ENDOSCOPY

Abstract Current antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is not standardized and may be inadequate. We aimed to evaluate the efficacy of 3 days of additional oral antibiotics in the prevention of ERCP-related sepsis. One hundred and fifty-six patients were randomized prospectively to receive either intravenous ticarcillin and clavulinic acid (Timentin® SmithKline Beecham, Dandenong, Victoria, Australia), pre-ERCP (group I) or Timentin® and 3 days of oral amoxycillin and clavulinic acid (Augmentin®; SmithKline Beecham, Dandenong, Victoria, Australia), group II). Blood cultures were taken 30 min after the procedure. The occurrence of sepsis, defined as a temperature over 38°C, occurring in the first 7 days was recorded and the risk factors for the development of sepsis were evaluated. Four patients had significant positive blood cultures despite the prior administration of Timentin.® Sepsis occurred in 10% of group I patients, but only 3% of group II patients (relative risk 3.30; 95% confidence intervals 0.74-14.8). The performance of sphincterotomy and the presence of common bile duct stones were significant risk factors for the development of sepsis. We would recommend 3 days of additional oral Augmentin® after a single dose of intravenous antibiotics in patients at increased risk of sepsis, which would include those with bile duct stones and/or those undergoing a therapeutic procedure.     

RNA editing in human cancer: review

Notice of Retraction: ‘RNA editing in human cancer: review’ (APMIS 2009;117:551–7) The following article from APMIS, ‘RNA editing in human cancer: review’ by Jozef Skarda, Ninette Amariglio and Gideon Rechavi, published online (2 July 2009) in Wiley InterScience ( http://www.interscience.wiley.com ) and in Volume 117, Issue 8 (August 2009), has been retracted by agreement between the authors, the journal Editors‐in‐Chief E. Ralfkiær and B. Norrild and John Wiley & Sons A/S. The retraction has been agreed as a result of textual overlap with a paper published in the journal RNA Biology, ‘A‐to‐I RNA editing and cancer: from pathology to basic science’ by Angela Gallo and Silvia Galardi, published in Volume 5, Issue 3 (September 2008). Jozef Skarda takes full responsibility for the textual overlap.     

Comparative efficacy of various routes of administration of thymopentin (TP-5) with consideration of degradative mechanisms

Thymopoietin32–36 (originally termed TP-5 and now called thymopentin) is a synthetic pentapeptide that can reproduce the biological activity of the 49 amino acid thymic hormone thymopoietin. The efficacy of various routes of administration of thymopentin was studied in mice and guinea pigs using an electromyographic assay as an end point to determine biological activity. In mice, the threshold dose necessary for a significant response when compared to controls was 0.03 mg/kg (mpk) for i.v. (intravenous) injection and 0.3 mpk for both i.p. (intraperitoneal) and s.c. (subcutaneous) injection. For the guinea pig, 0.03 mpk produced a significant response when compared to controls when injected either i.v. or s.c; 0.3 mpk was required for a significant response for i.n. (intranasal) administration and 0.6 mpk for i.p. injection. When saline or plasma was injected, it produced no change in the electromyographic response. In plasma the pentapeptide is rapidly degraded by proteolytic enzymes. Treatment of plasma with specific enzyme inhibitors followed by incubation with thymopentin or thymopoietin confirmed that serine protease and aminopeptidase M-like enzymes are responsible for the rapid inactivation of thymopentin in plasma, as measured by the electromyographic response.     

Thymopentin (TP-5) potency in vivo is enhanced by slow infusion

The in vivo activity of thymopentin in guinea pigs was assessed electromyographically 18 h after intravenous or subcutaneous injections or infusions ranging over varying periods of time. The lowest threshold dose required to establish a positive effect was obtained with a 30–60 min i.v. infusion (0.38–0.75 μg/kg) and we found that we needed X 5 times this dose with 30 min s.c. infusion, X 10 this dose with 10 min i.v. or s.c. infusion, X 200 this dose with bolus IV injection and X 400 this dose with bolus s.c. injection. The marked increase of potency of thymopentin with infusion should be considered in designing clinical regimens.     

Biologically active conformations of thymopentin Studies with conformationally restricted analogs

Four cyclic analogs of thymopentin were synthesized and evaluated for biological activity on the human T cell line CEM. Three of these conformationally restricted analogs were biologically active. The one analog which most closely mimicked the conformation predicted from NMR and theoretical energy minimization calculations proved to be inactive. These studies establish that the biologically active conformations of thymopentin differ from the most probable conformation predicted from solution NMR and theoretical energy minimization studies.