Local interferon-alpha2b is not an effective treatment in early-stage Peyronie's disease.
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Humans↗
Biomedical subjects
T F Lue
Publications and source records attributed to T F Lue.
Growth hormone enhances regeneration of nitric oxide synthase-containing penile nerves after cavernous nerve neurotomy in rats.
PURPOSE: As growth hormone has been reported to improve nerve regeneration, we studied the effect of rat growth hormone (GH) on the regeneration of nitric oxide synthase (NOS)-containing penile nerves and the neurons in the pelvic ganglia after unilateral cavernous nerve neurotomy in rats. MATERIALS AND METHODS: Male rats were divided into three groups: sham operation (n = 14); unilateral neurotomy of a 5 mm. segment of the cavernous nerve (n = 14) with subsequent injection of buffer solution only; and unilateral neurotomy with GH injection (n = 14). Electrostimulation of the intact cavernous nerve was performed at 1 and 3 months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was used to identify NOS in penile nerve fibers of the mid-shaft segment and in neurons of the pelvic ganglia. RESULTS: One month after unilateral neurotomy, both the buffer alone and GH-treated groups showed a significant decrease in NOS-containing nerve fibers in the dorsal and intracavernosal nerves on the side of neurotomy. At 3 months, the number of NOS-containing nerve fibers in the buffer alone group did not increase, while the GH-treated group showed a significant increase. In the GH-treated group at 3 months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of neurotomy (p <0.034), indicating that the regeneration derives from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the GH-treated group revealed a greater maximal intracavernosal pressure and a shorter latency period at 3 months than in those given buffer alone. CONCLUSIONS: Our results show that GH injection significantly enhances the regeneration of NOS-containing fibers in the dorsal and intracavernosal nerves after unilateral cavernous nerve injury. We believe that GH administration may present a new and more physiologic approach to the treatment of erectile dysfunction after radical pelvic surgery.
Animals↗
Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group.
BACKGROUND: Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder. METHODS: Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 microg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home. RESULTS: During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P<0.001). On average, 7 of 10 alprostadil administrations were followed by intercourse in men responsive to treatment. The efficacy of alprostadil was similar regardless of age or the cause of erectile dysfunction, including vascular disease, diabetes, surgery, and trauma (P<0.001 for all comparisons with placebo). The most common side effect was mild penile pain, which occurred after 10.8 percent of alprostadil treatments, but the pain rarely resulted in refusal to continue in the study. Hypotension occurred in the clinic in 3.3 percent of men receiving alprostadil. Hypotension-related symptoms were uncommon at home. No men had priapism or penile fibrosis. CONCLUSIONS: In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home.
Adult↗
An animal model of Peyronie's-like condition associated with an increase of transforming growth factor beta mRNA and protein expression.
PURPOSE: Transforming growth factor beta (TGF-beta) is involved in numerous vital processes including tissue fibrosis. Our objective was to study the role of TGF-beta in the induction of a Peyronie's-like condition and to produce an animal model for the further study of Peyronie's disease. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided into two groups. Different concentrations of cytomodulin, a synthetic heptopeptide with TGF-beta-like activity, were injected into the tunica of each rat from the first group (n = 18). Rats in the second group (n = 6) received saline injections as a control. The tunical tissues were taken after 3 days, 2 weeks, and 6 weeks and were examined using Hart and Trichrome stains. In the same tissue samples, TGF-beta mRNA and protein expression were studied. RESULTS: Histological alterations were observed in 15 out of 18 cytomodulin-injected rats, especially in tissue examined after 6 weeks. The most prominent changes were chronic cellular infiltration, focal and diffuse elastosis, thickening, disorganization and clumping of the collagen bundles. Results from immunoblot revealed remarkable TGF-beta1 protein expression in all the cytomodulin-injected rats only after 2 and 6 weeks. No remarkable TGF-beta2 or TGF-beta3 protein expression was observed. TGF-beta1 mRNA expression in the cytomodulin-injected rats was noticed in rats injected with higher concentrations after 3 days, while it was expressed in all rats after 2 weeks. There was no expression in the control group after either 3 days or 2 weeks. CONCLUSIONS: Cytomodulin can induce Peyronie's-like condition in the rat penis, which may explain the role of TGF-beta in the pathogenesis of Peyronie's disease.
Animals↗
Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft.
OBJECTIVES: To evaluate ureteral replacement by a free homologous graft of acellular matrix in a rat model. METHODS: In 30 male Sprague-Dawley rats, a 0.3 to 0.8-cm midsegment of the left ureter was resected and replaced with an acellular matrix graft of equal length placed on a polyethylene stent. The animals were killed at varying intervals, and the grafted specimens were prepared for light and electron microscopy. RESULTS: In all animals, the acellular matrix graft remained in its original position without evidence of incrustation or infection, and histologic examination showed complete epithelialization and progressive infiltration by vessels. At 10 weeks, smooth muscle fibers were observed; at 12 weeks, nerve fibers were first detected; at 4 months, smooth muscle cells had assumed regular configuration. CONCLUSIONS: The ureteral acellular matrix graft appears to promote the regeneration of all ureteral wall components.
Animals↗
mRNA and protein expression of nitric oxide synthase and adrenoceptor alpha 1 in young and old rat penile tissues.
OBJECTIVE: To investigate alterations of neuronal structure and the mRNA expression of nitric oxide synthase (NOS) and adrenoceptor alpha 1 in young and old rat penile tissues, and assess the importance of these factors in erectile dysfunction (ED) associated with ageing. MATERIALS AND METHODS: NOS was determined in the pelvic ganglia of 32 rats using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. Adrenergic neurons were identified by histofluorescence staining. The gene expression for NOS and for adrenoceptor alpha 1 was investigated in corporal tissue by differential reverse transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. b-actin was used as an internal standard in each tube to quantify the baseline gene expression. RESULTS: The following changes occurred in old rats: (i) an increase of lipofuscin and a decrease in both bNOS-containing neurons and fluorescent adrenergic neurons in the pelvic ganglia; (ii) significantly less expression of NOS mRNA than in young rat penile tissues; and (iii) no significant alteration in adrenoreceptor alpha 1 mRNA expression. CONCLUSIONS: The fewer adrenergic and NOS-containing neurons and neurotransmitters in pelvic ganglia from old rats may explain the enhanced penile smooth muscle tone previously reported in older impotent men. Furthermore, lower mRNA expression of NOS may be associated with structural and functional changes associated with ageing penile tissue.
Age Factors↗
Structural alterations in the tunica albuginea of the penis: impact of Peyronie's disease, ageing and impotence.
OBJECTIVE: To investigate whether changes in the structure of the tunica albuginea influence the development of erectile dysfunction. PATIENTS AND METHODS: Biopsy specimens taken from the tunica of 64 patients (both potent and impotent) with and without Peyronie's disease were evaluated. Tissue samples were stained and examined under light and electron microscopy, and the concentration of elastic fibres present in each was measured using computerized image analysis. RESULTS: The concentration of elastic fibres was lower in impotent than in potent patients (P = 0.0365) and was also significantly less in patients with Peyronie's disease. Furthermore, the concentration of elastic fibres decreased with age. Electron and light microscopy revealed the presence of distinct alterations in the tunica albuginea in impotent patients and patients with Peyronie's disease that might interfere with function. CONCLUSION: The decrease in elastic fibre concentration and changes in microscopic features may contribute to erectile dysfunction by impairing the veno-occlusive function of the tunica albuginea.
Adolescent↗
Continence mechanism of the isolated female urethra: an anatomical study of the intrapelvic somatic nerves.
PURPOSE: A neuroanatomical study was initiated to gain better insight into the continence mechanism of the isolated urethra in women. MATERIALS AND METHODS: We performed a detailed gross and histological neuroanatomical study to identify the intrapelvic somatic pathway from the sacral spinal cord to the female urethral sphincter. Gross anatomical dissection was performed in 5 formalin fixed female adult pelvises by tracing the autonomic nerves from the pelvic plexus and the spinal somatic nerves from S2-S4 to the urethral sphincter. Immunohistochemical staining of urethral step sections with a neuropeptide specific antibody was performed to demonstrate the course of the periurethral somatic nerves in relation to the vaginal wall. RESULTS: Our study demonstrated an intrapelvic somatic pathway derived from the S2, S3 and S4 sacral roots, distinct from the peripheral pudendal nerve, supplying the levator ani and the urethra. The somatic nerves travel beneath the endopelvic fascia in close relation to the inferior vascular pedicle of the bladder and are susceptible to injury during radical pelvic surgery. Mixed autonomic fibers from the pelvic plexus travel along the course of the ureter and are also intimately associated with the vascular pedicle of the bladder. Immunohistochemical staining of urethral step sections demonstrated that the periurethral nerves travel in close relation to the lateral and anterior vaginal wall. CONCLUSIONS: We believe that the identification of intrapelvic somatic pathways to the urethra provides a basis for developing surgical techniques to preserve urethral somatic innervation during radical pelvic surgery in women.
Adult↗
The anatomy of the tunica albuginea in the normal penis and Peyronie's disease.
PURPOSE: We studied the fine architecture of the tunica albuginea of the penis. MATERIALS AND METHODS: The study included 6 human male cadavers and 10 surgical patients (5 with Peyronie's disease and 5 with normal penile anatomy). RESULTS: The tunica albuginea of the corpora cavernosa is a bi-layered structure with multiple sub layers. Inner layer bundles support and contain the cavernous tissue and are oriented circularly. Radiating from this layer are intracavernous pillars acting as struts, which augment the septum and provide essential support to the erectile tissue. Outer layer bundles are oriented longitudinally. These fibers extend from the glans penis to the proximal crura, where they insert into the inferior pubic ramus. There are no outer layer fibers between the 5 and 7 o'clock positions. Elastic fibers normally form an irregularly latticed network on which collagen fibers rest. In Peyronie's disease the well ordered appearance of the collagen layers is lost: excessive deposits of collagen, disordered elastic fibers and fibrin are found within the region of the plaque. CONCLUSIONS: The normal 3-dimensional structure of the tunica affords great flexibility, rigidity and tissue strength to the penis, which are lost consequent to structural changes in Peyronie's disease.
Humans↗
Age decreases nitric oxide synthase-containing nerve fibers in the rat penis.
PURPOSE: To study the effect of aging on erectile function in a rat model. MATERIALS AND METHODS: We investigated: 1) the number and distribution of nerve fibers within the corpus cavernosum and dorsal nerve containing vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS); and 2) the erectile response to apomorphine (a central dopamine receptor agonist), electrostimulation of the cavernous nerve, and intracorporeal papaverine injection. RESULTS: The number of NOS-containing nerve fibers was significantly less in the old rats (24 months) than in the young (2.5 months) and intermediate (8.5 months)-aged (63.3 +/- 3.35 vs. 135.1 +/- 10.88 [p < or = 0.0002] and 127.8 +/- 11.65 [p < or = 0.0002]). The number of erections induced by apomorphine was significantly less in the old rats than in the young (1.0 +/- 3.1 vs. 3.6 +/- 0.26; p < 0.002). With electrostimulation, the latency period before the onset of the intracavernous pressure rise was noted to increase with age (2.3 +/- 0.24 sec. for the young vs. 6.77 +/- 0.98 sec. for the old, p < or = 0.0001). The maximal intracavernous pressure after intracavernous papaverine injection decreased with age. CONCLUSION: The erectile mechanism appears to remain intact as rats age, but the response to central and peripheral stimulation decreases. The reduction in NOS-containing nerve fibers might account for these observations.
Aging↗
Peyronie's disease is associated with an increase in transforming growth factor-beta protein expression.
PURPOSE: Transforming growth factor-beta (TGF-beta) has been implicated in many chronic fibrotic conditions such as pulmonary and hepatic fibrosis. We postulated that TGF-beta may play a role in the pathogenesis of Peyronie's disease. MATERIALS AND METHODS: Tissues from the tunica albuginea of 30 Peyronie's disease patients (study group) and from 6 patients without Peyronie's disease, who had undergone penile prosthesis surgery for organic impotence (control group), were subjected to histological examination using Hart and trichrome stains and Western blotting for the detection of TGF-beta protein expression. RESULTS: The results of these experiments demonstrate that all tissue from Peyronie's disease patients showed a variety of histological changes of the tunica, ranging from chronic inflammatory cellular infiltration to complete calcification and ossification of the tissues. The most prominent changes observed in the majority of patients were focal or diffused elastosis, fenestration and disorganization of the collagen bundles. TGF-beta1 protein expression was detected in 26 patients (86%), while only 7 (23%) and 5 (17%) patients showed TGF-beta2 and TGF-beta3 protein expression, respectively. One patient in the control group showed fibrosis of the tunica albuginea and protein expression of TGF-beta1 and TGF-beta2. This patient had undergone surgery for the revision of his prosthesis twice. Five patients from the control group showed normal histological patterns of the tunica albuginea and no protein expression for TGF-beta1, TGF-beta2 and TGF-beta3. CONCLUSIONS: TGF-beta1 protein expression is significantly associated with Peyronie's disease, which may provide a new insight and the potential for the prevention and treatment of this disease.
Humans↗
Ultrasound evaluation of the penis for assessment of impotence.
Image directed Doppler ultrasonography of the cavernous arteries provides functional, quantifiable assessment of penile arterial flow during a pharmacological erection. In this respect, this modality is superior to arteriography as a means of evaluating arteriogenic impotence. Peak flow velocity, arterial dilatation, and vessel pulsation are the most reliable ultrasonic indicators of arterial health. Aberrant arterial anatomy should be noted as this may contribute significantly to total penile blood flow. A thorough understanding of erectile physiology and anatomy is necessary to properly perform and interpret Doppler ultrasound results.
Humans↗
A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil.
OBJECTIVES: Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder. METHODS: This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration. RESULTS: Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study. CONCLUSIONS: Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction.
Adult↗
Intracavernous injection of linsidomine chlorhydrate in monkeys: lack of toxic effect with long-term use.
OBJECTIVE: We sought to investigate whether linsidomine chlorhydrate (SIN1, the active metabolite of molsidomine and a nitric oxide donor) has a toxic effect when used chronically for the treatment of impotence. METHODS: We gave 50 intracavernous injection of 1.5 mg SIN1 over 25 weeks to each of 5 monkeys. RESULTS: Four monkeys consistently responded with erections of sufficient rigidity and duration (mean 47.5 +/- 3.3 min), and none of the five evidenced histopathologic changes of the cavernous tissue. CONCLUSION: SIN1 appears to be a safe option for the pharmacotherapy of erectile dysfunction.
Animals↗
Veno-occlusive dysfunction of corpora cavernosa: comparison of diagnostic methods.
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Humans↗
Complications of penile lengthening and augmentation seen at 1 referral center.
PURPOSE: Complications of the recent cosmetic technique of penile lengthening and girth enhancement are reviewed. MATERIALS AND METHODS: During a 16-month period 12 men presented with complications of penile augmentation performed elsewhere. All 12 patients had undergone release of the suspensory ligament and 10 had received autologous fat injection. RESULTS: The chief complaint was poor cosmetic appearance (irregular residual fat nodules in 7 men, skin deformity and scarring in 4 and scrotalization in 4). Reoperation was necessary in 6 patients, wound complications occurred in 6 and sexual dysfunction was reported by 4. Only 1 patient reported a subjective increase in penile length. CONCLUSIONS: Although a verifiable complication rate may never be available, the morbidity of elective penile lengthening and girth enhancement is noteworthy. These cosmetic techniques should be regarded as experimental.
Adult↗