Surgery (St Vincent's) - Theses

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    Investigations of the patello-femoral joint in the osteoarthritic knee
    SWAN, JOHN ( 2013)
    Background Patello-femoral arthritis and anterior knee pain is common in patients with tibio- femoral arthritis. It is presumed that anterior knee pain is caused by patello-femoral arthritis and or malalignment. The predictors of anterior knee pain post total knee arthroplasty are unknown. There are no studies describing the nature and location of anterior knee pain. Methods A retrospective analysis of a prospectively followed cohort of 334 patients undergoing knee arthroplasty was performed. Radiological analysis of measures of patello- femoral malalignment and joint space narrowing was performed. These measures were analysed for association with anterior knee pain and function. A prospective cohort study of 105 patients was performed with minimum 12 months follow-up to analyse post-operative patello-femoral alignment in knees with and without patellar resurfacing. Statistical analysis was performed for possible clinical and radiological predictors of post-operative anterior knee pain. The location of anterior knee pain was reported in this cohort via drawings performed by patients and analysis of pre and post arthroplasty anterior knee pain location was performed. Results Patello-femoral malalignment as measured by lateral patellar tilt and lateral displacement were strongly associated with severe patello-femoral arthritis. Anterior knee pain was not associated with arthritis or malalignment of the patello-femoral joint. Knees that underwent patellar resurfacing during total knee arthroplasty had better post-operative patellar alignment compared to patellae left non-resurfaced. Better patello-femoral alignment did not correlate with improvement in function or decrease in anterior knee pain. Female gender was an independent factor associated with anterior knee pain both before and after arthroplasty. Anterior knee pain is felt more often peripherally around the patella than centrally. Anterior knee pain post-arthroplasty is most commonly similar in nature and location to pain felt pre arthroplasty. Conclusion Patello-femoral arthritis is more severe in knees with patello-femoral malalignment. The cause of anterior knee pain is multi-factorial and predicting anterior knee pain after total knee arthroplasty is difficult. Female gender was the only strong statistical predictor of anterior knee pain pre and post arthroplasty. Better patellar alignment post arthroplasty does not guarantee better function or less anterior knee pain at 12 months follow-up.
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    Cardiac surgery using cardiopulmonary bypass in adult patients, effects of pre-operative insulin resistance and the metabolic syndrome, dimethylamine dimethylaminohydrolase activity, and vasoreactivity of regional adipose tissue
    Conaglen, Paul Joseph ( 2013)
    Introduction: Atherosclerosis and coronary artery disease (CAD) are accelerated in Diabetes mellitus (DM) and the Metabolic Syndrome (MS). Insulin Resistance (IR) is thought to be central in its pathogenesis. Recently, Asymmetric Dimethylarginine (ADMA) has linked IR and CAD. ADMA inhibits the vasodilating and vasoprotective agent Nitric Oxide (NO), while the enzyme Dimethylarginine Dimethylaminohydrolase (DDAH)reduces circulating levels of ADMA. As an increase in visceral adiposity is associated with MS and IR, we sought to determine if there were clinically relevant differences in ADMA and DDAH levels in adipose tissue from patients undergoing cardiac surgery, with and without DM and MS. Adipose tissue may alter vascular function via production of vasoreactive paracrine factors. This may explain the acceleration of atherosclerosis in patients with DM and IR. We sought to determine if vasoreactive factors were altered in the adipose tissue of patients with IR or the MS. Methods: Between January 2002 and December 2011, clinical data was prospectively collected on all patients undergoing open cardiac surgery at St Vincent’s Hospital. During 2012, 40 patients undergoing non-emergency cardiac surgery were recruited and adipose tissue was harvested intra-operatively, as well as peri-operative blood and IR parameters. Adipose samples were analysed for DDAH activity, and serum was processed for measurement of ADMA levels. Adipose tissue was incubated with culture medium, and the resulting conditioned medium was used for vasoreactivity experiments. Rat aortic, as well as autologous bypass conduit vessel vasoreactivity was measured using organ bath methodology in the presence of conditioned medium. Results: Of 4542 patients who underwent cardiac surgery in the last 10 years, 1640 (36.1%) had 3 or more surrogate markers of the MS, and 1360 (29.9%) had DM. There was a greater incidence of atrial fibrillation (43.3% vs. 38.6%, p=0.026), renal failure (6.5% vs. 3.8%, p=0.004) and low systemic vascular resistance (16.5% vs. 11.7%, p=0.04) in elective patients undergoing CABG who had the MS. Pre-operative fasting glucose (r=0.63, p<0.001) and HbA1c (r=0.57, p=0.001) correlated with intra-operative hyperglycaemia. HbA1c also predicted post-operative hyperglycaemia (r=0.40, p=0.02). IR measures involving serum insulin (HOMA-IR, QUICKI, LogHOMA) did not predict peri-operative dysglycaemia. Erythrocyte DDAH activity did not appear to change over the course of Cardio-Pulmonary Bypass (CPB). There was an increase in subcutaneous adipose DDAH activity over the course of CPB in patients with the MS (0.02419-0.04318 μg Cit/μg protein/min, p=0.047, n=6), but no change in mediastinal or epicardial adipose DDAH activity was detected. There was also an increase in subcutaneous adipose DDAH activity in diabetic patients (0.02024-0.03127μg Cit/μg protein/min, p=0.013, n=10).There were positive correlations between pre- and post-operative DDAH activity in all depots in patients undergoing CABG with CPB, but not in visceral depots in patients who did not have CPB (OPCAB). Organ bath experiments revealed a significant factor in culture medium that delayed vaso-relaxation to acetylcholine. Vaso-constrictive responses to phenylephrine were not significantly different when conditioned medium was added to the organ bath. Conclusions: There is an increased incidence of post-operative renal failure, atrial fibrillation and low vascular resistance in patients with the MS undergoing CABG. These factors are common with the literature, and may reflect an increased inflammatory response to CPB and surgery. Simple measures of pre-operative dysglycaemia (fasting glucose and HbA1c) correlate with peri-operative dysglycaemia. Levels of DDAH activity in human subjects sustaining an inflammatory stimulus are reported, and appear to increase in subcutaneous adipose tissue. Culture medium utilised for adipose culture contains a significant vaso-active substance that needs to be considered in future experiments.