Impact of two extubation techniques on the intra-abdominal pressure: a preliminary study.

PURPOSE: High pressure peaks might be a risk factor for the development of abdominal hernia. The course of abdominal pressure during extubation remains unclear. This preliminary study assessed the impact of two established extubation techniques. METHODS: Twenty-four consecutive patients suffering from abdominal wall hernia with the indication for surgical treatment were included. Twelve patients were extubated directly after the intravenous anaesthesia was stopped, before they had spontaneous breathing (deep extubation). The other 12 were extubated after they had spontaneous breathing (awake extubation). Intra-abdominal pressure (IAP) was measured via bladder catheter continuously. RESULTS: The highest value during extubation as well as the main increase in IAP was significantly lower in patients who underwent deep extubation (p < 0.001). CONCLUSIONS: Therefore, this extubation technique might improve the outcome of hernia repair.

Azithromycin suppresses CD4(+) T-cell activation by direct modulation of mTOR activity.

Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4(+) T-cells. Isolated CD4(+) T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4(+) T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4(+) T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides.