Battlefield Medicine: Anesthesia and Critical Care in the Combat Zone.

The US Military Joint Trauma System has been developed to mitigate the harsh conditions under which medical providers care for combat casualties and provide continuity of care from the battlefield to US medical centers. We review the components of this system with emphasis on combat trauma care under fire and the role of the anesthesiologist and intensivist in this continuum of care. An important link in the chain of survival is the Air Force Critical Care Aeromedical Transport Team, which provides critical care while transporting casualties from the theater to higher levels of care outside the war zone and home.

Web-based sharing of cutting-edge teaching strategies.

The need to implement improved teaching methods in clinical pharmacology is critically important for health care globally. This need is driven by the overwhelming amount of information currently available on appropriate drug usage, by a proliferation of new biotechnology-derived pharmacologic agents, and by an expanded prescribing authority that is being granted to health professionals who have not traditionally had this responsibility and training. This discussion emphasizes the points that (a) the technology is available to share the best teaching materials for clinical pharmacology over the Internet, (b) clinical pharmacology organizations are best positioned to facilitate this exchange of educational materials, and that (c) continued discourse about problem-based learning and other curricular approaches to teaching clinical pharmacology is essential. The currently available information on the Internet includes case studies, slide sharing for lectures, educational programs and educational software. Clinical pharmacology organizations are not only starting to organize this information, but also to review the content of these programs and continuously add new material. These organizations have also developed a powerful tool through their journals in which to present educational series on rational therapeutics and to discuss educational approaches to instruction. Teaching forums, such as those presented annually at the American College of Clinical Pharmacology Annual Meeting, are essential to encourage discussion about teaching clinical pharmacology in the broadest context of the therapeutics, the economics and the legal aspects of clinical drug use.

Adaptation of resistance arteries to increases in pressure.

During the development of hypertension, hypertrophy of smooth muscle cells and deposition of extracellular matrix thicken the walls of large arteries without reducing the size of the lumen. The small arteries and arterioles remodel inwardly through a eutrophic process of rearrangement of the same smooth muscle cells around a smaller lumen. Pressure, through an increase in circumferential wall stress, can account for both hypertrophy and inward, eutrophic remodeling. The small arteries constrict during an elevation of pressure, thus restoring wall stress toward control levels. The large arteries have little vasoactivity and respond to the increase in wall stress by initiating a growth process. Mechanotransduction of the pressure stimulus to a growth response is being studied in small mesenteric arteries. Raising the pressure from 90 to 140 mmHg initiates a signaling process starting with phosphorylation of Src within 1 minute. This is followed by phosphorylation of Erk 1/2 peaking at 5 minutes and expression of c-fos mRNA within 30 minutes. Gene expression correlates with wall stress and is thus inhibited by a myogenic response. Maintained vasoconstriction in an isolated arteriole results in inward, eutrophic remodeling within 4 days. Thus, the current data support the hypothesis that wall thickness is determined by circumferential wall stress, and lumen size is determined by vascular tone.

Src autophosphorylation is an early event in pressure-mediated signaling pathways in isolated resistance arteries.

Elevated blood pressure is associated with varying degrees of arterial growth and remodeling. The mechanisms by which mechanical stress is converted into cellular alteration have yet to be fully elucidated. Our laboratory has demonstrated that Src tyrosine kinases and the extracellular signal-regulated kinase subtype of the mitogen-activated protein kinase family mediate pressure-induced c-fos expression in rat mesenteric arteries. Others have reported involvement of integrin and growth factor receptor signaling pathways. Our goal was to determine the role of Src, focal adhesion kinase (FAK), and platelet-derived growth factor (PDGF) receptor signaling in the upstream initiation of these events. Pairs of rat mesenteric arteries were pressurized to 90 mm Hg (control), and then one was raised to 140 mm Hg for 1, 3, or 5 minutes. Western blotting revealed that Src-pY(418) was elevated 2.4-fold over control values at 1 minute and 2.8-fold at 3 minutes and returned to control at 5 minutes. Significant FAK-Y(397) phosphorylation was observed only after 3 and 5 minutes of pressure stimulus and was blocked entirely by Src inhibition. Src-pY(215) activity (associated with PDGF receptor activation) does not seem to be involved at any of the time points tested. These data demonstrate that Src-Y(418) autophosphorylation is an early event in pressure mechanotransduction and leads to activation of FAK-Y(397). This finding suggests that Src may be the messenger that initiates and propagates the cellular growth response to pressure stimulus, and FAK is one of its downstream targets. Src phosphorylation due to PDGF receptor activation does not seem to be involved in the initial response.