Sonogram of safety: Ultrasound outperforms the fifth intercostal space landmark for tube thoracostomy site selection.

PURPOSE: Identification of tube thoracostomy insertion location is currently performed using a blind, landmark based approach at either the fifth intercostal space (ICS) or inframammary crease in the midaxillary line. A significant percentage of thoracostomies at this site result in complications. This pilot study aimed to assess whether bedside ultrasound could aid in identifying safer tube thoracostomy insertion sites in emergency department patients. METHODS: Fifty emergency department patients were enrolled in this study. Right and left hemidiaphragms were evaluated with ultrasound at the fifth ICS. Observations were made on if the diaphragm was below, above, or crossed the fifth ICS during an entire respiratory cycle. RESULTS: Eighty-one (95% confidence interval 72-82) of the diaphragms were below, 13 (95% confidence interval 8-21) of the diaphragms were at, and 6 (95% confidence interval 3-12) of the diaphragms were above the location marked using traditional landmark techniques. On the right and left hemidiaphragms, 20% (95% confidence interval 19.9%-20.1%) and 18% (95% confidence interval 17.9%-18.1%) of diaphragms were above or crossing the fifth ICS, respectively CONCLUSIONS: Ultrasound identified a significant number of potential chest tube insertion sites at the fifth ICS that would result in subdiaphragmatic insertion or diaphragmatic injury. Based on this data ultrasound can be used to identify safer insertion sites and reduce thoracostomy complications.

Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia.

Diverse molecules induce general anesthesia with potency strongly correlated with both their hydrophobicity and their effects on certain ion channels. We recently observed that several n-alcohol anesthetics inhibit heterogeneity in plasma-membrane-derived vesicles by lowering the critical temperature (Tc) for phase separation. Here, we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n-alcohols and effects on Tc. First, we show that hexadecanol acts oppositely to n-alcohol anesthetics on membrane mixing and antagonizes ethanol-induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described "intoxication reversers" raise Tc and counter ethanol's effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that elevated hydrostatic pressure, long known to reverse anesthesia, also raises Tc in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that ΔTc predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia.

Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy.

Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of "retinal failure." Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes.

Liquid general anesthetics lower critical temperatures in plasma membrane vesicles.

A large and diverse array of small hydrophobic molecules induce general anesthesia. Their efficacy as anesthetics has been shown to correlate both with their affinity for a hydrophobic environment and with their potency in inhibiting certain ligand-gated ion channels. In this study we explore the effects that n-alcohols and other liquid anesthetics have on the two-dimensional miscibility critical point observed in cell-derived giant plasma membrane vesicles (GPMVs). We show that anesthetics depress the critical temperature (Tc) of these GPMVs without strongly altering the ratio of the two liquid phases found below Tc. The magnitude of this affect is consistent across n-alcohols when their concentration is rescaled by the median anesthetic concentration (AC50) for tadpole anesthesia, but not when plotted against the overall concentration in solution. At AC50 we see a 4°C downward shift in Tc, much larger than is typically seen in the main chain transition at these anesthetic concentrations. GPMV miscibility critical temperatures are also lowered to a similar extent by propofol, phenylethanol, and isopropanol when added at anesthetic concentrations, but not by tetradecanol or 2,6 diterbutylphenol, two structural analogs of general anesthetics that are hydrophobic but have no anesthetic potency. We propose that liquid general anesthetics provide an experimental tool for lowering critical temperatures in plasma membranes of intact cells, which we predict will reduce lipid-mediated heterogeneity in a way that is complimentary to increasing or decreasing cholesterol. Also, several possible implications of our results are discussed in the context of current models of anesthetic action on ligand-gated ion channels.