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Extensive corporeal fibrosis after penile irradiation.

A potent man with early signs and symptoms of Peyronie's disease 3 months in duration received 1,200 rad of external beam radiation to the penis and presented 5 months later with impotence. Physical examination revealed diffusely woody indurated corporeal tissue. Nocturnal penile tumescence testing was abnormal and pharmaco-cavernosometry demonstrated diffuse corporeal veno-occlusive dysfunction. Treatment by penile injections was unsuccessful. During penile prosthesis implantation bilateral rubbery erectile tissue was encountered, requiring extensive bilateral corporotomy and sharp corporeal tissue excision for prosthesis insertion. Histological analysis of excised corporeal tissue demonstrated extensive corporeal fibrosis and arterial vasculopathy. Computer assisted color histomorphometry revealed that the mean percentage of trabecular smooth muscle area to total erectile tissue area was 26.5 +/- 15.8 (normal 40 to 52%). Immunohistochemical staining with desmin confirmed extensive fibrosis. The most likely explanation for severe corporeal fibrosis is penile irradiation. The hypothesized mechanism of radiation associated fibrosis is ionizing injury to the endothelial cells of the lacunar spaces and cavernous/helicine arteries, which induced irreversible corporeal extracellular matrix structural changes. Penile irradiation, like vascular disease and priapism, is a potential cause of diffuse corporeal fibrosis.

Adult↗

Acidosis impairs rabbit trabecular smooth muscle contractility.

PURPOSE: The aim of our study was to define the effects of acidosis on the contractility of trabecular smooth muscle. METHODS: Rabbit corpus cavernosal strips were mounted in organ chambers to measure isometric tension. Additionally, intracellular free Ca2+ concentration ([Ca2+]i) and tension were measured simultaneously utilising the intracellular fluorescent dye, FURA-2, and isometric tension recordings. RESULTS: Contraction of corpus cavernosum smooth muscle following transmural electrical stimulation (TES) of constrictor nerves or exposure to norepinephrine was depressed under acidic (pH 6.9) vs. control (pH 7.4) conditions. Twenty mM K(+)-induced contractions were also inhibited by acidosis, however 40, 80, and 120 mM K+ contractions were unaffected. Relaxation responses to acetylcholine and electrical stimulation, in phenylephrine contracted tissues, were unaffected by acidosis. Tissues contracted with 20 mM K+ under control conditions, relaxed approximately 50% when exposed to an acidic environment. This relaxation was blocked by exposing the tissue to 80 mM K+. Acidic conditions inhibited basal tone and [Ca2+]i as well as normal increases in both intracellular free Ca2+ and tension upon exposure to 20 mM K+, while 80 mM K(+)-induced increases in Ca2+ and tension were comparable under both neutral and acidic conditions. CONCLUSION: Acidosis impairs trabecular smooth muscle contractility. This alteration is probably secondary to the interference of [H+] with the intra and extracellular mechanisms that regulate homeostasis of [Ca2+]i. Since acidosis is an early complication of ischemic priapism, we propose that the reduced contractility of trabecular smooth muscle may be a significant factor in the perpetuation of the ischemic state.

Acetylcholine↗

A possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity.

PURPOSE: Digoxin use has long been recognized to affect adversely male sexual function but the underlying mechanism is poorly understood. Digoxin is a known inhibitor of sodium/potassium adenosine triphosphatase (sodium pump), a plasma membrane enzyme that has a role in the regulation of smooth muscle tone. We investigated the effects of digoxin on human corpus cavernosum smooth muscle contractility and overall erectile function. MATERIALS AND METHODS: In human corporeal smooth muscle strips the in vitro effects of digoxin were assessed on sodium pump activity as measured by digoxin inhibitable uptake of 86rubidium, basal tone and endothelium dependent, neurogenic and nitric oxide donor induced relaxation. An in vivo prospective double-blind, placebo controlled, crossover, 4-period investigation was performed in 6 healthy male volunteers. The effects of digoxin on serum hormones, erectile function questionnaire, visual sexual stimulation and nocturnal penile tumescence were recorded. RESULTS: In vitro digoxin caused concentration dependent inhibition of 86rubidium uptake (half maximum effect at 0.01 microM.) and contraction of corporeal smooth muscle (half maximum effect at 0.8 microM.). Therapeutic concentrations of digoxin (2 nM.) also inhibited relaxation induced by acetylcholine and electrical field stimulation, which release nitric oxide from corpus cavernosum endothelial cells and nonadrenergic noncholinergic nerves, respectively. In vivo digoxin diminished penile rigidity during visual sexual stimulation and nocturnal penile tumescence testing compared to placebo without influencing libido or serum testosterone, estrogen or luteinizing hormone levels. CONCLUSIONS: Digoxin associated alteration of human erectile function may be explained, in part, by inhibition of corporeal smooth muscle sodium pump activity, which promotes contraction and impedes nitric oxide induced relaxation. Such findings suggest therapeutic use of digoxin for treatment of recurrent priapism states.

Adenosine Triphosphate↗

Transgenic mouse models of sickle cell disease.

An array of sickle cell syndromes has been obtained in transgenic mice, expressing HbS or super HbS, from the asymptomatic phenotype similar to the human A/S state to a syndrome more severe than the human homozygous S/S state, inducing 100% fetal death. Anemia was observed in SAD and SAD (beta th/ beta +) neonates and disappeared during postnatal development. In adults, many features of sickle cell disease are found in transgenic mice, especially in SAD and SAD (beta th/ beta +) mice, including abnormal hemolysis, vasoocclusion, microthrombosis, infarct, priapism, chronic organ defects, and death on hypoxia. These mouse models are relevant to the study of the pathophysiology of sickle cell disease and the induction of vasoocclusion and to evaluate new therapeutic approaches in vivo. Clotrimazole and Mg2+ restore hydration of sickle cells and 12 C79 protected SAD mice from lethal acute hypoxia.

Anemia, Sickle Cell↗

Congenital severe protein C deficiency in adults.

Two unrelated families are described, of which four adult members were found to be suffering from severe protein C deficiency (less than or equal to 5% of normal plasma level). Newborn deaths were reported in the first family but the second family had no history of neonatal purpura fulminans and infant death. Thrombotic symptoms developed mainly in their early twenties, consisting chiefly of recurrent superficial and deep iliofemoral vein thromboses and pulmonary emboli. Other clinical features included generalized peritonitis due to massive mesenteric vein thrombosis, thrombosis of the cavernus sinus, renal vein thrombosis and priapism. In the second family, five members (all aged approximately 40 years) died of intravascular abdominal thrombosis. Massive thromboembolic episodes were associated with a compensated disseminated intravascular coagulation syndrome as evidenced by high concentrations of D-dimer (mean levels 5000 ng/ml plasma) and by a moderate reduction in platelet count and fibrinogen concentrations. D-dimer levels in noncrisis periods were also raised above normal (mean levels 400 ng/ml). The thrombotic problems of these patients were controlled satisfactorily by long-term administration of low molecular weight heparin alone or in combination with low dose warfarin.

Adolescent↗

Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension.

UNLABELLED: Pulmonary hypertension is a frequent complication of sickle cell disease that is associated with haemolysis, impaired nitric oxide bioavailability and high mortality. We sought to evaluate the safety and efficacy of selective pulmonary vasodilators and antiproliferative agents in this at-risk population. After optimising sickle cell disease therapy to stabilise haemoglobin and fetal haemoglobin levels, we evaluated the safety and efficacy of sildenafil in 12 patients with sickle cell disease and pulmonary hypertension. Sildenafil therapy (mean duration 6 +/- 1 months) decreased the estimated pulmonary artery systolic pressure [50 +/- 4 to 41 +/- 3 mmHg; difference 9 mmHg, 95% confidence interval (CI): 0.3-17, P = 0.043] and increased the 6-min walk distance (384 +/- 30 to 462 +/- 28 m; difference 78 m, 95% CI: 40-117, P = 0.0012). Transient headaches occurred in two patients and transient eye-lid oedema in four patients. No episodes of priapism occurred in the three men in the study; two of them were on chronic exchange transfusions and one had erectile dysfunction. IN CONCLUSION: (1) sickle cell disease patients with anaemia and pulmonary hypertension have significant exercise limitation; (2) the 6-min walk distance may be a valid endpoint in this population; (3) therapy with sildenafil appears safe and improves pulmonary hypertension and exercise capacity. Additional phase I studies in males with sickle cell disease followed by phase II/III placebo controlled trials evaluating the safety and efficacy of sildenafil therapy in sickle cell disease patients with pulmonary hypertension are warranted.

Adult↗

Phenotype/genotype relationships in sickle cell disease: a pilot twin study.

The roles of genetic and non-genetic factors in the haematology, growth and clinical features of sickle cell disease have been studied in nine identical twin pairs (six homozygous sickle cell disease, three sickle cell-haemoglobin C disease). A comparison group of 350 age-gender matched sibling pairs, selected to have an age difference of <5 years, was used for assessing the concordance of numerical data. Attained height, weight at attained height, fetal haemoglobin, total haemoglobin, mean cell volume, mean cell haemoglobin and total bilirubin levels showed significantly greater correlation in identical twins than in siblings. Twins showed similarities in the prevalence and degree of splenomegaly, susceptibility to priapism, and in onset of menarche, but other clinical complications were discordant in prevalence and severity. These findings suggest that physical growth and many haematological characteristics are subject to genetic influences, but that non-genetic factors contribute to the variance in disease manifestations.

Adolescent↗

Diagnosing erectile dysfunction: the penile dynamic colour duplex ultrasound revisited.

A number of disease processes of the penis including Peyronie's disease, priapism, penile fractures and tumors are clearly visualized with ultrasound. Diagnostic evaluation of erectile dysfunction (ED) by penile dynamic colour-duplex Doppler ultrasonography (D-CDDU) is actually considered a second level approach to ED patients because of the fact that intracavernous injections test IV with prostaglandin-E(1) may provide important information about the patients' erectile capacity. However, no direct vascular imaging and a high percentage of false negative diagnoses of vasculogenic ED are its major pitfalls and subsequent treatment decisions remain quite limited. The occurrence of ED and its sentinel relationship to cardiovascular disease has prompted more accurate vascular screening in all patients even in the absence of cardiovascular risk factors. The sonographic evaluation of the intima-media thickness of the carotid arteries may sometimes represent an early manifestation of diffuse atherosclerotic disease and endothelial damage. This latter finding is often the cause of failure to oral agents, i.e. phosphodiesterase inhibitors, because of inability of the dysfunctional endothelium to release nitric oxide. D-CDDU represents an accurate tool to investigate cavernous artery inflow and venous leakage when compared with more invasive diagnostic techniques i.e. selective arteriography and dynamic infusion cavernosometry along with cavernosography.

Arteriosclerosis↗

Polymorphism of the human platelet antigen-5 system is a risk factor for occlusive vascular complications in patients with sickle cell anemia.

BACKGROUND: Polymorphisms of platelet membrane glycoproteins such as human platelet antigen (HPA)-1b, HPA-2b, the -5T/C Kozak sequence and C807T have been described as risk factors for vascular disease. Vaso-occlusion episodes are a common feature of sickle cell anaemia (SCA), leading to complications such as stroke, acute chest syndrome, avascular head femur necrosis and priapism. Complex interactions are involved in vaso-occlusion, and activated platelets may play an important role. These data raised the question of whether platelet polymorphisms could be implicated in occlusive vascular complications (OVC) of SCA. MATERIALS AND METHODS: In this study, 97 patients with SCA were analysed in two groups: 34 patients presenting with OVC (SCA-VC) and 63 without these complications (SCA-N). The distribution of the HPA-1, -2 and -5 systems, as well as C807T dimorphism and -5T/C Kozak sequence alleles, was evaluated using DNA-based methods. RESULTS: Patients of the SCA-VC group showed a higher frequency of the HPA-5b allele (0.324) compared with those of the SCA-N group (0.111) (chi2 = 13.19, P = 0.0002). None of the other polymorphisms, isolated or associated as haplotypes, demonstrated any correlation with the development of OVC in these patients. CONCLUSIONS: The findings of this study suggest that the HPA-5b allele is a genetic risk factor for the development of OVC in patients with SCA. This allele could be explored as a target for the development of new therapeutic approaches.

Adolescent↗

Treatment of organic impotence.

A review of 86 patients referred to a urological clinic with impotence showed that in 58% the causation was predominantly psychogenic. These patients were managed with psychosexual counselling. The various treatment options were discussed with those patients with organic impotence and 14 underwent the implantation of a penile prosthesis. A review of 130 patients who received penile prostheses in the period 1983 to 1987 was carried out to compare the complications and results obtained with the various types of prosthesis. The overall satisfaction rate was 81%; dissatisfaction usually arose as a result of complications of surgery. These were highest in patients with diabetes and priapism. The complications were also related to the type of prosthesis used.

Bacterial Infections↗

The role of histamine in human penile erection.

OBJECTIVE: To investigate the relaxant action of histamine on human corpus cavernosum in vitro and the erectile response caused by the intracavernous injection of histamine in patients with psychogenic impotence. PATIENTS AND METHODS: Human corpus cavernosum (HCC) tissue was cut into strips of approximately 2 cm and suspended in a cascade bioassay. The strips were then superfused with oxygenated and warmed Krebs solution and precontracted with noradrenaline (3 microM). Glyceryl trinitrate, acetylcholine and histamine were injected as a single bolus in the absence or in the presence of mepyramine and cimetidine. For the in vivo studies, histamine (30-60 micrograms) was injected intracavernously as a single bolus into the right corpus cavernosum 1 cm from the balamo-preputial sulcus. Similar protocols were carried out for papaverine (50 mg). The erectile response was divided into four grades: no response, tumescence, partial and full erection. RESULTS: In vitro studies demonstrated that histamine (3-100 micrograms) caused dose-dependent relaxation of the HCC strips which was significantly inhibited by cimetidine (5-10 microM). The histamine H1 receptor antagonist mepyramine (1 microM) potentiated histamine-induced relaxation. The co-infusion of both mepyramine and cimetidine did not abolish histamine-induced relaxation. When injected intracavernously in humans, histamine (30 micrograms) caused full erection in 13% of the patients, whereas 87% had partial erection or tumescence. A higher dose of histamine (60 micrograms) caused full erection in 26% of the patients and 74% had partial erection or tumescence. Papaverine induced full erection in the majority of patients (66%). In contrast to papaverine, the duration of erection induced by histamine was markedly shorter (mean 200 and 6.5 min, respectively). The penile erections induced by papaverine were associated with complications such as pain, haematoma and priapism. Histamine did not induce any complications. Treatment of eight male patients with psychogenic impotence with the histamine H1 receptor antagonist astemizol (10 mg orally once daily for 1 week) did not affect histamine-induced erectile responses. CONCLUSION: These results indicate that histamine may play a role in human penile erection. The erection-promoting action of histamine is probably due to H2 receptor activation, although another histamine receptor, possibly H3, also seems to be involved. This study suggests that histamine could be a valuable tool in the diagnosis of erectile dysfunction.

Adult↗

Variable coding sequence protein A1 as a marker for erectile dysfunction.

OBJECTIVE: To investigate whether variable coding sequence protein A1 (Vcsa1) is down-regulated in rat models of diabetes and ageing, and to investigate the role of Vcsa1 in erectile function, as Vcsa1 is the most down-regulated gene in the corpora of a rat model of neurogenic erectile dysfunction (ED). MATERIALS AND METHODS: Quantitative reverse-transcriptase polymerase-chain reaction was used to determine Vcsa1 expression in the corpora of rats in three models of ED, i.e. streptozotocin-induced diabetes, retired breeder (old), and neurogenic (bilaterally ligated cavernosal nerves), and in control rats. To confirm a physiological role of Vcsa1 in erectile function, we carried out gene transfer studies using a plasmid in which Vcsa1 was expressed from a cytomegalovirus promoter (pVAX-Vcsa1). This plasmid was injected intracorporally into old rats, and the effect on physiology of corporal tissue was analysed by intracorporal/blood pressure (ICP/BP) measurement and histological analysis, and compared with the effects of a positive control plasmid (pVAX-hSlo, which we previously reported to restore erectile function in diabetic and ageing rats) and a negative control plasmid (pVAX). RESULTS: In each rat model of ED there was a significant down-regulation of the Vcsa1 transcript of at least 10-fold in corporal tissue. Remarkably, intracorporal injection with 80 microg pVAX-Vcsa1 caused priapism, as indicated by visible prolonged erection, histological appearance, and elevated resting ICP/BP. Lower doses of pVAX-Vcsa1 (5 and 25 microg) increased ICP/BP over that in untreated controls. CONCLUSION: These results show that Vcsa1 has a role in erectile function and might be a molecular marker for organic ED. The role of Vcsa1 in erectile function suggests that it could represent a novel therapeutic target for treating ED.

Aging↗

The management of crisis in sickle cell disease.

The symptoms and signs of sickle cell disease are exacerbated in times of crisis, characterized by tissue infarction or worsening anaemia. Prompt medical intervention is required in these distressing situations to provide relief and comfort to the patient. Effective analgesia is crucial in treating the painful crisis of sickle cell disease. The haemoglobinopathy may cause hyposthenuria with reduced ability to excrete the sodium load in normal saline. A 5% dextrose solution or 5% dextrose in 25% normal saline is therefore recommended for intravenous hydration. As the leading cause of morbidity and mortality in sickle cell disease, infections call for vigorous antibiotic therapy. Oxygen administration should be reserved for hypoxic patients, and blood transfusion given only when really indicated. Acute chest syndrome and cerebrovascular accidents are life-threatening complications of sickle cell disease whereas priapism can cause important long-term sequelae; all deserve urgent attention. In the long term, comprehensive care is cost-effective in reducing the frequency and adverse effects of sickle cell crisis.

Anemia, Sickle Cell↗

Effects of pinacidil on isolated human corpus cavernosum penis.

Intracavernous injection of vasoactive agents causing vasodilatation is widely recognized in the diagnosis and treatment of erectile dysfunction. However, papaverine, the drug most commonly used for this purpose, may produce priapism and fibrotic lesions, and alternatives without these disadvantages are desirable. In this study we investigated the effects of pinacidil, a vasodilator drug supposed to act through the opening of K+ channels, on isolated human corpus cavernosum penis. Besides abolishing spontaneous contractile activity, pinacidil effectively relaxed preparations precontracted by noradrenaline 10(-6) M and inhibited contractions induced by electrical field stimulation of nerves. Furthermore, pinacidil depressed contractions induced by low-K+ solutions (less than or equal to 20 mM) and concentration-dependently increased the efflux of 86Rb from preloaded tissue. The results suggest that pinacidil is effective in relaxing isolated human erectile tissue, probably by way of increased K+ permeability and subsequent hyperpolarization. Clinical testing seems justified in order to find out if K(+)-channel openers can be used in the pharmacological treatment of impotence.

Aged↗

Sickle cell disease in Britain.

Sickel cell disease is common in urban areas of Britain and it is estimated that in London alone there are nearly 2000 patients. One hundred and eighty four patients with sickle cell disease are known to the Central Middlesex Hospital, and 155 of those attend the sickle cell clinic regularly. The commonest cause for admission to hospital is acute painful or vaso-occlusive crisis, which accounts for 80% of all acute admissions; 12% of admissions are for acute chest syndrome. Comparison of clinical features in Brent and in Jamaica shows that the Brent patients with homozygous sickle cell anaemia are admitted with painful crises more frequently than Jamaican patients. However, the frequency of admissions for chest syndrome and priapism, and the incidence of splenomegaly are similar. Leg ulcers are uncommon in Brent. Patients with sickle cell haemoglobin C disease appeared more severely affected in Jamaica than in Brent. During the past two years 3165 newborn babies have been screened for sickle cell disease at the Central Middlesex Hospital: five babies with homozygous sickle cell anaemia and three babies with sickle cell haemoglobin C disease were detected. The overall incidence of sickle cell trait was 3.2% and of haemoglobin C trait 0.8%. A significant number of babies with sickle cell disease are born in London every year. It is essential that such babies are detected at birth and offered prophylaxis against pneumococcal infection, which is one of the major causes of infant mortality. Sickle cell disease is becoming an important blood disease in Britain and firm guidelines for the management of acute and chronic complications are required.

Adolescent↗

Color Doppler US of the postoperative penis: anatomy and surgical complications.

A number of surgical procedures that significantly change the penile anatomy and vasculature can be used to manage pathologic conditions of the penis (eg, congenital and acquired deformities, erectile dysfunction, priapism). Phallic reconstruction surgery can be used for sex reassignment and after penile amputation or for correction of congenital malformations. Color Doppler ultrasonography (US) clearly depicts the normal penile anatomy and postoperative changes (eg, changes of the tunica albuginea, extraalbugineal pathologic fluid collections, cavernosal tissue changes produced by scars and fibrosis). It is also effective in evaluating surgery-related complications and determining the causes of erectile dysfunction and other unsatisfactory long-term results. Moreover, color Doppler US of the penile vessels and vascular anastomoses following revascularization allows direct evaluation of flow characteristics, shunt patency, and venous engorgement. Color Doppler US is the imaging modality of choice in evaluating patients who have undergone penile surgery.

Adult↗

Safety and efficacy of alprostadil sterile powder (S. Po., CAVERJECT) in diabetic patients with erectile dysfunction.

OBJECTIVES: To evaluate the long-term efficacy and safety of intracavernosal alprostadil (CAVERJECT((R))) in diabetic patients with erectile dysfunction (ED). PATIENTS AND METHODS: This study included 31 diabetic men (aged 44-75 years) with ED of >/=4 months duration. All patients were initially instructed in the self-injection technique at the investigator's clinic. The optimal dose was determined for each patient and set at one of the following: 5, 10, 20, 30, 40, 50, or 60 microg. After the optimal dose was determined and the patient was well trained, the self-injection home phase was followed for 6 months. The efficacy and adverse events were documented. RESULTS: An optimal dose was determined for 29 men (93.5%) and in 16 men (55%) it was >/=20 microg. During the home phase, 76.5% of injections assessed by the patients resulted in satisfactory sexual activity and 72.5% of injections assessed by partners resulted in satisfactory intercourse. A total of 16 patients dropped out during the titration phase (n = 2) and the home phase (n = 14). The most common reasons included lack of efficacy (n = 3, all in the home phase), intolerable penile pain (1 in the titration phase, 2 in the home phase) and dissatisfaction with the higher dosage (n = 2). Penile pain occurred in 19 (61%) of 31 patients. Most were tolerable, and the incidence decreased with time. Prolonged erection occurred in 2 men (6.5%), and no priapism was noted. Penile fibrosis occurred in 1 patient (3. 2%). None of the systemic medical events were related to the study mediction. However, 1 patient suffered from right putaminal hemorrhage in the last month, and this was considered to be caused by underlying hypertension and not drug-related. CONCLUSION: Despite the high incidence of penile pain, most of the occurrences were tolerable. Despite a higher withdrawal rate in this study, intracavernosal alprostadil is still considered as a relatively effective and safe treatment in some diabetic patients with ED if the individual dose is established by titration and patients are trained in the self-injection technique with period supervision.

Adult↗

Effectiveness of vardenafil versus papaverine in penile Doppler ultrasonography.

PURPOSE: To evaluate erectile dysfunction, penile color Doppler ultrasound is currently considered the best method. But intracavernous injection is invasive and has adverse effects, such as prolonged erection and risk of priapism. In our study we want to evaluate whether vardenafil can be used instead of papaverine in penile Doppler ultrasonography. MATERIALS AND METHODS: A total of 24 patients with erectile dysfunction underwent color Doppler ultrasound before and after intracavernous injection of 60 mg papaverine with genital and audiovisual sexual stimulation. Peak flow and end diastolic velocity were measured in the recorded waveforms obtained 0, 1, 5, 10 and 20 min after injection. The patients also underwent color Doppler ultrasound after a 10-mg oral dose of vardenafil with genital and audiovisual sexual stimulation and at least 5 days after the prior examination. The same parameters were measured at 30, 45, 60, 75 and 90 min after the drug administration. We compared the results with the values obtained after papaverine injection. RESULTS: After oral vardenafil mean peak flow velocity significantly increased starting at 30 min and achieving a maximum value at 60 min. There were no significant differences in the 2 methods in mean peak velocity 1, 5, 10 and 20 min after papaverine injection, and 30, 45, 60, 75 and 90 min after oral vardenafil administration. Although papaverine injection is the gold standard for penile color Doppler ultrasound, it has severe adverse effects such as prolonged erection which we observed in 3 patients (12.5%) and required pharmacological detumescence. After vardenafil no severe adverse effects were observed. CONCLUSIONS: Vardenafil administration achieved increased peak flow velocity comparable to that after intracavernous papaverine injection. With no prolonged erection vardenafil is a safer alternative compared to more invasive intracavernous injection and is also an alternative for patients who fear injections.

Adult↗