Gram-scale purification of aconitine and identification of lappaconitine in Aconitum karacolicum.

Aconitum karacolicum from northern Kyrgyzstan (Alatau area) contains about 0.8-1% aconitine as well as other aconite derivatives that have already been identified. In this paper, we compare several methods for the further purification of an Aconitum karacolicum extract initially containing 80% of aconitine. Reverse-phase flash chromatography, reverse-phase semi-preparative HPLC, centrifugal partition chromatography (CPC) and recrystallization techniques were evaluated regarding first their efficiency to get the highest purity of aconitine (over 96%) and secondly their applicability in a semi-industrial scale purification process (in our case, 150g of plant extract). Even if the CPC technique shows the highest purification yield (63%), the recrystallization remains the method of choice to purify a large amount of aconitine as i) it can be easily carried out in safe conditions; ii) an aprotic solvent is used, avoiding aconitine degradation. Moreover, this study led us to the identification of lappaconitine in Aconitum karacolicum, a well-known alkaloid never found in this Aconitum species.

A clinical comparison of two formulations of tobramycin 0.3% eyedrops in the treatment of acute bacterial conjunctivitis.

PURPOSE: To compare the safety and efficacy of a new enhanced viscosity ophthalmic formulation of tobramycin, given twice daily (BID), with the existing four times daily (QID) treatment regimen in patients with acute bacterial conjunctivitis. METHODS: This was a 12-day, multicenter, observer-masked, randomized, parallel group study. Patients received one drop of tobramycin 0.3% (3 mg/mL) enhanced viscosity ophthalmic solution BID or tobramycin 0.3% (3 mg/mL) ophthalmic solution QID in the affected eyes for 7 days. The primary efficacy variable was the percentage of patients with sustained cure/presumed bacterial eradication based on clinical judgment at the test-of-cure visit (Day 12). Pretherapy bacterial isolates were obtained and tested for susceptibility to tobramycin by determination of minimum inhibitory concentrations (MIC). RESULTS: A total of 276 patients were enrolled in the study and 203 of these were culture positive and attended all follow-up examinations. In this group, 98% of those treated with tobramycin enhanced viscosity ophthalmic solution and 99% of those treated with tobramycin 0.3% ophthalmic solution were categorized as having sustained cure/presumed eradication at the test-of-cure visit (p = 0.6037). Reported adverse events were not serious, mild to moderate in severity, and generally did not prevent continuation in the study. Several pre treatment pathogens demonstrated tobramycin resistance (MIC > 4 mg/mL). However, therapy with both treatments was effective in the majority of the cases. CONCLUSIONS: Tobramycin enhanced viscosity ophthalmic solution is well tolerated and has equivalent efficacy to the established treatment regimen with a simplified posology. The formulation provides an alternative therapy for acute bacterial conjunctivitis that should improve patient compliance and satisfaction.

Meckel's diverticulum in adults: retrospective analysis of 119 cases and historical review.

OBJECTIVE: To publish our experience in the management of Meckel's diverticula in adults, and compare our results with those published elsewhere. DESIGN: Retrospective investigation of casenotes. SETTING: Multicentre study, Switzerland. SUBJECTS: 119 patients aged over 16 years who had Meckel's diverticula resected between 1980 and 1997. MAIN OUTCOME MEASURES: Assessment of the usefulness of various investigations and the criteria for removing asymptomatic diverticula. RESULTS: 67 diverticula (56%) were resected during laparotomy for another cause, and 52 (44%) for symptoms caused by the diverticula. In both groups the condition was more common in men, and most likely to present during the fourth decade. The most common investigation in the 52 symptomatic cases was a plain film of the abdomen (n = 47, 90%), and in none was a Meckel's diverticulum suggested as the cause of the symptoms. The success rates of other investigations were: small bowel enema 4/9, 99mTc scan 3/4, angiography 1/3, and computed tomography 1/14. No ultrasound scans were done. Our results compared favourably with those reported elsewhere, with no deaths in either group, 2 complications that required reoperation in the incidental group, and 1 in the symptomatic group. CONCLUSIONS: The criteria to be taken into account when deciding to resect an asymptomatic diverticulum are: male sex, age <40, ASA score, the operation being done, the size and position of the diverticulum, whether it is palpable, and whether there are other reasons for the patient's complaints.