Object-The activity of γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from mesial temporal sclerosis. To provide preliminary safety and distribution data on using convection-enhanced delivery of agents to treat complex partial seizures and to test the efficacy and safety of regional selective neuronal suppression, the authors infused muscimol, a GABA-A receptor agonist, directly into the hippocampus of nonhuman primates using an integrated catheter electrode.Methods-Ten rhesus monkeys were divided into three groups: 1) use of catheter electrode alone (four monkeys); 2) infusion of escalating concentrations of muscimol followed by vehicle (three monkeys); and 3) infusion of vehicle and subsequent muscimol mixed with muscimol tracer (three monkeys). Infusions were begun 5 days after catheter electrode placement and continued for 5.6 days before switching to the other agent. Head magnetic resonance (MR) images and electroencephalography recordings were obtained before and during the infusions. Brain histological studies and quantitative autoradiography were performed.Neurological function was normal in controls and when muscimol concentrations were 0.125 mM or less, whereas higher concentrations (0.5 and 1 mM) produced reversible apathy and somnolence. Fluid distribution was demonstrated on MR images and muscimol distribution was demonstrated on autoradiographs throughout the hippocampus and adjacent white matter.Conclusions-Targeted modulation of neuronal activity is a reasonable research strategy for the investigation and treatment of medically intractable epilepsy.

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Pulsus alternans is a rare hemodynamic condition characterized by beat-to-beat variability in systolic pressure. It is attributed to variations in stroke volume with alternate cardiac cycles and is typically seen in patients with advanced myopathic conditions. Left ventricular pulsus alternans is rare, and right ventricular pulsus alternans is even less common. There are only a few reports of biventricular pulsus alternans. We report the case of a 62-year-old female with a recent anterior wall myocardial infarction who had biventricular pulsus alternans at the time of cardiac catheterization.

Objective To determine factors regulating human aortic smooth muscle cells (HASMC) supported tissue factor-induced thrombin generation. Methods and Results The addition of nonlipidated tissue factor and Ca2+ to HASMCs maintained in reptilase-treated platelet-poor plasma resulted in the robust formation of thrombin after a lag phase of approximately 6 minutes. Pretreatment with low concentrations of α-thrombin before the addition of tissue factor and Ca2+ accelerated the rate of thrombin generation (time to reach half of peak thrombin was reduced by [mean±SD] 42.0±2.2%; P<0.05) but had no effect on the amount of peak thrombin generated. Protease-activated receptor (PAR) 3 activating peptides (APs) or PAR-4 APs accelerated thrombin generation without affecting peak thrombin levels (time to half of peak thrombin decreased by 17.4±5.6% and 21.7±3.5%; P<0.05 with PAR-3 AP and PAR-4 AP, respectively). The addition of PAR-3 AP and PAR-4 AP together had an additive effect, with a reduction in time to half of peak thrombin of 43.9±4.0%. PAR-3 AP or PAR-4 AP enhanced tissue factor–induced factor Xa production and phosphatidylserine exposure on the surface of HASMCs. PAR-1 activation had no effect on thrombin generation, factor Xa production, or phosphatidylserine exposure. Conclusion Low concentrations of α-thrombin accelerate tissue factor–induced thrombin generation on the surface of HASMCs, and this effect is mediated by PAR-3 and PAR-4.