Epidural labor analgesia and the incidence of cesarean delivery for dystocia.

UNLABELLED: We performed this retrospective study to examine the changes in cesarean delivery rates associated with the establishment of a labor epidural service. In April 1993, St. Louis Regional Medical Center established an on-demand labor epidural service. We obtained demographic data for all patients and reviewed the operative records of all patients undergoing cesarean section who delivered 12 mo before and 16 mo after the start of the labor epidural service. We compared labor epidural rates and total and nulliparous dystocia cesarean delivery rates before and after the epidural service started and among patients who did and did not receive labor epidural analgesia when it was available. Included were 3195 patients who delivered before and 3733 patients who delivered after epidural analgesia became available. Labor epidural rates were 1.2% vs 29.4% for the Before group versus the After group (P < 0.001). Total (9.1% vs 9.7%) and nulliparous dystocia (5.7% vs 6.4%) cesarean delivery rates did not significantly change with the availability of epidural analgesia. However, the total (11.6% vs 8.8%; P = 0.009) and dystocia (8.0% vs 1.0%; P = 0.001) cesarean delivery rates were higher among patients who received epidural analgesia when it was available. We conclude that epidural labor analgesia is associated with, but does not cause, cesarean delivery for dystocia. IMPLICATIONS: Increased epidural analgesia use did not change the overall dystocia cesarean delivery rate, although dystocia was more common among women who chose an epidural analgesia. Consequently, limiting epidural availability will not affect cesarean delivery rates. The evidence does not support advising patients that epidural labor analgesia increases the risk of cesarean delivery.

Anticryptococcal activity of amphotericin B-stimulated macrophages.

Amphotericin B (AmB) and its methyl ester derivative (AME) are immunoadjuvants with macrophage stimulating properties. Cultures containing AmB and murine peritoneal macrophages showed synergistic anticryptococcal activity. The antifungal activity was associated with AmB-stimulated macrophages and with their culture supernatants. Photoinactivation of the residual AmB in the macrophage culture supernatant did not result in the loss of antifungal activity. AmB-stimulated macrophage culture supernatants inhibited the growth of C. neoformans in a dose responsive manner and the activity was destroyed by incubation at 100 degrees C but not at 60 degrees C.

Studies on the molecular mechanisms of human neutrophil Fc receptor-mediated phagocytosis. Evidence that a distinct pathway for activation of the respiratory burst results in reactive oxygen metabolite-dependent amplification of ingestion.

Human neutrophils (PMN) possess at least two distinct mechanisms for the ingestion of IgG-opsonized pathogens; one is independent of and the other is dependent on products of the respiratory burst. Oxidant-mediated ingestion is not induced by exposure to the IgG-opsonized target but requires additional stimulation by phorbol esters or cytokines. The purpose of the present work is to elucidate the signal transduction pathways underlying these two distinct phagocytic mechanisms. Both phorbol ester- and cytokine-stimulated ingestion of IgG-opsonized targets and superoxide anion production were inhibited by the protein kinase C (PKC) inhibitors TFP and H7. In contrast, neither phagocytosis nor superoxide anion generation induced by stimulation with IgG-opsonized targets alone was affected by either of these inhibitors, even when IgG opsonization was increased to generate equal levels of ingestion and superoxide anion as that observed with cytokine stimulation. Moreover, TNF-alpha and IgG-opsonized target stimulation of PMN showed marked synergy in translocation of PKC activity from the cytosol to the plasma membrane. These data indicate that a pathway for activation of the respiratory burst which is dependent on protein kinase C is involved in oxidant-mediated amplification of ingestion. Cytokine stimulation of PMN not only augments IgG-dependent ingestion and generation of superoxide anion but also changes the signaling pathway for these two IgG-dependent functions from PKC-independent to PKC-dependent. In this regard, cytokine stimulation differentiates two pathways for activation of PMN by IgG.

Guanine nucleotide regulation of the interconversion of the two-state hepatic glucagon receptor system of rat.

To investigate whether guanine nucleotides regulate interconversion of the two-state hepatic glucagon receptor we have utilized kinetic assays of glucagon binding to partially purified rat liver plasma membranes. Dissociation of glucagon at 30 degrees C exhibited biexponential character in either the absence or presence of GTP, indicating that the system previously seen in intact hepatocytes is independent of intracellular modulators. In each case the receptors underwent a time-dependent conversion from a low affinity to a high affinity state. However, GTP decreased the fraction of receptors in the high affinity state. The rank order for stabilizing the low affinity state was Gpp(NH)p greater than GTP greater than GDP much greater than GMP = no nucleotides. Data from competition binding assays with increasing concentrations of GTP allow calculation of equilibrium constants which are 3.32 nM for glucagon and receptor in the absence of GTP, 18.6 nM for glucagon and receptor in the presence of GTP, 1.55 microM for the association of receptor and GTP presumably linked to an N protein, and 8.86 microM for the association of the glucagon-receptor complex and GTP again presumably linked to an N protein, Glucagon binding to receptor is noncooperative in both the absence and presence of GTP, distinguishing this system from the beta-adrenergic system. With GTP, binding to the low affinity state is favored because of the relative affinities reported. Therefore, GTP regulates the activation by slowing the conversion of the receptor from a low affinity to high affinity form.