Erectile dysfunction in relation to traumatic pelvic injuries or pelvic fractures.
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Fractures, Bone↗
Biomedical subjects
C G Stief
Publications and source records attributed to C G Stief.
Expression of different phosphodiesterase genes in human cavernous smooth muscle.
PURPOSE: Knowledge of intracellular signal propagation in smooth muscle tone regulation is of major importance in the understanding of the physiology of penile erection, and the development of new and selective pharmacological agents for the treatment of related disorders. Since phosphodiesterases (PDE) are key enzymes of the signaling pathway, we elucidate their presence and potential functional relevance in human cavernous tissue. MATERIALS AND METHODS: To identify PDE messenger RNA in human cavernous tissue, we constructed primers for 14 published PDE isoforms. Expression of the genes was then analyzed by reverse transcriptase polymerase chain reaction under standard conditions and by subsequent sequencing. RESULTS: Messenger RNA was detected in human corpus cavernosum for the human phosphodiesterase isoenzymes and isoforms PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE7A, PDE8A and PDE9A. CONCLUSIONS: A total of 13 PDE genes were expressed in human cavernous tissue, indicating a role of these enzymes in penile erection regulation. The intracellular mechanisms of hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate by PDEs are more complex than assumed previously. These findings open up new possibilities in the development of drugs for the treatment of erectile dysfunction.
Base Sequence↗
Systemic and cavernous plasma levels of endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction.
The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-1 (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated by various authors that ET-1 might be involved in the pathophysiology of erectile dysfunction. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels registered in systemic and cavernous blood cavities taken from healthy males and patients with ED during different penile conditions (flaccidity, tumescence/rigidity, detumescence). Thirty-two healthy adult males and 25 patients were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1/-2 was determined in plasma aliquots by means of an enzyme-linked immunoassay (ELISA). Mean systemic and cavernous plasma level of ET-1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernous blood during penile tumescence, rigidity and detumescence. In the group of patients, mean plasma ET-1/-2 levels in the phase of penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernous blood (flaccidity: 0.52+/-0.38 fmol/ml vs. 0.48+/-0.46 fmol/ml, respectively; detumescence: 0.53+/-0.33 fmol/ml vs. 0.27+/-0.11 fmol/ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and psychogenic etiology of ED. In the phase of detumescence, the mean ET-1/-2 level was lower in the cavernous blood cavities taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-1/-2 registered in the cavernous blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seems to be of no physiological significance, our data counteract the hypothesis of an ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding an involvement of ET-1 in the pathophysiology of erectile dysfunction.
Adult↗
Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate.
PURPOSE: Current pharmacological concepts in the treatment of benign prostatic hyperplasia are aimed at the static and dynamic component of the disease. Mainly alpha-blocking agents are used to reduce the adrenergic tone of prostatic myocytes, thus, increasing urine flow through the prostatic urethra by reducing urethral resistance. With the introduction of the phosphodiesterase (PDE) 5 inhibitor sildenafil the concept of PDE inhibition has gained tremendous interest in the field of urology. We characterized PDE isoenzymes from human prostatic tissue by molecular biology and protein chemistry, and investigated the effects of various PDE inhibitors compared with standard pharmacological agents on adrenergic tension in isolated human prostatic strips. MATERIALS AND METHODS: PDE isoenzymes were characterized by reverse transcriptase-polymerase chain reaction and anion exchange chromatography. Using the organ bath technique we determined the relaxing effects of the PDE inhibitors papaverine, vinpocetine (Biomol GmbH, Hamburg, Germany), erythro-9-[2-hydrox-3-nonyl]adenine hydrochloride (Tocris Cookson, Ltd., Bristol, United Kingdom) rolipram (Schering AG, Berlin, Germany), zaprinast (Rhône-Poulenc Rorer, Ltd., Dagenham, United Kingdom) and sildenafil (Pfizer, Ltd., Sandwich, United Kingdom), the adenylate cyclase activating agent forskolin (ICN Biomedicals, Aurora, Ohio) and the nitric oxide donor sodium nitroprusside on adrenergic tension in prostatic strips isolated from the transition zone. RESULTS: Reverse transcriptase-polymerase chain reaction revealed messenger RNA transcripts encoding for PDE 1, 2, 4, 5, 7, 8, 9 and 10 in the various anatomical regions of the human prostate, including the peripheral, central and transition zones. Except for complementary DNA encoding for PDE 1C, complementary DNA fragments encoding for PDE 1A, 1B, 2A, 4A, 4B, 4C, 4D, 5A, 7A, 8A, 9A and 10A were found at almost even ratios in the different histological regions of the prostate. The hydrolytic activities of PDE 4 and 5 were present in the cytosolic fraction of prostatic tissue, whereas in the particulate fraction only the hydrolytic activity of PDE 4 was detected. Adrenergic tension in prostatic strip preparations was reversed by forskolin, sodium nitroprusside, and inhibitors of PDE 4 and 5. CONCLUSIONS: Our results demonstrate the presence and functional relevance of PDE isoenzymes 4 and 5 in human prostatic tissue. These studies support the possible use of inhibitors of PDE 4 and 5 for treating urinary obstruction secondary to benign prostatic hyperplasia.
Humans↗
Systemic and cavernosal plasma levels of endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction.
The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-l (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated that ET-1 might be involved in the pathophysiology of penile erection. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels recorded in systemic and cavernosal blood taken from healthy males and patients with erectile dysfunction (ED) during different penile conditions (flaccidity, tumescence/rigidity, detumescence). The study groups comprised 33 healthy adult males and 25 patients. The subjects were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET- 1/-2 was determined in plasma aliquots by means of an enzyme-linked immunosorbent assay (ELISA). Mean systemic and cavernosal plasma levels of ET- 1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernosal blood during penile tumescence, rigidity and detumescence. In the patients, mean plasma ET-1/-2 levels during penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernosal blood (flaccidity 0.52 +/- 0.38 fmol/ml vs 0.48 +/- 0.46 fmol/ml, respectively: detumescence 0.53 +/- 0.33 fmol/ml vs 0.27 +/- 0.11 fmol/ ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and those with a psychogenic aetiology of ED. During detumescence, the mean ET-1/-2 level was lower in the cavernosal blood taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-l/-2 in the cavernosal blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seemed to be of no physiological significance, our findings contradict the hypothesis of the ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding the involvement of ET-1 in the pathophysiology of erectile dysfunction.
Adult↗
Pilot study of the transdermal application of testosterone gel to the penile skin for the treatment of hypogonadotropic men with erectile dysfunction.
Androgens influence important central and peripheral mechanisms of the erectile system. The relevance of a moderate decrease of serum testosterone level for erectile dysfunction (ED) has not been clarified so far. The aim of our study was to offer an easy transcutaneous method of androgen application. A previous study on the pharmacokinetic profile of the testosterone gel applied, showed marked elevation of the serum levels of testosterone. In our study, 46 hypogonadal patients with ED and total lack of vaginal penetration applied testosterone gel (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6-8 weeks, after a run-in period with placebo gel of 2 weeks. All patients showed decreased testosterone serum levels (<3 ng/ml) in at least two morning samples over a period of 3 weeks before treatment. Psychogenic etiology was excluded by a sexual psychologist. Patient age was 37-69 years (mean 53.5). Three patients (6.5%) responded to placebo in the run-in phase and were withdrawn from further treatment. Fifteen patients (32.6%) showed improved erection, allowing penetration and sexual intercourse. Twenty-eight patients (60.9%) did not respond to therapy. Local genital skin irritation was not observed. Elevation of peripheral testosterone was not correlated to a positive therapy response. A success-rate of 32.6% in this group of patients after exclusion of psychogenic patients and placebo-responders seems to justify further investigations. A medication period of 6-8 weeks is most probably too short to induce imaginable regenerative effects of testosterone on the erectile system. We therefore suggest that future double-blind and placebo-controlled studies should be designed for a minimum of 3 months. Testosterone gel may be a cost effective form of androgen administration.
Administration, Cutaneous↗
Initial clinical experience with the selective phosphodiesterase-I isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder.
Current pharmacological treatment modalities for urge incontinence and low compliance bladder are limited by a low clinical efficacy and the significant side effects of the standard drugs available. Previous in vitro studies indicated a possible functional relevance of the intracellular phosphodiesterase (PDE)-1 isoenzyme in the regulation of human detrusor smooth muscle contractility. We therefore investigated the effect of the PDE-1 inhibitor vinpocetine in nonresponders to standard pharmacological therapy. In 11/19 patients (57.9%) clinical symptoms and/or urodynamic parameters were improved. Although these initial data are preliminary, they represent the first evidence that isoenzyme-selective PDE inhibition may be a novel approach to the treatment of lower urinary tract disorders.
Compliance↗
Determination of nitric oxide metabolites by means of the Griess assay and gas chromatography-mass spectrometry in the cavernous and systemic blood of healthy males and patients with erectile dysfunction during different functional conditions of the penis.
Recent research implicated that the relaxation of cavernous arterial and trabecular smooth muscle-- the crucial event in penile erection--is initiated by the release of nitric oxide (NO) from nerve terminals within the cavernous tissue as well as from the endothelia that line the lacunar spaces and the intima of penile arteries. The present study was undertaken to determine whether plasma levels of the NO metabolites nitrate (NO3-) and nitrite (NO2-) in the systemic and cavernous blood of male subjects change during different penile conditions, and whether there is a difference in the NO3- and NO2- levels of normal males and patients with erectile dysfunction (ED). Twenty-four potent adult male volunteers and 15 patients with ED were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and NO3- and NO2- levels were determined in plasma aliquots by means of the Griess reaction and a method combining gas chromatography and mass spectrometry (GC-MS). The mean systemic and cavernous plasma NO3-/NO2- level in blood samples obtained from the healthy volunteers was 25-31 microM when determined by means of the Griess reaction and 37-41 microM when measured by GC-MS. Both approaches revealed that NO3-/NO2- levels in the peripheral and cavernous blood do not change appreciably during developing erection, rigidity and detumescence. Moreover, no significant differences were found between NO3-/ NO2- plasma levels in the systemic and cavernous blood samples taken from the normal subjects and patients during penile flaccidity, tumescence and detumescence. Our results may reflect the fact that NO metabolism in the corpora cavernosa in the phases of penile tumescence and rigidity may account for only a minor fraction of local levels of NO3- and NO2-, which may also derive from exogenous sources. Moreover, the basal levels of NO metabolites in the blood flushing the lacunar spaces of the cavernous body in the state of developing erection could conceal any release of NO that may occur within the penile tissue. Thus, we conclude that the quantification of NO metabolites by means of advanced detection methods, such as GC-MS, is of no use in the workup of ED.
Adult↗
Computerized classification of corpus cavernosum electromyogram signals by the use of discriminant analysis and artificial neural networks to support diagnosis of erectile dysfunction.
Corpus cavernosum electromyogram (CC-EMG) provides diagnostic information on cavernous autonomic innervation and a measure of the degree to which the cavernous smooth muscle cells are intact. The complicated CC-EMG is evaluated and used in the diagnosis of patients suffering from erectile dysfunction. The evaluation procedure has been simplified by applying digital signal processing techniques. Since mathematically-based interpretations require quantitative data, spectral analysis was performed. The derived biosignals were analyzed by fast Fourier transform (FFT). Besides various other spectral parameters, specific frequency bands were determined in the power spectrum using factor analysis. The parameters were used for the computerized classification of normal and pathological CC-EMG data and the classification was performed using two independent methods: discriminant analysis (DA) and artificial neural networks (ANN). A medical expert analyzed a total of 200 CC-EMG recordings from patients with and without erectile dysfunction and separated these into normal (136) and pathological (64) cases. Although each independent method had already resulted in a relatively high number of correct classifications, the classification success rate could be slightly improved by using a combination of both classification methods. A total of 72.79% and 77.94% were successfully classified using DA and ANN, respectively. The combination of both methods increased the classification success to 80.15%. The results of this study enabled impartial evaluation of the CC-EMG signals for clinical diagnostic purposes of erectile dysfunction. This method provided an objective and easy way to analyze the CC-EMG. Furthermore, this results in patient diagnosis becoming an easier task for less experienced doctors, since little knowledge of the raw signal is needed.
Algorithms↗
Relaxation of human ureteral smooth muscle in vitro by modulation of cyclic nucleotide-dependent pathways.
Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide turnover and, thus, smooth muscle tension. Recent reports have indicated the presence of PDE isoenzymes 1, 2, 4, and 5 in cytosolic supernatants prepared from human ureteral smooth muscle homogenates and the ability of second-generation inhibitors of PDE 3, 4, and 5 to relax KCl-induced tension of human ureteral muscle in vitro. The aim of the present study was to evaluate the functional effects of recently developed, third-generation isoenzyme-selective PDE inhibitors, the nitric oxide (NO)-donating agents sodium nitroprusside (SNP) and dihydropyridine (DHP), which is also described as an antagonist of L-type calcium channels, and the adenylyl cyclase-stimulating drug forskolin on tissue tension and cyclic nucleotide levels of human ureteral smooth muscle segments in vitro. Relaxant responses of human ureteral smooth muscle were investigated in vitro using the organ bath technique. Cyclic nucleotides cAMP and cGMP were determined by specific radioimmunoassay following time and dose-dependent incubation of the ureteral tissue with the drugs. The most pronounced relaxing effects on KCl-induced tension of ureteral smooth muscle were exerted by nitrovasodilator SNP, PDE4 inhibitor rolipram, and PDE5 inhibitors E 4021 and morpholinosulfonyl-pyrazolopyrimidine (MSPP). Relaxing potency of the drugs was paralleled by their ability to elevate intracellular levels of cGMP and cAMP, respectively. Our data suggest the possibility of using selective inhibitors of PDE isoenzymes 4 and 5 in the treatment of ureteral stones and ureteral colic.
Colforsin↗
Systemic and cavernous plasma levels of endothelin 1 in healthy males during different functional conditions of the penis.
The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters might be involved in this process. Endothelin 1 (ET-1), a 21-amino-acid peptide with potent and long-lasting vasoconstrictor activity, may be one of the factors contributing to such control. The present study was undertaken to determine whether plasma levels of ET-1 changed during flaccidity, tumescence, rigidity, and detumescence. We determined plasma levels of ET-1 in the peripheral and cavernosal blood of 32 potent adult male volunteers, in whom penile tumescence and erection were elicited by exposure to visual and tactile erotic stimuli. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1 was quantified in plasma aliquots obtained from the blood samples. Using the organ bath technique, we evaluated the contractile effects of ET-1 and norepinephrine (NE) on isolated human corpus cavernosum musculature. No significant change in ET-1 levels was observed in the peripheral or cavernosal blood in the process of developing erection, rigidity, or detumescence. The mean plasma level of ET-1 was 0.2-0.7 fmol/ml. In the organ bath, ET-1 elicited concentration-dependent contractions of isolated human corpus cavernosum, which were much more pronounced than those evoked by the adrenergic agonist NE. Our data indicate that despite the in vitro efficacy of ET-1 in stimulating contractile activity in isolated human cavernous smooth muscle, the peptide may not be of ultimate importance for the mechanism of flaccidity and detumescence in healthy males. Nevertheless, the exact role of ETs in the control of penile smooth muscle tone remains to be established.
Adult↗
Cavernous and systemic testosterone levels in different phases of human penile erection.
OBJECTIVES: To examine changes in testosterone levels in the cavernous and peripheral blood during different phases of erection because, although the determination of systemic testosterone levels has been well established in the diagnostic workup of erectile dysfunction, the exact role of testosterone in adult male sexual function remains unclear. METHODS: Blood samples were drawn simultaneously from the corpus cavernosum and the cubital vein of 54 healthy and normally potent volunteers during four different stages of the cavernous erectile tissue (flaccidity, tumescence, rigidity, and detumescence). Penile erections were induced by audiovisual and tactile stimulation, and testosterone levels were determined by radioimmunoassay. RESULTS: The mean testosterone level in the corpus cavernosum plasma during the flaccid state was 2.9 +/- 1.2 ng/mL. During tumescence and rigidity, the testosterone levels in the cavernous blood significantly increased, to 4.3 +/- 1.3 ng/mL and 4. 4 +/- 1.4 ng/mL, respectively. During detumescence, the cavernous testosterone levels dropped to 3.5 +/- 1.4 ng/mL. The changes in the testosterone levels in the peripheral plasma were less pronounced. A significant increase was also found in the peripheral testosterone levels from flaccidity (4.1 +/- 1.1 ng/mL) to tumescence (4.4 +/- 1. 4 ng/mL). No further increase in testosterone occurred during the phase of rigidity. From rigidity to detumescence, the peripheral testosterone levels dropped to 4.1 +/- 1.2 ng/mL. CONCLUSIONS: Penile erection was found to be accompanied by a significant increase in cavernous and systemic testosterone plasma levels. The estimated difference between the systemic and cavernous testosterone levels during penile flaccidity, when blood flow through the cavernous body is minimized, might be a diagnostic tool to evaluate the amount of bioavailable testosterone and the activity of testosterone receptors in the corpus cavernosum smooth musculature.
Adult↗
Effects of sildenafil on cAMP and cGMP levels in isolated human cavernous and cardiac tissue.
OBJECTIVES: To further investigate the mechanism of action of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5 (PDE5), that has been proved to be effective in the treatment of male erectile dysfunction. We assessed the effects of sildenafil on the in vitro formation of cGMP and cyclic adenosine monophosphate (cAMP) in isolated human corpus cavernosum and cardiac muscle. METHODS: Isolated segments of human corpus cavernosum and cardiac muscle were exposed to increasing concentrations of sildenafil. The dose-dependent accumulation of cGMP and cAMP was determined in the tissue samples by means of radioimmunoassays. Responses of the isolated tissue preparations to sildenafil were compared with those obtained with the reference compounds sodium nitroprusside, forskolin, and milrinone. RESULTS: In the concentration range 0.01 to 1 microM, there was only a minor effect of sildenafil on cGMP levels in isolated human cavernous and cardiac tissues. In contrast, sildenafil was found to increase cAMP significantly in both cavernous and cardiac tissue in physiologic and supraphysiologic concentrations. The stimulation of cAMP by sildenafil was more pronounced in cavernous than in cardiac tissue. Concentrations of cGMP in the cardiac strips were unaltered by milrinone; cAMP was stimulated starting at a concentration of 0.05 microM. In the range of 0.1 to 1.0 microM, the in vitro effect of sildenafil on cAMP levels in the cardiac samples was almost equivalent to that of milrinone. CONCLUSIONS: Our findings provide a potential mechanism for the cardiovascular side effects that have been reported with sildenafil use, highlighting the fact that a "cross-talk" between cGMP and cAMP-dependent signal transduction pathways might exist in human cavernous and cardiac muscle that may be of pharmacologic significance.
Colforsin↗
Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder.
The spasmolytic activity of flavoxate (CAS 15301-69-6) and the anticholinergic agents oxybutynin (CAS 5633-20-5), tolterodine (CAS 124937-51-5) and trospium chloride (CAS 10405-02-4), all of which are commonly utilized in the treatment of urinary incontinence, on muscarinic tension and electrically evoked contractions of isolated human detrusor smooth muscle strips was studied using the organ bath technique. Within the concentration ranges tested (trospium chloride 10(-11)-10(-6) mol/l, flavoxate and oxybutynin 10(-9)-10(-5) mol/l, tolterodine 10(-10)-10(-5) mol/l), each drug caused a concentration-dependent relaxation of the tension elicited by muscarinic stimulation and dose-dependently attenuated the contractions induced by electrical field stimulation (EFS). The effects of trospium chloride and tolterodine on carbachol-induced muscarinic tension were more pronounced than those of oxybutynin, while trospium chloride and oxybutynin were most effective in inhibiting the contractions induced by EFS. Flavoxate was significantly less effective than all other drugs tested. Regardless the individual drug concentrations needed for maximal efficacy, the potency of oxybutynin and flavoxate to reverse muscarinic tension and attenuate EFS-evoked contractions was almost comparable while tolterodine and trospium chloride were more effective in relaxing the muscarinic tension of the detrusor strip preparations than causing inhibition of EFS-induced contractions. Our results again underline the ratio for the use of nortropane analogues (trospium chloride) and phenylpropylamine cresols (tolterodine) in the treatment of frequency, urgency and urge incontinence secondary to an overactive bladder.
Carbachol↗
Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis.
OBJECTIVE: The following study was performed to evaluate the importance of phosphodiesterases 3A (PDE3A) and 5A (PDE5A) for the regulation of penile smooth muscle tone. Furthermore, indications of side effects of specific inhibitors in certain tissues as well as of a possible relation between the level of PDE3A and PDE5A gene expression and erectile dysfunction should have been deduced from the results obtained. METHODS: Total ribonucleic acid was isolated from different human tissues (urogenital tract, gastrointestinal tract, cardiovascular system and central nervous system) and subjected to RTPCR analysis and Northern blotting using primers and probes specific for PDE3A and PDE5A. RESULTS: As shown by RT-PCR and Northern blotting, PDE3A and PDE5A mRNAs exhibit a distinct distribution throughout the tissues examined but were 2-fold higher in cavernous tissue than in all other tissues investigated. However, there were no significant differences in the levels of gene expression between the two subgroups of patients. CONCLUSIONS: Very high expression levels of PDE3A and PDE5A in human cavernous tissue underscore the physiological importance of these enzymes for the regulation of penile erection, emphasizing their therapeutical and pharmacological relevance. The distribution pattern of the mRNA for the isoenzymes PDE3A and PDE5A may explain the pharmacological effects as well as the side effects of milrinone and sidenafil.
3',5'-Cyclic-AMP Phosphodiesterases↗
Congenital and acquired penile deviation treated with the essed plication method.
OBJECTIVES: To evaluate our results with the Essed procedure for the correction of penile curvature, either congenital or due to Peyronie's disease, and compare it with the data from the literature, both for the Essed and the Nesbit procedure. METHODS: From 1991 to 1996 the Essed procedure was performed in 61 patients. 65.6% (n = 40) had congenital deviation and 34.4% (n = 21) suffered from secondary deviation due to Peyronie's disease. In all patients 2-6 nonabsorbable inverting interrupted sutures were placed bringing the knot between the plicated tunica. RESULTS: Patients' ages ranged from 15 to 65 (mean 31.3) years and the mean follow-up time was 39.8 (12-75) months. The preoperative penile deviation was between 20 and 90 degrees (mean 47.4 degrees ). Eighteen patients (29.5%) had a recurrent deviation following surgery. This failure rate was higher in the patient group with Peyronie's disease (42.9%) than in the group with congenital deformation (22.5%). Postoperatively, 2 patients (3.3%) with Peyronie's disease reported de novo erectile dysfunction. Twenty patients (32.8%) complained of persistent discomfort or pain at the area of the still palpable plication sutures, but this inhibited sexual intercourse only in 1 case. 45.9% stated penile shortening after surgery but only 21.3% felt bothered by this. CONCLUSION: The results reported are in accordance with the literature showing a higher recurrence rate of the deviation with the Essed compared to the Nesbit procedure. For both methods the risk of recurrent disease is higher in patients with Peyronie's disease and with both techniques, an equally low incidence of erectile dysfunction is evident. However, since with the Essed technique one third of all patients complained of discomfort from the nonabsorbable sutures, the Nesbit procedure seems to be superior.
Adolescent↗
Intratesticular self-injection of testgasoline.
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Adolescent↗
Plasma levels of cavernous and systemic norepinephrine and epinephrine in men during different phases of penile erection.
PURPOSE: Knowledge of the functional anatomy, hemodynamics, neurophysiology and pharmacology of penile erection has improved tremendously during the last 2 decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out up until now. Therefore, we conducted a study to examine plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in the peripheral and cavernous blood of healthy men during penile flaccidity and in different phases of erection. MATERIALS AND METHODS: Blood samples were drawn simultaneously from the corpus cavernosum (CC) and the cubital vein (P) in 53 healthy volunteers with normal erectile function, in four different functional states of the cavernous erectile tissue (flaccidity = 1, tumescence = 2, rigidity = 3, detumescence = 4). Penile erections were induced by audiovisual and tactile stimulation and the plasma concentrations of NE and E were determined by means of a radioimmunoassay (RIA). RESULTS: A significant (p <0.001) reduction of NE in CC plasma was found from flaccidity (362 + or - 173 pg./ml.) to rigidity (248 + or - 122 pg./ml.), followed by an increase in the detumescence phase (336 + or - 199 pg./ml.), (p <0.001). In contrast, changes in NE levels in the peripheral plasma were less pronounced from 1P (202 + or - 102 pg./ml.) to 3P (229 + or - 118 pg./ml.), (p = 0.006) and from 3P to 4P (222 + or - 127 pg./ml.), respectively (p = 0.370). The most pronounced increase in cavernous E levels were observed from flaccidity (47 + or - 41 pg. /ml.) to tumescence (130 + or - 106 pg./ml.) (p <0.001). Cavernous E levels dropped significantly from 113 + or - 67 pg./ml. during rigidity to 76 + or - 57 pg./ml. + or - during detumescence (p <0.001). The course of peripheral plasma levels of E was similar to that in the cavernous blood. Mean peripheral E level was 69 + or - 55 pg./ml. in the state of penile flaccidity, reaching 98 + or - 78 pg./ml. in tumescence and 82 + or - 64 pg./ml. in rigidity (p <0.001), respectively, and finally decreasing to 62 + or - 46 pg./ml. in detumescence. CONCLUSION: Penile erection, based on the relaxation of cavernous and arterial smooth muscle, is accompanied by a significant reduction of NE in cavernous blood, while E levels rose in peripheral and cavernous blood during developing erection.
Adult↗