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PubMed2001

Nonadrenergic, noncholinergic relaxation of human isolated corpus cavernosum induced by scorpion venom.

OBJECTIVES: To examine the effects of Tityus serrulatus scorpion venom (TSV) on human corpus cavernosum (HCC) using a bioassay cascade. Priapism is occasionally observed in scorpion envenomation, mostly in children. METHODS: HCC strips were suspended in a cascade system and superfused with aerated and warmed Krebs' solution at 5 mL/min. Noradrenaline (3 micromol/L) was infused to induce a submaximal contraction of the HCC strips. The release of cyclooxygenase products was prevented by infusing indomethacin (6 micromol/L). RESULTS: N(omega)-nitro-L-arginine methyl ester (10 micromol/L; n = 10) increased the tone of the preparations and significantly reduced (P <0.01) the acetylcholine (ACh) and TSV-induced relaxations. Subsequent infusion of L-arginine (300 micromol/L) partially reversed the increased tone and significantly restored the relaxations induced by TSV and ACh (P <0.01). The soluble guanylyl cyclase inhibitor ODQ (10 micromol/L; n = 8) markedly reduced (P <0.01) the relaxations induced by TSV, ACh, glyceryl trinitrate, and bradykinin. 7-Nitroindazole (10 micromol/L; n = 8) inhibited the relaxations induced by TSV by 84% (P <0.01) and also caused small, but significant, reductions in the ACh and bradykinin-induced HCC relaxations (P <0.05). Atropine (1 micromol/L; n = 6) abolished the relaxations evoked by ACh (P <0.01), but had no effect on those elicited by TSV. Tetrodotoxin (1 micromol/L; n = 6) abolished the relaxations induced by TSV (P <0.01) and also reversed the established TSV-induced relaxation (n = 4). CONCLUSIONS: Our results indicate that TSV relaxes HCC through the release of nitric oxide from nonadrenergic, noncholinergic (NANC) nerves. The elucidation of the mechanism responsible for the TSV-induced relaxations might be useful for a better understanding of the development of priapism in cases of scorpion envenomation.

Acetylcholine↗
PubMed1992

Metastasis to the penis from malignant melanoma: case report and review of the literature.

A case of metastatic malignant melanoma to the shaft of the penis is described and the literature reviewed to collate the incidence of primary sites which metastasize to the penis. Less than 260 cases of metastasis to the penis have been reported. Of these, 76% are from genitourinary primary sites and 17% are from gastrointestinal primary sites but only one case of metastatic melanoma to the penis has been previously reported. The described case presented with painful priapism while receiving combination chemotherapy for metastatic disease. A CT scan demonstrated a deposit in the left corpora cavernosa and needle aspiration cytology of a plaque attached to the shaft confirmed malignant melanoma cells. Palliation of the painful priapism was achieved by treatment with radiotherapy using large doses per fraction. Retrograde venous or lymphatic spread may have been the cause of a metastasis at this site. Prognosis is very poor.

Adult↗
PubMedDate not supplied

A prospective randomized study to optimize the dosage of trimix ingredients and compare its efficacy and safety with prostaglandin E1.

Intracavernous injection of Trimix (Tx) is indicated for patients unsuitable for prostaglandin E1 (PgE1) injection due to lack of response, pain or cost. We believe that the ideal ratio of ingredient doses in Tx is yet to be found. We postulated that increasing the doses of individual drug components in an orderly manner would convey important data on penile hemodynamic response. Such information is needed to choose an effective and less costly alternative to PgE1 with least side effects. We set out to evaluate the impact of varying the ingredient dosage on response and short-term safety of Tx compared with PgE1. We prospectively randomized 180 consecutive patients with erectile dysfunction into nine equal groups and each group received a different dose of Tx, namely phentolamine (1 mg) plus one dose of PgE1 (2.5, 5 or 10 microg) and one dose of papaverine (5, 10 or 20 mg). Each patient was injected with 20 microg PgE1 and one dose of Tx in two clinic visits 1 week apart. Following injection, duplex ultrasound of cavernous arteries and axial rigidometry were carried out. Patients ranked the quality of erection, estimated overall satisfaction and reported time to detumescence and side effects. Patients' mean age was 50.5+/-11.7 y with underlying organic condition in 91.1%. There were no significant differences between PgE1 and Tx with regard to peak cavernous artery flow, time to erection, patients' satisfaction, average axial rigidity and pain. PgE1 produced higher end diastolic velocity, shorter duration of erection and less priapism. Patients did not show a preference for either drug or any particular dosage. We conclude that even at the smallest dose of ingredients of Tx, there are no significant differences in hemodynamic effects, rigidity, pain and self-satisfaction between the two drugs. However, Tx produces a longer duration of erection and more priapism than PgE1.

Adrenergic alpha-Antagonists↗
PubMed1988

"Bicycle kickstand" phenomenon: prolonged erections associated with antipsychotic agents.

The purpose of this paper is to draw attention to the ability of some antipsychotic agents to produce sustained erection short of priapism. They appear to have this effect consistently over time in some individuals. The effect is rapidly reversible on discontinuation of the drug, and appears to be dose-dependent. In one of our patients, the "active metabolite" of that same drug could not duplicate the effect. Prevalence and mechanism require clarification. If even a small proportion of patients with the sustained erection phenomenon are found to progress to priapism, this would have profound ramifications. If this phenomenon could be confidently predicted or safely and readily implemented, the benefits for some patients with impotence or premature ejaculation might be considerable. Given all the potential adverse side effects of antipsychotics, it should be appreciated that the potential direct effects on male sexual function are not always adverse.

Adult↗
PubMed2003

20-year experience with iatrogenic penile injury.

PURPOSE: We review our experience with the management of iatrogenic penile injuries. Apart from circumcision, serious damage to the penis can occur following hypospadias repair, surgery for priapism or total loss of the penis following surgical repair of bladder exstrophy. MATERIALS AND METHODS: A retrospective analysis of patients with iatrogenic penile amputation referred to us between 1980 and 2000 was undertaken. Causes of injury and choice of management were reviewed. RESULTS: Of the 13 cases treated during the 20-year period mechanism of primary injury was circumcision in 4, hypospadias repair in 6, priapism in 1, bladder exstrophy repair in 1 and penile carcinoma in 1. A variety of techniques were used for phallic reconstruction. Penile degloving, division of suspensory ligament and rotational skin flaps achieved penile augmentation and enhancement. Reasonable cosmesis and penile length were achieved in all cases. In indicated cases microsurgical phalloplasty was technically feasible. However long-term followup showed various complications including erosions from the use of a penile stiffener. CONCLUSIONS: The ultimate goal of reconstructive surgery is to have a penis with normal function and appearance. The management of penile injury requires a wide variety of surgical techniques that are tailored to the individual patient. Expedient penile reconstruction is successful and therapeutic delay is associated with complications.

Adolescent↗
PubMed2004

Inhibition of factor VIII with a partially inhibitory human recombinant monoclonal antibody prevents thrombotic events in a transgenic model of type II HBS antithrombin deficiency in mice.

Venous thromboembolic disease is a major cause of morbidity and mortality, necessitating antithrombotic therapy. A human monoclonal anti-factor (F)VIII antibody, LCL-mAb-LE2E9, produced by a lymphoblastoid cell line derived from a hemophilia A patient with inhibitor to wild-type but not mutant self FVIII, was previously reported to achieve efficient inhibition of thrombosis in an experimental vena cava thrombosis model in mice. Here, the antithrombotic efficacy of a recombinant DNA-derived version of this anti-FVIII antibody (rec-mAb-LE2E9) was tested in mice which carry a type II heparin binding site antithrombin deficiency mutation and display spontaneous chronic thrombosis in several sites including the penile vein of sexually active males. The recombinant anti-FVIII antibody (100 microg, repeated after 3 days) prevented thrombotic priapism in all treated males, whereas all control animals treated with saline (group of four animals) developed priapism within 6 days after mating (P < 0.05 for treated vs. saline). The rec-mAb-LE2E9 and the original LCL-mAb-LE2E9 were equally effective (five and seven males/group, respectively). These results confirm that FVIII inhibition represents a potent antithrombotic strategy, and show that both LCL-mAb-LE2E9 and rec-mAb-LE2E9 efficiently prevent thrombosis in a physiological model representative of thrombosis in patients with a severe prothrombotic risk.

Animals↗
PubMed1994

Comparison of a mixture of papaverine, phentolamine and prostaglandin E1 with other intracavernous injections.

OBJECTIVE: evaluation of a self-injection program with a mixture of papaverine, phentolamine and prostaglandin E1 (PGE1). METHOD: a self-injection program for erectile dysfunction was started by 48 patients, using a 1-ml mixture of 4.5 mg papaverine, 0.2 mg phentolamine and 1.5 micrograms PGE1. Patients completed a questionnaire at 6 weeks and at 3 months and were followed at the Outpatients Department for an average of 1 year. RESULT: of these patients 25 had previous experience with 20 micrograms PGE1 for intracavernous use and 22 patients had previously used 30 mg papaverine with 1 mg phentolamine. None of these 3 self-injection drugs is obviously superior in its ability to induce erections. Priapism occurred twice on a total of 1,290 injections. After 1-year follow-up, 4 patients had developed problems with fibrosis of the corpora, 2 of whom had encountered this problem also in a previous self-injection program. CONCLUSION: this triple mixture has the disadvantage of causing fibrosis and priapism in susceptible patients.

Alprostadil↗
PubMed2001

Genitourinary complications of sickle cell disease.

PURPOSE: In the last half century the molecular biology, pathophysiology and natural history of sickle cell disease have been well defined. Sickle cell disease causes microvascular occlusion, which is manifested in most organ systems. The genitourinary tract is most commonly affected by hematuria, urinary tract infection and priapism but other more serious sequelae have been identified. MATERIALS AND METHODS: We performed a computerized MEDLINE search from 1965 to the present and a bibliographic review of cross references. These references were analyzed for meaningful findings and case reports. RESULTS: The diagnosis and management of sickle cell disease have advanced rapidly with a significant increase in the life expectancy of affected patients and recognition of a greater number of genitourinary complications. Renal function may be mildly altered or lost completely. Patients with sickle cell disease are at increased risk for urinary tract infection. Priapism is a painful complication of sickle cell disease that is poorly understood and challenging to treat and prevent. Testicular infarction has also been noted. Furthermore, renal medullary carcinoma, a highly lethal tumor, develops almost exclusively in young patients with sickle cell trait. CONCLUSIONS: Heightened awareness of the genitourinary complications of sickle cell disease may prevent end stage disease, including renal failure and impotence. New forms of therapy for sickle cell disease, such as hydroxyurea, may prevent these complications in the future.

Anemia, Sickle Cell↗
PubMed1990

[Prostaglandin E1 injection in erectile dysfunction. Current diagnostic and therapeutic possibilities].

In erectile dysfunction formerly, for both diagnostic and therapeutic purposes, intracavernous injections of papaverine and the combination papaverine/phentolamine were employed. In recent years, promising results have been reported with prostaglandin E1. In a multicenter study, 10 to 20 micrograms prostaglandin E1 were administered for testing corpus cavernosum function. One hundred and fifteen out of 187 patients self-injected themselves with prostaglandin E1 at an average dose of about 13 micrograms. While priapism occurred in 5 to 10% of the patients injecting papaverine or papaverine/phentolamine, and fibrosis and tunica induration in 10 to 57% patients on long-term treatment, the risk of priapism was low in prostaglandin E1. Subsequently, induration and penile deviation were reported in 2 patients each. In this multicenter study, a subjective efficacy of more than 90% was observed, thus confirming similar results with prostaglandin E1 found in other studies. The present results show that prostaglandin E1 can be considered the drug of first choice for intracavernous injection treatment of erectile dysfunction.

Alprostadil↗
PubMed1988

Injection therapy for impotence.

Injection of vasoactive drugs is an effective form of treatment for selected patients with impotence from virtually all causes. The two most commonly employed drugs in the United States are either papaverine alone or various combinations of papaverine and phentolamine. Patients with organic and mixed impotence are best suited for injection treatment, but selected patients with psychogenic impotence also benefit from therapy. After the patient is selected for injection therapy, he undergoes a series of trial injections in the physician's office. The incidence of priapism will be minimized if the initially administered doses are low and the patient is titrated to an appropriate dose level. Uncontrolled trials have revealed that injection treatment produces a satisfactory erection in 65 to 100 per cent of patients for a follow-up period of as long as 2 years with minimal side effects, but the dropout rate is high. If priapism does occur, it almost always responds readily to treatment with aspiration, low doses of an alpha-adrenergic agent, or both. The other common side effects are bruising or ecchymosis and nodule formation at the injection site. This latter complication has not been noted to cause significant abnormal penile curavature necessitating cessation of the program.

Clinical Trials as Topic↗
PubMed1994

Pharmacologic erection: time-dependent changes in the corporal environment.

Priapism is a persistent erection which fails to subside after climax and is accompanied by penile pain and tenderness. The most common form of priapism to confront contemporary urologists is persistence of erection following pharmacologic stimulation. We reviewed our experience over 18 months with initial diagnostic intracavernous challenges of prostaglandin E1. Three-hundred and sixty-six new impotence patients presented to our center and underwent PGE1/color duplex Doppler assessment; 14 patients developed persistent rigidity of two or more hours accompanied by penile discomfort. Each of these patients was successfully managed with penile aspiration and direct corporal instillation of the alpha-adrenergic agonist phenylephrine. The mean PGE1 dosage injected was 6 micrograms and mean duration of erection preceding aspiration 180 minutes. Penile blood gases were obtained from the initial aspirate in all cases. The duration of pharmacologic erections were correlated with the partial pressures of oxygen, carbon dioxide, bicarbonate and the pH using linear regression analysis. There was a clear trend towards deoxygenation, acidosis, and hypercarbia with prolonged erection (105-342 minutes). The relationship between duration of pharmacologic erection and acidosis/hypercarbia was highly significant.

Adult↗
PubMed1993

[The role of magnetic resonance in the evaluation of pathological processes involving the penis].

The above paper was aimed at defining the usefulness of MRI in the study of pathologies involving the penis. Disorders considered include Peyronie's disease, fibrosis of the penis, priapism, trauma, congenital anomalies, and tumors. In Peyronie's disease and in fibrosis of the penis, MRI permits to demonstrate the abnormal thickening of tunica albuginea and erectile tissue; after administration of gadolinium, it becomes possible in some cases to demonstrate plaques of the albuginea that are not palpable. In priapism, MRI is useful both for identifying the cause and for assessing the time elapsed since blood extravasation. In traumatic and congenital pathologies, MRI is essential for the acquisition of all information on anatomy that may be useful for selecting the most suitable surgical therapy. In neoplastic pathology, MRI has proved useful for accurately assessing the extension of lesions involving the basis of the penis.

Diagnosis, Differential↗
PubMed1993

Association of fluoxetine and return of sexual potency in three elderly men.

BACKGROUND: Fluoxetine, a highly specific serotonin reuptake inhibitor, has been reported to cause sexual dysfunction in a minority of patients. Although priapism has been associated with other serotonergic antidepressants, no published reports have correlated restoration of sexual potency with use of fluoxetine. METHOD: The case histories of three geriatric patients treated with fluoxetine for depression or obsessive compulsive disorder are presented. RESULTS: Three patients with histories of impotence experienced a return of sexual potency after treatment with fluoxetine. In two of the cases, the patients had documented histories of vascular disease, which their internists had identified as the cause of their impotence. The improvement in sexual response was seemingly unrelated to abatement of depression or obsessive compulsive disorder, and there was no description of priapism by any of the patients. CONCLUSION: Sexual side effects of fluoxetine may be more variable than previously thought. Animal models showing paradoxical or opposing responses to serotonin-enhancing agents may apply to human sexual functioning as well.

Age Factors↗
PubMed1993

[Urological emergencies].

Every general practitioner has to deal with urologic emergencies. The most frequent illnesses are urinary retention, acute scrotum, priapism, macrohematuria, nephritic colic, obstructive pyelonephritis and pyonephrosis. Whereas urinary retention, as well as acute ureteric stone colic must generally be treated by the practitioner, the urologist must often be consulted in case of an acute scrotum or for priapism. Testicular torsion is one situation, where surgical treatment needs to be performed within 6 hours. Of utmost importance is his timely assistance with the obstructive pyelonephritis and pyonephrosis. These are initially often not recognized, especially because the first ultrasound examination of the intrarenal pyelone may not show a dilatation of the collecting system despite obstruction. If the adequate treatment with drainage and antibiotics is applied too late, this can result in serious and potentially lethal consequences.

Adult↗
PubMed1996

Intracavernous pharmacotherapy: comparison of Moxisylyte and prostaglandin E1.

We report in this retrospective study the results obtained with the first two drugs proposed to reduce the relatively high rates of priapism and fibrosis bound to the papaverine intracavernous injections, i.e. the alpha-blocking agent Moxisylyte (Mox), and prostaglandin E1 (PGE1). Each drug was used for auto-injections in 130 patients with a comparable mean follow up (14.8 months with Mox compared to 14.6 with PGE1). PGE1 proved to be significantly more efficacious (good results in 71% of the patients vs 50% with Mox), especially in the arteriogenic patients (respectively 96% vs 46%). Conversely PGE1 induced prolonged erections in significantly more patients (11 vs 1 with Mox), including 2 priapisms, and also induced pain in more patients (12 vs 1 with Mox). The rate of fibrotic nodules and plaques was low (2 and 3 patients). Despite the better tolerance of Mox, its continuation rate was significantly lower than that of PGE1, PGE1 can be the first choice agent in most cases. Mox is mainly indicated in the patients with supersensitivity to the injections and in those with significant pain following PGE1.

Adult↗
PubMed2005

Imaging of penile traumas--therapeutic implications.

Injury to the penis may result from penetrating or nonpenetrating trauma. Nonpenetrating injury to the erect penis can produce albugineal tear, intracavernous hematoma or extraalbugineal hematoma from rupture of the dorsal vessels. Nonpenetrating injury to the flaccid penis usually follows blunt perineal traumas producing extratunical or cavernosal haematomas, or cavernosal artery tear followed by high flow priapism. Differential diagnosis between albugineal tear and other penile injuries must be obtained as soon as possible, since early surgical repair of albugineal tear reduces significantly the rate of postraumatic curvature and fibrosis. Ultrasonography (US) is able to detect the exact site of the tear in most patients as an interruption of the thin echogenic line of the tunica albuginea. Other imaging techniques are rarely required in the clinical practice. Color Doppler US is the imaging modality of choice to evaluate patients with high flow priapism. Focal or diffuse cavernosal fibrosis can be identified with US as echogenic areas in the cavernosal bodies. Postraumatic erectile dysfunction can result from fibrotic changes, nerve and vascular impairment or both. Doppler evaluation of penile vasculature is required in young patients with postraumatic impotence before surgical revascularization procedures.

Diagnosis, Differential↗
PubMed1994

Contemporary management of depression.

Major depression is a common and disabling disorder with far-reaching social and economic implications. Nonetheless, major depression is treatable by one of the many currently available antidepressants with response rates of approximately 65-70%. Treatment of depression has improved in recent years because of the availability of effective and well-tolerated antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). The currently available antidepressants are generally equally effective and are distinguished primarily by side-effect profiles. The side effects of tricyclic antidepressants (TCAs) are attributed to their nonspecific interaction with cholinergic, histaminergic, serotonergic, and dopaminergic receptors in the central nervous system. The secondary amine TCAs, nortriptyline and desipramine, are preferred among the TCAs because of a more favorable side-effect profile. The TCAs are cardiotoxic, and overdoses are frequently fatal. Adverse effects, including potentially fatal drug and food interactions, limit the use of the monoamine oxidase inhibitors (MAOIs); however, these agents have a role in the treatment of depression with comorbid anxiety, refractory depression, atypical depression, and bulimia. The SSRIs possess a class side-effect profile of headache, nausea, and sexual dysfunction. Individual differences in side effects may distinguish fluoxetine (nervousness, restlessness), sertraline (diarrhea, loose stools), and paroxetine (dry mouth). The SSRIs all inhibit certain cytochrome P450 isoenzymes involved in the metabolism of drugs, such as the TCAs, and each SSRI has been reported to increase plasma concentrations of concomitantly administered TCAs. Bupropion therapy is associated with a risk of seizure development, which can be minimized by multiple daily doses. Trazodone is sedating and can rarely cause priapism. The related compound, nefazodone, does not cause sexual dysfunction or priapism, but is associated with sedation. Venlafaxine, a recently available antidepressant that appears to have efficacy in treatment-refractory depression, may cause nausea that requires gradual upward dosage titration. Higher doses of venlafaxine may also cause elevations in blood pressure, heart rate, and serum cholesterol. As more is learned about the pathophysiology of depression, even more specific and well-tolerated antidepressants will be developed.

Antidepressive Agents↗