Thrombosis is a vascular pathological process which frequently affects the veins of the lower limbs, and embolisation of thrombotic material is common. Thromboembolic disease is a common cause of death in Western societies, predominantly affecting the elderly. Numerous risk factors and co-morbidities have been identified. Safe and effective means of prophylaxis are available but are underutilised. Anticoagulant drugs are very effective in preventing thromboembolic disease, but their effects on the evolution of the thrombotic process remain poorly documented. These drugs are difficult to use, and treatment errors and treatment failures are common. The factors which determine the embolisation of deep vein thrombosis are poorly understood. When such embolisation occurs it is usually asymptomatic. Symptomatic pulmonary embolism presents in 3 general ways-pleuritic pain, shortness of breath, or collapse. Tachypnea is the commonest sign. Tests which are available to assist in the diagnosis of thromboembolic disease include the ventilation perfusion lung scan, ultrasound of the lower limbs, pulmonary angiography and echocardiography. The commonest investigation requested in this context is the lung scan. Although the results are often inconclusive, this is frequently the only specific investigation which is performed. The accurate interpretation of lung scans requires consideration of the pretest probability of pulmonary embolism. The D-dimer assay is another test which may be useful. The finding of a normal D-dimer level substantially reduces the probability of thromboembolic disease and may render a lung scan unnecessary. / Subscription resource available via Digital Dissertations only.

Thrombosis is a vascular pathological process which frequently affects the veins of the lower limbs, and embolisation of thrombotic material is common. Thromboembolic disease is a common cause of death in Western societies, predominantly affecting the elderly. Numerous risk factors and co-morbidities have been identified. Safe and effective means of prophylaxis are available but are underutilised. Anticoagulant drugs are very effective in preventing thromboembolic disease, but their effects on the evolution of the thrombotic process remain poorly documented. These drugs are difficult to use, and treatment errors and treatment failures are common. The factors which determine the embolisation of deep vein thrombosis are poorly understood. When such embolisation occurs it is usually asymptomatic. Symptomatic pulmonary embolism presents in 3 general ways-pleuritic pain, shortness of breath, or collapse. Tachypnea is the commonest sign. Tests which are available to assist in the diagnosis of thromboembolic disease include the ventilation perfusion lung scan, ultrasound of the lower limbs, pulmonary angiography and echocardiography. The commonest investigation requested in this context is the lung scan. Although the results are often inconclusive, this is frequently the only specific investigation which is performed. The accurate interpretation of lung scans requires consideration of the pretest probability of pulmonary embolism. The D-dimer assay is another test which may be useful. The finding of a normal D-dimer level substantially reduces the probability of thromboembolic disease and may render a lung scan unnecessary. / Subscription resource available via Digital Dissertations only.

Thrombosis is a vascular pathological process which frequently affects the veins of the lower limbs, and embolisation of thrombotic material is common. Thromboembolic disease is a common cause of death in Western societies, predominantly affecting the elderly. Numerous risk factors and co-morbidities have been identified. Safe and effective means of prophylaxis are available but are underutilised. Anticoagulant drugs are very effective in preventing thromboembolic disease, but their effects on the evolution of the thrombotic process remain poorly documented. These drugs are difficult to use, and treatment errors and treatment failures are common. The factors which determine the embolisation of deep vein thrombosis are poorly understood. When such embolisation occurs it is usually asymptomatic. Symptomatic pulmonary embolism presents in 3 general ways-pleuritic pain, shortness of breath, or collapse. Tachypnea is the commonest sign. Tests which are available to assist in the diagnosis of thromboembolic disease include the ventilation perfusion lung scan, ultrasound of the lower limbs, pulmonary angiography and echocardiography. The commonest investigation requested in this context is the lung scan. Although the results are often inconclusive, this is frequently the only specific investigation which is performed. The accurate interpretation of lung scans requires consideration of the pretest probability of pulmonary embolism. The D-dimer assay is another test which may be useful. The finding of a normal D-dimer level substantially reduces the probability of thromboembolic disease and may render a lung scan unnecessary. / Subscription resource available via Digital Dissertations only.

Thrombosis is a vascular pathological process which frequently affects the veins of the lower limbs, and embolisation of thrombotic material is common. Thromboembolic disease is a common cause of death in Western societies, predominantly affecting the elderly. Numerous risk factors and co-morbidities have been identified. Safe and effective means of prophylaxis are available but are underutilised. Anticoagulant drugs are very effective in preventing thromboembolic disease, but their effects on the evolution of the thrombotic process remain poorly documented. These drugs are difficult to use, and treatment errors and treatment failures are common. The factors which determine the embolisation of deep vein thrombosis are poorly understood. When such embolisation occurs it is usually asymptomatic. Symptomatic pulmonary embolism presents in 3 general ways-pleuritic pain, shortness of breath, or collapse. Tachypnea is the commonest sign. Tests which are available to assist in the diagnosis of thromboembolic disease include the ventilation perfusion lung scan, ultrasound of the lower limbs, pulmonary angiography and echocardiography. The commonest investigation requested in this context is the lung scan. Although the results are often inconclusive, this is frequently the only specific investigation which is performed. The accurate interpretation of lung scans requires consideration of the pretest probability of pulmonary embolism. The D-dimer assay is another test which may be useful. The finding of a normal D-dimer level substantially reduces the probability of thromboembolic disease and may render a lung scan unnecessary. / Subscription resource available via Digital Dissertations only.

Thrombosis is a vascular pathological process which frequently affects the veins of the lower limbs, and embolisation of thrombotic material is common. Thromboembolic disease is a common cause of death in Western societies, predominantly affecting the elderly. Numerous risk factors and co-morbidities have been identified. Safe and effective means of prophylaxis are available but are underutilised. Anticoagulant drugs are very effective in preventing thromboembolic disease, but their effects on the evolution of the thrombotic process remain poorly documented. These drugs are difficult to use, and treatment errors and treatment failures are common. The factors which determine the embolisation of deep vein thrombosis are poorly understood. When such embolisation occurs it is usually asymptomatic. Symptomatic pulmonary embolism presents in 3 general ways-pleuritic pain, shortness of breath, or collapse. Tachypnea is the commonest sign. Tests which are available to assist in the diagnosis of thromboembolic disease include the ventilation perfusion lung scan, ultrasound of the lower limbs, pulmonary angiography and echocardiography. The commonest investigation requested in this context is the lung scan. Although the results are often inconclusive, this is frequently the only specific investigation which is performed. The accurate interpretation of lung scans requires consideration of the pretest probability of pulmonary embolism. The D-dimer assay is another test which may be useful. The finding of a normal D-dimer level substantially reduces the probability of thromboembolic disease and may render a lung scan unnecessary. / Subscription resource available via Digital Dissertations only.

Master of Science / Department of Human Nutrition / Denis M. Medeiros / Copper deficiency has been linked with many health problems, among them cardiac hypertrophy. Because of its potential for causing oxidative damage, copper within the cell must be bound to chaperone proteins. In this thesis, we examined the role of dietary copper deficiency in the regulation of select copper chaperone proteins in cardiac tissue of rats. Sixteen weanling male Long-Evans rats were randomized into treatment groups, one group receiving a copper deficient diet (< 1 mg Cu/kg diet) and one group receiving a diet containing adequate copper (6 mg Cu/kg diet) for 5 weeks. Rats were sacrificed and a small blood sample was removed to determine hematocrit. Also, heart and liver tissues were removed for subsequent analysis. Rats fed the copper deficient diet had lower body weights but greater heart weights and heart:body weight. Hematocrit levels and liver copper concentrations were markedly decreased in copper deficient rats. These variables indicated that the copper deficient diet did in fact induce a copper deficiency in these animals. Non-myofibrillar proteins from the hearts were removed and separated by SDS-PAGE. Western Blotting was used to determine the concentrations of CTR1, CCS, Cox17, SCO1, Cox1 and Cox4. No changes were observed in the concentrations of CTR1 and Cox17. CCS and SCO1 were up-regulated as a result of copper deficiency, while Cox1 and Cox4 were both down-regulated. However, use of another antibody against Cox subunits suggested that only the nuclear encoded subunits including subunit IV were decreased, but not subunits I and II. These data provide new insight into the cardiac hypertrophy observed in copper deficiency, which suggests that select chaperone proteins may be up-regulated by a dietary copper deficiency.

Neuropsychological deficits may perpetuate the risk and chronicity of psychiatric disorder. Borderline Personality Disorder, characterized by significant suicide risk, intense affect and behavioural dysregulation, is frequently associated with the executive function (EF) deficits of decision making and inhibitory control. However, the role of inhibitory control on decision making remains poorly understood. This study examined the relationships among working memory, cognitive and motor inhibitory control, and IGT decision-making performance in 41 women with BPD and 41 healthy controls. Associations among EF and suicide risk were also explored. Experimental tasks included the Iowa Gambling Task, Digit Span, Stroop and Stop Tasks, and Raven’s Matrices. Only IGT decision-making deficits distinguished BPD subjects from healthy controls. Weaker yet normal range IQ and EFs in BPD women did not explain their disadvantageous IGT performance. Contrary to expectations, IGT deficits in BPD women did not predict any suicidal risk; however, intact interference control was as sensitive to suicidal risk as was depression. Normal interference control was associated with a reduction in suicide risk. While IGT decision making may be a marker for BPD, Stroop interference control is more sensitive to suicide risk and may represent a vulnerability for suicide that exists beyond psychiatric diagnosis.

Neuropsychological deficits may perpetuate the risk and chronicity of psychiatric disorder. Borderline Personality Disorder, characterized by significant suicide risk, intense affect and behavioural dysregulation, is frequently associated with the executive function (EF) deficits of decision making and inhibitory control. However, the role of inhibitory control on decision making remains poorly understood. This study examined the relationships among working memory, cognitive and motor inhibitory control, and IGT decision-making performance in 41 women with BPD and 41 healthy controls. Associations among EF and suicide risk were also explored. Experimental tasks included the Iowa Gambling Task, Digit Span, Stroop and Stop Tasks, and Raven’s Matrices. Only IGT decision-making deficits distinguished BPD subjects from healthy controls. Weaker yet normal range IQ and EFs in BPD women did not explain their disadvantageous IGT performance. Contrary to expectations, IGT deficits in BPD women did not predict any suicidal risk; however, intact interference control was as sensitive to suicidal risk as was depression. Normal interference control was associated with a reduction in suicide risk. While IGT decision making may be a marker for BPD, Stroop interference control is more sensitive to suicide risk and may represent a vulnerability for suicide that exists beyond psychiatric diagnosis.

Doctor of Philosophy / Department of Anatomy and Physiology / David C. Poole / The components of the O2 transport pathway can be divided into (along with their respective circulations) the pulmonary, cardiovascular, and skeletal muscle systems. They must operate in tight conjunction with one another, especially during dynamic exercise, to sustain ATP production within muscle mitochondria. Any limitation placed on the O2 transport pathway will result in decreased performance. The purpose of this dissertation is to present four novel studies which examine specific limitations on (1) the pulmonary system (i.e. lungs and circulation) within the highly athletic Thoroughbred horse (Studies A & B), and (2) within the peripheral circulation (i.e. microcirculation) within a disease model of Type II diabetes, the Goto-Kakizaki (GK) rat (Studies C & D). Study A demonstrates that locomotory respiratory coupling (LRC) is not requisite for the horse to achieve maximal minute ventilation (VE) during galloping exercise because VE remains at the peak exercising levels over the first ~13 s of trotting recovery (VE at end exercise: 1391±88; VE at 13 s: 1330±112 L/sec; P > 0.05). The horse also experiences exercise-induced pulmonary hemorrhage (EIPH) which has been linked mechanistically to increased pulmonary artery pressure (Ppa) during high intensity exercise. Therefore, in Study B, we hypothesized that endothelin-1 (ET-1), a powerful vasoconstricting hormone, would play a role in the augmented Ppa and therefore, EIPH. However, contrary to our hypothesis, an ET-1 receptor antagonist did not decrease Ppa nor prevent or reduce EIPH. Studies C and D examine potential mechanisms behind the exercise intolerance observed in humans with Type II diabetes. Utilizing phosphorescence quenching techniques (Study C) within the GK spinotrapezius muscle, we found lowered microvascular PO2 (PO2mv; Control: 28.8±2.0; GK: 18.4±1.8 mmHg; P<0.05) at rest and a PO2mv “undershoot” during muscle contractions. After conducting intravital microscopy within the same muscle (Study D), we discovered the percentage of RBC-perfused capillaries was decreased (Control: 93±3; GK: 66±5 %; P<0.05) and all three major hemodynamic variables (i.e. RBC velocity, flux, and capillary tube hematocrit) were significantly attenuated. Both studies (C & D) indicate that there is reduced O2 availability (via decreased O2 delivery; i.e. ↓QO2/VO2) within Type II diabetic muscle.

Master of Science / Department of Clinical Sciences / Daniel U. Thomson / Bovine respiratory disease complex (BRDC) is the most common, and costly, disease in feed yard cattle. A review of the literature shows a correlation between the diagnosis of BRDC ante-mortem and respiratory lesions at slaughter. The objectives of the studies reported here were to: 1) validate a thoracic auscultation scoring system by correlating ante-mortem lung sounds with post-mortem lung lesions and 2) evaluate thoracic auscultation and rectal temperature as diagnostic tools to predict case outcome in the feeder cattle treated for BRDC. First, a prospective cohort study involving thirty four head of cattle that had been realized from commercial cattle feeding operations were used to validate the use of a lung auscultation scoring system to identify cattle suffering from BRDC. Ante-mortem auscultation scores were compared to post-mortem lung lesions evaluated using a previously described scoring system. There was a positive correlation (P < .0001) between ante-mortem lung auscultation scores and post-mortem lung lesion scores in the population of feeder cattle that were tested. Subsequently, a retrospective cohort study was conducted using data obtained from three commercial feed yards. Cattle enrolled in the study (n = 4,341 head) were treated for BRDC between January 2007 to October 2007 by trained feed yard personnel. Data recorded included animal identification, rectal temperature, lung score, and antibiotic therapy at first treatment. Treatment outcome data were recorded by feed yard personnel utilizing an animal health computer. The outcome data tracked for this study included subsequent BRDC treatment or death of the animal. Our findings indicated that as lung auscultation score (P < .0001) or rectal temperature (P < .0001) increased there was an increased risk for cattle to require a second BRDC treatment. Also, we observed an increased risk for death loss in cattle with higher lung auscultation scores (P < .0001) or higher rectal temperature (P < .0001) at the time of treatment for BRDC. We have demonstrated that lung auscultation score and rectal temperature can be used as tools to predict treatment outcome in cattle treated for BRDC. Future research with these tools could be used to develop more precise therapeutic protocols for BRDC in feeder cattle.