Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and proliferation.

CD40 was originally described as a functionally significant B cell surface molecule. However, CD40 is also expressed on monocytes, dendritic cells, epithelial cells, and basophils. We now report that synovial membrane (SM) or dermal fibroblasts also express cell surface CD40 in vitro. Fibroblast CD40 expression declines with increasing time in culture and recombinant interferon-gamma (rINF-gamma) induces fibroblast CD40 up-regulation. This effect of rINF-gamma is augmented by recombinant interleukin-1 alpha or recombinant tumor necrosis factor-alpha. CD40 expression on fibroblasts is functionally significant because CD40L-CD40 interactions induce SM fibroblast CD54 (intercellular adhesion molecule-1) and CD106 (vascular cell adhesion molecule-1) up-regulation. Moreover, ligation of CD40 augments IL-6 production by SM fibroblasts and induces fibroblasts to proliferate. In addition, rINF-gamma enhances the effect of CD40L-CD40 interactions on fibroblast proliferation. Taken together, these studies show that fibroblasts can express CD40, cytokines can regulate fibroblast CD40 expression, and CD40 ligation induces fibroblast activation and proliferation.

Multianalyte profiling of serum cytokines for detection of pancreatic cancer.

Early detection of pancreatic cancer might improve clinical outcome. Significant alterations in the levels of individual serum cytokines have been reported in pancreatic cancer. We hypothesized that a multicytokine panel could serve as biomarkers for pancreatic cancer. To evaluate the diagnostic utility of such a panel, we have utilized a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple markers. In this study, a panel of 31 serological markers including cytokines, chemokines, growth and angiogenic factors in combination with CA 19-9 was analyzed in sera of pancreatic cancer patients, patients with chronic pancreatitis, and matched control healthy subjects. Statistical analysis identified a multicytokine panel that was able to distinguish pancreatic cancer from healthy controls with a sensitivity of 85.7% and specificity of 92.3%, which was superior to performance of CA 19-9 alone. Importantly, a multicytokine panel allowed the discrimination of pancreatic cancer from chronic pancreatitis with high sensitivity of 98% and specificity of 96.4%. In conclusion, we demonstrated that analysis of multiple serum cytokines using a novel LabMAP technology is a promising approach for development of a diagnostic assay for pancreatic cancer.

An alternative oxygen delivery system for infants and children in the post-anaesthesia care unit.

This randomized controlled trial compared the compliance of a blow-by oxygen method with the standard face mask by children recovering from anaesthesia. The rate at which a face mask was rejected when applied to infants and children in PACU was compared with that of a proposed "hose" method. The efficacy of the "hose" as a method of oxygen supplementation in children at low and high risk for developing postoperative hypoxaemia was also compared with the face mask. Using a Nellcor N-200 pulse oximeter, 66 infants and children (mean age 2.3 yr, range 2 mo-6 yr) were continuously monitored for 30 min upon arrival in the PACU. Patients were randomized to receive oxygen supplementation with either the face mask or the proposed "hose" method. The results showed a greater than 80 per cent rejection of the face mask in contrast to 100 per cent compliance with the "hose" method. The SaO2 measurements following 5, 15 and 30 min of O2 supplementation with the hose were all significantly higher than the SaO2 measurements obtained on room air upon arrival to the PACU. Patients with pre-existing cardiopulmonary disease had a 20 per cent incidence of arterial oxygen desaturation upon arrival to the PACU versus 2.1 per cent of patients with no pre-existing disease. It is concluded that the "hose" is associated with high patient compliance and is effective in the PACU in increasing the SaO2 in children at low or high risk of developing postoperative hypoxaemia.