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Full Text, Thesis (Masters), Master of Medical Research (MMedRes), School of Pharmacy & Med Sci, Griffith Health, Background and Aims Peripheral intravenous catheters (PIVCs) are the most commonly used vascular access device for short term medical therapy [1-3]. Despite their ubiquitous use, up to 69% of PIVCs fail before therapy is complete [4-6]. The failure of PIVCs delays treatment, causes discomfort and increases the risk of infection [5]. Reducing the PIVC failure rate by 10% (assuming a 69% failure rate and a 70 AUD replacement cost) would save 210 million AUD per annum, with 30 million PIVCs used annually [7] in Australia. Considering the impact that PIVC failure has on clinical practice and patient outcomes, there is a significant need to improve our understanding of the causative factors of PIVC failure. Firstly, this thesis aimed to develop a vascular access phantom that mimics the ultrasonic nature of a human’s subcutaneous tissue within the antebrachium and various standardised operating procedures that quantify anatomical volumes (blood vessel and artificial thrombus) from a three-dimensional (3D) ultrasound transducer. Secondly, this thesis sought to determine whether inserting 18G or 22G PIVCs affects vessel diameter and volume, blood flow velocity and PIVC-associated thrombosis volume change over five hours. Methods The current thesis was comprised of three parts; 1, 2 and 3. Part 1 developed an in vitro vascular access phantom that mimicked the ultrasonic appearance of the distal cephalic vein with a luminal thrombus. Part 2 quantified the internal luminal volume of various sized silicone rubber microtubes, in addition to artificial thrombi within the silicone tubing, using various three-dimensional (3D) volume rendering methods (Virtual Organ Computer-Aided Analysis (VOCAL), Tomographic Ultrasound Imaging (TUI) area and diameter measurements, and Materialise Interactive Medical Image Control System (MIMICS) software). Part 3 investigated the impact of bilateral insertion of 18G and 22G PIVCs into the distal cephalic veins of volunteers by assessing blood vess

Full Text, Thesis (Masters), Master of Medical Research (MMedRes), School of Pharmacy & Med Sci, Griffith Health, Background and Aims: Peripherally inserted catheters (PIVCs) are one of the most commonly utilised invasive device globally [1-3]. However, despite the frequent usage of PIVCs, up to 69% [4-8] of these devices fail (unplanned removal) before the completion of therapy. Failure of PIVCs can delay treatment, cause discomfort (due to the requirement for new cannula insertion) as well as increase the risk of infection [9]. Reducing the failure rate of PIVCs by 10% (assuming a 69% failure rate and a $70 replacement fee) would also save AUD 210 million per annum, given that approximately 30 million PIVC's are used annually [2] in Australia. Considering the impact of PIVC failure on clinical practice and patient outcomes, there is a significant need to improve our understanding of the determinants of PIVC failure. The current thesis aimed to develop a method that measures the velocity of saline infusion by measuring the pressure within the infusion line. Secondly, this thesis sought to determine whether high, yet clinically relevant infusion rates (i.e. 1.5 mL/s), result in vascular damage. Methods: The current thesis was comprised of three main parts; part 1, 2 and 3. Part 1 developed a software application using LabVIEW to assess real-time infusion flow rates from a pressure transducer. Part 2 identified the relationship between pressure and flow rate in an in vitro and in vivo system. Part 3 investigated the impact of high (1.5 mL/s) and low (0.1 mL/s) infusion flow rates on platelet activation, haemolysis, and plasma concentrations of single-stranded deoxyribonucleic acid (ssDNA). Results: A second-order polynomial relationship existed between pressure and flow rate; with the pressure increase being proportional to the flow rate squared. The pressure values within the 22G PIVC were significantly greater than that of the 18G PIVC at the same flow rate, in both the in vitro and in vivo experiments. No significant increase was observed in blood platelet activation, haemoly

Full Text, Thesis (Masters), Master of Medical Research (MMedRes), School of Medical Science, Griffith Health, Introduction: Elevation in serum bilirubin concentration is associated with reduced risk of cardiovascular disease (CVD). Silymarin, an extract of the Milk Thistle plant, inhibits UGT1A1 enzymes, the main enzyme responsible for the conjugation and elimination of bilirubin from the body. This effect of elevated serum bilirubin may potentially protect against CVD. Aim/Objective: Using a single-blind, placebo-controlled crossover trial to investigate the in-vivo effects of Legalon®, on circulating bilirubin concentrations, platelet characteristics, and coagulation, recognised CVD biomarkers. Method: The effects of Milk Thistle (Silibinin) On circulating unconJugated bilirubin levels and markers of Oxidative stress and inflammation (MOJO) study was a randomised single-blind, crossover, placebo-controlled trial. The required number of participants, based on power calculation and basis of the trial was sixty-five participants. Participants were provided Legalon® and placebo during two supplementation phases, each of 14 days duration with a 28 day washout period in between. Demographic data and blood samples were collected during seven participant visits (screening, Day 0, Day 7, and Day 14 for each arm). Light transmission aggregometry, flow cytometry, clinical biochemistry, haematology, coagulation analysis, and high-pressure liquid chromatography (HPLC) were performed for collecting blood samples. Subsequent statistical analysis was conducted for seventeen participants who had satisfactory compliance (> 80% compliance for both study arms). Results: Twenty-five male participants were enrolled into the MOJO trial. Seventeen male participants completed the trial with satisfactory compliance (>80% for both the Legalon® and placebo capsules). Circulating total bilirubin (TB) and direct bilirubin (DB) showed no significant difference between time points, and between the study arms (TB ANOVA time p=0.8773, treatment p=0.8971; DB ANOVA time p=0.9210, treatment p=0.9849). This w

Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Medical Science, Griffith Health, Bilirubin is a haem catabolite that is excreted through the hepatobiliary pathway and is therefore, commonly used as a biomarker of hepatic dysfunction and haemolysis in the clinical setting [1]. Although, bilirubin has been considered toxic [2], recent evidence suggests that mildly elevated circulating bilirubin concentrations may be protective against obesity, cardiovascular diseases (CVDs) and all-cause mortality [3–5]. Generally, the protective effects of bilirubin are attributed to its antioxidant potential [6–8], however, recent studies demonstrate that bilirubin modulates lipid metabolism and reduces adiposity, which could partly contribute to CVD protection [5,9–12]. However, a shortage of studies have examined the precise mechanisms of cholesterol metabolism and adiposity that could be affected by bilirubin. The main aims of this thesis were to: 1) determine whether hyperbilirubinaemia affects cholesterol synthesis, transport, and excretion; 2) explore bilirubin’s impact on body composition and bioenergetics including mitochondrial function in liver/skeletal muscle and changes in mitochondrial density and quality; 3) determine the effectiveness of oral Legalon® ingestion on circulating bilirubin concentrations, to investigate whether inducing mild hyperbilirubinaemia could impact circulating lipid concentrations in human participants. The first study measured the effect of hyperbilirubinaemia in mutant Gunn rats on circulating lipid concentrations, cholesterol synthesis, lipid excretion, and expression of hepatic genes/proteins involved in cholesterol metabolism. Female hyperbilirubinaemic (Gunn) rats had reduced serum cholesterol concentrations (0.60 ± 0.12 vs 1.56 ± 0.34 mM, P<0.001), elevated cholesterol synthesis (33.8 ± 3.77 vs 28.4 ± 5.73 % [13C]-cholesterol, P<0.05), enhanced LDL receptor (LDLr; P<0.01) expression, and increased biliary cholesterol excretion (232 ± 32.7 vs 141 ± 42.1 nmol hr-1 100g-1 bodyweight, P<0.001) compared to female normobilir

Full Text, Thesis (Masters), Master of Medical Research (MMedRes), School of Medical Science, Griffith Health, Introduction/Aims: Patients undergoing interventional neuroradiology (IVN) procedures to treat intracranial aneurysms experience a minor, but potentially life threatening risk of thromboembolic or haemorrhagic complications. Antiplatelet medications, such as clopidogrel and aspirin, are routinely administered pre-operatively for elective IVN procedures to reduce the risk of thromboembolic events. There are known hyper- or hypo-effective responses to these pre-operative antiplatelet medications, notably clopidogrel, which may insufficiently inhibit platelet function in some patients and increase the risk of complication. The point-of-care (POC) Multiplate® analyser was used to assess platelet function (aggregation) at numerous time points. Patient outcome (ie. those who suffered surgical complications, and those who did not) was assessed to establish whether platelet functionality was related to IVN complication. Additionally, analysing platelet response data in patients with and without complications aimed to establish the potential diagnostic value of Multiplate® response for negative clinical outcomes. In addition, platelet aggregation as recorded by Multiplate® analysis was with platelet activation as assessed using flow cytometry in an attempt to compare functional Multiplate® data to sensitive molecular activation markers. Methods: This project received ethical approval from Griffith University and the Gold Coast University Hospital (GCUH), including amendments for the inclusion of flow cytometric analysis. Demographic and surgical data, as well as blood samples were collected from adult patients admitted to the GCUH for elective or emergent treatment of intracranial aneurysms between March 2015 and April 2018. Blood samples were collected at five separate time points: admission (pre-antiplatelet administration), pre-operatively (post-antiplatelet administration), post-surgically, and at days 1 and 4 post-operatively. The samples of 120 patients and 131 procedu

Introduction: Vascular access devices are commonly inserted devices that facilitate the administration of fluids and drugs, as well as blood sampling. Despite their common use in clinical settings, these devices are prone to occlusion and failure, requiring replacement and exposing the patient to ongoing discomfort/pain, local vessel inflammation and risk of infection. A range of insertion and maintenance strategies are employed to optimize device performance; however, the evidence base for many of these mechanisms is limited and the mechanisms contributing to the failure of these devices are largely unknown. Aims/objectives: (1) To revisit existing understanding of blood, vessel physiology and biological fluid dynamics; (2) develop an understanding of the implications that different clinical practices have on vessel health, and (3) apply these understandings to vascular access device research and practice. Method: Narrative review of biomedical and bioengineering studies related to vascular access practice. Results/outcomes: Current vascular access device insertion and maintenance practice and policy are variable with limited clinical evidence to support the theoretical assumptions underpinning these regimens. This review demonstrates the physiological response to vascular access device insertion, flushing and infusion on the vein, blood components and blood flow. These appear to be associated with changes in intravascular fluid dynamics. Variable forces are at play that impact blood componentry and the endothelium. These may explain the mechanisms contributing to vascular access failure. Conclusion: This review provides an update to our current knowledge and understanding of vascular physiology and the hemodynamic response, challenging some previously held assumptions regarding vascular access device maintenance, which require further investigation.