Giuliano Pizzini

RECOVERY OF SPONTANEOUS ERECTILE FUNCTION AFTER NERVE-SPARING RADICAL RETROPUBIC PROSTATECTOMY WITH AND WITHOUT EARLY INTRACAVERNOUS INJECTIONS OF ALPROSTADIL: RESULTS OF A PROSPECTIVE, RANDOMIZED TRIAL

PURPOSE This study was aimed at assessing prospectively the effect of postoperative intracavernous injections of alprostadil on the recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy. MATERIALS AND METHODS A total of 30 potent patients with clinically localized prostate cancer (clinical stage B1 or B2, Gleason sum 7 or greater, prostatic specific antigen less than 20 ng./ml.) underwent nerve-sparing radical retropubic prostatectomy and was subsequently randomized to alprostadil injections 3 times per week for 12 weeks (group 1, 15 patients) or observation without any erectogenic treatment (group 2, 15 patients). Patients were assessed at the 6-month followup by sexual history, physical examination, color Doppler sonography of the cavernous arteries and polisomnographic recording of nocturnal erections. RESULTS In group 1, 12 patients (80%) completed the entire treatment schedule and were evaluated at the long-term followup. Eight patients in this group (67%) reported the recovery of spontaneous erection sufficient for satisfactory sexual intercourse, compared with 3 patients (20%) in group 2. The difference between the 2 groups was statistically significant (p <0.01). In group 1, all but 1 patient reporting normal postoperative erections also showed normal erections at nocturnal testing, whereas color Doppler sonography demonstrated normal penile hemodynamics in all of them. In these patients, failures were the result of cavernous veno-occlusive dysfunction (2 cases, 17%) and cavernous nerve injury (2 cases, 17%). In group 2, patients with normal erections showed both normal nocturnal testing and penile hemodynamics, whereas failures were the result of cavernous veno-occlusive dysfunction (8 cases, 53%), cavernous arterial insufficiency (2 cases, 13%) or cavernous nerve injury (3 cases, 20%). Complications in patients treated with alprostadil injections accounted for 2 cases (13%) of a penile nodule and 1 further case (6%) of prolonged penile erection. Complications were not seen in group 2 patients. CONCLUSIONS Early postoperative administration of alprostadil injections significantly increases the recovery rate of spontaneous erections after nerve-sparing radical retropubic prostatectomy. It is our belief that programmed vasoactive injections improve cavernous oxygenation, thereby limiting the development of hypoxia-induced tissue damage. The potential complications related to the use of intracavernous injections must be clearly explained to patients.

Sildenafil taken at bedtime significantly increases nocturnal erections: results of a placebo-controlled study

OBJECTIVES Nighttime erections occur at all ages and contribute to the maintenance of the morphodynamic integrity of smooth muscle cells within the corpora cavernosa. This study was aimed at evaluating the effect on nocturnal erections of sildenafil versus a placebo taken at bedtime. METHODS A double-blind, crossover, placebo-controlled study design was used to examine the effects of sildenafil and placebo on sleep-related erectile activity. Thirty selected patients with erectile dysfunction (vasculogenic etiology, 22 patients [73%]; psychogenic etiology, 8 patients [27%]) were submitted to a polysomnographic recording of nocturnal erections, using a RigiScan device during 3 consecutive nights. After a first night of adaptation, the 2 following nights were used to study patients after the administration of sildenafil (100 mg) or a placebo taken at bedtime. RESULTS Twenty-three patients (77%) showed a significantly improved nocturnal erectile activity (according to the calculation of rigidity and tumescence activity units) after the administration of sildenafil (P <0.01), 5 patients (17%) showed comparable nocturnal erections with sildenafil and placebo, and 2 patients (6%) showed a significantly improved nocturnal erectile activity after taking the placebo (P <0.05). Overall, mean rigidity and tumescence activity values at the tip and base of the penis were significantly improved after sildenafil rather than placebo administration (P <0.001). The duration of tip rigidity greater than 60% was significantly longer during the night with sildenafil (P <0. 001). Although the number of erectile episodes was greater during the sildenafil night, this did not reach statistical significance. CONCLUSIONS In most patients with good sleep efficiency and who have erectile dysfunction, sildenafil, rather than a placebo, taken at bedtime produces a significantly improved nocturnal erectile activity. Further studies are needed to verify whether this preliminary finding may constitute the basis for the use of sildenafil as a tool for preventing erectile dysfunction.

EVIDENCE BASED ASSESSMENT OF LONG-TERM RESULTS OF PLAQUE INCISION AND VEIN GRAFTING FOR PEYRONIE’S DISEASE

PURPOSE We assessed the long-term outcome of plaque incision and vein grafting in select patients with Peyronies disease by extensive preoperative and postoperative subjective and objective analysis. MATERIALS AND METHODS From January 1995 to June 1998, 50 men 28 to 62 years old (mean age 44) underwent surgery. Patients were evaluated preoperatively, 3 months after surgery and at a mean long-term followup of 32 months by sexual history, physical examination, determination of penile length and degree of curvature, dynamic color power Doppler sonography of the penile vessels and nocturnal RigiScan* evaluation for 3 nights. Study inclusion criteria were penile curvature 45 degrees or greater that made vaginal intromission impossible, stable disease for at least 6 months, patient reported normal penile rigidity, normal penile hemodynamics on color power Doppler ultrasound, normal nocturnal penile rigidity with at least 1 erection nightly (including base and tip rigidity greater than 60%, and a duration of 10 minutes) and absent base-tip discrepancies. Plaque was usually approached via a combined subcoronal and midline sagittal scrotal incision. Maximal rigidity was created intraoperatively and 1 to 3 plaque incisions were made. Saphenous vein patches were then grafted at the incision sites. Postoperatively patients were systemically treated with neurotrophic factors and low molecular weight heparin. Local vacuum supported corporeal stretching was done and weekly alprostadil injections were given to optimize corporeal oxygenation. RESULTS At long-term followup complete penile straightening was achieved in 40 cases (80%), minor residual curvature of 30 degrees or less persisted in 7 (14%) and significant disease recurred in 3 (6%). Penile rigidity was equal to that preoperatively in 47 patients (94%), while 3 (6%) reported clinically significant decreased potency. Penile length was equal to that preoperatively in 30 patients (60%), while 20 (40%) noticed slight penile shortening. Postoperatively penile color power Doppler sonography showed vascular impairment in 5 men (10%) and nocturnal RigiScan testing revealed a significant decrease in nightly erections in 5 (10%). Surgical complications included penile hypoesthesia in 1 case (2%), penile hematoma in 2 (4%), wound infection in 1 (2%) and glandular ischemia in 1 (2%). CONCLUSIONS Plaque incision and vein grafting achieved satisfactory clinical results in the majority of patients with severe and stable Peyronies disease, intact penile rigidity preoperatively, normal penile color power Doppler ultrasound and normal nocturnal RigiScan testing.

Effect of yohimbine-trazodone on psychogenic impotence : a randomized, double-blind, placebo-controlled study

OBJECTIVES The aim of this study was to determine the effectiveness and safety of yohimbine and trazodone used together for the treatment of pure psychogenic impotence. METHODS Sixty-three patients who had psychogenic impotence diagnosed on the basis of sexual history, results of physical examination, laboratory analysis, polysomnographic recording of nocturnal erections, and dynamic color Doppler sonography of the cavernosal arteries were entered into a randomized, double-blind, placebo-controlled, partial crossover study comparing placebo with yohimbine (15 mg per day orally) and trazodone (50 mg per day orally) used together. Treatment consisted of two 8-week courses. Patients who initially received placebo for 8 weeks were then switched to the 2-drug combination for 8 weeks. Erectile function, ejaculation, interest in sex, and sexual thoughts were investigated at the end of drug treatment and at 3- and 6-month follow-up. For statistical analysis chi-square, McNemar, and Students t test for unpaired data were used. RESULTS Fifty-five patients (87%) completed the whole treatment schedule. Positive clinical results (complete and partial responses) were obtained in 39 (71%) patients at the end of the drug treatment phase. These results were significantly better than those obtained with placebo (p < 0.01). Positive results were maintained in 32 (58%) and 31 (56%) patients at 3- and 6-month follow-up, respectively. Minor drug-related adverse effects occurred in 6 (11%) of the patients in the yohimbine-trazodone group and in 2 (4%) in the placebo group. CONCLUSIONS The combination of yohimbine and trazodone is a safe and effective first-line treatment for psychogenic impotence.

Vascular Abnormalities in Peyronie’s Disease: The Role of Color Doppler Sonography

We attempted to clarify the role of color Doppler sonography in assessing the vascular function of untreated Peyronies disease. A total of 50 patients with a mean 20-month history of penile curvature underwent color Doppler sonography with the penis in the flaccid state and after intracavernous injection of 20 micrograms. prostaglandin E1. Of the patients 41 (82%) complained of various degrees of erectile dysfunction, while 9 (18%) reported sustained rigid erections. Pathological peak systolic flow velocities (less than 30 cm. per second) of the cavernous arteries were found bilaterally in 10 patients (20%) and unilaterally in 10 (20%). Peak systolic flow velocity correlated positively with cavernous artery flow volume and with acceleration. Cavernous artery end diastolic velocity and resistance index, measured 15 and 30 minutes after vasoactive injection and genital manipulation, were indicative of corporeal veno-occlusive dysfunction (greater than 10 and less than 0.75 cm. per second, respectively) in 32 patients (65%). Of these patients, 11 (22%) had mixed arteriovenous dysfunction and 9 (18%) had normal cavernous artery flow velocities. Flow along the cavernous arteries is sometimes altered in cases of Peyronies disease while corporeal veno-occlusive dysfunction seems to be the main hemodynamic abnormality. Color Doppler sonography should be considered as the initial step in the diagnostic evaluation of patients with Peyronies disease who may be eligible for surgical treatment.

The effect of intracorporeal injection plus genital and audiovisual sexual stimulation versus second injection on penile color doppler sonography parameters

PURPOSE We assessed whether genital and audiovisual sexual stimulation following 1 or 2 intracorporeal injections caused the greatest changes in penile hemodynamics as recorded by color Doppler sonography. MATERIALS AND METHODS A total of 50 impotent patients underwent multiphasic color Doppler sonography of the cavernous arteries before and after intracorporeal injection (phase 1), subsequent genital and audiovisual sexual stimulation (phase 2), a second injection (phase 3) and repeat genital and audiovisual sexual stimulation (phase 4). Peak systolic velocity, end diastolic velocity, resistance index and erectile response were studied. RESULTS Penile erection after injection 1 was upgraded in 41 patients (82%) by genital and audiovisual sexual stimulation. Further upgrading due to injection 2 with stimulation was noted in 11 patients (22%). Among the patients who completed the 4 phases of the test the maximal peak systolic velocity was noted after 1 and 2 injections in 20 (59%) and 14 (41%), respectively. The resistive index was always increased by genital and audiovisual sexual stimulation compared to post-injection values. The maximal resistive index occurred after initial and repeat genital and audiovisual sexual stimulation in 15 (48%) and 16 (52%) patients, respectively. After injection 1 with genital and audiovisual sexual stimulation, impotence was diagnosed as nonvasculogenic in 14 patients (28%), arteriogenic in 9 (18%), venogenic in 17 (34%) or mixed arteriovenogenic in 10 (20%). After injection 2 with stimulation these results were noted in 18 (36%), 9 (18%), 13 (26%) and 10 (20%) patients, respectively. Thus, there were 4 false-positive cases (8%) of venogenic impotence. CONCLUSIONS To study cavernous artery inflow and veno-occlusive function, color Doppler sonography should be performed after injection plus genital and audiovisual sexual stimulation. When the erectile response does not equal the maximal physiological erection reported by the patient, a second injection with stimulation should be given.

Effectiveness and safety of multidrug intracavernous therapy for vasculogenic impotence

A four-drug vasoactive mixture (papaverine hydrochloride, prostaglandin E1, phentolamine mesylate, atropine sulfate) was used for intracavernous injection therapy in 94 patients with vasculogenic impotence as diagnosed by color Doppler sonography and dynamic infusion cavernosometry-cavernosography. At a mean follow-up of twenty months, 66 patients (70%) are using the injections with the initial dose and are satisfied; 14 patients (15%) are using the injections with a smaller dose than initially given; and 14 patients (15%) dropped intracavernous treatment. Only 4 patients (4%) were unable to achieve a sustained rigid erection during the mixture titration phase. Selected cases of vasculogenic impotence can be safely and effectively treated by the association of drugs which rely on different mechanisms of action, producing a pharmacologic synergism which enhances the overall therapeutic effect.

The ultrastructure of the nucleus of the oculomotor nerve (somatic efferent portion) of the cat.

SummaryThe ultrastructure, of the somatic efferent portion of the nucleus of the oculomotor nerve was studied in four adult cats. The neuronal population is composed of neurons of variable size. A continuous pattern of morphological aspects is evident between the large neurons, which show abundant cytoplasm with well developed organelles and the small neurons which have a reduced amount of cytoplasm. The dendrites are generally smooth, with few short spines. Axo-somatic and axo-dendritic synapses are numerous. Synaptic boutons are also present on the axon hillock.The neuropil is characterized by the occurrence of small groups of dendrites which may be in direct touch with their membranes. Direct membrane appositions may also occur between neighbouring neurons and between the cell somata and tangentially running dendrites. Generally beneath the site of apposition there is accumulation of mitochondria, multivesicular bodies, coated vesicles and moderately dense amorphous material. The morphological features suggest the possibility of cellular interchanges at the sites of direct membrane apposition.Five types of synaptic boutons were recognized on the basis of their vesicular content, the presence of abundant filaments in the pre-synaptic bag, the occurrence of post-synaptic specializations. The, different synaptic types and their distribution are similar to those reported in the spinal motor nuclei. Many of the synapses make synaptic contacts with two or more post-synaptic elements. Axo-axonic synapses were also observed.

Genital plus audiovisual sexual stimulation following intracavernous vasoactive injection versus re-dosing for erectile dysfunction - Results of a prospective study

PURPOSE We assessed whether re-dosing of a vasoactive agent or the combination of a vasoactive injection and genital plus audiovisual sexual stimulation caused the greatest erectile effect to determine which of the 2 procedures would be better for dynamic penile color Doppler sonography in patients with erectile dysfunction. MATERIALS AND METHODS A total of 20 consecutive patients with erectile dysfunction underwent 2 sessions under real-time RigiScan* recording of penile erection. Session 1 consisted of adaptation in 10 minutes, intracavernous injection of 10 micrograms. alprostadil in 10 minutes and re-dosing of 10 micrograms. alprostadil in 10 minutes. Session 2 consisted of adaptation in 10 minutes, injection of 10 micrograms. alprostadil in 10 minutes and genital plus audiovisual sexual stimulation in 10 minutes. The total duration of each session was 30 minutes. The order of the 2 sessions was randomly assigned with a week interval between each session. RESULTS Re-dosing and genital plus audiovisual sexual stimulation caused a significant increase in erectile response compared to the result seen after the first injection (re-dosing p < 0.05, injection plus stimulation p < 0.01). However, erectile response after the genital stimulation session was significantly greater than that after re-dosing (p < 0.01). An erection comparable to the greatest spontaneous erection reported by the patient was much more frequently achieved after genital stimulation than after the re-dosing session (p < 0.01). CONCLUSIONS The combination of injection and stimulation caused a significantly greater erectile response than re-dosing. We suggest that the former should always be used during color Doppler sonography to optimize the accuracy of the test. Re-dosing is suggested when an incomplete erectile response occurs after the injection plus stimulation phase.

FUNCTIONAL ANATOMY OF CAVERNOUS HELICINE ARTERIOLES IN POTENT SUBJECTS

PURPOSE We investigated the morphological and functional features of cavernous helicine arterioles in male potent subjects. MATERIALS AND METHODS Ten young men reporting normal rigid erections which were confirmed by polysomnographic recording underwent power Doppler sonography of the cavernous helicine arterioles during flaccidity, after intracavernous injection of alprostadil, and after subsequent genital and audiovisual sexual stimulation. RESULTS During flaccidity the helicine arterioles were never detected by power Doppler imaging while they became evident in all cases after alprostadil injection. They usually originated from the cavernous artery forming an acute angle and showed 3 orders of ramifications. Systolic and diastolic flow was present. After genital and audiovisual sexual stimulation, and achievement of maximum rigidity, the helicine arterioles were still evident but with only 1 or 2 orders of distal ramifications. Only systolic flow was present. During penile tumescence the helicine arterioles disappeared in all cases. CONCLUSIONS Using power Doppler sonography it is possible to investigate the functional anatomy of the cavernous helicine arterioles during the various phases of the erectile cycle. Our preliminary study suggests that the helicine arterioles are functionally inactive during penile flaccidity while they are activated during penile tumescence and continue to supply blood to the corpora also during maximum penile rigidity.