Effect of urethral dilation on vesical motor activity: identification of the urethrovesical reflex and its role in voiding

PURPOSE: We investigated the hypothesis that mild urethral distention, which presumably occurs during the passage of urine through the urethra, stimulates stretch receptors in the urethral wall, leading reflexively to vesical contraction. MATERIALS AND METHODS: We evaluated 9 male and 10 female healthy volunteers with a mean age +/- SD of 39.6 +/- 8.3 years. The posterior urethra was distended by a balloon filled with saline in 1 ml. increments up to 6 ml., while recording vesical pressure. The test was repeated after individual anesthetization of the urethra and bladder. RESULTS: Vesical pressure increased significantly at 1 and 2 ml. urethral distention (p <0.01). Increases in urethral distention effected further vesical pressure elevation (p <0.001), although there was no significant difference in distention at 3 to 6 ml. (p >0.05). No significant vesical pressure response of the individually anesthetized urethra or bladder occurred during urethral distention. CONCLUSIONS: Urethral distention is thought to cause vesical contraction through the stimulation of urethral stretch receptors. Vesical contraction at urethral distention postulates a reflex relationship that was abolished by individual anesthetization of the urethra and bladder. This relationship, which we call the urethrovesical reflex, appears to have a role in maintaining vesical contraction during voiding. Further studies are required to investigate the role of this reflex in voiding disorders.     

Role of the Enteric Nervous Plexus in Rectal Motile Activity: An Experimental Study

The gut innervation is formed by an intrinsic and an extrinsic component. The former is responsible for the intestinal contractions that occur in the total absence of extrinsic innervation. We hypothesize that the intrinsic plexuses do not produce local contraction, but mediate reflex actions of the gut musculature. This hypothesis was investigated in the rectum of the experimental animal. In 16 anesthetized mongrel dogs, the rectum was exposed, and 3 monopolar silver-silver chloride electrodes were sutured serially to the rectal wall and connected to a rectilinear pen recorder. The rectal electric activity was recorded at rest and on rectal inflation while the anal pressure was synchronously registered. The tests were repeated after separate drug administration using phentolamine, propranolol (adrenoceptor blocking agents), atropine (cholinergic blocking agent), drotaverine (direct smooth muscle relaxant), and nitroglycerine. (NO donor, inhibitory noncholinergic, nonadrenergic mediator). Slow waves or pacesetter potentials (PPs) and action potentials (APs) were recorded from the three electrodes. Rectal balloon distension caused an increase of frequency, amplitude, and conduction velocity of these waves, as well as a decrease of anal pressure. Repetition of the test after administration of phentolamine, propranotol, and atropine effected no change in rectal electromyelographic (EMG) activity or anal pressure, while drotaverine and nitroglycerine administration aborted both the electric activity and the anal pressure response. We conclude that the rectal electric activity, presumably responsible for rectal motility, was not aborted by enteric nervous plexus block but by direct muscle relaxant. This suggests that the enteric plexus has no direct action on the rectal motile activity but mediates the rectal reflex actions. This concept might explain some of the hitherto unknown mechanisms of rectal dyssynergia syndromes.     

The "opening time" and "pelvic floor electromyographic lag time": two novel tools in the assessment of the anorectal evacuation time.

Rectal evacuation necessitates rectal contraction and pelvic floor muscles relaxation; it is not known which action precedes the other. We investigated the hypothesis that pelvic floor muscles relaxation precedes rectal contraction so that rectal contents find the anal canal already opened. Electromyographic activity of the external anal sphincter as well as anal and rectal pressures were recorded during rectal balloon distension and evacuation. Pelvic floor muscles electromyographic lag time (time from start of pelvic floor muscles relaxation to start of evacuation) and opening time (time from start of rectal contraction to start of evacuation) were measured. Rectal balloon distension in increments of 20 mL up to 100 mL effected progressive increase of both external anal sphincter electromyography and anal pressure. At 120 mL balloon distension up to 180 mL, external anal sphincter electromyography and anal pressure exhibited gradual decrease whereas rectal pressure showed no changes. At 200 to 220 mL rectal balloon distension, rectal pressure increased and anal pressure decreased, while external anal sphincter showed no electromyographic activity; rectal balloon was expelled. The opening time recorded a mean of 1.8 +/- 0.7 s and pelvic floor muscles electromyographic lag time of 2.2 +/- 0.9; the two recordings showed no significant difference (p > .05). These, two diagnostic tools in anorectal investigations are presented: the opening time and pelvic floor muscles electromyographic lag time. Pelvic floor muscles relaxation preceded rectal contraction. As there is no significant difference between opening time and pelvic floor muscles electromyographic lag time, it appears easier to apply the latter as it is simple, objective, and noninvasive.     

Anal submucosal injection: a new route for drug administration in pelvic malignancies. II. Methotrexate anal injection in the treatment of advanced bladder cancer. Preliminary study

The clinical efficacy of submucosal anal injections of methotrexate in advanced bladder cancer is investigated. An experimental study on 20 mice has shown that methotrexate injected into the anal submucosa has no clinicopathological effect on the anorectum. The clinical study comprised 18 patients with advanced bladder cancer (13 with stage T3 and 5 with stage T4 disease) as a test group in whom methotrexate was injected into the anal submucosa and 8 (6 with stage T3 and 2 with stage T4 cancer) treated concurrently with intravenous methotrexate. The dose in both groups was 50 mg. every 5 days for 5 consecutive doses. The course was repeated at 3-week intervals. Most patients received methotrexate as outpatients. Methotrexate blood levels were measured 4 and 24 hours after administration in both groups. In the test group 10 of the 18 patients showed complete tumor regression and were alive 21 to 50 months after the start of treatment. Partial regression was observed in 8 patients. Hematological reserve remained unchanged. Mild toxicity occurred in 3 patients. Of the 8 patients treated intravenously the tumor showed partial regression in 1, was stable in 3 and progressed in 4. Side effects were severe in 5 patients. Our results show that methotrexate injection is highly effective in the treatment of advanced bladder cancer. It is safe, well tolerated and can be used on an outpatient basis.