"Do not quench your inspiration and your imagination; do not become the slave of your model."
Vincent van Gogh
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One consequence of major injury, whether from surgery, burns or trauma, is whole-body inflammation. In most injured patients, this whole-body inflammation resolves promptly with appropriate clinical attention in an intensive care unit. However, in certain patients the inflammation persists, increases in intensity and leads to serious complications that are very difficult to treat effectively. At this time, there is no proven method to identify, on an individual basis, which patients will develop complications and which patients will not.
While medical researchers know a considerable amount about whole-body inflammation, the genetic revolution has provided us with an opportunity to learn much more. The more we know, the better we will be able to predict which patients will suffer from serious complications of whole-body inflammation. Patients identified as being at risk can then be treated earlier and more aggressively, thus reducing morbidity and mortality.
Studies of actual injured patients are extremely valuable
to extend our knowledge of whole-body inflammation, and such studies
are a major focus of this grant. However, one major problem with these
sorts of studies is that it is difficult to compare patients with different
kinds of injuries: for instance, is a patient with a broken leg comparable
to a patient with a blunt abdominal injury such as might occur in an
automobile accident? Another difficulty from a statistical viewpoint
is that one can never study a trauma or burn patient prior to the injury,
and invariably, the duration of time between the injury and the study
is not constant among patients.
Our studies using endotoxin have been very helpful to show that endotoxin administration produces changes in genes over time, and associated with these changes are not only changes in systems related to the innate immune response, but also other important pathways associated with the body’s biological processes.