Experimental model of pudendal nerve innervation of a skeletal muscle neosphincter for faecal incontinence

BACKGROUND: Faecal incontinence is difficult to treat. A variety of reconstructive procedures has been described, but none is entirely satisfactory. This study evaluated the feasibility of cross-innervating a skeletal muscle neosphincter with the pudendal nerve in a canine model. METHODS: Thirty dogs were rendered surgically incontinent (the pudendal nerve was cut and the external sphincter was partially excised). A neosphincter was then created using the semitendinosus muscle. In ten dogs pudendal nerve transposition (PNT) to the nerve to the semitendinosus muscle was performed. Ten dogs were given a dynamic neosphincter by inserting a pulse generator at 6 weeks. The remaining ten dogs served as controls with passive semitendinosus wraps. Anal manometry was performed before operation and monthly for 5 months. Muscle biopsies, performed at the initial operation and at 5 months, were stained for slow- and fast-twitch fibres, and were examined histologically. RESULTS: At 1 month, mean sphincter function was 32 per cent of the preoperative value in the control animals, 34 per cent in the PNT group and 27 per cent in the electrostimulation group; all dogs were incontinent. At 5 months the mean recovery of sphincter function was 42 per cent of the preoperative value in controls, 100 per cent in dogs with PNT (P < 0.001) and 63 per cent in dogs having electrostimulation (stimulator on) (P = 0.02). Six dogs with PNT had squeeze pressures equal to or greater than preoperative levels. At 5 months the ratio of slow to fast fibres was significantly greater in all dogs (control P = 0.01, PNT P < 0.005, electrostimulation P < 0.001). CONCLUSION: Use of the pudendal nerve to innervate a canine skeletal muscle anal wrap produced a functional anal sphincter that was superior to electrically stimulated and passive wraps.     

The importance of sodium pyruvate in assessing damage produced by hydrogen peroxide

OBJECTIVES: The external striated urethral sphincter (rhabdosphincter) is a tubular muscle sleeve that extends from the prostato-membranous urethra and perineal membrane to the bladder neck. The male rhabdosphincter neuroanatomy remains unclear, and a better understanding of its innervation may provide insight into potential modifications of radical pelvic surgery to improve urinary continence. METHODS: Fresh cadaveric dissections of 12 male hemipelves were undertaken to investigate the neuroanatomy of the urinary rhabdosphincter. RESULTS: Neuroanatomic courses of the nerve supply to the rhabdosphincter revealed that, in the perineum, the perineal nerve (a terminal branch of the pudendal nerve) provided branches directly to the bulbospongiosus muscle and the urinary rhabdosphincter. In the pelvis, the course of the pelvic nerve was as follows: (1) arising from the inferior hypogastric plexus, it had a weblike course beneath the muscle fascia of the levator ani muscle; (2) traveling posterolateral to the rectum, it gave many branches that perforated into the lateral rectum; and (3) at the level of the prostatic apex, still beneath the levator ani muscle fascia (superior fascia), it sent multiple direct branches to the inferolateral aspect of urinary rhabdosphincter. The pudendal nerve traversed the pelvis in the pudendal canal, and, before leaving the pelvis to enter the perineum, it gave an intrapelvic branch that courses with the pelvic nerve to innervate the rhabdosphincter. CONCLUSIONS: Our understanding of the neuroanatomy of what may be the continence nerves has been improved by fresh cadaveric dissection. The rhabdosphincter receives nerve fibers from the pelvic nerve and dual innervation from an intrapelvic branch and a perineal branch of the pudendal nerve. Better understanding of these anatomic findings may have potential surgical significance with respect to improvement in postoperative urinary continence.     

Innervation of the striated muscle of the membranous urethra of the male dog

PURPOSE: To identify the functional innervation of the striated muscle layer of the post-prostatic urethra of male dogs. MATERIALS AND METHODS: Detailed anatomic dissection of the pelvic and pudendal nerves was carried out. The pressure and contractile responses to stimulation of these nerves were recorded in vivo and in vitro. RESULTS: Small branches of the pelvic nerve entered the membranous urethra but passed through the striated muscle to the inner smooth muscle layer. Stimulation of the nerve with 1 msec pulses at 10 Hz produced a slow contraction of the urethra which was unaffected by d-tubocurarine. Pudendal nerve branches entered the striated layer from the caudal end. Stimulation produced a rapid, visible contraction that was abolished by d-tubocurarine. Field stimulation of isolated strips of striated muscle resulted only in rapid, d-tubocurarine sensitive contractions. CONCLUSIONS: The striated muscle of the membranous urethra is innervated exclusively by the pudendal nerve.     

Plasma cell and sclerosing osteomyelitis. A follow-up of 21 patients

Ten consecutive patients with incapacitating fecal incontinence were treated with 'anal dynamic graciloplasty' (transposition of the gracilis muscle around the anal canal and implantation of intramuscular electrodes connected with an implanted pulse generator, 6 weeks later) to achieve continence. We measured the gracilis muscle diameter immediately after transposition and before implantation of the stimulation device. It was found that gracilis diameter decreased from 12 (5 days after transposition) to 8 mm, 6 weeks later (mean decrease: 4 mm (95% confidence interval 3.6), n = 10, P < 0.05). In addition, morphology demonstrated a decrease of both Type I and Type II muscle fiber diameter and an increase in endomysial collagen. Despite this decrease in muscle (and muscle fiber) diameter, electrical stimulation of the transposed gracilis muscle increased the pressure into the anal canal from 37 to 55 mmHg (mean increase: 17 mmHg (95% confidence interval 6.29), P < 0.05). Fecal continence was achieved in seven (70%) of these patients. Further analysis revealed no correlations between reduction of the gracilis muscle diameter before implantation of the stimulation device and clinical outcome in terms of achieved continence and/or anal canal pressures. MRI is an excellent method to demonstrate the shape of gracilis muscle after transposition. However, the size of transposed gracilis muscle is not associated with the functional outcome.     

GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function

Gamma-aminobutyric acid (GABA) antagonist (bicuculline methiodide, BIC; picrotoxin, PIC) or agonist (muscimol, MUS) microinjections were made into the dorsal motor nucleus of the vagus nerve (DMV), and effects on lower esophageal sphincter pressure (LESP), gastric motility, and gastric acid secretion were determined in chloralose-anesthetized cats. Right or left DMV sites were microinjected with BIC, PIC, MUS, or isotonic tonic saline (140 nl) through a glass micropipette having a tip diameter of 15-21 microns. Esophageal body, LESP, and gastric fundic pressures were measured manometrically. Circular smooth muscle contractions of the antrum and pylorus were recorded with strain-gauge force transducers. Gastric acid secretion was measured every 15 min through a gastric cannula and titrated to pH 7.0. DMV microinjection sites were verified histologically. Direct BIC microinjections (0.275 or 0.550 nmol) into the DMV primarily produced a decrease in LESP (71% of all sites tested), with mean LESP changing from 23.2 +/- 1.7 mmHg to 3.7 +/- 0.7 mmHg (p < 0.01). Tonic LESP increases and phasic LESP contractile activity occurred less frequently. BIC-induced LESP responses were abolished by vagotomy or by microinjections of MUS (0.5 to 10 nmol) into the DMV. Direct PIC microinjection (0.232 nmol) into the DMV produced a pattern of responses similar to those observed with BIC (which were also abolished by vagotomy or by MUS microinjections into the DMV). The antrum and pylorus were also responsive to DMV microinjections of both GABA antagonists. Microinjections of BIC or PIC into the DMV produced increases in gastric circular muscle activity that occurred less frequently than LESP effects, but also were eliminated by vagotomy. The high (0.550 nmol) dose of BIC increased gastric motility significantly more often than the low dose of BIC (p < 0.05). In addition, BIC (0.550 nmol) microinjections into the DMV increased gastric secretory volume (from 0.6 +/- 0.2 to 6.0 +/- 2.5 ml/15 min; p < 0.01) and total titratible acid (from 34.4 +/- 8.9 to 86.0 +/- 19.1 mEq/15 min; p < 0.01), and decreased gastric pH (from 4.63 +/- 0.44 to 3.50 +/- 0.49; p < 0.05). Vagotomy also eliminated the gastric secretory effects of DMV BIC. Direct microinjections of MUS into the DMV also blocked BIC- or PIC-induced changes in gastric motility and/or gastric acid secretion. Isotonic saline microinjected into the DMV did not increase basal or decrease stimulated gastric esophageal motility or gastric secretion. These data indicate that LESP, gastric motility, and gastric secretion are influenced by a tonic DMV inhibition mediated by GABAA receptor stimulation of the DMV. Because disinhibition of these receptors clearly activates the upper gut, future work should focus on identifying the nuclei providing this synaptic input to the DMV that might be involved in the functional regulation of upper gut motor and secretory function.     

TNM classification for urological cancer

The 5th edition of the new TNM classification for urological cancer has been published by UICC in 1997. Herein, the classification of 4 urological carcinomas (kidney, urinary bladder, renal pelvis and ureter, and urethra) is presented and discussed in comparison with the latest revisions in 1987 and 1992. In the 5th edition, the main revised points are as follows: As for kidney, the primary tumor cut off between T1 and T2 was changed from 2.5 cm to 7.0 cm, and the N classification was simplified as for urinary bladder, all muscle invasive tumors (T2 or T3a in the 1992 classification) are included in the T2 category, which is then subdivided into T2a and T2b; in the urethra, new T categories on transitional cell carcinoma of the prostate and prostatic urethra have been added, and the N classification is simplified; there is no change in the classification for the renal pelvis and ureter. According to these changes, a new system of stage grouping is proposed. There may still be widespread disagreement over the appropriateness of some of the changes introduced in the 5th edition of 1997. It is essential to continue efforts to improve the accuracy of determining the clinical extent of malignant tumors, and to work together in order to achieve our objectives for a unified system of TNM classification.     

A novel in vitro bladder pelvic nerve afferent model in the rat

OBJECTIVE: To develop an in vitro model to allow electrophysiological recordings from pelvic nerve afferents of the urinary bladder in the rat and to ascertain the stability and reproducibility of the model with time. MATERIALS AND METHODS: Six male Wistar rats (body weight approximately 100 g) were used in the study. The bladder (complete with accessory organs of prostate and seminal vesicles), urethra and penis, together with the attached pelvic nerve and L6/S1 nerve trunk, were removed intact and placed in a specially designed recording chamber containing oxygenated Krebs solution maintained at 30 degrees C. The bladder was catheterized urethrally and attached to a continuous-infusion pump and a pressure transducer. The L6/S1 nerve trunk was placed across a silicone-gel wall into a separate chamber containing liquid paraffin, in which multiunit recordings from pelvic nerve afferents originating from the bladder were made. The afferent nerve activities in response to repeated bladder distension with saline, at 0.04 mL/min for 8 min over 3 h, were compared using the paired t-test to assess the reproducibility of the model. Conduction velocity studies were also carried out to ascertain the proportion of C- and A delta-fibres in the multiunit recordings. RESULTS: Repeated bladder distension with saline over 3 h produced consistent and reproducible afferent nerve responses, signifying that the afferent nerves recorded in this study neither sensitize nor desensitize over time. This is an essential prerequisite when using this model to study the effects of pharmacological manipulation of the bladder on its afferent nerve response. Conduction velocity studies showed that approximately 30% of the afferent fibres recorded from were C-fibres with the remaining being A delta-fibres. CONCLUSIONS: An in vitro bladder pelvic nerve afferent model for the rat was developed successfully; it is stable and produces reproducible results with repeated bladder distension over at least 3 h.     

Adrenergic and Cholinergic Nerves of the Human Urethra and Urinary Bladder. A histochemical study

The occurrence and distribution of adrenergic and acetylcholine esterase (AChE) positive nerves in the human urethra and urinary bladder were studied histochemically with the fluorescence method of Falck and Hillarp, and the copper thiocholine method of Koelle and Friedenwald. Both types of nerves were mainly confined to the layers of smooth muscle cells in the walls of the organs. In all parts of the urethra, there was a scanty supply of adrenergic nerves. Few adrenergic nerves were also found in the urinary bladder, except in the trigone area, where they were abundant. AChE-positive nerves were uniformly and richly distributed in the urinary bladder. Throughout the urethra the distribution of AChE-positive nerve fibres was uniform, but the number was clearly less than in the urinary bladder. No intrmurally located adrenergic or AChE-Positive ganglion cells could be demonstrated.     

Neurovascular supply of the gracilis muscle: a study in the monkey and human

A comparison of the gross anatomy, extramuscular nerve branches, and intramuscular blood supply of the gracilis muscle showed similar patterns in both monkey and human. The number and pattern of distribution of the extramuscular terminal branches to the muscle were similar. The intramuscular neural pattern demonstrated with the Sihler's staining technique was also similar in both species. In vivo electrical stimulation studies in the monkey revealed that stimulating each extramuscular terminal nerve branch produced a distinct segmental contraction of the muscle. Independent contraction with force generation was observed when the monkey muscle was split into anterior and posterior segments and stimulated through each of the two subdivisions of the main nerve trunk to the muscle. Angiograms verified that circulation was preserved in these two segments.     

Water balance of Dermatophagoides pteronyssinus (Acari: Pyroglyphidae) maintained by brief daily spells of elevated air humidity

OBJECTIVES: To review the urological abnormalities in conjoined twins, a rare congenital abnormality arising from an incomplete separation of a pair of monozygotic twins, and who can be joined from the head to the pelvis with varying degrees of union. PATIENTS AND METHODS: The records and urological anomalies of conjoined twins presenting from 1985 to 1995 were reviewed retrospectively and the management and surgical reconstruction described. RESULTS: Seven of 11 sets of conjoined twins underwent surgical exploration. Complex urological problems occurred in all twins with omphalo-ischiopagus. The urological anomalies were: Set 1; both twins had one lateral crossed fused renal ectopia with uncrossed ureters draining into a single bladder with one urethra. They had one set of genitalia. Each twin received one crossed fused ectopic kidney, half the bladder and genitalia, with one retaining the urethra and one a vesicostomy. Set 2; these twins had four kidneys (two lateral and two central that were fused), four ureters (two of which crossed) and these drained into two sagittal bladders that emptied by one urethra associated with a single set of external genitalia containing three corpora cavernosa. At separation, the crossed ureters were re-routed, each received a bladder and the genitalia were split. Set 3; there were four kidneys with two crossed ureters draining into two collateral bladders, there was a partial duplication of the urethra and a single hypospadiac penis. After separation, each had kidneys draining into a bladder, one received the urethra and external genitalia, and one a urostomy. CONCLUSION: Complex urological problems occur in conjoined twins, although restricted to those with pelvic fusion (ischiopagus). Assessment and treatment needs to be individualised and overseen by a surgeon with experience in complex urology.     

Electrically stimulated colonic reservoir for total anorectal reconstruction

Total anorectal reconstruction after abdominoperineal excision of the rectum has failed to achieve perfect continence. Electrically stimulated reservoir evacuation in combination with an electrically stimulated gracilis neoanal sphincter might improve results. A J pouch was constructed in an isolated colonic loop of seven dogs. Bipolar square wave pulses were delivered via two intramural stainless steel electrode pairs at 10 Hz. Stimulation parameters were varied to achieve adequate contraction. Serosal strain gauges recorded spontaneous and stimulated pouch motility. Evacuation was quantified by a volume displacement technique and observed fluoroscopically. Recordings were performed for a median of 3 (range 1-11) months. At 10 Hz and 0.5 ms pulse width, stimulation was required for 2 min and at voltages of 15 V (n = 4), 18 V (n = 1) and 20 V (n = 2) to obtain a contraction of amplitude comparable to that of a spontaneous contraction. Suprathreshold stimulation invariably resulted in colonic pouch contraction. The mean(95 per cent confidence interval (c.i.)) stimulus-response latency was 25.5(1.9) s. The mean(95 per cent c.i.) intraluminal pressure generated during stimulation was 114.1(17.0) cmH2O and 64.6(12.0) cmH2O during spontaneous activity (P < 0.001). In conclusion, electrical stimulation via intramural electrodes produced contraction generating sufficient intraluminal pressure to effect evacuation of a canine colonic pouch. This has potential for incorporation with an electrically stimulated neoanal sphincter in total anorectal reconstruction to improve evacuation and continence.     

Distribution of doxorubicin in the bladder wall and regional lymph nodes after bladder submucosal injection of liposomal doxorubicin in the dog

PURPOSE: Liposome-encapsulated doxorubicin (Lip-Dox) has increased therapeutic efficacy and reduced toxicity compared to free doxorubicin (Dox). To assess the utility of Lip-Dox for local control of bladder cancer, we examined the distribution of Dox in the bladder wall and the regional lymph nodes of dogs after bladder submucosal injection of Lip-Dox. MATERIALS AND METHODS: In 8 dogs (group SM), Lip-Dox (2 mg.:1 ml.) was injected into the submucosal layer of each lateral bladder wall by using a flexible cystoscope. The other 8 dogs (group IV) underwent intravenous injection of free Dox (4 mg.). Both groups of animals were sacrificed at 1, 3, 5 or 7 days after the injections. The concentration of Dox was measured in both the mucosal and muscle layers of 5 bladder wall sites and also in the external iliac lymph nodes bilaterally. RESULTS: The Dox-concentration in the lymph nodes of group SM was significantly higher (about 15-100 times) than that of group IV throughout the whole follow-up period. The Dox-concentration in the bladder wall for group SM was significantly higher than that in group IV (about 70-930 times at the lateral walls and 2-830 times at the other sites). CONCLUSION: The present results demonstrate that Lip-Dox injected into the bladder submucosally distributes well, both in the whole bladder wall and in regional lymph nodes and remains at a high concentration in these tissues for at least one week after injection.     

Diphallus with urethral duplication: a rare case

We report on a case of glandular diphallus with incomplete urethral duplication associated with rotation anomaly in the right kidney, and a bifid pelvis and an ectopic ureteral orifice in the left kidney. The bladder was single with good sphincter control. At operation, the hipoplasic glans was resected and the urethra which opened into this glans anastomosed alongside the other urethra. Diphallus and incomplete urethral duplication are discussed.     

Nitric oxide synthase in the heterogeneous population of intramural striated muscle fibres of the human membranous urethral sphincter

PURPOSE: Nitric oxide (NO) is known to relax urethral smooth muscle. The role of NO in the control of urethral striated muscle remains unknown. We have investigated the distribution of nitric oxide synthase (NOS) immunoreactivity and its possible relationship with subtypes of intramural striated muscle fibers in the human male membranous urethra. MATERIALS AND METHODS: Whole transverse cryostat sections from seven membranous urethrae were studied using NOS immunohistochemistry and NADPH diaphorase histochemistry. Striated fiber subtypes were demonstrated using immunohistochemistry for troponin T and histochemistry for myofibrillary adenosine triphosphatase (ATPase). Consecutive sections were used to assess the correlation between the distribution of NOS immunoreactivity and the type of striated fibers. RESULTS: NOS immunoreactivity and NADPH diaphorase activity were detected in the sarcolemma of 48.5% of the intramural striated muscle fibers. NOS immunoreactive nerve trunks and fine nerve fibers, a few of which appeared to end on muscle fibers, were present in the striated sphincter. Fast twitch fibers were detected by ATPase staining, and also exhibited positive immunoreactivity for troponin T, constituting 34.6% of the total number of striated fibers. Two populations of slow twitch fibers were identified; one with small diameter (mean: 15.7 microns) and another of larger diameter (mean: 21.7 microns) comparable to that of fast twitch fibers. 86% of the fast twitch fibers and 29% of slow twitch fibers (most of which had larger diameters) exhibited NOS immunoreactivity and NADPH diaphorase activity in the sarcolemma. CONCLUSIONS: The presence of nitrergic nerve fibers in the striated urethral sphincter suggests an involvement in the innervation of urethral striated muscle. Furthermore, the presence of NOS immunoreactivity in the sarcolemma may indicate a role for NO in the regulation of urethral striated muscle metabolism and contraction.     

An experimental implantable urinary sphincter

An artificial urethral sphincter was implanted in 10 dogs and observed for periods up to 18 months. No necrosis or strictures of the urethra developed. The plastic part of the device failed in 10 to 18 months.     

Greater disorderliness of ACTH and cortisol release accompanies pituitary-dependent Cushing''s disease

BACKGROUND: We examined the mechanism of urinary bladder motility return after bladder areflexia induced by interruption of the sacral parasympathetic outflow to the urinary bladder following damage to the sacral cord or pelvic nerves in the rat. METHODS: The L6 and S1 nerve bundles were resected near the vertebrae, and bilateral pelvic nerve resections (PNR) performed. Spinal cord injury (SCI) was performed by means of a legion generator at the T12 vertebra. Thirty days after PNR and SCI, cystometrograms were recorded under anesthesia. RESULTS: In all rats subjected to PNR or SCI, overflow incontinence continued, yet some rats subjected to SCI recovered within 2 weeks after the operation. Cystometrograms showed that repetitive bladder contractions appeared in rats subjected to SCI irrespective of hypogastric nerve (HGN) innervation, while bladder contractions did not appear in rats subjected to PNR. Electrical stimulation of the HGN induced higher bladder pressure elevation in rats who underwent PNR than in rats subjected to SCI. CONCLUSIONS: These results suggest that the generation of repetitive bladder contractions induced by bladder distention after bladder areflexia requires the presence of intact pelvic nerves that transmit sacral cord-originating excitatory information to the bladder. However, the HGN system and functioning pelvic nerve ganglia are not involved in this process. Also, the connection from the preganglionic HGN to the postganglionic parasympathetic nerves in the pelvic plexus did not form after PNR.     

Ultrasonographic assessment of bladder neck mobility in continent bitches and bitches with urinary incontinence attributable to urethral sphincter mechanism incompetence

OBJECTIVE: To determine bladder neck positional changes between standing and recumbent positions in bitches and whether change is related to continence status or general anesthesia, or both, and to evaluate reproducibility of measurements. ANIMALS: 45 continent animals and 46 incontinent bitches with urethral sphincter mechanism incompetence (SMI). PROCEDURE: Distance between the bladder neck and perineal skin was measured ultrasonographically via the perineum while each dog was conscious in standing and right lateral recumbency and in right lateral recumbency under general anesthesia. Measurements of the bladder neck position obtained in right lateral recumbency under anesthesia were compared with radiographic measurements of the same parameter. Reproducibility of the ultrasonographic measurements of the distance between bladder neck and perineum was assessed on 3 occasions for each position in 50 dogs. RESULTS: In all dogs, differences in bladder neck position between standing and recumbent conscious-associated positions were not significant. However, caudal bladder neck movement between standing conscious- and recumbent anesthesia-associated positions and between recumbent conscious- and anesthesia-associated positions was significant for all dogs. Incontinent bitches had greater degree of caudal bladder movement during anesthesia. Mean difference in bladder neck positions between recumbent conscious- and recumbent anesthesia-associated positions was 0.24 cm in continent, compared with 0.73 cm in incontinent, bitches. Radiographic measurements were significantly greater than ultrasonographic measurements. Differences between repeated measurements for standing position were not significant, but those for recumbent conscious- and recumbent anesthesia-associated positions were significant. CONCLUSIONS: Additional vesicourethral support mechanisms in continent dogs, are deficient in bitches with SMI, allowing the bladder neck to move further caudad.     

Comparison of muscle mass preservation in denervated muscle and transplanted muscle flaps after motor and sensory reinnervation and neurotization

The gracilis muscle model was used either as a denervated muscle in situ or as a transplanted flap in 273 rats to compare the trophic effects of muscle reinnervation and neurotization using sensory and motor nerves. The average gracilis muscle flap weighed 626 +/- 94 mg at the time of the initial procedure. Experimental muscles were examined 6 months following the procedure. In denervated, nontransplanted muscles, both motor nerve reinnervation and neurotization resulted in significantly preserved muscle mass, averaging 570 +/- 69 and 521 +/- 116 mg, respectively, compared with the denervated control average of 178 +/- 22 mg (p < 0.05). Sensory nerve reinnervation and neurotization produced much smaller trophic effects (p > 0.05). In transplanted gracilis free flaps, however, only direct reinnervation with motor or sensory nerves resulted in improved bulk preservation, with average weights of 313 +/- 83 and 327 +/- 91 mg compared with the control average of 201 +/- 76 mg (p < 0.05). Neither sensory nor motor neurotization was significantly effective in the free-flap model (p > 0.05). These data suggest that transplantation may alter the response of muscle to reinnervation.     

Facilitation of Chemoreceptor-induced reflex vasoconstriction by intravertebral arterial administration of clonidine

The influence of clonidine on the reflex vascular responses to stimulation of carotid body chemoreceptors and bilateral carotid occlusion was studied in morphine, chloralose-urethane anesthetized dogs. Bilateral carotid occlusion and intracarotid injection of nicotine (30 and 100 microgram) or sodium cyanide (200 and 500 microgram) elicited reflex vasoconstriction in the perfused gracilis muscle vascular bed. Infusion of clonidine (2-4 microgram/kg) into the vertebral artery significantly lowered blood pressure. Reflex vasoconstrictor responses to chemoreceptor stimulation were significantly enhanced after clonidine administration whereas reflex vasoconstrictor responses to carotid occlusion were markedly reduced. The facilitation of chemoreceptor reflex responses by clonidine was observed in dogs with intact or sectioned vagi and in animals in which the carotid arteries were perfused at constant blood flow. Inhibition of carotid occlusion responses by clonidine was observed in dogs with intact or sectioned vagi. Infusion of clonidine directly into the carotid arteries did not significantly alter responses to chemoreceptor stimulation. These experiments demonstrate that clonidine antagonizes the reflex vasoconstriction caused by carotid occlusion while potentiating the vasoconstriction elicited by chemoreceptor stimulation. The data suggest that clonidine exerts central actions which result in a facilitation of the chemoreceptor reflex and a simultaneously occuring hypotension which is probably due to an action on baroreceptor pathways.     

Transitional carcinomas of the urinary tract: synchronous and metachronous lesions

OBJECTIVE: The urothelium is a pseudostratified cylindrical epithelium that lines the calices, renal pelvis, urethers, bladder, part of the urethra and part of the prostate ducts. Transitional cell carcinoma (TCC) is a malignant neoplasia that can appear in any site where urothelium is present, being the bladder the most frequently affected organ. We performed an analysis of our experience and conducted a literature-based metanalysis to evaluate the coexistence of tumoral lesions at different locations in the urinary tract. MATERIAL AND METHODS: Between 1983 and 1993, 397 patients with TCC lesions involving the upper urinary tract (UUT), bladder, urethra or prostate, were diagnosed and treated. Coexistence, either synchronic or metachronic, of several lesions in different sites of the urinary tract was considered as a multiple tumor. RESULTS: Overall, 440 tumors were diagnosed in 397 patients. A single lesion appeared in 360 patients, while 37 presented multiple locations with a total of 79 tumors. The lesions were located at the following levels: 17 renal, 21 uretheral, 372 vesical, 13 in the urethra and 17 in the prostate ducts. According to the location, the frequency of single lesions was: UUT 58%, bladder 91%, urethra 8% and prostate ducts 35%. Synchronic UUT and intravesical tract tumors develops in 1% and 4% of patients with bladder TCC, respectively. Two percent of vesical tumors showed metachronic relationship with UUT tumors and the same rate was seen for intravesical lesions. CONCLUSIONS: Urothelial UUT tumors have a typical nosologic entity with specific features. Their coexistence with vesical tumors is frequent. When tumors of the bladder occur after a UUT tumor the interval of highest incidence between diagnoses is 2-3 years, and there are no histological risk factors among them for prognosis. Transitional cell prostatic urethral tumors are most often secondary to histologically similar, poor prognosis, bladder tumors, and usually synchronic.