Relaxation by beta 3-adrenoceptor agonists of the isolated human internal anal sphincter.

AIMS: In this study, responses of beta(3)-adrenoceptor agonists were examined on human isolated internal anal sphincter (IAS) in order to explore their relaxant effects on hypertonicity of IAS. MAIN METHODS: The relaxant efficacy (E(max)) and potency (-logIC(50)) of BRL37344 and SR58611A, beta(3)-adrenoceptor agonists, were examined in contracted IAS muscle strips. The presence of beta(3)-adrenoceptors, and changes in intracellular calcium and cyclic nucleotide levels in IAS muscle were tested by Western blotting, epifluorescence microscopy and enzyme immunoassay, respectively. KEY FINDINGS: BRL37344 and SR58611A relaxed contracted IAS muscle (E(max)=27+/-3% and 35+/-3%; -logIC(50)=6.26+/-0.24 and 4.87+/-0.13; respectively). These relaxant responses were blocked by SR59230A, a selective beta(3)-antagonist but not by beta(1)/beta(2)-selective antagonists, neuronal inhibitor or inhibition of nitric oxide synthase. The E(max) of beta(3)-agonists was similar to that of beta(2)-selective agonists but smaller than that of isoprenaline (nonselective agonist) or beta(1)-selective agonists. BRL37344 (100 microM) increased cAMP (1.5-fold) without cGMP change, and depressed intracellular calcium signal. beta(3)-Adrenoceptor expression was smaller than that of beta(1)- and beta(2)-adrenoceptors. SIGNIFICANCE: This is the first study demonstrating the presence of beta(3)-adrenoceptor in human IAS muscle and beta(3)-mediated relaxation of augmented sphincter tone. However, direct beta(3)-relaxation appears smaller than that obtained for nonselective agonists which may limit their potential use in the treatment of anorectal hypertonicity disorders.

Clinical and manometric results of endorectal advancement flaps for complex anal fistula.

BACKGROUNDS AND AIM: Endorectal advancement flap repair is a well-recognized method for the treatment of complex anorectal fistula. The purpose of this study was to prospectively assess the clinical and functional results of endorectal advancement flaps for complex anorectal fistula and to identify factors that affect outcome. MATERIALS AND METHODS: A prospective study of 56 patients was performed. Clinical and functional results were studied using the Wexner continence scale and anal manometry before and after surgery. Factors associated with recurrence and incontinence were analyzed by univariate and multivariate regression analysis. RESULTS: Sixty endorectal flaps were constructed in 56 patients. Mean age was 49 years (range 24-74). The fistula was of cryptoglandular origin in 91.1% cases. Mean follow-up was 43.8 months. The technique was repeated in four patients because of recurrence (7.1%), with subsequent healing in all cases. There were significant reductions in maximum resting pressure 3 months after surgery (83.6+/-33.2 vs 45.6+/-18.3, p<0.001) and maximum squeeze pressure (208.8+/-91.5 vs 169.5+/-75, p<0.001). Before surgery, five patients (8.9%) reported incontinence symptoms. After surgery, 78.6% patients had normal continence, seven patients (12.5%) complained of minor incontinence, and five (9%) had major continence disturbances. None of the variables studied (age, sex, previous fistula surgery, rectovaginal fistula, and Crohn's disease) affected the outcome of the procedure in multivariate analysis. CONCLUSIONS: Endorectal advancement flap repair is an effective technique for complex anal fistula, with a low recurrence rate (7.1%). Patients (21.4%) reported disturbed anal continence. It is still not possible to identify factors that are predictive of failure or incontinence.

[Treatment of chronic anal fissure]. / Tratamientos de la fisura anal crónica.

Current treatment of chronic anal fissure continues to be based on conventional conservative measures in a high percentage of cases. What is known as chemical sphincterotomy aims to achieve a temporary decrease of anal pressures that allows fissures to heal. There are various alternatives such as nitroglycerine or diltiazem ointment and botulinum toxin injections. However, because of collateral effects and recurrences in the medium term, the definitive role of these treatments remains to be elucidated. Nevertheless, chemical sphincterotomy should be the first option in patients with a high risk of incontinence. "Open" or "closed" lateral internal sphincterotomy performed in the ambulatory setting with local anesthesia can currently be considered the ideal treatment of chronic anal fissure refractory to conservative measures so long as the patient is informed about the risk of minor incontinence. This procedure provides rapid and permanent recovery in more than 95% of patients. There is evidence demonstrating that the incontinence rate is related to the extent of the lateral internal sphincterotomy and consequently the extent of this procedure should be reduced to the length of the fissure.