Non-surgical interventions for eosinophilic oesophagitis.

BACKGROUND: Patients with eosinophilic oesophagitis (EO) present with difficulty swallowing, vomiting, regurgitation, chest and/or abdominal pain. People with EO frequently fail to respond to treatment with gastric acid suppressants or anti-reflux surgery. OBJECTIVES: To evaluate the benefits and harms of medical interventions for eosinophilic oesophagitis. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register (The Cochrane Library Issue 1, 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February 2004) and EMBASE (1980 to February 2004). SELECTION CRITERIA: Randomised controlled trials were included if they compared a medical or dietary intervention for eosinophilic oesophagitis with a placebo or one medical intervention with another medical intervention. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened the title of abstracts. MAIN RESULTS: No completed RCTs were found in the published literature. We found one abstract reporting preliminary data from an RCT (not completed) comparing oral prednisolone with topical (swallowed metered dose) fluticasone in children. In this study (50 children enrolled to date) healing rates of oesophagitis and symptom resolution with fluticasone were similar to those with prednisolone. For another ongoing RCT, comparing the efficacy of swallowed fluticasone with placebo for eosinophilic oesophagitis in males and females aged 3 to 21 years no results are available. REVIEWERS' CONCLUSIONS: The lack of completed RCT's makes it impossible to compare the relative benefits and harms of the wide range of medical interventions currently used for treating EO. Published case series suggest that an elemental diet, oral steroids and topical steroids all offer some benefits. However, lack of a comparison group in these studies makes it impossible to evaluate the effect of these interventions.

Anthracycline antibiotic blockade of SV40 T antigen helicase action.

We previously showed that anthracycline antibiotics potently block SV40 large T antigen helicase; in the present study, we describe the kinetics and the structure-activity characteristics of this process. The concentration vs effect data for helicase blockade were fitted by the Hill equation to yield nearly parallel log-concentration effect curves for a series of active anthracycline antibiotics. The effective concentration for 50% helicase blockade (EC50) values ranged from 0.34 microM for daunorubicin to 40.8 microM for 3'-deaminodaunorubicin. Clinically inactive 3'-N-acyl anthracyclines produced no blockade. The Hill constants for the blockade ranged from 1.1 to 1.6 for the entire series of active anthracyclines, indicating no positive cooperativity and suggesting that a single molecule of bound drug is sufficient to block helicase action. The EC50 values for several clinically effective anthracyclines showed a relationship to the average DNA binding constants for these drugs, and Lineweaver-Burk analysis of the blockade kinetics indicated non-competitive inhibition. The kinetics of the blockade indicated that the anthracycline, DNA, and helicase form a ternary complex that is irreversible under the reaction conditions. This mechanism may be central to the cytotoxic and anti-cancer activities of anthracycline antibiotics and may be useful in understanding the enzymatic mechanism of DNA helicase action.