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General Hospital

Patient and Volunteer Studies

Inflammation and the Host Response to Injury researchers aim to identify which trauma or burn patients will go on to develop multi-system organ failure. Scientists sample whole blood and other available tissues from trauma patients in an effort to correlate molecular markers with white blood cell behavior, and ultimately, with patient outcome. Clinical researchers from 13 to 15 participating hospitals nationwide collect blood and tissue samples from four groups of human subjects: burn patients, trauma patients, lipopolysaccharide (LPS)-challenged volunteers, and normal volunteers. Predefined standard operating procedures (SOPs) for sample collection and sample processing help minimize variation in sample quality between centers and permit data analysis of the highest quality.

We selected two patient groups and two categories of human volunteers for these clinical studies because we believe that there is a critical need to separate responses that are common from responses that are unique to a particular condition. For the volunteer studies, researchers administer LPS to study participants according to a carefully defined protocol. An LPS "challenge" to volunteers should cause an acute, limited inflammatory process, which we predict will be very different from the acute inflammatory process provoked by injury. We anticipate finding common as well as contrasting features in the proteomic and genomic data gathered from both sets of research subjects. These findings should distinguish the molecular mechanisms involved in producing inflammation in each group of patients. Scientists working under this grant deposit appropriately consented human studies data into comprehensive databases to help sort and define the clinical, physiological, cellular, genomic, and outcomes information from research subjects. Patient confidentiality is strictly maintained through a stringent data coding system.

Model Validation Studies

Another key goal of the research program is to evaluate established models of burn injury, trauma-hemorrhage, and acute inflammation. Researchers will examine changes in gene expression patterns and evaluate the cellular and molecular changes in organs, blood, and other tissues using well-established models of injury.

Research results from these model validation studies are deposited into a database that will house data on post-injury genomic and proteomic changes. This database serves as a firm foundation for comparisons between genomic changes observed in human and murine studies.

We may discover that the molecular changes occurring after injury are substantially different between humans and the models used for validation. This might simply reflect the fact that established experimental designs have isolated control mechanisms that differ between murine and human physiology, or that the models only took into account a single component of the human disease process. The new knowledge we gain from performing validation studies will have two implications. Our findings may show that the interpretation of results from these studies would be applicable only within the context of the limitations of a particular model. Or, perhaps more importantly, the models used for validation could now be redesigned to more closely mimic the human injury phenotype and genotype.

Model validation studies are necessary if the injury research community is to develop better strategies to prevent the complications that take the lives of seriously injured patients.