Study of efficacy and safety of a new local cream ('healer') in the treatment of chronic anal fissure: a prospective, randomized, single-blind, comparative study. A stable prostacyclin analogue (iloprost) in the treatment of ischaemic ulcers of the lower limb. A Scandinavian-Polish placebo controlled, randomised multicenter study. Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes. 5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. Double blind randomised controlled trial of topical glyceryl trinitrate in anal fissure. A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial. Randomized, double-blind trial comparing topical nitroglycerine with xylocaine and Proctosedyl in idiopathic chronic anal fissure. The efficacy and safety of 50 mg penicillin G potassium troches for recurrent aphthous ulcers. [Therapy of varicose ulcer using crilanomer and dextranomer].
To determine the efficacy and safety of 'healer' cream as monotherapy in the treatment of acute and chronic anal fissure.
                A prospective, randomized, single blinded, comparative trial.
                Sixty patients suffering from anal fissure were included in the study. Patients were randomly divided into three groups: group A: treated with 'healer' local cream application 3 times daily; group B: treated with nitroglycerine 0.25% local cream 3 times daily; group C: treated with a lidocaine 2% cream applied locally 3 times daily. All the followings were followed up and compared between groups. (1) Visual pain analogue score after defecation; (2) severity of straining and discomfort during defecation; (3) frequency of ulcer healed at 30 days; (4) any side effects or complications.
                The pain scoring after defecation was significantly reduced in the three treatment groups. The group treated with 'healer' isosorbide-di-nitrate showed the greatest reduction of the visual pain analogue score median from 9 before treatment to 3 & 1 after 10 and 20 days respectively, while the median visual pain analogue score in group B treated with nitroglycerine cream was 9 reduced to 4 & 2 after 10 and 20 days respectively, and the median visual pain analogue score in lidocaine group only dropped from 9 to 6 and 4, respectively. The reduction of both pain scoring and defecation scoring with 'healer' was statistically significantly greater than the other two treatments by Kruskal-Wallis test, P<0.001. The number of patients experiencing complete relief and passing stools easily after 10 days was significantly higher in 'healer' group, by Pearson Chi square = 22.94, P<0.001. After 30 days, the fissures were healed in 18 (90%) of 20 patients in the 'healer' group and in 12 (60%) of 20 in the nitroglycerin group, while only 6 (30%) of patients treated with lidocaine cream had their fissures healed by the 30 days treatment. Chi square = 15 (P = 0.001).
                'Healer' is a promising effective and safe line of treatment in acute and chronic anal fissure. The characteristic pharmacokinetics of isosorbide-di-nitrate leads to a better effect than nitroglycerin in healing (more prolonged action). Also the less fast absorption than nitroglycerin leading to a smoother dose concentration curve, may be the cause that headache is less frequent and less severe in 'healer' treatment versus nitroglycerin. The clinical efficacy of the prostacyclin analogue iloprost was studied during a 2 week treatment and 6 month follow-up period in 103 patients with ischaemic ulcers who were randomised to receive active treatment or placebo. Responders were defined as those patients who achieved healing of at least one third of the ulcer area during the study period. The overall responder rate was 41.3%, compared with 25% for the control group (P = 0.086). Side effects including flushing and headache, were common. The study population had a mortality of 23% during the 6 month period, the amputation rate was 43.5% for iloprost and 50% for placebo treated patients. In this severely diseased population of patients a treatment period limited to 2 weeks did not sufficiently improve ulcer healing. In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI.
                The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting <or=72 hours of the index revascularization and then 5 days per week for 8 weeks. The study primary end point was the composite end point of death or amputation at or above the level of the ankle at 180 days.
                The study randomized 322 patients, and 284 received at least one dose of study medication and were included in the intention-to-treat population. A total of 213 patients underwent surgical bypass, and 71 underwent endovascular revascularization before receiving study medication. The distribution of index revascularization procedures and location of distal target arteries were similar for both placebo and lipo-ecraprost groups. At 180 days, 21 patients (7.4%) were lost to follow-up before reaching the primary end point. Seventy-one percent of the patients taking the placebo completed at least half the doses of the study medication compared with 48% of those taking lipo-ecraprost. Index leg revascularization-assisted primary patency was 82% in the placebo group and 84% in the lipo-ecraprost group (P = .874). Changes in lower extremity hemodynamics as a result of the revascularization during the study period did not differ between the placebo and lipo-ecraprost treatment arms. For the primary event of amputation-free survival, there were no differences between groups: 19 major amputations occurred in the placebo group and 17 in the lipo-ecraprost group; 19 deaths occurred in the placebo group and 13 in the lipo-ecraprost group.
                Eight weeks of parenteral therapy with lipo-ecraprost after distal revascularization in patients with CLI provided no additional benefit in the reduction of major amputation or death at 180 days. Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5-ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis. To determine the effectiveness and safety of topical glyceryl trinitrate (GTN) in the management of acute anal fissure in children.
                Individual children were randomised to receive GTN paste or placebo for six weeks in addition to oral senna and lactulose. Patients took laxatives alone for a further 10 weeks. Each week a research nurse telephoned families to assess pain scores and give advice. Main outcome measures were validated standardised pain scores and time to painless defaecation.
                Forty subjects were recruited from 46 eligible children; 31 children completed the trial (13 in the GTN group and 18 in the placebo group). No differences in the proportion of those achieving pain free defaecation with relation to time were seen between the two groups. Similarly, there were no significant differences in pain scores between the two groups over the 16 week study period. However, in both groups pain scores had decreased significantly. There were no differences in the incidence of rectal bleeding, faecal soiling, presence of visible fissure, skin tag, or faecal loading at outpatient review at the time of recruitment, or at 6 weeks and 16 weeks. No serious adverse effects were observed.
                This study suggests that 0.2% GTN paste is ineffective in the treatment of acute anal fissures in childhood. However the overall fissure healing rate is high (84%) with associated reduction in pain scores, suggesting that a nurse based treatment programme can achieve a high rate of fissure healing. A prospective, randomized, double-blind, placebo-controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8-week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P < 0.0002). Investigators' global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P < 0.001). Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double-blind therapy for an additional 4 weeks. Eleven active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non-surgical therapy for recalcitrant venous leg ulcers. To compare symptomatic relief, healing, and changes in maximal anal resting pressure with the use of topical formulations in patients with chronic anal fissure.
                Sixty-four consecutive patients with chronic anal fissure were randomized into 4 groups that received, in a double-blind manner, a topical ointment that contained 0.2% nitroglycerine (GTN), 5% xylocaine, Proctosedyl (hydrocortisone acetate, heparin, framycetin sulfate, esculoside, ethoform, butoform) or petroleum jelly (Vaseline), to be applied twice daily. Patients were reviewed at 2-week intervals for 6 weeks. Anal manometry was done before, and 20 minutes after, the first application of the ointment.
                There was significant (p < 0.0001) reduction in mean anal resting pressure after application of GTN, but not any other ointment. Of 16 patients receiving GTN, complete pain relief occurred in 6 and 15 patients after 2 and 4 weeks of treatment, respectively; this was more frequent than in the other 3 groups. At 6 weeks also, complete pain relief occurred more often with GTN than with Vaseline or xylocaine. After 4 weeks of treatment, 3 patients on GTN had complete healing of fissure as compared to one each in the xylocaine and Proctosedyl groups and none in the Vaseline group. At 6 weeks, healing of fissure had occurred in 15 of 16 patients receiving GTN as compared to 4 receiving Vaseline, 11 receiving xylocaine, and 12 on Proctosedyl.
                Topical nitroglycerine produces 'chemical sphincterotomy' with reduction in mean anal resting pressure. Pain relief and healing of fissure occurred earlier with GTN than with other treatments. GTN should be considered as the treatment of choice for the non-surgical management of patients with chronic anal fissure. To determine both the efficacy and safety of the topical application of 50 mg penicillin G potassium troches (Cankercillin) in the treatment of minor recurrent aphthous stomatitis (RAS).
                The investigation used a phase 2 double-blind, randomized placebo-controlled trial with a no-treatment arm. Subjects with minor aphthous ulcers of duration <48 hours were followed for 1 week. The primary endpoint for efficacy was time (days) to complete ulcer resolution, and the secondary endpoint was time (days) to complete pain relief.
                Thirty-one, 33, and 36 subjects were randomized to the active treatment, placebo, and no-treatment arms, respectively. Baseline findings were heterogeneous across arms. Subjects who received penicillin G treatment had complete ulcer healing and pain relief significantly earlier than those in the placebo and no-treatment arms. No allergic reactions were observed.
                Topical penicillin G, by mechanisms which remain unclear, reduces the time of healing and pain relief of minor aphthous ulcers with minimal safety concerns. Larger phase 3 studies are necessary to confirm these findings. 148 patients with leg ulcers were treated in 14 clinics with Clinagel or with Debrisan Paste for four weeks. The size of the surface of the ulcer and the overall evaluation of the ulcer by physician before and after treatment were the most important criteria for the assessment of efficacy. The comparison between the two treatments was carried out by t- and x2-test at the level of a = 0.05. Clinagel was shown to be better than Debrisan. Its superiority was statistically significant in regard to reduction of area, depth, pain and swelling, increase of granulation tissue, reepithelialisation of ulcer and the subjective judgement of physician and patient. No systemic side effects were observed in any of the patients and only slight local side effects were registered.
Despite some positive results regarding rest-pain relief, ulcer healing and amputations, there is no conclusive evidence based on this meta-analysis of the long-term effectiveness and safety of different prostanoids in patients with CLI. Further well-conducted, high quality randomised double-blinded trials should be performed.