Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis(Oxford University Press, 1998) Ismail, M.M.; Jayakody, R.L.; Weil, G.J.; Nirmalan, N.; Jayasinghe, K.S.A.; Abeyewickreme, W.; Sheriff, M.M.R.; Rajaratnam, H.N.; Amarasekera, N.; de Silva, D.C.; Michalski, M.L.; Dissanaike, A.S.In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 microg/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micro g/kg over a period of 15 months after treatment. All but one subject, with 67 micro filariae (mf)/mL, had pre-treatment counts 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69 percent) were amicro filaraemic by membrane filtration 15 months after treatment compared to one of 12 (8 percent), 3 of 11 (27 percent), and 3 of 10 (30 percent) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77percent 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of micro filaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasisItem Prolonged clearence of microfilaraemia in patients with bancroftian filariasis after multiple high doses of ivermectin of diethylacarbamizine(Oxford University Press, 1996) Ismail, M.M.; Weil, G.J.; Jayasinghe, K.S.A.; Premaratne, U.N.; Abeyewickreme, W.; Rajaratnam, H.N.; Sheriff, M.M.R.; Perera, C.S.; Dissanaike, A.S.In a double-blind trial on 37 asymptomatic microfilaraemic subjects (minimum 400 microfilariae [mf] per mL) with Wuchereria bancrofti infection, the safety, tolerability and macrofilaricidal efficacy of 12 fortnightly doses of ivermectin, 400 microg/kg (ivermectin group), was compared with 12 fortnightly doses of diethylcarbamazine (DEC), 10 mg/kg (DEC group), over a period of 129 weeks after treatment. A control group (LDIC group) was treated with low dose ivermectin to clear microfilaraemia, for ethical reasons. Both ivermectin and DEC in high multiple doses were well tolerated and clinically safe. Macrofilaricidal efficacy was assessed by prolonged clearance of microfilaraemia, appearance of local lesions, and reduction of circulating W. bancrofti adult antigen detected by an antigen capture enzyme-linked immunoassay based on the monoclonal antibody AD12. Mf counts fell more rapidly after ivermectin than after DEC, but low residual mf levels were equivalent in these groups after week 4. Conversely, filarial antigen levels fell more rapidly after DEC than after ivermectin, but low residual antigen levels in these groups were statistically equivalent at all times beyond 12 weeks. Mild, self-limited systemic reactions to therapy were observed in all 3 treatment groups. Local reactions, such as development of scrotal nodules, were observed in several subjects in the DEC and ivermectin groups. These results suggested that high dose ivermectin and DEC both had significant macrofilaricidal activity against W. bancrofti, but neither of these intensive therapeutic regimens consistently produced complete cures. Thus, new drugs or dosing schedules are needed to achieve the goal of killing all filarial parasites in the majority of patients.Item Randomized trial of internal anal sphincter plication with pelvic floor repair for neuropathic fecal incontinence(Lippincott Williams and Wilkins, 1995) Deen, K.I.; Kumar, D.; Williams, J.G.; Grant, E.A.; Keighley, M.R.B.PURPOSE:This study was designed to examine the role of adjuvant internal anal sphincter plication in women with neuropathic fecal incontinenceundergoing pelvic floor repair. METHODS: We completed a randomized trial with symptomatic and physiologic assessment before and after surgery. RESULTS: There was no symptomatic advantage of adding internal sphincter plication; the mean improvement of functional score was 3.61 +/- 1.82 (standard deviation; P < 0.01) following pelvic floor repair alone compared with 2.80 +/- 1.66 (standard deviation; P < 0.01) when adjuvant internal and sphincter plication was added. The addition of internal sphincter plication was associated with a significant fall in maximum anal resting and squeezing pressures (P < 0.01). CONCLUSIONS: Addition of internal sphincter plication is not advised in women with neuropathic fecal incontinence treated by pelvic floor repair.Item Randomised trial to determine the optimum level of pouch-anal anastomosis in stapled restoractive proctocolectomy(Lippincott Williams and Wilkins, 1995) Deen, K.I.; Williams, J.G.; Grant, E.A.; Billingham, C.; Keighley, M.R.B.PURPOSE:This study was undertaken to identify the optimum level of stapled ileal pouch-anal anastomosis. METHOD: A prospective, randomized trial was completed to compare double-stapled ileoanal anastomosis placed at the top of anal columns (high, n = 26) with anastomosis at the dentate line (low, n = 21). RESULTS: There was no significant difference in the overall complication rate between operations (high, n = 7, vs. low, n = 8; P < 0.21). Pouch-anal functional score (scale 0-12; 0 = excellent, 12 = poor) was significantly better in the high anastomosis group (median (range): 2 (1-9) vs. 5.5 (1-12); P < 0.05). Incontinence occurred in only two patients randomized to high anastomosis compared with six in the low anastomosis group. Nocturnal soiling was reported in three patients after high anastomosis and in six patients after dentate line anastomosis. Both operations caused a significant but comparable reduction of maximum and resting pressure (31 percent after high anastomosis (P < 0.05); 23 percent after low anastomosis (P < 0.05)). However, a significant fall in functional length of the anal canal was only seen after a low pouch-anal anastomosis (P < 0.05). CONCLUSION: Stapled pouch-anal anastomosis at the top of anal columns gives better functional results compared with a stapled anastomosis at the dentate line.Item Optimum dose of olsalazine for maintaining remission in ulcerative colitis(British Medical Assosiation, 1994) Travis, S.P.L.; Tysk, C.; de Silva, H.J.; Sandberg-Gertzen, H.; Jewell, D.P.; Jarnerot, G.To evaluate the optimum dose of olsalazine for maintaining remission in ulcerative colitis, 198 patients in remission for more than three months were randomly assigned to receive 0.5 g, 1.0 g, or 2.0 g/day for 12 months. A dose-ranging effect was detected in the per protocol analysis, with remission rates of 60% (0.5 g), 70% (1.0 g), and 78% (2.0 g) (p = 0.03, trend in proportions). The higher dose was most effective in patients with proctitis (90% remission on 2 g/day, p = 0.03) or those in remission for less than 12 months before the trial (88% remission on 2 g/day, p = 0.0006). There was little dose-ranging effect in patients with extensive colitis or those in remission for more than 12 months. Diarrhoea necessitated treatment withdrawal in 12%. The optimal dose of olsalazine for maintaining remission in ulcerative colitis is 1 g/day. For patients with proctitis or recent relapse, 2 g/day may be preferable, although the dose seems to be less important in patients with more extensive disease or those in long term remissionItem Abdominal resection rectopexy with pelvic floor repair versus perinealn rectosigmoidectomy and pelvic floor repair for full-thickness rectal prolapse(1994) Deen, K.I.; Grant, E.; Billingham, C.; Keighley, M.R.A randomized trial was performed to compare abdominal resection rectopexy and pelvic floor repair (n = 10) with perineal rectosigmoidectomy and pelvic floor repair (n = 10) in elderly female patients with full-thickness rectal prolapse and faecal incontinence. There were no recurrences of full-thickness prolapse following resection rectopexy but one after rectosigmoidectomy. Continence to liquid and solid stool was achieved in nine patients, with faecal soiling reported in only two, after resection rectopexy and in eight, with soiling in six, following rectosigmoidectomy. The median (range) frequency of defaecation was only 1 (1-3) per day following resection rectopexy compared with 3 (1-6) per day after rectosigmoidectomy. There was an increase in the mean(s.d.) maximum resting pressure after resection rectopexy (19.3(15.28) cmH2O) compared with a reduction following rectosigmoidectomy (-3.4(13.75) cmH2O) (P = 0.003). Mean(s.d.) compliance was also greater after resection rectopexy than following rectosigmoidectomy (3.9(0.75) versus 2.2(0.78) ml/cmH2O, P < 0.001). Abdominal resection rectopexy gives better functional and physiological results than perineal rectosigmoidectomy.Item Randomized trial comparing three forms of pelvic floor repair for neuropathic faecal incontinence(1993) Deen, K.I.; Oya, M.; Ortiz, J.; Keighley, M.R.A randomized controlled trial in women with neuropathic faecal incontinence compared total pelvic floor repair (n = 12) with anterior levatorplasty and sphincter plication alone (n = 12) and postanal repair alone (n = 12). Review at 6 and 24 months indicated that results were significantly better for total pelvic floor repair than either of the other procedures. Comlete continence was achieved in eight of the 12 patients 2 years after total pelvic floor repair. Only total repair significantly elongated the anal canal. Both total pelvic floor repair and anterior levatorplasty improved sensation in the upper anal canal.Item Does pralidoxime affect outcome of management in acute organophosphorus poisoning?(Lancet Publishing Group, 1992) de Silva, H.J.; Wijewickrema, R.; Senanayake, N.Acute organophosphorus (OP) poisoning is usually treated with atropine plus cholinesterase reactivators such as oximes, but controlled trials to assess the efficacy of oximes in OP poisoning have not been done. A period when the acetyl cholinesterase reactivator pralidoxime chloride was not available in Sri Lanka gave us the opportunity to compare atropine alone for treatment of moderate to severe OP poisoning (21 patients) with atropine plus pralixodime (24 patients). Outcome, as assessed clinically, was similar in the two groups. These results cast doubt on the necessity of cholinesterase reactivators for treatment of acute OP poisoning.Item Clinical and functional outcome after restorative proctocolectomy(1991) de Silva, H.J.; de Angelis, C.P.; Soper, N.; Kettlewell, M.G.; Mortensen, N.J.; Jewell, D.P.Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) has been carried out on 88 patients since 1982. Three different pouch designs (J, S and W) were used. Ten pouches had to be removed. Detailed analysis was performed on 61 patients (J = 23, S = 15, W = 23) whose pouches had been functioning for at least 6 months. There was no significant difference in surgical complications before or after ileostomy closure between pouch designs but the hospital stay was greater after construction of an S pouch (P less than 0.05). There were no significant differences in stool frequency, degree of continence or urgency between the three types. Twelve patients with J pouches required antidiarrhoeal medication compared with only one with S and five with W pouches. Only seven patients with S pouches could defaecate spontaneously compared with 22 with W pouches and all patients with J pouches (P less than 0.001). Twenty-five of 29 patients who had preservation of the anal transition zone had perfect continence compared with 23 of 32 with a mucosal proctectomy (P = n.s.). Pouchitis occurred in 13 patients, all of whom had ulcerative colitis. In a subgroup of 23 patients, pouch evacuation was assessed scintigraphically. There was no difference in pouch capacity or total volume evacuated, but spontaneous evacuation was better in J and W pouches compared with S pouches