Is the management of epidural analgesia associated with an increased risk of cesarean delivery?

OBJECTIVE: The aim of this study was to quantify the association of cesarean delivery with epidural analgesia management, specifically with the timing of epidural catheter placement in relation to labor, the type of epidural analgesia, and the use of bolus dosing. STUDY DESIGN: A retrospective cohort design was used to investigate 1561 consecutive nulliparous parturients whose labor occurred between November 1, 1996, and June 30, 1997, at Northwestern Memorial Hospital and who were delivered of term, singleton neonates in a cephalic presentation. The relationship between the management of epidural analgesia and the risk for cesarean delivery was determined with stepwise logistic regression to control for potential confounding variables. RESULTS: There was a significantly increased risk of cesarean delivery associated with decrements in cervical effacement (P =.001), cervical dilatation (P =.001), and fetal station (P =.001) at the time of epidural catheter placement. An increasing number of epidural boluses during the first stage of labor was also associated with increased risk of cesarean delivery (P =.001). After we controlled for maternal age, maternal body mass index, gestational age, infant birth weight, induction of labor, use of magnesium sulfate, and presence of chorioamnionitis, the adjusted odds of cesarean delivery associated with fetal station (odds ratio, 1.45; 95% confidence interval, 1.2-1.7) and epidural boluses (odds ratio, 1.55; 95% confidence interval, 1.3-1.8) during the first stage of labor remained significant. CONCLUSION: The management of epidural analgesia during labor was associated with the potential for increased risk of cesarean delivery. This risk increased with higher stations of the fetal head at the time of epidural catheter placement and with more frequent epidural boluses of local anesthetic during the first stage of labor.

Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor.

RATIONALE AND OBJECTIVES: The authors developed a new method for delivering contrast agents to tumors and tumor cells. Gadolinium complexes of folate-conjugated dendrimer-chelates increased the longitudinal relaxation rate of tumor cells expressing the high-affinity folate receptor, hFR. The coupling of folate to polymeric chelates, composed of a dendrimer backbone, targets these chelates to endogenous folate binding proteins. These proteins exist in both the serum of patients with cancer and on the cell surface of many human cancers of epithelial origin. METHODS: The authors attached folic acid to a generation four ammonia core polyamidoamine dendrimer. The folate-dendrimer was reacted with 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid to form the polymeric chelate f-PAMAM-TU-DTPA. For fluorescent studies, the generation four dendrimer was reacted with fluorescein-5-isothiocyanate and carboxytetramethylrhodamine succinimidyl ester, followed by capping the remaining amines with succinic anhydride. RESULTS: The study results show that cells accumulate the folate-conjugated dendrimer in a receptor specific manner. Tumor cells expressing the high-affinity folate receptor showed a 650% increase in the mean fluorescence. This increase occurred with a rapid rise to 325%, followed by a slow increase to 650%. It required both the expression of the hFR and the coupling of folic acid to the dendrimer. Excess free folic acid inhibited the binding of the folate conjugated polymer. Fluorescent microscopic study showed that the folate-conjugated dendrimer binds to the cell surface and is accumulated within the cells. Treatment of tumor cells that express the hFR with gadolinium complexes of the folate-conjugated polymeric chelate increases the longitudinal relaxation rate by 110%. This increase was inhibited by an excess of free folic acid. CONCLUSIONS: These data demonstrate that folate-conjugated magnetic resonance imaging contrast agents represent a promising new approach to tumor targeting.

Characterization of a lipopeptide-resistant strain of Candida albicans.

Lipopeptides are antifungal agents that inhibit cell wall beta-(1,3)-glucan biosynthesis in fungal organisms. A mutant resistant to lipopeptides was generated by UV mutagenesis and characterized. The Candida albicans mutant (LP3-1) was stable and showed resistance specificity to a broad range of lipopeptides and certain glycolipid inhibitors. Other antifungal agents with diverse modes of action had a normal minimum inhibitory concentration profile for LP3-1 compared with the wild-type strain (CCH 442). In the in vitro beta-(1,3)-glucan synthase assay, both the lipopeptides and papulacandin-related agents had considerably higher 50% inhibitory concentration values in the LP3-1 strain than in the wild-type strain. In reconstitution assays, the resistance factor was associated with the integral membrane pellet rather than the peripheral GTP-binding protein. The LP3-1 strain had a membrane lipid profile similar to that of the parent strain and was virulent in a murine model of systemic candidiasis. Taken together, these results indicate that the resistance factor is associated with the integral membrane component of beta-(1,3)-glucan synthase. Lipopeptides are common antifungal agents encountered during screening of natural products. The LP3-1 strain was resistant to natural product extracts known to contain various lipopeptides. Thus, LP3-1 can be used in a dereplication assay.