Mohamad H. Djamilian

Preliminary Results with the Nitric Oxide Donor Linsidomine Chlorhydrate in the Treatment of Human Erectile Dysfunction

Recent experimental studies showed an important role of endothelium derived relaxing factor for cavernous smooth muscle relaxation. Since nitric oxide seems to account for the biological actions of endothelium derived relaxing factor, a study was done to examine a possible role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the treatment of erectile dysfunction. To determine a therapeutically useful dose 0.1, 0.2, 0.5 and 1 mg. SIN-1 were injected intracavernously in patients with erectile dysfunction. Each dose was given to 2 patients. Then, 63 patients received 1 mg. SIN-1, including 7 who had prolonged erections to minimal doses of papaverine plus phentolamine and 4 who did not respond with a full erection to other pharmacological agents. Intracavernous injection of SIN-1 induced a dose-dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscles. Of the patients 29 had a full, 21 an almost full and 13 a moderate erection to 1 mg. SIN-1. There were no systemic or local side effects. In the patients with prolonged erections to papaverine plus phentolamine the mean duration of a full erectile response to SIN-1 was 57 minutes. Compared to the responses to a papaverine (15 mg./ml.) and phentolamine (0.5 mg./ml.) mixture, the erection induced by SIN-1 was superior in 10, comparable in 47 and inferior in 6 patients. Our data suggest a possible role for SIN-1 in the treatment of erectile dysfunction. Possible advantages may be that erection is induced by a mechanism similar to that occurring physiologically, a decreased risk of inducing prolonged erections and low therapy costs.

Role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the diagnosis and treatment of erectile dysfunction

OBJECTIVES Recently, nitric oxide was shown to be a mediator of penile erection in men and the nitric oxide donor linsidomine chlorhydrate (SIN-1) was introduced as a novel treatment option in patients with erectile dysfunction. We now present our follow-up results with the intracavernous application of SIN-1. METHODS One hundred thirteen patients with erectile dysfunction of various etiologies and 10 normal control subjects underwent intracavernous pharmacotesting with 1 mg SIN-1. Of the 113 patients, 71 (62.8%) underwent additional pharmacotesting with a mixture of papaverine (15 mg/mL) and phentolamine (0.5 mg/mL) (P/P). Forty-eight responders to SIN-1 were enrolled in an autoinjection program with this substance. RESULTS All normal control subjects had full rigid erections lasting 40 to 70 minutes. Of 113 patients, 78 (69%) had responses sufficient for intercourse with SIN-1, and the other 35 patients (31%) demonstrated inadequate responses. All 44 responders to SIN-1 who also received P/P had erections sufficient for intercourse with P/P in doses of 0.25 to 2 mL (mean, 0.6 +/- 0.3 mL). Six patients (13.6%) had prolonged erections with minimal to moderate doses of P/P. From the total of 27 patients who had erections insufficient for intercourse with SIN-1, 20 (74.1%) had good responses with 0.25 to 2.0 mL P/P (mean, 1.5 +/- 0.5 mL). One patient (4%) had a prolonged erection with 1.0 mL P/P: After 10 to 150 injections/patient (total of 1160 injections; mean, 24.1 injections), no significant side effects were noted with SIN-1. CONCLUSIONS Our data suggest that intracavernous SIN-1 is safe and efficacious in the majority of patients with erectile dysfunction; however, it has a lower smooth muscle relaxing effect than a combination of P/P. The absence of severe side effects, including priapisms, may be explained by the use of a physiologic pathway for induction of the erectile response and the rapid intracavernous decomposition of SIN-1.

Single potential analysis of cavernous electric activity —a possible diagnosis of autonomic impotence?

SummaryThe aim of our study was to examine the cavernous smooth-muscle electric activity in normal and impotent patients as well as in those with (presumably) well-defined neurologic lesions. Single potential analysis of cavernous electric activity (SPACE) was done in 12 consecutive impotent patients, 34 normal patients, and 19 patients referred especially for SPACE. In the normal patients, similar potentials with a mean duration of 9.5 s, a mean amplitude of 153 μV and a mean polyphasity of 8.5 were recorded (cutoff frequencies, 2–2000 Hz), with cutoff frequencies set at 0.5–500 Hz, the mean duration was 12.8 s, amplitude was 444 μV and the mean polyphasity was 13.8 Upper spinal cord lesions showed potentials of long duration as well as whips and bursts. Patients with lower motor-neuron lesions showed either short potentials of high amplitude or potentials of small amplitude. In 49% of the impotent patients, abnormal SPACE was found. Our results suggest that SPACE is a reproducible and minimally invasive method for the diagnosis of autonomic neurogenic impotence.

Prognostic Factors for the Postoperative Outcome of Penile Venous Surgery for Venogenic Erectile Dysfunction

Since penile venous surgery is usually associated with a poor postoperative outcome, a study was done to evaluate possible prognostic factors for this procedure. A total of 77 patients with erectile dysfunction underwent ligation of all dorsal penile veins and resection of the deep dorsal penile vein for venous incompetence. In all patients a comprehensive evaluation was done preoperatively. All patients did not respond to pharmacotherapy and had a venous leak. After a followup of 6 months, patients were classified as having full spontaneous erections, failure and response to pharmacotherapy. Of the 77 patients 31 (40.3%) had full spontaneous erections, 8 (10.3%) were currently responding to pharmacotherapy and 38 (49.4%) failed. The maintenance flow was 75 +/- 45 ml. per minute in the group with spontaneous erections and 103 +/- 60 ml. per minute in the failure group (p = 0.20). Mean patient age was 49.8 +/- 11.7 and 49.1 +/- 10.2 years, respectively (p = 0.23). Of the 41 patients wih normal single potential analysis of cavernous electrical activity 28 had full erections postoperatively, 5 responded to pharmacotherapy and 8 failed, compared to 3, 3 and 30, respectively, of the 36 patients with abnormal single potential analysis of cavernous electrical activity. After a mean followup of 21 months (range 6 to 47 months), 4 patients with full erections at 6 months postoperatively currently require intracavernous pharmacotherapy. Our results indicate that single potential analysis of cavernous electrical activity seems to be an important prognostic factor for the postoperative outcome of penile venous surgery for venogenic impotence.

Single Potential Analysis of Cavernous Electrical Activity in Impotent Patients: A Possible Diagnostic Method for Autonomic Cavernous Dysfunction and Cavernous Smooth Muscle Degeneration

Cavernous electrical activity was recorded in 214 patients with erectile dysfunction and in 39 normal patients. In 34 of the 39 normal patients potentials of a uniform shape were recorded during flaccidity. At cutoff frequencies of 0.5 to 500 Hz. the duration was 8 to 18 seconds (mean 12.8 +/- 2.8, seconds, standard deviation), the amplitude was 250 to 750 microv. (mean 444 +/- 109 microv.) and the polyphasity was 8 to 22 (mean 13.8 +/- 3.3). With increasing tumescence and rigidity during audiovisual sexual stimulation, high frequency potentials of low amplitude and short duration were found in the normal patients. In impotent patients with an upper motor neuron or peripheral lesion specific types of potentials were observed. In 11 of 14 impotent patients with insulin-dependent diabetes for more than 20 years and with clinical findings of cavernous myopathy the potentials showed low amplitude, irregular shape and slow depolarizations. Abnormal findings of cavernous electrical activity were recorded in 51.6% of the consecutive impotent patients. Our clinical study suggests that single potential analysis of cavernous electrical activity may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy.

Followup results of a combination of calcitonin gene-related peptide and prostaglandin E1 in the treatment of erectile dysfunction.

Recent human and animal studies have shown a possible role for calcitonin gene-related peptide in penile erection and a therapeutic benefit in combination with prostaglandin E1 for autoinjection therapy. The ethical committee approved calcitonin gene-related peptide-prostaglandin E1 combination for cases of nonresponse or cavernous fibrosis to papaverine-phentolamine. Since June 1990, 65 patients (59 nonresponders and 6 with fibrosis) were injected with 5 micrograms. calcitonin gene-related peptide plus 10 micrograms. prostaglandin E1. Of the 59 nonresponders to papaverine-phentolamine 31 and of the 6 patients with fibrosis 5 had full erectile response. Of these 36 patients 2 experienced pain during the pharmacologically induced erection. A total of 39 patients who had had at least 20 autoinjections of calcitonin gene-related peptide plus prostaglandin E1 was available for minimum followup. There were no side effects, such as pain (the 2 patients with pain mentioned previously were not included in the autoinjection therapy group), systemic side effects or (increased) fibrosis. Our results show that a combination of calcitonin gene-related peptide and prostaglandin E1 may be beneficial to the treatment of impotence in carefully selected patients.

Transcutaneous Registration of Cavernous Smooth Muscle Electrical Activity: Noninvasive Diagnosis of Neurogenic Autonomic Impotence

Registration of cavernous electrical activity was shown to be a possible method for the evaluation of cavernous autonomic innervation. Recent studies in patients with normal erectile function showed that cavernous electrical activity is synchronous throughout the entire cavernous bodies. Therefore, we examined the feasibility of transcutaneous registration of cavernous electrical activity in 8 normal and 62 impotent patients. In the sitting patient cavernous electrical activity was recorded with a 2-channel electrophysiological unit. Recording was done with a coaxial needle electrode in the proximal left cavernous body and with surface electrodes bilaterally on the penile shaft. In 7 of 8 normal patients swelling of the penile shaft after circumcision resulted in a dramatically decreased amplitude of the potentials. In 41 of 62 impotent patients recordings were similar. In 10 of 62 patients no recording or markedly decreased amplitudes were noted with the surface electrodes and in these patients a small penis or penile retraction with consecutive electrode displacement was found. Careful repositioning of the surface electrodes with the patient in the supine position resulted in similar recordings in 9 (inconsistently in 4). In 11 of the 62 patients more information was obtained with the surface than with the needle electrode. Our results show that recording of cavernous electrical activity can be done in a completely noninvasive manner using surface electrodes with similar or even better information obtained than with needle electrodes.

Predictive Value of Real-Time Rigiscan Monitoring for the Etiology of Organogenic Impotence

We performed routine diagnostic evaluations in 160 consecutive patients from our impotence clinic. After the diagnostic studies were completed, the results of RigiScan* monitoring during visual sexual stimulation before and after intracavernous injection of vasoactive drugs were compared to the results of standardized pharmacological testing, single potential analysis of cavernous electrical activity and pharmacocavernosometry. The results suggest RigiScan monitoring to be a highly accurate method to evaluate and document objectively the erectile response after intracavernous injection of vasoactive drugs. Although pathological monitoring after intracavernous injection is significantly associated with pathological findings in the specific evaluation, the predictive value of RigiScan monitoring for specific organogenic etiologies is not satisfactory, since normal monitoring showed no convincing correlation to single potential analysis of cavernous electrical activity or cavernosometry.

ESWL™ in patients suffering from sialolithiasis

In a prospective study, results of the extracorporeal shock wave lithotripsy (ESWL™) of salivary stones were evaluated. The study was performed with the currently available technical aid of electromagnetic systems to produce indication criteria for this particular procedure. With accurate sonographical localization a therapeutical outcome with complete emission of the concrement or an adequate disintegration of these stones was achieved in 100% of the parotid gland stones and in 29% of the sub-mandibular gland stones. Considering the risks of parotid surgery we see an absolute indication for lithotripsy in stones localized distally from the masseter banding of the parotid duct. Due to the low rate of success and the comparatively low risk connected with surgical therapy, the indication regarding concrement formations must be more critically viewed in the outlet path system of the submandibular gland. At present the lack of clinical symptoms observed following lithotripsy does not give any bearing on long-...

Proliferative behaviour and cytogenetic changes in human renal-cell carcinoma

SummaryFrom 1986 until 1990, in vivo proliferation rates (PRs) in 110 patients with renal-cell carcinoma (RCC) were immunohistochemically determined by the Ki-67 assay. It could be demonstrated that the PRs of RCCs range between only 1% and 15%. Due to its low proliferative kinetics in vivo, tumor cytogenetic investigations of this malignancy remain rare. During short-term in vitro culture, the PRs of this neoplasm increased (21%–82%). Therefore, 36 untreated human RCCs were cultured in vitro for cytogenetic analysis using the G-banding technique. In all, 77.8% (28/36) of the renal malignancies investigated exhibited an aberration of chromosome 3, which seems to serve as a marker for this malignancy. Whereas tumor stage showed no correlation with PR, tumor grade exhibited a strong correlation with this parameter. According to the data presented herein, immunohistochemical determination of the tumor-specific PR using the monoclonal antibody Ki-67 is a practicable, reliable and reproducible method that complements conventional histological tumor grading and staging. This parameter appears to be useful in identifying RCC patients at high risk, especially at early stages that are identical in tumor stage and grade.