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Perianal Application of Glyceryl Trinitrate Ointment Versus Tocopherol Acetate Ointment in the Treatment of Chronic Anal Fissure: A Randomized Clinical Trial.
Ruiz-Tovar, J, Llavero, C
Diseases of the colon and rectum. 2022;(3):406-412
Abstract
BACKGROUND Medical treatment, including glyceryl trinitrate ointment, represents the first step for the management of chronic anal fissure. However, glyceryl trinitrate ointment is associated with headache and, consequently, a high withdrawal rate of the treatment. OBJECTIVE The aim of the present study was to evaluate the effect of the topical application of tocopherol acetate ointment on pain relief and chronic anal fissure epithelialization, comparing it with the effect of a standard treatment with glyceryl trinitrate ointment. DESIGN This is a 2-parallel-group, single-center, randomized controlled, intent-to-treat clinical trial. SETTINGS This study was conducted at the Garcilaso Clinic affiliated with Universidad Alfonso X (Madrid, Spain). PATIENTS Patients with chronic anal fissure were selected. INTERVENTIONS Patients were randomly assigned into 2 groups: patients receiving tocopherol acetate ointment and patients receiving glyceryl trinitrate ointment. MAIN OUTCOME MEASURES The primary end point was quantification of anal pain 8 weeks after beginning the treatment as measured by a Visual Analogue Scale ranging from 0 to 100 mm. The secondary end points were the healing rate (during the treatment period of 8 weeks) and the recurrence rate. RESULTS One hundred sixty consecutive patients were treated, 80 in each group. By 8 weeks after treatment, mean anal pain score declined by 56.2 mm in the glyceryl trinitrate ointment group compared with a mean anal pain score decline of 67.1 mm in the tocopherol acetate ointment group (mean difference, 10.9 mm (95% CI, 4.3-18.6); p = 0.018). Sixteen weeks after finishing the therapy, the recurrence rate was 13.2% in the glyceryl trinitrate ointment group vs 2.9 in the tocopherol acetate ointment group (p = 0.031). LIMITATIONS Limitations of the study include the absence of manometric measurements of the internal anal sphincter before and after the treatments and the use of glyceryl trinitrate ointment as an active comparator, whereas calcium channel blockers are actually the standard treatment. CONCLUSIONS Anal pain was significantly lower in the tocopherol acetate ointment group than in the glyceryl trinitrate ointment group at 8 weeks after treatment. Tocopherol acetate ointment achieved a greater healing rate and a lower recurrence rate 16 weeks after finishing the treatment. See Video Abstract at http://links.lww.com/DCR/B751. REGISTRATION URL: https://www.clinicaltrials.gov; Identifier: NCT03787030.APLICACIÓN PERIANAL DE POMADA DE TRINITRATO DE GLICERILO FRENTE A LA POMADA DE ACETATO DE TOCOFEROL EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: UN ENSAYO CLÍNICO ALEATORIZADOANTECEDENTESEl tratamiento médico, incluida la pomada de trinitrato de glicerilo, representa el primer paso para el tratamiento de la fisura anal crónica. Sin embargo, la pomada de trinitrato de glicerilo se asocia con cefalea y, en consecuencia, una alta tasa de cancelación del tratamiento.OBJETIVOEl objetivo del presente estudio fue evaluar el efecto de la aplicación tópica de pomada de acetato de tocoferol en el alivio del dolor y la epitelización de la fisura anal crónica, comparándolo con el efecto de un tratamiento estándar con pomada de trinitrato de glicerilo.DISEÑO:Ensayo clínico con intención de tratar controlado, aleatorizado, de un solo centro, con dos grupos paralelos.ESCENARIOClínica Garcilaso adscrita a la Universidad Alfonso X (Madrid, España).PACIENTESPacientes con fisura anal crónica.INTERVENCIONESLos pacientes fueron aleatorizados en 2 grupos: pacientes que recibieron pomada de acetato de tocoferol y pacientes que recibieron pomada de trinitrato de glicerilo.PRINCIPALES MEDIDAS DE RESULTADOEl criterio de valoración principal fue la cuantificación del dolor anal 8 semanas después de comenzar el tratamiento, medido por la escala analógica visual que varía de 0 a 100 mm. Los criterios de valoración secundarios fueron la tasa de curación (durante el período de tratamiento de 8 semanas) y la tasa de recurrencia.RESULTADOSSe trataron ciento sesenta pacientes consecutivos, 80 en cada grupo. A las ocho semanas después del tratamiento, la puntuación media de dolor anal se redujo en 56.2 mm en el grupo de pomada de trinitrato de glicerilo en comparación con una disminución de la puntuación de dolor anal medio de 67.1 mm en el grupo de pomada de acetato de tocoferol (diferencia media: 10.9 mm (intervalo de confianza del 95%; 4.3 a 18.6; p = 0.018) Dieciséis semanas después de finalizar la terapia, la tasa de recurrencia fue del 13.2% en el grupo de pomada de trinitrato de glicerilo frente a 2.9 en el grupo de pomada de acetato de tocoferol (p = 0.031).LIMITACIONESAusencia de medidas manométricas del esfínter anal interno antes y después de los tratamientos. Ungüento de trinitrato de glicerilo como comparador activo, mientras que los bloqueadores de los canales de calcio son en realidad el tratamiento estándar de oro.CONCLUSIONESEl dolor anal fue significativamente menor en el grupo de ungüento de acetato de tocoferol que en el grupo de ungüento de trinitrato de glicerilo a las 8 semanas después del tratamiento. La pomada de acetato de tocoferol logró una mayor tasa de curación y una menor tasa de recurrencia 16 semanas después de finalizar el tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B751. (Traducción-Dr. Jorge Silva Velazco).
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Myocardial protective effect of intracoronary administration of nicorandil and alprostadil via targeted perfusion microcatheter in patients undergoing elective percutaneous coronary intervention: A randomized controlled trial.
Zhang, W, Dai, J, Zheng, X, Xu, K, Yang, X, Shen, L, Wang, X, Hao, Z, Qiu, X, Jiang, L, et al
Medicine. 2021;(15):e25551
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Abstract
BACKGROUND The aim of the study was to evaluate the efficacy of nicorandil and alprostadil on myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI). METHODS In this prospective, single-blinded, randomized controlled study, 90 consecutive patients scheduled for elective PCI for de novo coronary lesions were assigned to the nicorandil, alprostadil, and nitroglycerin groups in a 1:1:1 ratio. Drugs were administered intracoronary via a targeted perfusion microcatheter. The primary endpoint was the thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC). Additionally, the corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), and incidence of periprocedural myocardial injury (PMI) were assessed. RESULTS Both nicorandil and alprostadil were significantly effective in reducing TMPFC (114.6 ± 33.7 vs 93.4 ± 30.9, P = .016; 114.3 ± 34.3 vs 94.7 ± 33.3, P = .029, respectively). Similar findings were observed in the improvement of cTFC (20.3 ± 10.5 vs 13.5 ± 5.0, P = .003; 20.2 ± 7.4 vs 15.2 ± 5.2, P = .003, respectively) and percentage of TMPG 3 (100% vs 82.8%, P = .052; 83.3% vs 96.7%, P = .196, respectively); whereas, nitroglycerin produced a limited effect on TMPFC (114.4 ± 30.9 vs 112.1 ± 31.9, P = .739), cTFC (19.4 ± 7.2 vs 19.3 ± 7.2, P = .936), and percentage of TMPG 3 (86.7% vs 86.7%, P = 1.000). No significant difference was found in the incidence of PMI (16.7% vs 16.0% vs 27.6%, P = .537), though it was comparatively lower in the nicorandil and alprostadil groups. Furthermore, the intracoronary administration of nicorandil and alprostadil had a mild effect on blood pressure and heart rate. CONCLUSIONS The intracoronary administration of nicorandil and alprostadil via a targeted perfusion microcatheter was more effective in improving myocardial perfusion in patients undergoing elective PCI than nitroglycerin.
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Effects of Nicorandil Versus Nitroglycerin on Arterial Oxygenation During Two-Lung Ventilation and One-Lung Ventilation in Patients With Risk Factors for Myocardial Ischemia: A Prospective, Randomized, Double-Blind Study.
Murakami, C, Kawano, H, Kinoshita, M, Kondo, A, Inoue, M
Journal of cardiothoracic and vascular anesthesia. 2019;(3):702-709
Abstract
OBJECTIVES To compare the effects of nicorandil and nitroglycerin on arterial oxygenation during two-lung ventilation (TLV) and one-lung ventilation (OLV) in patients with risk factors for myocardial ischemia. DESIGN A prospective, randomized, double-blind study. SETTING A tertiary care hospital. PARTICIPANTS Fifty-six patients scheduled for elective video-assisted thoracic surgery were assigned randomly to either the nicorandil group or the nitroglycerin group. INTERVENTIONS Patients in the nicorandil group received a bolus dose of nicorandil, 0.08 mg/kg during induction of anesthesia, followed by a continuous infusion at a rate of 0.08 mg/kg/h. Patients in the nitroglycerin group received a continuous infusion of nitroglycerin at a rate of 1 µg/kg/min from the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS Arterial blood gas analysis was performed at the following points: before induction of anesthesia; during TLV; at 5, 10, 20, and 30 minutes after the initiation of OLV. PaO2 at TLV (479.7 ± 57.1 v 408.2 ± 70.9 mmHg, p < 0.001); and at 5 minutes (344.8 ± 85.1 v 282.6 ± 85.8 mmHg, p = 0.012), 20 minutes (215.7 ± 103.0 v 158.2 ± 74.5 mmHg, p = 0.027), and 30 minutes (198.8 ± 103.5 v 147.5 ± 64.1 mmHg, p = 0.039) after OLV was significantly higher in the nicorandil group than in the nitroglycerin group. CONCLUSION This study demonstrated that oxygenation during TLV and OLV was significantly higher in patients receiving nicorandil than in those receiving nitroglycerin.
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Route of Feeding as a Proxy for Dysphagia After Stroke and the Effect of Transdermal Glyceryl Trinitrate: Data from the Efficacy of Nitric Oxide in Stroke Randomised Controlled Trial.
Woodhouse, LJ, Scutt, P, Hamdy, S, Smithard, DG, Cohen, DL, Roffe, C, Bereczki, D, Berge, E, Bladin, CF, Caso, V, et al
Translational stroke research. 2018;(2):120-129
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Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured at day 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ≤6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke. Clinical Trial Registration Clinical Trial Registration-URL: http://www.controlled-trials.com . Unique identifier: ISRCTN99414122.
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Percutaneous Posterior Tibial Nerve Stimulation vs Perianal Application of Glyceryl Trinitrate Ointment in the Treatment of Chronic Anal Fissure: A Randomized Clinical Trial.
Ruiz-Tovar, J, Llavero, C
Diseases of the colon and rectum. 2017;(1):81-86
Abstract
BACKGROUND Current therapeutic guidelines for the treatment of chronic anal fissure establish a medical approach as the first step. Glyceryl trinitrate ointment is the most popular of the available topical treatments in Spain but it is associated with the appearance of headache. OBJECTIVE The purpose of this study was to compare the compliance rate among patients receiving glyceryl trinitrate treatment for chronic anal fissure with that among patients receiving percutaneous posterior tibial nerve stimulation. DESIGN This was a prospective randomized study. SETTINGS The study was conducted at Garcilaso Clinic (Madrid, Spain). PATIENTS Subjects with persistent anal fissure despite hygiene and dietary measures applied over at least a 6-week period were included. INTERVENTIONS Study interventions were perianal application of glyceryl trinitrate ointment (twice daily for 8 weeks) and percutaneous posterior tibial nerve stimulation (30-minute session 2 days per week for 8 weeks). MAIN OUTCOME MEASURES Compliance with the treatment and healing rate of chronic anal fissure in patients receiving glyceryl trinitrate ointment or undergoing percutaneous posterior tibial nerve stimulation were evaluated. RESULTS Forty patients were included in each group. In the glyceryl trinitrate ointment group, 15% of the patients discontinued treatment because of disabling headaches. There were no adverse effects or treatment withdrawals in the percutaneous posterior tibial nerve stimulation group (p = 0.033). After 8 weeks of treatment, the healing rate in the percutaneous posterior tibial nerve stimulation group was 87.5% vs 65.0% in the glyceryl trinitrate ointment group (p = 0.018). LIMITATIONS Because the patients were not blinded to the treatment, we cannot rule out a placebo effect derived from the needle insertion in the percutaneous posterior tibial nerve stimulation group. CONCLUSIONS Percutaneous posterior tibial nerve stimulation is a safe and effective alternative that is in some ways superior to glyceryl trinitrate ointment for the treatment of chronic anal fissure.
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Acute improvement of pulmonary hemodynamics does not alleviate Cheyne-Stokes respiration in chronic heart failure-a randomized, controlled, double-blind, crossover trial.
Bitter, T, Fox, H, Schmalgemeier, H, Wellmann, B, Zwenke, A, Spiesshöfer, J, Dimitriadis, Z, Horstkotte, D, Oldenburg, O
Sleep & breathing = Schlaf & Atmung. 2016;(2):795-804
Abstract
OBJECTIVES This randomized, controlled trial aimed to investigate whether acute improvement of pulmonary congestion would reduce the severity of Cheyne-Stokes respiration (CSR) in patients with chronic heart failure (CHF). METHODS Twenty-one consecutive patients with CHF and CSR (apnea-hypopnea index [AHI] ≥15/h) underwent right heart catheterization with titration of intravenous (IV) glyceryltrinitrate (GTN) to a maximum tolerable dosage and inhalation of iloprost 10 μg/mL after a washout phase. Maximum tolerable dosages of GTN and iloprost were randomly applied during full cardiorespiratory polysomnography within two split-night procedures and compared with IV or inhaled sodium chloride (NaCl) 0.9 %, respectively. RESULTS GTN (6.2 ± 1.5 mg/h) and iloprost significantly lowered \mean pulmonary artery pressure (20.1 ± 9.0 to 11.6 ± 4.2 mmHg, p < 0.001 and 16.9 ± 7.9 to 14.2 ± 6.4 mmHg, p < 0.01, respectively). Pulmonary capillary wedge pressure was only reduced by GTN (14.0 ± 5.6 to 7.2 ± 3.9 mmHg, p < 0.001), and there was no significant change in the cardiac index. Sleep studies revealed no significant improvement in markers of CSR severity, including AHI, central apnea index, and CSR cycle length following GTN or iloprost treatment. Significant decreases in blood pressure, mean oxygen saturation, and S3 sleep were documented during GTN infusion. CONCLUSIONS Acute improvement of pulmonary congestion by GTN had no immediate impact on CSR severity. Future investigations must therefore include longer treatment periods and treatment regimens that have positive, rather than negative, additional effects on peripheral and central chemoreceptors and sleep structure. TRIAL REGISTRATION German Clinical Trial Registry-ID:DRKS00000467 ( www.germanctr.de ).
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Nicorandil Versus Nitroglycerin for Symptomatic Relief of Angina in Patients With Slow Coronary Flow Phenomenon: A Randomized Clinical Trial.
Sani, HD, Eshraghi, A, Nezafati, MH, Vojdanparast, M, Shahri, B, Nezafati, P
Journal of cardiovascular pharmacology and therapeutics. 2015;(4):401-6
Abstract
OBJECTIVE Patients with the coronary slow flow phenomenon frequently experience angina episodes. The present study aimed to compare the efficacy of nicorandil versus nitroglycerin for alleviation of angina symptoms in slow flow patients. METHODS In a single-center, single-blind, parallel-design, comparator-controlled, randomized clinical trial (NCT02254252), 54 patients with slow flow and normal or near-normal coronary angiography who presented with frequent angina episodes were randomly assigned to 1-month treatment with nicorandil 10 mg, 2 times a day (n = 27) or sustained-release glyceryltrinitrate 6.4 mg 2 times a day (n =27). Frequency of angina episodes, pain intensity, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were assessed at baseline and after 1 month of treatment. RESULTS In all, 25 patients in the nicorandil arm and 24 patients in the nitroglycerin arm were analyzed. After 1 month, patients treated with nicorandil had fewer angina episodes (adjusted mean number of episodes per week, nicorandil versus nitroglycerin; 1.68 ± 0.15 vs 2.29 ± 0.15, P = .007, effect size = 14.6%). Patients also reported greater reductions in pain intensity with nicorandil versus nitroglycerin (adjusted mean of self-reported pain score; 3.03 ± 0.29 vs 3.89 ± 0.30, P = .046, effect size = 8.4%). A significantly higher proportion of patients in the nicorandil arm were categorized in CCS class I (76% vs 33.3%, P = .004) or class II (16.0% vs 45.8%, P = .032). CONCLUSION In slow flow patients, nicorandil provides better symptomatic relief of angina than nitroglycerin.
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Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.
Ito, N, Nanto, S, Doi, Y, Kurozumi, Y, Natsukawa, T, Shibata, H, Morita, M, Kawata, A, Tsuruoka, A, Sawano, H, et al
Cardiovascular drugs and therapy. 2013;(4):279-87
Abstract
PURPOSE In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. METHODS We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 μg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. RESULTS As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. CONCLUSION Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.
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Use of antispastic nicardipine and nitroglycerin (NG) cocktail solution increases graft flow during off-pump coronary artery bypass grafting.
Zheng, SY, Wu, M, Huang, JS, Mai, MJ, Chen, TB, He, GW
The Journal of cardiovascular surgery. 2012;(6):783-8
Abstract
AIM: NG solution composed of nicardipine and nitroglycerin is a new anti-spastic solution for arterial grafts. We investigated its efficacy on the left internal thoracic artery (LITA) during off-pump coronary artery bypass grafting (OPCAB). METHODS The free flow of LITA in 41 OPCAB patients was measured. The patients were divided to four groups: LITA pedicle wrapped with normal saline (Group I, N.=10) or NG (Group II, N.=11); or in addition to wrapping, 2 cc NG (Group III, N.=10) or normal saline (Group IV, N.=10) injected into LITA. After 30 min, the distal end free flow and the graft flow by an ultrasound probe were measured. RESULTS The free flow significantly increased in Group II (30.0±4.7 vs. 21.6±4.5 cc/min, P=0.007) and III (70.0±11.5 vs. 24.5±6 cc/min, P=0.001) but not in Group I (20.8±4.7 vs. 19.4±4.1 cc/min, P=0.33) or IV (35.8±7.5 vs. 29±9.2 cc/min, P=0.06) with significant differences between the Group III to all other groups (P=0.016-0.001). The graft flow by ultrasound probe was significantly higher in Group III (41.2±6.2 cc/min) than that in Group IV (24.1±3.1 cc/min, P=0.028). CONCLUSION Use of NG solution for LITA graft preparation is a choice of antispastic protocol. NG solution used either topically or intraluminally significantly increases the blood flow of IMA grafts with the best effect obtained by intraluminal injection. The present study provides an additional anti-spastic method by using second generation of calcium antagonists and nitric oxide donor in coronary artery bypass surgery.
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Long-term prospective randomised clinical and manometric comparison between surgical and chemical sphincterotomy for treatment of chronic anal fissure.
Abd Elhady, HM, Othman, IH, Hablus, MA, Ismail, TA, Aboryia, MH, Selim, MF
South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie. 2009;(4):112-4
Abstract
AIM: To compare surgical and chemical sphincterotomy for treatment of chronic anal fissure. METHODS The 160 patients studied were randomly divided into four equal groups, treated by lateral internal sphincterotomy (group S), local diltiazem ointment (group D), local glyceryl trinitrate ointment (group GTN), or injection of botulinum toxin into the internal anal sphincter (group BT). Anal manometry was performed before and 3 months after treatment. Patients were followed up for 5 years. RESULTS Complete pain relief was achieved in means (+/- standard deviation) of 5.7+/-7.8 days (group S), 15.7+/-5.9 days (group D), 15.6+/-5.9 days (group GTN) and 2.7+/-3.6 days (group BT). The mean times to healing were 4.5+/-1.2 weeks (group 1), 5.1+/-1.1 weeks (group D), 5.0+/-1.1 weeks (group GTN) and 5.1+/-1.3 weeks (group BT). Mean resting and squeeze anal pressures decreased significantly after sphincterotomy. Recurrence rates were 10% in group S, 65% in group D, 57.5% in group GTN and 52.5% in group BT. CONCLUSION Lateral internal sphincterotomy is an easy procedure with satisfactory results, minimal complications and a low recurrence rate. Medical sphincterotomy is safe and easy, with mild complications. Its effect is reversible, and relapse is common. We recommend that medical sphincterotomy be tried before surgery or in patients who are unable or unwilling to undergo surgery.