Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/ fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 lCi of iodinated LPS ( 125 I-LPS) and its distribution was assessed in maternal/fetal tissues (1-8 h). In addition, induction of the inflammatory cytokines, TNF-a, IL-1b and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2-8 h). 125I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-a, IL-1b and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1b was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.

No abstract

We sought to examine the significance of the number of nodes examined in node-positive colorectal cancer. Between January 1, 1994, and December 31, 2003, 7192 patients with colorectal cancer underwent potentially curative resection in Region 5 of the California Cancer Registry. Of these patients, 2636 patients were node-positive: 65.1 per cent were N1 and 34.9 per cent were N2. The median follow up was 39.5 months. The mean number of nodes examined was 10.4 (range, 1-89) for NO, 11.0 (range, 1-72) for N1, and 14.6 (range, 4-79) for N2 ( P < 0.0001). N1 and N2 patients were stratified according to the percentage of positive nodes into quintiles (0.19 or less, 0.20 to 0.39, 0.40 to 0.59, 0.60 to 0.79, and 0.80 to 1.0). In both N1 and N2 disease, a lower percentage of lymph nodes involved with metastatic disease was associated with improved survival ( P < 0.0001). The increasing ratio of positive to total nodes was the result of a decrease in the total number of nodes examined in N1 disease and a steeper decline in total nodes examined in relation to the increase in the number of positive nodes in N2 disease. The ratio of positive to total nodes has prognostic significance in node-positive colorectal cancer.