Biomedical subjects
T F Lue
Publications and source records attributed to T F Lue.
Veno-occlusive dysfunction of corpora cavernosa: comparison of diagnostic methods.
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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.
Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation.
Prazosin (an alpha-1-adrenergic blocker) and cromakalim (potassium channel opener), given alone, induced significant fatigue of the urethral sphincter at a concentration of 10(-4) M; both drugs combined achieved a significant sphincteric fatigue at a concentration of 10(-5) M each. To 10(-4) M hexamethonium (ganglionic smooth muscle blocker) and 10(-4) M decamethonium (nicotinic blocker of striated muscle) the striated urethral sphincter responded like striated muscle with no detectable function of its smooth muscle component. Therefore, the striated component seems to play a dominant role in sphincteric function. With calcium depletion or in the presence of a calcium channel blocker (10(-4) M nifedipine) the urethral sphincter showed a relative enhancement of response to electrical field stimulation when compared with smooth and skeletal muscle, whose responses were both significantly reduced. This phenomenon could not be explained with calcium-dependent, inhibitory, nitric oxide-releasing nerves, as the NO-synthase blocker N-nitro-L-arginine (10(-5) M to 5 x 10(-5) M) failed to induce the enhancement of sphincter contraction during electrostimulation found with calcium depletion. Still, NO-releasing nerves might play a role in sphincteric relaxation because sodium nitroprusside (10(-5) M) induced a significant relaxation of the urethral sphincter precontracted with 80 mM potassium. The potential to weaken sphincteric closure with drugs, exemplified by the results obtained in response to prazosin and cromakalim, would represent a therapeutic advance in the patient with neurogenic bladder dysfunction.
Intraoperative electrostimulation of the cavernous nerve: technique, results and limitations.
PURPOSE: We studied the feasibility of inducing penile erection intraoperatively by stimulation of the cavernous nerves. MATERIALS AND METHODS: In 16 men undergoing retropubic radical prostatectomy and 6 undergoing penile surgery for venous leakage electrostimulation was applied to both sides of the prostatic apex (prostatectomy group) or the hilum of the penis (venous surgery group). RESULTS: Electrostimulation produced visible erection in 8 of the 16 prostatectomy patients and an increase in intracavernous pressure in 5 of the 6 venous surgery patients. CONCLUSIONS: Electrostimulation of the cavernous nerves intraoperatively to produce penile erection is feasible. However, the technique must be further refined to be clinically useful, that is to localize the neurovascular bundle in men undergoing prostatectomy.
Radiation-induced decrease in nitric oxide synthase--containing nerves in the rat penis.
PURPOSE: Evaluate effect of prostatic irradiation on erectile function. MATERIALS AND METHODS: Forty-seven male adult rats were divided into three groups according to a single radiation dose to the prostate: control (no irradiation) (n = 15), 1,000 cGy (n = 15), and 2,000 cGy (n = 17). Five months after irradiation, rats underwent evaluation of penile vascularity and of erectile response to central and peripheral stimulation. After the study a proximal-shaft penile segment was obtained for staining. RESULTS: Histologic evaluation demonstrated that, with increasing radiation, the number of nitric oxide synthase-containing nerve fibers per penile segment decreased significantly: control, 225.6 +/- 9.7; 1,000 cGy, 156.3 +/- 12.0; 2,000 cGy, 85.8 +/- 10.1 (standard error of the mean). Maximal intracavernous pressure induced with electrostimulation decreased significantly with increasing radiation dose. After injection of papaverine, maximal intracavernous pressure was significantly decreased in only the 2,000-cGy group. CONCLUSION: A dose of 2,000 cGy over the prostatic bed induces erectile dysfunction by causing defects in the vascular supply of the erectile tissue and in the nerves and smooth muscle.
Regeneration of nitric oxide synthase-containing nerves after cavernous nerve neurotomy in the rat.
In patients who recover erectile function after radical prostatectomy (with preservation of at least 1 neurovascular bundle), a recovery time of 6 to 18 months is not uncommon. As this is also the usual time required for regeneration of spinal nerves, we believe that regeneration of cavernous nerves, partially damaged inadvertently, may be responsible. In a rat model, we examined the long-term effect of unilateral and bilateral cavernous nerve transection on the nonadrenergic/noncholinergic (NANC) nervous system and erectile function. In 31 rats, nitric oxide synthase (NOS), the enzyme that catalyzes nitric oxide production, was identified in penile nerve fibers from a mid-shaft segment with nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and antibody to neuronal NOS. Animals were divided into three groups: 5 rats underwent pelvic exploration without transection of cavernous nerves (sham group); 13 rats underwent unilateral neurotomy of a 5-mm. segment of the cavernous nerve; and 13 rats underwent bilateral neurotomy. After bilateral ablation, the NOS-positive nerve fibers were significantly decreased at 3 weeks and remained so at 6 months; no erectile response could be elicited by pelvic nerve stimulation. After unilateral ablation, the NOS-positive nerve fibers were similarly decreased on the side of the neurotomy at 3 weeks, but by 6 months the number had increased significantly and approximated the level on the contralateral side. Furthermore, electrostimulation of the intact side induced a greater intracavernous pressure response at 6 months than at 3 weeks (N.B. the rat has an incomplete septum). Fibers positive for NOS were also identified in the dorsal nerve. The staining pattern diminished as rapidly and significantly on the side of neurotomy as in tissue from the corpus cavernosum. However, regeneration was not seen. To our knowledge, this is the first demonstration of regeneration of NOS-containing nerves after cavernous nerve neurotomy. Our findings support the reports by others that unilateral nerve-sparing is sufficient to preserve erectile function.
The effect of intracavernous injection of potassium channel openers in monkeys and dogs.
Cavernous smooth muscle relaxation is effected through a complex biochemical pathway; therefore, a defect in any step of this pathway may result in erectile dysfunction. Administration of pharmacologic agents which cause relaxation of the cavernous smooth muscle through a different mechanism may serve as an effective therapeutic alternative for impotent patients. To test this hypothesis two potassium channel openers, pinacidil and cromakalim, were used to initiate and maintain cavernous smooth muscle relaxation. The drugs were given as intracavernous injections in two animal models. In 10 dogs pinacidil and cromakalim produced full erection. With pinacidil (10(-2) M), the mean intracavernous pressure increased from a baseline pressure of 32.6 +/- 3.43 cm H2O to a peak intracavernous pressure of 131.8 +/- 12.01 cm H2O, and remained elevated for a period of 17.8 +/- 9.4 min. With cromakalim (10(-2) M) intracavernous pressure rose from a baseline pressure of 32 +/- 2.55 cm H2O to a peak intracavernous pressure of 140 +/- 3.39 cm H2O, for a period of 19.4 +/- 0.89 min. Additionally, in 5 primates injected with cromakalim (10(-2) M) intracavernous pressure rose from 24 +/- 3.81 to 131.2 +/- 7.56 cm H2O, for 27.0 +/- 4.79 min. It is concluded that both pinacidil and cromakalim can initiate and maintain erection in dogs and that cromakalim produces a similar erectile response in monkeys. Further study of the local and systemic effects of chronic injection is needed to determine whether this class of pharmacologic agents can provide therapy for impotent patients.
Sodium nitroprusside: physiologic effects as a nitric oxide donor in three species.
Recent in vitro and in vivo studies have suggested that nitric oxide may be the neurotransmitter responsible for cavernous smooth muscle relaxation and penile erection. Sodium nitroprusside, after combining with different kinds of thiols in the cellular cytoplasm, can effect nitric oxide release. We undertook this study to determine the physiologic response to sodium nitroprusside injection when used to induce and maintain penile erection in three species. Sodium nitroprusside was injected in increasing concentrations into the cavernous tissue of rats, dogs and monkeys. Dosages injected were 10(-4) M, 10(-3) M and 10(-2) M in 10 rats; 10(-4) and 10(-3) M in five dogs and five monkeys. The volume of drug injected was 0.05 ml for the rats and 0.5 ml for dogs and monkeys. The results show a dose-dependent erectile response to sodium nitroprusside injection (mean intracavernous pressure increase of 102.4 cm H2O in dogs, and 98.4 cm H2O in monkeys after injection of 10(-3) M nitroprusside). However, only a slight increase in intracavernous pressure (mean increase 28.4 cm H2O after injection of 10(-2) M of sodium nitroprusside) was noted in rats. The drop in blood pressure was > 15 mmHg in dogs and monkeys, while in rats it varied according to the dose studied. Sodium nitroprusside induced excellent erections in dogs and monkeys with minimal alteration in blood pressure. However, administration in rats resulted in hypotension. Nitroprusside may not be an acceptable nitric oxide donor for the treatment of male erectile dysfunction.
Duplex ultrasonography after prostaglandin E1 injection of the clitoris in a case of hyperreactio luteinalis.
We report an unusual case of persistent postpartum clitorimegaly due to ovarian hyperreactio luteinalis. Duplex ultrasonography of the clitoris after intracorporeal injection of prostaglandin E1 revealed marked clitoral erection and increased arterial flow, as in the penis.
Intracellular mechanism of penile erection in monkeys.
To elucidate the sequence of events between the release of neurotransmitters and cavernous smooth muscle relaxation in erection, we studied the role of the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) systems. In a well-established simian model, the effects of specific agonists and antagonists of the intracellular sequence for smooth muscle relaxation and potassium channel openers on the intracavernous pressure were examined. Sodium nitroprusside (10(-3) M), a nitric oxide releaser and thus a stimulant of the cGMP system, caused an increase in the intracavernous pressure from 82 to 115 cm H2O for 7 to 19 min and penile diameter from 24.8 +/- 2.28 to 43 +/- 4.87 mm. When nitroprusside was injected after methylene blue (10(-3) M), a specific antagonist of the enzyme guanylate cyclase, intracavernous pressure rise decreased significantly, but cromakalin, a potassium channel opener, provoked excellent increases after the block. A smaller dose of sodium nitroprusside (10(-4) M) caused an increase in intracavernous pressure from 35 to 85 cm H2O for 7 to 11.5 min. When nitroprusside was injected after zaprinast, a phosphodiesterase inhibitor, the increase in pressure ranged from 80 to 116 cm H2O for 15 to 30 min. Prostaglandin E1, an activator of the cAMP system, caused an increase in the intracavernous pressure of 20-80 cm H2O for 5 to 10 min, and an increase in penile diameter from 25 +/- 2.22 to 35 +/- 3.48 mm. The erectile response to PGE1, but not to cromakalin, was nearly abolished by ethylmaleimide, an adenylate cyclase blocker. The response to nitroprusside was significantly greater (P < 0.05) than to PGE1. Both systems, cAMP and cGMP, may be involved in cavernous smooth muscle relaxation, and cGMP is probably the predominant intracellular second messenger in penile erection in monkeys. Stimulants of the cGMP system, such as nitric oxide releasers, could represent a more physiological and effective approach in the treatment of erectile dysfunction.
Improved hemodynamic response after long-term intracavernous injection for impotence.
OBJECTIVE: To investigate the phenomenon of spontaneous erections in patients on long-term intracavernous injection therapy. METHODS: We undertook an objective assessment of the penile circulation of 35 patients; 21 used prostaglandin E1 (PGE1) alone and 14 used a combination of papaverine, phentolamine, and PGE1. All underwent duplex ultrasonography before initiation of home self-injection and again after a mean of thirty-one months of treatment (most patients performed injections once or twice a week). RESULTS: The diameter of the cavernosal arteries did not change significantly after treatment. However, the mean peak flow velocity increased highly significantly (P < 0.001): 17.9 cm/second in the right cavernous artery and 21.2 cm/second on the left before treatment; 24 cm/second on the right and 29 cm/second on the left after treatment. More than one third (13 of 35 patients [35%]) achieved functional erection without injection at least some of the time, giving clinical support to the sonographic findings. CONCLUSIONS: We suggest that the combination of vasodilatory drugs and sexual stimulation may act to improve sinusoidal and penile arteriolar smooth muscle function.
Erectile dysfunction associated with cavernous and neurological disorders.
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Anatomy and strength of the tunica albuginea: its relevance to penile prosthesis extrusion.
In 7 male cadavers the anatomical structure, thickness and tensile strength of the tunica albuginea of the penis, measured at specific locations, were determined. The tunica is composed of inner circular and outer longitudinal layers made up of collagen bundles. The outer layer appears to determine, to a large extent, the variation in thickness and strength of the tunica. The ventral groove (found between the 5 and 7 o'clock positions), which houses the corpus spongiosum, lacks outer bundles and appears vulnerable to perforation. The thickness of the tunica measured at the 7, 9 and 11 o'clock positions was 0.8 +/- 0.1 mm, 1.2 +/- 0.2 mm and 2.2 +/- 0.4 mm, respectively. Differences in the thickness of the tunica at specific locations were statistically significant (all p < or = 0.018). Symmetrical measurements were nearly identical in a mirror image arrangement (3, 5 and 1 at the 9, 7 and 11 o'clock positions, respectively). The stress on the tunica at penetration (breaking point pressure) measured at the 7, 9 and 11 o'clock positions was 1.6 +/- 0.2 x 10(7) N/m.2, 3.0 +/- 0.3 x 10(7) N/m2 and 4.5 +/- 0.5 x 10(7) N/m.2, respectively. The strength and thickness of the tunica correlated in a statistically significant manner with location (r = 0.911 and p = 0.0001). The most vulnerable area is on the ventral aspect (which lacks the longitudinally directed outer layer bundles), where most prostheses tend to extrude. This finding supports our belief that prosthesis extrusion often has an anatomical basis and is not merely a phenomenon caused by infection or compression.
Is colchicine effective in Peyronie's disease? A pilot study.
OBJECTIVES: The treatment of Peyronie's disease with oral or topical agents has not been entirely satisfactory. In this pilot study, we hypothesized that colchicine, known to induce collagenase activity and decrease collagen synthesis, might be an ideal agent in the treatment of Peyronie's disease. METHODS: Colchicine was administered orally for 3 to 5 months to a group of 24 previously untreated patients with Peyronie's disease. RESULTS: Peyronie's plaque decreased or disappeared in 12 of the 24 patients, 7 of 9 patients with painful erections reported significant relief, and penile curvature was improved in 7 of 19 cases. Erectile status, narrowing of the penis, and accompanying Dupuytren's contracture did not change in any of the cases. CONCLUSIONS: Although this pilot study shows some promising results of the use of colchicine in the treatment of Peyronie's disease, the ultimate usefulness of this agent will be determined only by a prospective double-blind clinical study.
Laparoscopically implantable nerve-stimulating electrode (LINSE): application to the cavernous nerve in acute and chronic canine models.
Using a new laparoscopic procedure, we investigated stimulation of the cavernous nerves to achieve erection in a canine model. The technique was developed during acute experiments in four dogs, following which, chronic studies (4- to 6-weeks survival after surgery) were undertaken in three dogs. A monopolar cuff electrode was inserted laparoscopically by a transperitoneal approach and placed around the cavernous nerve. The leads were brought out to the subcutaneous space, where they were attached to stimulation receivers that could be activated by an external radiofrequency transmitter. An intracavernous pressure elevation indicative of successful stimulation was obtained acutely in five of eight cavernous nerves in the four acute-study dogs and in four of six nerves in the three chronic-study dogs. The implanted equipment associated with four of six cavernous nerves failed mechanically in the chronic-study animals, such that only two receiver-electrode sites were intact at the time of sacrifice 4 to 6 weeks later. Transmitter-driven stimulation of one of these two sets produced an intracavernous pressure rise above 100 cm H2O. We present this technique as part of the continuing evolution of laparoscopy as both a research and a clinical tool. The present use of the laparoscopically implantable nerve-stimulating electrode is a new animal research tool and a potential first step in the human application of the technology.
The distribution of elastic fibrous elements within the human penis.
OBJECTIVE: To determine the distribution of elastic fibres in the tunica albuginea and the erectile tissue of the penis. MATERIALS AND METHODS: Samples of tunica albuginea or penile erectile tissue were taken from seven cadavers and five patients undergoing surgery. Light and electron microscopy were performed. RESULTS: There were two anatomical regions in which elastic fibres were seen rarely: the proximal crus and the distal tunica. In the rest of the corpora cavernosa where the tunica was more compliant, the elastic fibres were in relative abundance. In the corpus spongiosum, abundant irregularly oriented elastic fibres were present; the densest elastic network was found in the glans penis and was composed of coarse elastic fibres. A perisinusoidal fibroelastic shell was seen in the glans, which was probably an extension of Buck's fascia. The elastic components within the sinusoids (cavernosal, spongiosal, and glanular) were similar but finer than the elastic lamellae in the penile arterial wall. CONCLUSION: The elastic fibres were unevenly distributed, often forming an irregular network on which the collagen component rested. Elastic fibres were more abundant in the corpus spongiosum, around the blood vessels and surrounding the sinusoid of the corpus cavernosum.