Volatile anesthetic effects on isolated GABA synapses and extrasynaptic receptors.

The volatile anesthetics enhance GABAergic inhibitory transmission at synaptic and extrasynaptic sites at central neurons. In the present study, we investigated the effects of three volatile anesthetics (isoflurane, enflurane and sevoflurane) on synaptic and extrasynaptic GABA(A) receptor responses using mechanically dissociated rat hippocampal CA1 neurons in which functional native nerve endings (boutons) were retained. The extrasynaptic GABA(A) receptors were activated by exogenous GABA application while synaptic ones were assessed by miniature and evoked inhibitory postsynaptic currents (mIPSCs and eIPSCs, respectively). All volatile anesthetics concentration-dependently enhanced the exogenous GABA-induced postsynaptic responses. The structural isomers, isoflurane and enflurane, increased mIPSC frequency while sevoflurane had no effect. None of these anesthetics altered mIPSC amplitudes at their clinically relevant concentrations. Sevoflurane prolonged event kinetics by increasing decay time of mIPSCs and eIPSCs at clinically relevant concentration. On the other hand, both isoflurane and enflurane only prolonged the kinetics of these events at 1 mM of high concentration. For GABAergic eIPSCs, both isoflurane and enflurane decreased the evoked response amplitude and increased the failure rate (Rf), while sevoflurane decreased the amplitude without affecting Rf. These results suggest that isoflurane and enflurane at the clinically relevant concentrations predominantly act on GABAergic presynaptic nerve endings to decrease action potential dependent GABA release. It was concluded that these anesthetics have heterogeneous effects on mIPSCs and eIPSCs with different modulation of synaptic and extrasynaptic GABA(A) receptors.

Staphylococcus aureus--human endothelial cell interactions.

Staphylococcus aureus is an invasive pathogen capable of causing life-threatening disease. A major component of this pathogen's virulence is its ability to invade normal endovascular tissue. We examined the interaction of S. aureus with cultured human endothelial cells and with human and rabbit endovascular tissue. Our ultrastructural study demonstrated a sequence of steps which occurred with staphylococcal invasion of human endothelial cells; adhesion, endocytosis, and intracellular replication. Ultimately, this resulted in cell disruption and death. Cytochemical staining of lysosomes demonstrated lysosomal fusion with both viable and killed intracellular bacteria without evidence of staphylococcal degradation. Quantitative studies using an in vitro infection assay demonstrated comparable rates of adhesion by viable and ultraviolet-killed bacteria, phagocytosis at a slower rate, and intracellular replication. The present study demonstrates an active role for the endothelial cell in the development and spread of endovascular staphylococcal infections. It also supports the use of this in vitro tissue culture system as a model for the study of bacterial invasion of the endothelium.

Tuberculous meningitis in an urban medical center.

Forty-five cases of tuberculous meningitis at a large urban medical center were reviewed. Reasons for the continued incidence, prognostic factors, and current therapy of this life-threatening form of tuberculosis were examined. Thirty-nine of 45 patients were black, Hispanic, and/or 65 years of age or older (87%). Underlying conditions included alcohol abuse in 12, intravenous drug abuse in 7, recent steroid therapy in 4, head trauma in 4, recent pregnancy in 4, and the acquired immunodeficiency syndrome in 1. Thirty-four patients (76%) presented with altered mental status and/or focal neurologic findings. Significant mortality (31%) occurred despite the administration of antituberculous therapy to all but 1 patient. Six of 14 deaths (43%) occurred in the first week of hospitalization. One-third of survivors had neurologic sequelae at the time of follow-up. Neurologic deficits on admission, advanced age, and alcohol abuse were frequent among those who succumbed. Early recognition and treatment in hospital failed to improve outcome in advanced cases. From these findings we conclude that both aggressive treatment of primary tuberculous infections as well as prevention of secondary cases are necessary to effect any further reduction in the incidence, morbidity, and mortality of tuberculous meningitis.

Bacterial adherence to human endothelial cells in vitro.

Differences in the ability of bacteria to adhere to normal valvular endothelium may account for the predominance of particular species as pathogens in acute endocarditis. An in vitro adherence assay was developed to simulate the host surface encountered in acute bacterial endocarditis by using confluent monolayers of human endothelial cells. Adherence of 32 gram-positive and -negative blood culture isolates to this surface was compared. All five Staphylococcus aureus strains tested were highly adherent to endothelial cells, as was one gram-negative strain (Serratia marcescens). The remaining gram-positive and -negative isolates, including four viridans streptococci, were relatively nonadherent. Transmission electron microscopy demonstrated attachment of Staphylococcus aureus and invagination of the underlying endothelial cell membrane at 1 h followed by engulfment of large numbers of bacteria after 3 h. The intracellular bacteria appeared to be contained within vacuoles. Preferential attachment of some strains of bacteria, in particular Staphylococcus aureus, to human endothelial cells occurred in vitro, suggesting that adherence is an important determinant of bacterial pathogenicity in acute endocarditis. Active uptake of bacteria by endothelial cells may help account for the virulence of Staphylococcus aureus in endovascular infections and for the ability of this organism to establish multiple metastatic foci of infection.