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The adrenergic, cholinergic and NANC nerve-mediated contractions of the female rabbit bladder neck and proximal, medial and distal urethra.

1. The nerve-mediated contraction of the female rabbit bladder neck and different portions of the urethra (proximal, medial and distal) was studied in vitro by electrical stimulation (50 V, 30 Hz, 0.05 ms width, trains of 5 s every 5 min) by use of a superfusion system. 2. The amplitude (Emax) and the duration (Dmax) of the stimulated contraction were studied in the four tissues. The Emax value was significantly higher in distal urethra (2.07+/-0.15 g) compared to the bladder neck (1.08+/-0.10 g), proximal urethra (0.73+/-0.07 g) and medial urethra (0.87+/-0.07 g). In contrast, the Dmax value appeared slightly but significantly lower (P<0.05) in distal urethra (68.5+/-2.3 s) than in bladder neck (76.7+/-6.0 s), proximal urethra (84.5+/-5.0 s) and medial urethra (81.3+/-3.5 s). 3. Cocaine (1 microM) significantly increased the basal Emax values in medial and distal urethra and the basal Dmax values in the four tissues. 4. Prazosin (1 microM) significantly reduced E max value in proximal, medial and distal urethra and Dmax value in bladder neck and proximal urethra. Atropine (1 microM) also significantly reduced Emax values in bladder neck and proximal urethra and reduced Dmax value in bladder neck, but not in other tissues. Yohimbine (0.1 microM) was devoid of effect in the four tissues. 5. The association of prazosin (1 microM) and atropine (1 microM) did not modify the Emax and the Dmax values of the electrically-induced contractions, except in proximal urethra and in bladder neck where an additive inhibitory effect (on Emax only) was observed compared to prazosin and atropine alone. 6. The residual contractile response after combined treatment with prazosin and atropine was significantly diminished by tetrodotoxin (TTX; 1 microM) but not completely abolished. These NANC contractions were insensitive to P2X-purinoceptor desensitization by continuous tissue perfusion with alpha,beta-methylene ATP (30 microM). 7. These results demonstrate that bladder neck and proximal urethra are mainly innervated by the parasympathetic nervous system, whereas medial and distal urethras are to a greater extent under the control of the sympathetic innervation. The residual responses, insensitive to prazosin and atropine, may indicate a NANC innervation in the four tissues. However, the nature of the NANC neurotransmitter remains to be identified.

Adrenergic alpha-Antagonists↗

Nitric oxide synthase in dog urethra: a histochemical and pharmacological analysis.

1. To examine the presence of nitric oxide synthase (NOS) activity in female dog urethra, pharmacological experiments were performed using electrical field stimulation (EFS), guanethidine, atropine, NG-nitro-L-arginine methyl ester and L-arginine, NOS immunohistochemistry using specific anti-NOS antibody, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining were also performed. 2. EFS caused frequency-dependent contractions in all urethral preparations, but in the presence of guanethidine and atropine, EFS caused significant relaxation in the proximal urethra and was without effect on the distal urethra. 3. In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, small contractions to EFS were re-established in the proximal urethra, but not in the distal urethra. NG-nitro-D-arginine methyl ester had no such effect. 4. In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, the addition of L-arginine, restored the EFS-elicited relaxant responses previously seen with guanethidine and atropine alone in the proximal urethra (at 30 Hz; 12.89 +/- 5.27% to -2.44 +/- 4.43%, mean +/- s.e., P < 0.05). D-Arginine had no such effect. 5. In the distal urethra, the addition of NG-nitro-L-arginine methyl ester and then L-arginine had no effect on responses to EFS in preparations treated with guanethidine and atropine. 6. Sodium nitroprusside caused relaxation in both the proximal and distal urethra. The relaxant responses per cm2 cross sectional area in the proximal and distal urethra were 1.23 +/- 0.29, and 2.02 +/- 0.54 g cm-2 cross sectional area (mean +/- s.e.), respectively: there was no significant difference between them. 7. Both NOS and NADPH diaphorase-positive neurones were present in dog urethra, the densities of both being higher in the proximal urethra than in the distal urethra. 8. These results show that female dog urethra possesses NOS nerves and that endogenous NO may play a role in relaxation in the proximal but not the distal urethra.

Adrenergic Agents↗

[The inherent liability to infection of various tissue for urethra reconstruction].

OBJECTIVE: Observing the long-term results of reconstructed urethra to reduce the postop infection rate of hypospadias. To explore the standard of selecting tissue for urethra reconstruction by comparing the different inherent liability to infection in use of different kinds of tissue for urethra reconstruction. METHODS: Neo-urethra inner wall and normal urethra were observed through urography and urethroscope. The tissue section of neo-urethra, normal urethra and tissue for urethra reconstruction were observed through light microscope, scanning electron microscope and transmission electron microscope. RESULTS: The structure and liability to infection of neo-urethra made of bladder mucosa, buccal mucosa or skin never changed after long time. Metaplasia never took place in neo-urethra. CONCLUSIONS: The structure and liability to infection of neo-urethra were the same as those of the congeneric tissue. Bladder or buccal mucosa is the best tissue for urethra reconstruction considering urethra microenvironment. Neo-urethra made of skin is more liable to infection by nature. The best opportunity of hypospadias operation should be before puberty.

Adolescent↗

Contractile responses to alpha1-adrenoceptor agonists in isolated human male and female urethra.

OBJECTIVE: To investigate the contractile responses mediated through alpha1-adrenoceptors in human urethra and to evaluate the effectiveness of NS-49 [(R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulphonanilide++ + hydrochloride], a novel alpha1-adrenoceptor agonist, against contraction of the human urethra. MATERIALS AND METHODS: The contractile responses were assessed in 10 male prostatic urethrae and six female urethrae. Antagonism was evaluated in the urethra using phenylephrine, a nonselective alpha1-adrenoceptor agonist, cumulatively applied > 20 min after applying 0.1 micromol/L prazosin or 0.1 micromol/L 5-methylurapidil, a selective alpha1A-adrenoceptor antagonist. Agonism was determined in both male and female urethrae to obtain the concentration-response curve for the agonist. RESULTS: Phenylephrine caused both male and female urethrae to contract, and showed high potency and efficacy. Prazosin antagonized these contractions with low affinity (apparent pKB of 8.30 in male urethrae). 5-Methylurapidil, also antagonized the contractions with low affinity (apparent pKB of 7.88 in male urethrae). Noradrenaline and phenylephrine caused both male and female urethrae to contract, with high potency and efficacy. A novel and selective alpha1A-and alpha1L-adrenoceptor agonist, NS-49, induced contractile responses with high potency and moderate efficacy, whereas methoxamine induced contractions with low potency and moderate efficacy. Norephedrine was a very weak contractile agonist. CONCLUSION: In the human urethra, phenylephrine-induced contractions were mediated through alpha1L-adrenoceptors and not through alpha1A-adrenoceptors. Contractions of the human urethra induced by NS-49 were also mediated mainly through alpha1L-adrenoceptors, with high potency and moderate efficacy. NS-49 may therefore be useful for the treatment of urinary stress incontinence, with minimal side-effects because it has subtype selectivity.

Adrenergic alpha-Agonists↗

[The surgical treatment of closed injuries and strictures of the urethra].

Under analysis were results of operative treatment of 291 patients aged from 7 to 76 years with traumas and strictures of the urethra at the period from 1970 to 1990. Totally 325 operations have been performed. The primary suture of the urethra was successfully used in 8 of 36 patients with trauma of the urethra. Tunneling of the urethra for its strictures which was widely used in the clinic up to 1980 gave 46.2% of recurrences during the first 3 months after operation. It required the surgical methods to be changed. During the recent 11 years 161 operative interventions have been performed: 103 (64.0%) resections of the urethra, 45 (28.0%) internal optical urethrotomies and transurethral resections (TUR) of scarry tissues, 7 (4.3%) epidermoplasties of the urethra and 6 (3.7%) tunnelings of the urethra. The amount of recurrences dropped up to 13.7%. The primary suture of the urethra is necessary for penetrating ruptures of the urethra if the patient's state allowed. Resection of the urethra must be the operation of choice in patients with strictures and obliteration of the urethra. The endoscopic methods of treatment (urethrotomy and TUR) are indicated for short strictures and scarry deformity of the posterior urethra after operations on the prostate. The epidermoplasty is expedient for lengthy strictures.

Adolescent↗

Staged pendulous-prostatic anastomotic urethroplasty followed by reconstruction of the anterior urethra: an effective treatment for long-segment bulbar and membranous urethral stricture.

OBJECTIVES: To describe a novel surgical technique for male long-segment urethral stricture after pelvic trauma using the intact and pedicled pendulous urethra to replace the bulbar and membranous urethra, followed by reconstruction of the anterior urethra. METHODS: Two patients with long-segment post-traumatic bulbar and membranous urethral strictures with short left pendulous urethras who had undergone several failed previous surgeries were treated with staged pendulous-prostatic anastomotic urethroplasty followed by reconstruction of the anterior urethra. This procedure was divided into three stages. First-stage surgery was mobilization of the anterior urethra down to the coronary sulcus and then rerouted to the prostatic urethra followed by pendulous-prostatic anastomotic urethroplasty with transposition of the penis to the perineum. Second-stage surgery was transecting the anterior urethra at the revascularised coronary sulcus 6 mo later, followed by straightening of the penis and urethroperineostomy. Third-stage surgery was reconstruction of the anterior urethra 6 mo later. RESULTS: Postoperatively, the two patients reported satisfactory voiding. For patient 1, retrograde urethrography showed that the urethra was patent, and that the mean maximal flow rate (MFR) was 18.4 ml/s with no postvoiding residual urine after the third-stage surgery and at 3-yr follow-up. For patient 2, a 22F urethral catheter could pass smoothly through the urethra, and the MFR was 19.5 ml/s with no postvoiding residual urine at 2-yr follow-up. CONCLUSIONS: This procedure was an effective surgical option for men with complex long-segment post-traumatic bulbar and membranous urethral strictures, especially for those who had undergone failed previous surgical treatments.

Adult↗

Sphincteric musculature of female canine urethra in comparison to woman including 3D reconstruction.

The circular arranged sphincteric musculature of bladder neck of female dogs and women were studied histomorphologically. 3D reconstructions of the anatomy of the bladder neck improve the understanding of construction principles of the musculature of the lower urinary tract and help to compare both species. Our own investigations based on 12 adult female canine and 15 female human autopsy preparations. The special feature of our study was the extensive en bloc preparation of all the organs of the lower urinary tract and surrounding organs. The organ blocks were reprocessed in complete serial sections from the bladder outlet down to the bulb of vestibuli. Despite different detailed construction, in both species the striated sphincter musculature of the urethra is an independent morphological unit. There is no continuation of pelvic floor muscles to the urethra. In humans, the urethral sphincter consists of a smooth muscular part (m. sphincter urethrae glaber) and a striated part (m. sphincter urethrae transversostriatus). In the female dog, striated muscle fibres encircle the urethra in the middle third exclusively. In the distal third of the urethra, it encircles the urethra and the vagina. In the female dog, the lamellae of detrusor continue directly to the urethra. Throughout the cranial and middle third of the urethra, smooth muscle cell bundles form a homogenous compact sphincteric muscle originating from the middle circular layer of detrusor. In that way, no true bladder neck sphincter according to the m. sphincter vesicae in women exists in dogs. According to the smooth muscular part of the m. sphincter urethrae in women, for this musculature the term m. sphincter urethrae glaber is suggested. Despite a superficial resemblance, this study revealed a considerable difference of circular sphincteric muscle components between female dog and woman suggesting that functional studies in respect to urinary continence obtained in dogs cannot be attributed without qualification to humans.

Animals↗

[Epidermoid carcinoma of the male urethra. Our experience in 5 cases].

OBJECTIVES: Epidermoid carcinoma of the male urethra is a rare tumor that accounts for 70% of primary neoplasms of the urethra. The present study reviews our experience of 5 years in the diagnosis and treatment of this tumor type. METHODS: From 1991 to 1994, we diagnosed and treated 5 male patients with epidermoid carcinoma of the urethra; mean age 58 years (range 43 to 76 years). The tumor was localized in the bulbomembranous urethra in 3 cases (60%) and in the penile urethra in the remaining 2 cases (40%). All patients presented with urethral stricture and complications following treatment (internal urethrotomy and dilatation). The tumors of the posterior urethra were Levine stage C and D at the time of diagnosis, while those of the anterior urethra were Levine stage B and C. RESULTS: Two patients with tumor in the posterior urethra underwent radical cystoprostatourethrectomy and bilateral inguinal lymphadenectomy, whereas the remaining patients underwent emasculation or urethrectomy. Patient survival has ranged from 1 to 2.5 years at the present time. One patient with tumor in the bulbous urethra has died despite postoperative radio and chemotherapy, the outcome has been poor in another patient with tumor in the posterior urethra and no progression has been observed in the remaining patients at present. CONCLUSIONS: a) Urethral stricture with a torpid course and localized complications (fistula, periurethral abscess, etc.) following standard therapy have been the only widely accepted etiologic factors that we have observed in our patients; b) This tumor type must be suspected since treatment by radical surgery will have some likelihood of success if the carcinoma is diagnosed early, while it is still localized; c) To date, radio and chemotherapy have achieved poor results, the former being effective in tumors of the penile urethra only when given at a high dose; d) Patients generally die from localized complications, tumor recurrence, or lymph node metastasis (sepsis, hemorrhage, etc.).

Adult↗

Proximity of prostate cancer to the urethra: implications for minimally invasive ablative therapies.

OBJECTIVES: The delivery of thermotherapy, cryotherapy, and interstitial radiation with minimal morbidity is dependent on the preservation of the prostatic urethra. Our aim was to determine the distribution of the distance between the urethra and the nearest prostate cancer. METHODS: We determined the location of cancer in 350 prostate cancers treated by radical prostatectomy between 1991 and 1993. Each pathologic specimen was totally embedded, serially sectioned, and whole mounted. For each prostate, the radial distance from the urethra to the nearest cancer was determined (urethral-cancer distance). The urethra-cancer distance was correlated with the clinical, pathologic, and laboratory factors. Univariate and multivariate associations with progression-free survival were determined. RESULTS: The mean follow-up was 6.1 years. Ninety-three patients had biochemical, local, or systemic cancer recurrence. The mean +/- SD distance from the urethra to the nearest cancer was 3 +/- 3 mm (range 0 to 18). In 58 patients (17%), the cancer touched the urethra. A decreasing urethra-cancer distance was associated with increasing rates of cancer recurrence (P = 0.009). The urethra-cancer distance correlated with each of the following preoperative factors: preoperative prostate-specific antigen (r = -0. 22, P <0.001), Gleason score in biopsy specimen (r = -0.13, P = 0.02), and percentage of Gleason score 4 or 5 in the biopsy specimen (r = -0.17, P = 0.008). CONCLUSIONS: The distance between the urethra and the nearest cancer was associated with prostate cancer outcome. Many patients have cancer close to the urethra. This finding may have implications for nonsurgical ablative therapies for prostate cancer.

Aged↗

Dosimetric consequences of using a surrogate urethra to estimate urethral dose after brachytherapy for prostate cancer.

PURPOSE: To assess the accuracy and dosimetric consequences of defining a surrogate urethra at the geometric center of the prostate in postimplant CT scans. METHODS AND MATERIALS: Eighty postimplant CT scans were obtained with a Foley catheter in place at Day 0 and at 1 month for 40 patients who had undergone (125)I prostate brachytherapy. The percentage of urethral volume receiving at least 275% of the prescribed dose (uV(275)), uV(250), uV(200), uV(150), maximal dose received by 90% of urethral volume (uD(90)), uD(70), uD(30), and uD(1) were measured for the Foley catheter and surrogate urethra. The distance between the Foley catheter and surrogate urethra was measured at the base, middle, and apex of the prostate. RESULTS: A statistically significant difference was found in all the above-listed dosimetric parameters between the Foley catheter and surrogate urethra at Day 0 (p <or= 0.001). At 1 month, the uD(90), uD(70), and uD(1) remained significantly different between the Foley catheter and surrogate urethra (p <or= 0.05). The difference in the uV(275) (p = 0.055) and uV(150) (p = 0.059) between the Foley catheter and surrogate urethra showed a trend toward statistical significance at 1 month. The uV(250), uV(200), and uD(30) were greater for the surrogate urethra than for the Foley catheter at 1 month, but were not significantly different statistically. The mean distance between the Foley catheter and the surrogate urethra was greatest at the base (1.2 cm) in the vertical axis at Day 0 and decreased substantially to 0.87 cm at 1 month (p = 0.0004). CONCLUSION: Using a surrogate urethra at the geometric center of the prostate may significantly overestimate the urethral dose at Day 0 and certain dosimetric parameters at 1 month. An alternative position for a surrogate urethra accounting for the difference in the location of the Foley catheter near the base of the prostate at Day 0 and 1 month could be considered in future studies.

Brachytherapy↗

Mechanical properties and innervation of the smooth muscle layers of the urethra of greyhounds.

OBJECTIVE: To investigate the properties of the smooth muscle layers in the urethral wall of male and female greyhounds, and to consider their roles in continence and micturition. MATERIALS AND METHODS: The distribution and innervation of the smooth muscle layers of the prostate capsule and membranous urethra of male greyhounds were assessed. Strips of smooth muscle from these regions were used to determine the neuropharmacological properties by assessing the excitatory and inhibitory responses to nerve stimulation, and the effects of blocking agents. These were compared with strips from the proximal urethra and from the female urethra. RESULTS: The smooth muscle of the membranous urethra comprised 9% of the wall and received its innervation exclusively in branches from the pelvic plexus. The cholinergic innervation in the male produced 80% of the total contractile response in the longitudinal membranous urethra, 50% in the prostate capsule and 13% in the circular muscle of the proximal urethra. In the female all areas had poor contractile responses. Inhibitory fibres produced relaxation in all parts of male and female urethrae with the major effect caused by nitric oxide. Adrenergic nerves contributed to both residual excitation (alpha receptors) and inhibition (beta receptors). CONCLUSIONS: The longitudinal smooth muscle of the male membranous urethra probably shortens the urethra during micturition, through the activity of cholinergic nerves, whereas the circular smooth muscle of the proximal urethra, under adrenergic control, may be contracted during continence and ejaculation. In the female, the smooth muscle plays a minor role.

Animals↗

Regional variations in the neural control of the female pig urethra.

OBJECTIVE: To establish the regional variation, if any, in the distribution of sympathetic and parasympathetic nerves within the urethra of the female pig and to correlate this with regional variations in the response of the smooth muscle to sympathetic and parasympathetic nerve stimulation and the application of phenylephrine and carbachol. MATERIALS AND METHODS: Female pig urethras were obtained from a local abattoir. Serial sections were cut from the proximal, middle and distal regions of the urethra and stained using tyrosine hydroxylase immunohistochemistry and acetylcholinesterase histochemistry for the demonstration of sympathetic and parasympathetic nerves, respectively. Strips of smooth muscle dissected from the same regions of the urethra were also mounted in organ baths to record isometric tension. Responses to nerve stimulation and alpha-adrenoceptor and muscarinic receptor activation were recorded. RESULTS: Tyrosine hydroxylase- and acetylcholinesterase-positive staining was demonstrated throughout the urethra. However, the density of sympathetic innervation was greatest in those strips dissected from the distal urethra, whilst the parasympathetic innervation was uniform throughout the length. Strips of urethral smooth muscle mounted for tension recording generated spontaneous tone. Smooth muscle dissected from the proximal urethra developed the greatest tone, whilst strips from the distal urethra generated significantly less. Responses to nerve stimulation were complex; sympathetic nerve stimulation elicited frequency-dependent contraction in all strips, but the response was most pronounced in the distal strips where tone was low. Conversely, parasympathetic nerve stimulation elicited the greatest contractile response from the proximal urethral strips. In all strips, but in particular those dissected from the proximal urethra, the contractile responses were attenuated by the occurrence of a non-adrenergic, non-cholinergic (NANC), non-nitrergic relaxation as stimulation frequency was increased. Phenylephrine and carbachol also produced concentration-dependent contraction of all urethral strips. Like the nerve-mediated responses, contraction in response to phenylephrine was most pronounced in the distal urethral strips whilst the response to carbachol was most pronounced in the proximal urethral strips. CONCLUSIONS: The results demonstrated a regional variation in the distribution of sympathetic nerves within the urethra of the female pig which would appear to be mirrored not only in the responsiveness of the tissue to sympathetic nerve stimulation but also in its response to alpha-adrenoceptor stimulation. In contrast, although no regional variation in the distribution of parasympathetic nerves could be demonstrated histologically, responses to nerve stimulation and the muscarinic agonist carbachol were most pronounced in the proximal urethral strips.

Acetylcholinesterase↗

[A case of male duplicated urethra in recurrent urinary tract infection].

A dorsal incomplete duplicated urethra was found in a 13-year-old male, who had noticed occasional urinary incontinence and recurrent urinary tract infection. The accessory urethra lay dorsal from the glans to bladder neck in parallel with the normal ventral urethra. The external orifice of the accessory urethra was also dorsal to the normal urethral orifice in the glans. Voiding cystourethrogram demonstrated double stream but the patient did not notice it because of pseudophimosis. Retrograde urethrogram showed the accessory urethra which arised from the dorsal surface of the prostatic urethra with a parallel normal urethra. The pendular portion of the accessory urethra was surgically removed, the glans portion of the urethra and posterior urethra were cautilized with electrocoagulation for the purpose of preservation of urinary continence. The patient was postoperatively free from urinary tract infection and urinary incontinence.

Adolescent↗