Martyn A. Vickers

Tissue Angiotensin II as a Modulator of Erectile Function. I. Angiotensin Peptide Content, Secretion and Effects in the Corpus Cavernosum

PURPOSEnAlthough Angiotensin II (Ang II) is a major modulator of regional blood flow in the extracavernosal segments of the vascular bed, its role in erectile function is unknown. The corpus cavernosum penis is a modified vascular tissue that contains endothelial and smooth muscle cells. In other segments of the vascular bed, these cell types produce Ang II. Therefore, we explored the presence and function of an Ang II producing paracrine system in the corpus cavernosum.nnnMETHODSnThe angiotensin content of the human corpus cavernosum was measured by radioimmunoassay. The distribution pattern of Ang II containing cells within the corpus cavernosum was assessed by an immunohistochemical technique, and the rate of its secretion was determined by superfusion. The effects of Ang II and its antagonist, losartan, on intracavernosal pressure were determined under in vivo conditions, in anesthetized dogs.nnnRESULTSnHuman corpus cavernosum contained 1178 +/- 223 (SEM) fmol Ang II, 528 +/- 171 fmol Ang I, 475 +/- 67 fmol des-asp-Ang I, and 1897 +/- 371 fmol des-asp-Ang II/gm. tissue (n = 4). Ang II was found mainly in endothelial cells lining blood vessels and smooth muscle bundles within the corpus cavernosum. Superfused cavernosal tissue secreted immuno-reactive Ang II (Ang II(ir)) at a rate of 57 +/- 36.5 fmol Ang II(ir)/gm. tissue/minute (n = 10). The amount of Ang II released per gram of tissue in an hour was 3-fold greater than the Ang II content/gm. tissue, suggesting a local production of Ang II. Papaverine and prostaglandin E1 suppressed Ang II secretion significantly (p <0.001, p = 0.013). The responsiveness to inhibition was a function of the initial rate of Ang II secretion. Tissue samples with a high rate of secretion were less responsive to the inhibitors than tissue that secreted small amounts of Ang II (n = 6). In anesthetized dogs, intra-cavernosal injection of Ang II terminated spontaneous erections, while losartan increased the intracavernosal pressure in a dose dependent manner up to the mean arterial pressure (n = 4).nnnCONCLUSIONSnThe corpus cavernosum produces and secretes physiologically relevant amounts of Ang II. The rate of Ang II secretion can be modulated by pharmacologic agents that regulate cytosolic calcium levels and are used clinically to treat erectile dysfunction. Intracavernosal injection of Ang II causes contraction of cavernosal smooth muscle and terminates spontaneous erection in anesthetized dog, while administration of an Ang II receptor antagonist results in smooth muscle relaxation and thus erection.

Correlation of American Urological Association Symptom Index With Obstructive and Nonobstructive Prostatism

The precise role of the American Urological Association (AUA) symptom index in the management of benign prostatic hyperplasia (BPH) is not well established. The AUA symptom index has been recommended only for quantifying the symptoms of BPH but not for its diagnosis. However, to our knowledge the ability to discriminate obstructive from nonobstructive BPH using the AUA symptom index has never been investigated. To establish the relationship between the AUA symptom index and prostatic obstruction 125 men (mean age 67.7 +/- 8.4 years) with voiding dysfunction presumably related to BPH were analyzed. Patients were given the AUA symptom questionnaire, following which video urodynamic studies were done, including micturitional urethral pressure profilometry for specifically diagnosing outlet obstruction. The patients were divided into 2 groups: group 1-78 with primary BPH dysfunction and group 2-47 with prostatism of ambiguous etiology. The mean AUA symptom index in group 1 (15.5 +/- 7.1) was not statistically different from that in group 2 (14.8 +/- 7.9). In both groups the mean AUA symptom index in the patients with obstruction (15.3 +/- 7.2 for group 1 and 13.9 +/- 7.9 for group 2) was not statistically different from that in the nonobstructed group (17.0 +/- 5.4 and 16.1 +/- 7.9, respectively). Of the severely symptomatic patients 22% did not have obstruction whereas all mildly symptomatic patients did. No significant correlations were found between the severity of obstruction and the AUA symptom index in either group. These observations indicate that the AUA symptom index cannot discriminate obstructed from nonobstructed BPH cases, not all severely symptomatic BPH patients will have outlet obstruction, a significant proportion of mildly symptomatic BPH patients can have outlet obstruction and voiding dysfunctions in elderly men, regardless of the etiology, produce similar symptoms.

Entubulization repair of severed cavernous nerves in the rat resulting in return of erectile function

Erectile dysfunction is a significant complication of radical pelvic surgery in men. Using the rat as an experimental model, we investigated the feasibility of repairing surgically ablated cavernous nerves utilizing silastic tube nerve growth conduits filled with nerve growth enhancing media. Known fertile male Sprague-Dawley rats were randomly divided into four surgical groups consisting of nerve ablation, immediate nerve reconstruction utilizing the entubulization technique (two groups) and control. The nerve ablation group had five mm. sections of the cavernosal nerve excised bilaterally. The entubulization nerve graft group had five mm. sections of the cavernous nerve excised bilaterally, followed by immediate microsurgical reconstruction with a silastic nerve tube conduit filled with either Matrigel and heparin (MA) or Matrigel and heparin plus acidic fibroblast growth factor (MA/aFGF), interposed between the severed cavernous nerve stumps bilaterally. The control group underwent sham operations with the cavernous nerves being exposed only. Erectile function was evaluated at one, two, and four months postoperatively. Return of erectile function was defined as tumescence of the corporal bodies with application of direct electrical stimulation (four volts of five millisecond pulses at 20 Hertz) to the proximal cavernous nerves. The two and four month electrical stimulation studies resulted in tumescence from 50% and 58% of the entubulization nerve reconstructed nerves with MA/aFGF versus 29% and 30% for the MA only group and only 5% and 11% for the ablated group, respectively. We conclude that in this experimental model immediate nerve graft repair utilizing entubulization techniques with the addition of nerve growth enhancing media appears to be a successful method of salvaging erectile function when the cavernous nerves have been divided.

Prostate cancer screening: Role of digital rectal examination and prostate-specific antigen

AbstractBackground: This study was designed to determine the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) for early detection of prostate cancer in men ≥50 years of age.nMethods: A prospective single-center clinical trial was conducted to screen 644 asymptomatic men, who were elicited by newspaper and radio advertisements, with DRE and PSA. Quadrant biopsy examinations of the prostate were performed if PSA >4 ng/ml or if DRE was suspicious.nResults: Thirty-seven percent of the men (n=241) had an abnormality of DRE or elevated PSA. Of the 163 patients who underwent transrectal ultrasound and quadrant biopsies of the prostate, 77% had normal biopsies, 14 (8%) had prostatic intraepithelial neoplasia, and 24 (15%) had carcinoma of the prostate. PSAs ranged from 0.3 to 65.5 ng/ml, with a mean of 2.35 and a median of 1.6. Ninety-five patients had a PSA >4 ng/ml, of whom 17 had a PSA >10 ng/ml. Sensitivity of PSA was 75% and specificity 87%; for DRE the sensitivity was 75% and the specificity 69%. Clinical stage of patients who underwent radical prostatectomy was B1 in 15 and B2 in five. Fifteen of 20 patients (75%) had organ-confined disease; the other five had specimen-confined disease. No patient was found to have nodal involvement.nConclusion: The combination of PSA and DRE seems to improve the stage of diagnosis of patients with prostate cancer. Larger, randomized studies will be necessary to evaluate the effect of screening on overall survival.

The Current Cavernosometric Criteria for Corporovenous Dysfunction Are too Strict

In an attempt to define the hemodynamic and radiographic parameters of normal erectile function 6 patients 20 to 41 years old (mean age 30.3 years) with erectile dysfunction that spontaneously resolved after a comprehensive evaluation were reviewed. The results included normal hormonal assays, normal penile biothesiometry and normal penile brachial index. The sleep tumescence and rigidity tracings were abnormal according to the criteria that sleep erections occur every 90 minutes, are associated with penile rigidity of greater than 550 gm. plus an increase in penile circumference of greater than 1.5 cm. and last longer than 15 minutes. High resolution ultrasonography, pulse wave Doppler ultrasound, dynamic pharmacocavernosometry and dynamic cavernosography were performed. After testing the patients were informed that no organic abnormalities had been detected. No medical or surgical treatment was given. The hemodynamic values are presented as suggested normal parameters: maintenance rate (mean 11 +/- 3 cc per minute), initial decompression rate (mean 59 +/- 17 mm. Hg/30 seconds) and radiographic findings (visualization of the cavernous, external pudendal and deep dorsal veins during pharmacocavernosography, performed at intracorporeal pressures of 100 mm. Hg). All 6 patients had maintenance rates of greater than 5 cc per minute. Of these 6 patients 5 had initial decompression rates of greater than 48 mm. Hg/30 seconds and 4 had 5-minute, post-infusion steady state values of less than 50 mm. Hg, criteria that have been used to define corporovenous dysfunction.

High resolution ultrasonography and pulsed wave Doppler for detection of corporovenous incompetence in erectile dysfunction

Cavernosometry and cavernosography have been the primary modalities available for detection and mapping of corporovenous incompetence in patients with erectile dysfunction. These procedures are expensive, time-consuming and associated with some morbidity, prompting us to study a less invasive method, high resolution ultrasonography and pulsed wave Doppler ultrasound. We evaluated 13 patients with nonendocrinological, nonneurological erectile dysfunction by high resolution and Doppler ultrasound for flow in the dorsal and cavernosal veins after intracorporeal papaverine. All patients had a nonrigid response to papaverine and a mean maximum cavernous arterial systolic velocity of greater than 25 cm. per second. The 13 patients were subsequently studied by dynamic cavernosometry and cavernosography, which revealed evidence of venous incompetence (12 with dorsal venous leaks and 11 with cavernous venous leaks). Only 5 of the 12 patients with dorsal venous incompetence had flow detected in the dorsal vein by ultrasound and Doppler studies. High resolution and Doppler ultrasound was unable to detect leakage in the cavernous veins. Among the 2 groups of patients with dorsal venous leaks (those with and without flow detectable by Doppler ultrasound) there was no significant difference in mean cavernous artery diameter or mean cavernous arterial maximum velocity. Similarly, there was no significant difference between the 2 groups in induction, maintenance or initial decompression rates on cavernosometry. We conclude that high resolution and Doppler ultrasound cannot replace dynamic cavernosometry and cavernosography as the diagnostic modality for venous incompetence.

Diagnosis and treatment of psychogenic erectile dysfunction in a urological setting: outcomes of 18 consecutive patients.

The diagnostic criteria and treatment outcomes of 18 consecutive patients with psychogenic erectile dysfunction were examined. Average patient age was 38 years, and all patients had either awakening penile or masturbatory rigidity. Each patient was studied with home monitoring (ART-1000) on 2 consecutive nights. The average number of maximum erectile episodes, the event during which the maximum rigidity was maintained for at least 5 minutes, was 1.6. The maximum sleep erectile episodes averaged 11.2 minutes during which penile rigidity averaged 572 gm. The main predictor for remission of erectile dysfunction in this study was whether the dysfunction was primary or secondary. Of 14 patients with secondary psychogenic erectile dysfunction, that is history of being able to achieve and maintain penile rigidity sufficient for at least 5 minutes of vaginal intercourse, 10 (71%) experienced remission. Three patients noticed spontaneous remission during the initial evaluation and another 3 experienced remission within 3 months of completion of the evaluation and reassurance that they had normal erectile capacity. Two patients had remission while considering penile vascular surgery and in 2 normal erectile function returned during injection therapy. Only 2 of 3 patients referred for sex therapy actually received it (Freudian theory), and neither noticed improvement in erectile function. One patient received yohimbine without benefit. None of the patients elected treatment with the vacuum constriction device. All 4 patients with primary psychogenic erectile dysfunction, that is never able to achieve and/or maintain penile rigidity sufficient to achieve vaginal intercourse, failed to respond to physician reassurance and time. Of 2 patients who received sex therapy (1 Freudian and 1 behavioral) without improvement in erectile function 1 has entered the pharmacological erection program and has achieved vaginal penetration, and the other is considering the pharmacological erection program. The remaining 2 patients have deferred all therapy. Based on this experience, we currently reassure patients with secondary psychogenic erectile dysfunction that they have erectile capacity for sustained vaginal intercourse and schedule a followup visit in 3 months. Additional individualized therapy (pharmacological erection program, vacuum constriction device, sensate focus/psychodynamic specific therapy or penile prosthesis) is offered as needed and requested. Patients with primary psychogenic erectile dysfunction are initially offered the pharmacological erection program or the vacuum constriction device and sex sensate focus/psychodynamic specific therapy. The penile prosthesis is considered for treatment failures.

Correlation of American Urological Association Symptom Index With Obstructive and Nonobstructive Prostatism Reply by Authors

The precise role of the American Urological Association (AUA) symptom index in the management of benign prostatic hyperplasia (BPH) is not well established. The AUA symptom index has been recommended only for quantifying the symptoms of BPH but not for its diagnosis. However, to our knowledge the ability to discriminate obstructive from nonobstructive BPH using the AUA symptom index has never been investigated. To establish the relationship between the AUA symptom index and prostatic obstruction 125 men (mean age 67.7 +/- 8.4 years) with voiding dysfunction presumably related to BPH were analyzed. Patients were given the AUA symptom questionnaire, following which video urodynamic studies were done, including micturitional urethral pressure profilometry for specifically diagnosing outlet obstruction. The patients were divided into 2 groups: group 1-78 with primary BPH dysfunction and group 2-47 with prostatism of ambiguous etiology. The mean AUA symptom index in group 1 (15.5 +/- 7.1) was not statistically different from that in group 2 (14.8 +/- 7.9). In both groups the mean AUA symptom index in the patients with obstruction (15.3 +/- 7.2 for group 1 and 13.9 +/- 7.9 for group 2) was not statistically different from that in the nonobstructed group (17.0 +/- 5.4 and 16.1 +/- 7.9, respectively). Of the severely symptomatic patients 22% did not have obstruction whereas all mildly symptomatic patients did. No significant correlations were found between the severity of obstruction and the AUA symptom index in either group. These observations indicate that the AUA symptom index cannot discriminate obstructed from nonobstructed BPH cases, not all severely symptomatic BPH patients will have outlet obstruction, a significant proportion of mildly symptomatic BPH patients can have outlet obstruction and voiding dysfunctions in elderly men, regardless of the etiology, produce similar symptoms.