just before reperfusion. Blood biochemical analyses and penile histopathological evaluations were performed. RESULTS: In Group 3, significant improvements were observed in all histopathological scores, including desquamation, edema, inflammation, and vasocongestion compared to Group 2 (p<0.001). Blood biochemical analyses showed that the malondialdehyde (MDA) levels were recorded as 10 in Group 2, with a significant decrease in Group 3 (p=0.013). Similarly, proinflammatory cytokine levels, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were found to be suppressed in Group 3 compared to Group 2 (p=0.003, p=0.022, and p=0.028, respectively). Antioxidant enzyme activities, such as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were higher in Group 3 compared to Group 2 (p=0.016 and p=0.024, respec-tively). CONCLUSION: Ketamine is an effective anesthetic agent in alleviating the effects of penile ischemia-reperfusion injury.

A case of priapism following intrathecal morphine injection in a dog.

Background: Priapism refers to prolonged erection unrelated to sexual stimulation, with severe sequelae unless treated. In humans, it is a rare complication associated with epidural or spinal opioid administration. Its pathophysiology is unclear. This is the first report of priapism following neuraxial anesthesia in dog. Case Description: An intrathecal morphine injection (30 mcg/kg) at L5-L6 for postoperative analgesia was given at the end of surgery for removal of cutaneous mastocytomas of the abdomen and left axillary lymphadenectomy. Painless penile erection occurred 2 hours later and lasted 6 hours, before spontaneously resolving 7-8 hours after the injection. No pain or other adverse events (e.g., nausea, urinary retention, and itching) were recorded. Recovery was complete without treatment. Conclusion: Painless, self-resolving priapism is a rare complication associated with intrathecal morphine injection in dogs.

Recurrent Priapism From Cabergoline and Bromocriptine in a Hypogonadal Man With Prolactinoma.

Dopamine agonists are generally well tolerated and represent the first-line therapy for prolactinomas. We report a case of a 20-year-old man with a macroprolactinoma who developed recurrent priapism with cabergoline and bromocriptine. Transsphenoidal pituitary adenoma resection was done with normalization of the prolactin level. Priapism is a rare side effect of dopamine agonists that warrants discontinuation of therapy. Patients should be educated about this potential side effect at the time of prescribing the medication.

Treatments for priapism in boys and men with sickle cell disease.

BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. This is an update of a previously published review. OBJECTIVES: To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 September 2019. Date of most recent search of trial registries and of Embase: 01 October 2019. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed the risk of bias of the trials. MAIN RESULTS: Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and a four-arm trial which compared ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence. However, all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome; and from the evidence included in this review, we are uncertain whether stilboestrol, etilefrine or ephedrine reduce the frequency of stuttering priapism as the certainty of the evidence has been assessed as very low. Additionally, we conclude that sildenafil may make little or no difference (low-certainty evidence). Two trials reported on immediate side effects and we are uncertain whether etilefrine or ephedrine reduce the occurrence of these (very low-certainty of evidence) and also conclude that sildenafil may make little or no difference in side effects (low-quality evidence). Given that all of the trials were at risk of bias and all had low participant numbers, we considered the certainty of the evidence to be low to very low. AUTHORS' CONCLUSIONS: There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.

Mechanisms underlying priapism in sickle cell disease: targeting and key innovations on the preclinical landscape.

Introduction: Priapism is prolonged penile erection in the absence of sexual arousal or desire and is a devastating condition affecting millions of patients with sickle cell disease (SCD) globally. Available drug treatments for SCD-related priapism remain limited and have been primarily reactive rather than preventive. Hence, there is an unmet need for new drug targets and pharmacologic therapies.Areas covered: We examine the molecular mechanisms underlying SCD-associated priapism evaluated mostly in animal models. In mouse models of SCD, molecular defects of priapism operating at the cavernous tissue level include reduced tonic NO/cGMP signaling, elevated oxidative/nitrosative stress, vascular adhesion molecule derangements, excessive adenosine and opiorphin signaling, dysregulated vasoconstrictive RhoA/ROCK signaling, and testosterone deficiency. We discuss the consequences of downregulated cGMP-dependent phosphodiesterase type 5 (PDE5) activity in response to these molecular signaling derangements, as the main effector mechanism causing unrestrained cavernous tissue relaxation that results in priapism.Expert opinion: Basic science studies are crucial for understanding the underlying pathophysiology of SCD-associated priapism. Understanding the molecular mechanisms could unearth new therapeutic targets for this condition based on these mechanisms. Treatment options should aim to improve deranged erection physiology regulatory signaling to prevent priapism and potentially restore or preserve erectile function.

The role of apoptosis and the effect of epidermal growth factor on proapoptotic BNIP 3 in an experimental rat priapism model

Background/aim: This study aimed to investigate the effects of apoptosis-inducing Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP 3) and antiapoptotic epidermal growth factor (EGF) on the pathophysiology of experimental low-flow priapism. Materials and methods: Twenty-four adult Sprague-Dawley rats were divided into four equal groups. Group I was the control group. Ischemic priapism was induced for 4 h in Group II rats. In Group III, intraperitoneal EGF at 10 µg/kg was given for 7 days before induction of ischemic priapism for 4 h. In Group IV, intraperitoneal EGF at 20 µg/kg was given for 7 days before induction of ischemic priapism for 4 h. The western blot method was used to determine BNIP 3 expression levels and the TUNEL method was used to determine the apoptotic cells in the cavernosal tissue samples. Results: Although BNIP 3 expression levels were significantly higher in all three study groups compared to the controls, BNIP 3 was significantly higher in EGF-administered groups when compared to Group II (P < 0.05). The TUNEL score of group II was significantly higher than those of the other groups. Conclusion: Decreased apoptosis in cavernosal tissues obtained by antagonizing the apoptotic effect of BNIP 3 with EGF may facilitate the development of new conservative treatment methods via those pathways.

[Early implantation of a penile prosthesis as an optimal treatment of retractory low flow priapism]. / Implantation précoce d'une prothèse pénienne comme traitement optimal du Priapisme réfractaire à bas débit.

Low flow priapism is a urologic emergency because it leads to erectile dysfunction due to cavernosal fibrosis. Several treatments exist, including cavernosal aspiration, washing with or without alpha-mimetic agent or shunting surgery. In case of failure of these methods or prolonged priapism (superior to 36 hours), the option of early penile prostheses implantation should be discussed with a motivated patient in order to improve sexual satisfaction.

Le priapisme à bas débit est une urgence urologique car il conduit inévitablement à la fibrose des corps caverneux et donc à une dysfonction érectile totale. Différentes méthodes de détumescence existent allant de la ponction évacuatrice, le lavage avec ou sans agent vasoconstricteur à la chirurgie de «shunting¼. En cas d'échec de ces manoeuvres ou en cas de priapisme de plus de 36 heures, les recommandations actuelles sont de proposer au patient motivé l'implantation précoce d'une prothèse pénienne pour optimiser la satisfaction sexuelle ultérieure.

Treatments for priapism in boys and men with sickle cell disease.

BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. OBJECTIVES: To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 September 2017.Date of most recent search of trial registries and of Embase: 12 December 2016. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed the risk of bias of the trials. MAIN RESULTS: Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence but all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome. No significant effect of any of the treatments was seen compared to placebo. Immediate side effects were not found to be significantly different from placebo in the two trials where this information was reported. We considered the quality of evidence to be low to very low as all of the trials were at risk of bias and all had low participant numbers. AUTHORS' CONCLUSIONS: There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.

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)

Beneficial Effect of the Nitric Oxide Donor Compound 3-(1,3-Dioxoisoindolin-2-yl)Benzyl Nitrate on Dysregulated Phosphodiesterase 5, NADPH Oxidase, and Nitrosative Stress in the Sickle Cell Mouse Penis: Implication for Priapism Treatment.

Patients with sickle cell disease (SCD) display priapism, and dysregulated nitric oxide (NO) pathway may contribute to this condition. However, current therapies offered for the prevention of priapism in SCD are few. The 3-(1,3-dioxoisoindolin-2-yl)benzyl nitrate (compound 4C) was synthesized through molecular hybridization of hydroxyurea and thalidomide, which displays an NO-donor property. This study aimed to evaluate the effects of compound 4C on functional and molecular alterations of erectile function in murine models that display low NO bioavailability, SCD transgenic mice, and endothelial NO synthase and neuronal NO synthase double gene-deficient (dNOS-/) mice, focusing on the dysregulated NO-cGMP- phosphodiesterase type 5 (PDE5) pathway and oxidative stress in erectile tissue. Wild-type, SCD, and dNOS-/- mice were treated with compound 4C (100 µmol/kg/d, 3 weeks). Intracavernosal pressure in anesthetized mice was evaluated. Corpus cavernosum tissue was dissected free and mounted in organ baths. SCD and dNOS-/- mice displayed a priapism phenotype, which was reversed by compound 4C treatment. Increased corpus cavernosum relaxant responses to acetylcholine and electrical-field stimulation were reduced by 4C in SCD mice. Likewise, increased sodium nitroprusside-induced relaxant responses were reduced by 4C in cavernosal tissue from SCD and dNOS-/- mice. Compound 4C reversed PDE5 protein expression and reduced protein expressions of reactive oxygen species markers, NADPH oxidase subunit gp91phox, and 3-nitrotyrosine in penises from SCD and dNOS-/- mice. In conclusion, 3-week therapy with the NO donor 4C reversed the priapism in murine models that display lower NO bioavailability. NO donor compounds may constitute an additional strategy to prevent priapism in SCD.

Priapism: What cause: mental illness, psychotropic medications or poly-substance abuse?

We present a case of priapism in a homeless patient with a psychiatric history of major depression, PTSD, polysubstance abuse (alcohol and cocaine) and past psychotropic medication use who was admitted to a local hospital for suicidal ideation. Priapism is a serious urological and a medical emergency which has often been associated with psychotropic medications (including the antidepressant trazodone), use of marijuana and alcohol, and other factors. This clinical case highlights the additive risks of medications and comorbid conditions in contributing to onset of priapism, emphasizing the importance of any pre-existing medical illness, diagnoses, and comorbid mental illnesses. Moreover, clinicians should consider potential side effects of all medications used and their drug interactions as they manage patients who develop this condition.

Partial Priapism Treated with Pentoxifylline.

MAIN FINDINGS: A 26-year-old man suffering from partial priapism was successfully treated with a regimen including pentoxifylline, a nonspecific phosphodiesterase inhibitor that is often used to conservatively treat Peyronie's disease. CASE HYPOTHESIS: Partial priapism is an extremely rare urological condition that is characterized by thrombosis within the proximal segment of a single corpus cavernosum. There have only been 36 reported cases to date. Although several factors have been associated with this unusual disorder, such as trauma or bicycle riding, the etiology is still not completely understood. Treatment is usually conservative and consists of a non-steroidal anti-inflammatory and anti-thrombotic. Promising future implications: This case report supports the utilization of pentoxifylline in patients with partial priapism due to its anti-fibrogenic and anti-thrombotic properties.

Partial Priapism Treated with Pentoxifylline

ABSTRACTMain findings:A 26-year-old man suffering from partial priapism was successfully treated with a regimen including pentoxifylline, a nonspecific phosphodiesterase inhibitor that is often used to conservatively treat Peyronie's disease.Case hypothesis:Partial priapism is an extremely rare urological condition that is characterized by thrombosis within the proximal segment of a single corpus cavernosum. There have only been 36 reported cases to date. Although several factors have been associated with this unusual disorder, such as trauma or bicycle riding, the etiology is still not completely understood. Treatment is usually conservative and consists of a non-steroidal anti-inflammatory and anti-thrombotic.Promising future implications:This case report supports the utilization of pentoxifylline in patients with partial priapism due to its anti-fibrogenic and anti-thrombotic properties.

Priapism as a result of chronic myeloid leukemia: case report, pathology, and review of the literature.

INTRODUCTION: Priapism is rare-presenting feature in male patients with chronic myeloid leukemia (CML). Several hypotheses for pathogenesis have been described. Management has been controversial; some authors described resolution following priapism-specific interventions, and others recommended addition of CML-specific therapy or even CML-specific therapy alone. AIM: In this report, we describe presentation and management of a man with refractory priapism that was the first presenting manifestation of CML. We also report, for the first time, the pathology sections of the sinusoidal tissue in such cases. Literature is reviewed for similar cases and their outcome. METHODS: A 21-year-old male patient presented with painful priapism that started 6 days earlier and failed aspiration-irrigation. CBC revealed marked leucocytosis. Oncology care diagnosed CML, and treatment with Imatinib was commenced with prior semen cryopreservation. Following remission, a penile prosthesis was implanted, assisted by optical corporotomy. Sinusoidal tissue biopsy was stained by hematoxylin/eosin (H&E) and CD34. MAIN OUTCOME MEASURES: Pathology sections of cavernous tissue following CML-induced priapism. RESULTS: The penile implant survived without complications. H&E examination of the sinusoidal tissue biopsy revealed leukemic infiltration associated with vascular endothelial damage. CD34 staining showed the mixed picture of leukemic infiltrates, intact vascular endothelium with lumena showing leukemic cells, alternating with destroyed vessels, and no vascular lumena and ruminants of endothelial cells. CONCLUSION: Priapism can be the first manifestation of previously undetected CML. The pathological picture of sinusoidal tissue in such cases is presented. In the case at hand, a complete blood picture was helpful in early diagnosis of CML and early initiation of targeted chemotherapy along with the corporal irrigation/aspiration or shunt surgery. It is therefore recommended to have a CBC examined at presentation of any case of ischemic priapism of unknown etiology, early initiation of CML therapy along with aspiration/irrigation, preferably cryopreserving a semen sample before CML therapy.

[Partial priapism].

Partial priapism, also called partial segmental thrombosis of the corpus cavernosum, is a rare urological condition. Factors such as bicycle riding, drug usage, penile trauma and haematological diseases have been associated with the condition. Medical treatment with low molecular weight heparin (LMWH) or acetylsalicylic acid is first choice treatment, and surgery is preserved for patients unresponsive to analgesics. In this report we describe the case of a 70-year-old man with partial priapism after blood transfusions treated successfully with LMWH.

Excess adenosine A2B receptor signaling contributes to priapism through HIF-1α mediated reduction of PDE5 gene expression.

Priapism is featured with prolonged and painful penile erection and is prevalent among males with sickle cell disease (SCD). The disorder is a dangerous urological and hematological emergency since it is associated with ischemic tissue damage and erectile disability. Here we report that phosphodiesterase-5 (PDE5) gene expression and PDE activity is significantly reduced in penile tissues of two independent priapic models: SCD mice and adenosine deaminase (ADA)-deficient mice. Moreover, using ADA enzyme therapy to reduce adenosine or a specific antagonist to block A(2B) adenosine receptor (ADORA2B) signaling, we successfully attenuated priapism in both ADA(-/-) and SCD mice by restoring penile PDE5 gene expression to normal levels. This finding led us to further discover that excess adenosine signaling via ADORA2B activation directly reduces PDE5 gene expression in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. Overall, we reveal that excess adenosine-mediated ADORA2B signaling underlies reduced penile PDE activity by decreasing PDE5 gene expression in a HIF-1α-dependent manner and provide new insight for the pathogenesis of priapism and novel therapies for the disease.

Female clitoral priapism: an over-the-counter option for management.

INTRODUCTION: Female priapism is a rare condition that is not commonly described in the literature. There are many treatment strategies for the management of priapism, including conservative and safe over-the-counter options. AIM: To describe a case of a woman who presented with clitoral priapism, who was managed conservatively with a simple over-the-counter treatment plan. METHODS: A 29-year-old gravida 0 para 0 presented to the emergency room with painful clitoral priapism lasting for 5 days. Despite cessation of the suspected causal agents, trazodone and wellbutrin, her symptoms persisted. RESULTS: The patient was managed conservatively with analgesics and around-the-clock oral pseudoephedrine and experienced complete resolution of her symptoms. CONCLUSIONS: Oral pseudoephedrine may be a reasonable option for certain patients, and may be considered as a first-line therapy and adjunct to conservative measures.

Prostate cancer risk after anti-androgen treatment for priapism.

BACKGROUND: Patients with recurrent ischemic priapism have historically been treated with anti-androgen therapy due to the limited available evidence for more targeted therapies to treat the underlying pathophysiologic mechanisms of this condition. We report a case in which anti-androgen therapy caused significant adverse side effects and likely masked this patient's elevated prostate-specific antigen (PSA) levels, which adversely impacted the timely diagnosis and treatment of his prostate cancer. CASE REPORT: A 69-year-old man treated with anti-androgens for priapism initially developed unwanted anti-androgenic side effects such as gynecomastia, erectile dysfunction, and decreased libido. After decreasing his anti-androgen dosage and starting a specified regimen of phosphodiesterase type 5 inhibitor therapy, his serum PSA levels were found to be elevated. He was subsequently diagnosed with adenocarcinoma of the prostate and underwent a radical prostatectomy with the pathologic finding of high-grade, locally progressive disease. CONCLUSION: Anti-androgen therapy carries significant complication risks, including the potential to alter the diagnosis and treatment of prostate cancer. Clinicians administering this therapy for priapism management should be aware of these possible risks.