The Centre for Clinical Research in Emergency Medicine (CCREM) is focused on research activities within the spectrum of Emergency Medicine. Our research involves collaboration between clinical academics working in the Emergency Department (ED), research nurses collecting clinical samples from patients presenting to the ED with acute illnesses and basic scientists analysing samples in the laboratory using immunological and molecular biological techniques. Students with a keen interest in clinical immunology may join our group and contribute to the research projects below. All would be suitable starting points for PhD projects, should a student wish to pursue a higher degree.
If you are interested in joining our research group, please contact either Shelley Stone or Simon Brown.
This research program aims to improve our understanding of the immunological responses triggered by traumatic brain injury by identifying key leukocyte signalling pathways and the timing of their activation post-injury. Our main hypothesis is that the activation of leukocyte signalling pathways will be closely correlated with clinical outcomes defined by the Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS). Damage to the brain occurs in two phases; (i) the primary phase which is the initial injury itself and (ii) the secondary phase which consists of delayed responses over ensuing days/weeks, including physiological, cellular and molecular responses aimed at healing the damaged tissue. To establish effective treatment for patients with traumatic brain injury, the complex molecular cascades of gene activation regulating and contributing to neuroinflammation and clinical outcome must be elucidated.
We are collecting blood samples (at arrival and 1, 3, 6, 12, 24, 48 and 72 hours post-arrival) from all patients presenting to the Royal Perth Hospital Emergency Department immediately after isolated head trauma (Injury Severity Score (ISS) >15) for isolation of RNA and separation of serum and plasma. We will (i) compare differential gene expression in two carefully selected groups of patients with matched presentations but clinically distinct early outcomes (based on GOS and DRS scores 3 months after injury), then: (ii) confirm differential expression of candidate proteins deemed the most likely to play a significant role in regulating persistent neuroinflammation and subsequent ongoing disability after traumatic brain injury by quantitative PCR (qPCR) and measurement of serum protein levels in a larger cohort of patients.
More than 60% of patients with severe sepsis seen in the Emergency Department (ED) are elderly (>65 years) and they are twice as likely to die as younger patients with this condition. Chronic illness and poor physiological reserve alone are not responsible for this disparity. Ageing is associated with impaired inflammatory and neurohumoral responses to infection and immunological senescence may predispose to high bacterial load. Septic patients differ greatly with regard to co-morbidities, physiological reserve, immune response, infective agent (type and virulence), initial site of infection, time to presentation and treatments given.
We hypothesise that, in elderly septic patients, high bacterial load is associated with leukocyte inflammatory pathway activation and cytokine surges not seen with low bacterial loads, and that these changes are amplified by initial antibiotic therapy. We also hypothesise that high bacterial load will be such an important determinant of outcome in elderly patients with sepsis that a clear correlation between bacterial load and early (28 day) mortality.
We will measure (in serial blood samples) bacterial load, leukocyte signalling pathway activation and key serum cytokine levels in elderly patients with sepsis on arrival to the ED and during the first 24 hours of treatment. We will also determine the timing and magnitude of the inflammatory (leukocyte activation and key cytokine) response with respect to first antibiotic administration, and whether this differs in those with high versus low bacterial load. The results will help us design future studies of strategies to modulate the impact of inflammatory responses to sepsis and bacterial lysis.