Optical analysis of glutamate spread in the neuropil.

Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.

An application of continuing medical education to decrease excessive lengths of stay.

The focus of political and public attention on health care costs has created pressures on hospitals to devise effective methods to decrease costs and still maintain excellent medical care. After identifying four medical specialty services in a unit of a tertiary-care hospital where lengths of stay were excessive, even when the average severity of the discharged patients' illnesses in these services was considered, the authors developed two educational interventions to decrease lengths of stay. First, individual meetings were held with each of the attending physicians from three of the four specialty services, and the data on lengths of stay on that particular service were discussed. The fourth service was used as a control. Second, a continuing education meeting was held with attending physicians on all of the specialty services admitting patients to the unit. The data on lengths of stay for all services were discussed. The lengths of stay subsequently decreased significantly in the three targeted specialty services without any measurable change in the quality of care. This improved efficiency persisted for the 16 months after the intervention. Significant changes in length of stay were not observed in the control service or in any of the other specialty services in which the attending physicians experienced only the continuing education meeting.

The efficiency of inpatient medical care in a hospital secure unit.

A method was developed and tested to analyze the efficiency of medical care using each patient's length of hospital stay (LOS) and comparing these LOS with patients with similar diagnoses, ages, and operative conditions. The method assigns a percentile score to each discharged patient's LOS in comparison with the group of patients in the referent population with the same medical condition. A percentile score calculated in this way removes the effect of case mix and intensity of service from each patient's LOS, and allows the efficiency of medical care to be analyzed. This method was applied to patients who were discharged from a secure unit of a general hospital that serves the tertiary medical needs of patients from the state's correctional system. The LOS for our patients on average corresponded to the 60th percentile for the LOS in other patients with comparable ages and medical conditions. This difference was significantly greater than an expected value of 50.0 (P less than 0.01). The LOS of patients discharged from each specialty service were examined. Two services were identified, in which an increased LOS represented a difference in the practice patterns of physicians in these specialties, in comparison with those of other physicians in this area. An application of the method described in this report should enable hospitals to identify units or services where patients are managed inefficiently and to guide the need for managerial intervention.

Cephalexin concentrations in sputum during acute respiratory infections.

In 20 patients with acute pulmonary infections, sputum purulence, sputum volume, and concentration and excretion of cephalexin in the sputum significantly decreased concurrently during therapy. The concentration of cephalexin in the serum remained unchanged. Significant correlations were observed between drug concentrations in sputum and serum and between drug excretion in sputum and concentration in serum. These observations may be explained by decreased integrity of the "blood-bronchus barrier" during inflammation, with diffusion of serum into bronchial mucus, without the necessity of postulating active transport.