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This thesis is missing page 222, the other copies of this thesis are missing the page as well. -Digitization Centre / N/A / Thesis / Master of Science (MS)

<p> This study investigated the circulatory response to double-arm weightlifting exercise and compared the responses during free weight and machine equipment weightlifting in eight patients (mean age = 57.6±10 years) with well-documented coronary artery disease. Subjects performed bench press and overhead press exercises at 40 and 60% of 1 repetition maximum using both the free weights and machine equipment. Intra-arterial pressure was measured in the subclavian artery using a Millar catheter-tip pressure transducer. Arterial pressures rose in parallel with both modes of lifting (free weight and machine equipment), while heart rate did not increase substantially. Mean peak systolic (169 to 197 mmHg) and diastolic (95 to 119 mmHg) pressures recorded during the final repetitions of each weightlifting set did not, however, exceed values considered to be acceptable for dynamic exercise. Individual subjects recorded diastolic pressures as high as 150 mmHg during one or more of the weightlifting exercises, and individual mean arterial pressures reached values as high as 181 mmHg during overhead press machine equipment exercise at 60% of 1RM. While these high arterial pressures associated with weightlifting exercise increased myocardial oxygen demand (RPP=9643 to 15290), the increase in diastolic pressure may have augmented oxygen supply (DPTI=3448 to 3926 mmHg.s.min-1). However, because of the proportionately larger increase in RPP compared to DPTI, the ratio of oxygen supply to demand decreased with arm weightlifting exercise (DPTI:RPP=0.3741 to 0.2629). Nevertheless, the estimated myocardial oxygen supply to demand relationship appears to be more favourable during double-arm weightlifting exercise compared to estimated values from previous maximal cycle ergometer testing. These results suggest that double-arm weightlifting exercise at 40 to 60% of 1RM is safe and appropriate for patients with coronary artery disease and can be performed using either free weights or machine weightlifting equipment.</p> / Thesis / Master of Science (MSc)

Thesis (MMed)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: OBJECTIVE: The aim of this study was to compare the accuracy of non-invasive brachial blood pressure measurements, using automated and manual devices, to invasive brachial intra-arterial blood pressure measurements in patients with preeclampsia, during acute severe hypertension. STUDY DESIGN: A prospective descriptive cross sectional study was conducted in the Obstetrics Critical Care Unit (OCCU) of Tygerberg Hospital. Pre-eclamptic patients with acute severe hypertension, who required the placement of brachial intra-arterial lines due to failed radial intra-arterial line placement, were included in the study. Both automated oscillometric and blinded manual aneroid sphygmomanometric blood pressures were recorded during hypertensive peaks and after stabilization of BP using intravenous Labetalol or Nepresol. These two noninvasive methods of blood pressure measurements were compared to brachial intraarterial blood pressure measurements. RESULTS: There was weak correlation between manual and intra-arterial SBP (r = 0.27, p = 0.048) for SBP≥160mmHg. The calculated mean difference between manual SBP compared to the intra-arterial SBP in this group was -23.19mmHg (+/- 19.40). There was moderate correlation between automated and intra-arterial SBP (r = 0.69, p < 0.05). The calculated mean difference between automated SBP compared to the intra-arterial SBP in this group was -16.85mmHg (+/- 11.58). CONCLUSION: This study of pre-eclamptic women demonstrated that both non-invasive methods of BP measurement were inaccurate measures of the true systolic intra-arterial BP and significantly underestimated SBP≥160mmHg when compared to brachial intra-arterial measurements. The SBP was also underestimated, to a lesser degree, for mild moderate hypertension. This study also demonstrated that direct invasive BP monitoring using the brachial artery is a safe method for accurate haemodynamic monitoring. We recommend the use of intra-arterial BP monitoring in pre-eclamptic women with acute severe hypertension. Radial arterial cannulation should be used as the first option and the brachial artery should be used if the first option fails. / AFRIKAANSE OPSOMMING: DOELWIT: Die doel van hierdie studie was om die akuraatheid van nie indringende bragiale bloeddruk metings, wat met outomatiese en manuele aparate geneem is, te vergelyk met bragiale intra-arteriele bloeddruk metings gedurend akute erge hipertensie in pasiente met pre-eklampsie, STUDIE ONTWERP: ʼn Prospektiewe beskrywende dwarssnit studie was in die Obstetriese Kritiese Sorg Eenheid (OCCU) van Tygerberg Hospitaal uit gevoer. Preeklamptiese pasiente met akute erge hipertensie, wat bragiale intra-arteriele lyne nodig gehad het, as gevolg van gefaalde radiale intra-arteriele lyn plasing, was in hierdie studie ingesluit. Beide outomatiese ossilometriese en geblinde aneroide sfigmomanometriese bloeddrukke, tydens hipertensiewe pieke en na stabilisering van bloeddrukke met binneaarse Labetalol of Nepresol, was aangeteken, Die twee nie indringende metodes van bloeddruk meting was met bragiale intra-arteriele bloeddruk metings vergelyk. RESULTATE: Daar was ʼn swak korrelasie tussen manuele en intra-arteriele sistoliese bloedrukke SBP (r = 0.27, p = 0.048) vir SBP≥160mmHg. Die berekende gemiddelde verskil tussen manuele SBP en intra-arteriele SBP was -23.19mmHg (+/- 19.40) in hierdie groep. Daar was ʼn matige korrelasie tussen outomatiese en intra-arteriele SBP (r = 0.69, p < 0.05). Die berekende gemiddelde verskil tussen outomaties SBP vergelyk met intra-arteriele SBP was -16.85mmHg (+/- 11.58) in hierdie groep. GEVOLGTREKKING: Hierdie studie van pre-eklamptiese vrouens, het getoon dat beide nie indringende metodes van bloeddruk meting, nie akurate metings van ware sistoliese intraarteriele bloeddruk is nie, en SBP≥160mmHg word aansienlik onderskat wanneer dit met bragiale intra-arteriele metings vergelyk word. Die SBP was ook tot ʼn minder mate onderskat vir matige hipertensie. Die studie het ook getoon dat die direkte bragiale intra-arteriele metode van bloeddruk monitering, ʼn veilige metode van hemodinamiese monitering is. Ons beveel die gebruik van intra-arteriele bloeddruk monitering aan, in preeklamptiese vrouens met akute erge hipertensie. Radiale arteriele kanulasie moet gebruik word as die eerste opsie en die bragiale arterie moet gebruik word as die eerste opsie faal.

Stroke is the 5th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to include selective intra-arterial pharmacotherapy administration. Using the tandem transient common carotid and middle cerebral artery occlusion (MCAo) model to induce stroke, we threaded micro-angio tubing into the external carotid artery (ECA) towards the bifurcation of the common carotid and internal carotid arteries (CCA/ICA) allowing for the delivery of agents to the site of acute ischemia. Our model was optimized through a flow rate and injection volume study using carbon black ink injected through the intra-arterial model at different flow rates and injection volumes. The purpose of this study was to demonstrate that our injections were arriving at the site of ischemia and to improve injection volumes for future dosing while mitigating systemic side effects by preventing or minimizing systemic distribution. We determined that a flow rate of 2.5 µl/minute and injection volume of 10 µl was optimal. Next, we tested potential neuroprotective compounds nitroglycerin, verapamil, and a combination of verapamil and lubeluzole. Compounds were chosen for drug synergy and to target specific pathways in either an acute or delayed manner. Acute treatments included nitroglycerin and/or verapamil while delayed treatment included lubeluzole. The known mechanism of action for FDA approved nitroglycerin is through vessel dilation that results in increased blood flow to the treated region. A secondary mechanism of nitroglycerin is the production of nitric oxide, which has demonstrated antioxidant and anti-apoptotic effects when processed and released from cells surrounding the blood vessels. Verapamil, a calcium channel blocker, also FDA-approved for cerebral artery vasospasm: is thought to act by blocking the L-type calcium channels on the cell membrane from opening following membrane depolarization after insult. Finally, lubeluzole, also FDA-approved, is proposed to work as an NMDA modulator inhibiting the release of glutamate and nitric oxide synthase and blocking sodium and calcium channels. Through our stroke model we were able to demonstrate that each drug(s) showed a significant decrease in infarct volume and improved functional recovery while simultaneously minimizing potential systemic side effects suggesting that our stroke model may improve the preclinical validation of potential stroke therapies and help bridge the bench to bedside divide in developing new stroke therapies.

O exercício resistido dinâmico é recomendado, em complemento ao aeróbico, para indivíduos hipertensos. O aumento da pressão arterial durante sua execução se faz, primordialmente, pelo aumento da resistência vascular periférica, porém o aumento do débito cardíaco também parece estar envolvido. A elevação da pressão arterial parece ser exacerbada em hipertensos não medicados. Entretanto, grande parte dos hipertensos está sob terapêutica medicamentosa e vários fazem uso de -bloqueadores, que reduzem o débito cardíaco pela diminuição da resposta taquicárdica e inotrópica à estimulação simpática. Assim, é possível supor que o uso de -bloqueadores reduza o aumento da pressão arterial nos exercícios resistidos. Porém, pelo nosso conhecimento, este efeito ainda não foi estudado. Assim, esta investigação teve por objetivo investigar o efeito do atenolol sobre a resposta da pressão arterial durante o exercício resistido de diferentes intensidades. Foram estudados 10 hipertensos essenciais com pressão arterial sistólica/diastólica sob placebo entre 140 e 160/90 e 105 mmHg. Os pacientes foram estudados após 6 semanas de uso de placebo e de atenolol, sendo que os indivíduos estavam cegos para a medicação. Em cada fase, os voluntários fizeram o exercício de extensão de joelhos na cadeira extensora até a exaustão, seguindo 3 protocolos realizados em ordem aleatória: a) uma série em 100% de 1RM (repetição máxima), b) três séries em 40% de 1RM e; c) três séries em 80% de 1RM. Antes, durante e após os exercícios, a pressão arterial foi medida diretamente na artéria radial. Os dados foram comparados pelo teste t student ou pela ANOVA de dois fatores para amostras repetidas. Quando necessário, foi utilizado o post-hoc de Newman-Keuls e aceito como significante o índice de P&#8804;0,05. Verificou-se que o atenolol reduziu os valores absolutos atingidos pela pressão arterial sistólica durante a execução do exercício nas três intensidades (valores máximos: 100% = 186&#177;4 vs. 215&#177;7, 80% = 224&#177;7 vs. 247&#177;9 e 40% = 223&#177;7 vs. 252&#177;16, mmHg, P&#8804;0,05). Além disso, ele reduziu o aumento desta pressão arterial na 1ª série do exercício nas 3 intensidades (100% = +38&#177;5 vs. +54&#177;9; 80% = +68&#177;11 vs. +84&#177;13 e 40% = +69&#177;7 vs. +84&#177;14, mmHg, P&#8804;0,05). Em relação à pressão arterial diastólica, o atenolol diminuiu os valores máximos absolutos e o aumento desta pressão arterial (126&#177;6 vs. 145&#177;6 e +41&#177;6 vs. +52&#177;6, mmHg, P&#8804;0,05) no exercício em 100% de 1RM, mas não a alterou nas demais intensidades. Dessa forma, é possível concluir que o atenolol foi eficaz em atenuar tanto o valor absoluto quanto a resposta da pressão arterial sistólica durante o exercício resistido de diferentes intensidades em hipertensos, conferindo-lhes uma certa proteção cardiovascular. Este achado reforça o conceito de que o aumento do débito cardíaco é um mecanismo importante para o aumento da pressão arterial sistólica durante este tipo de exercício / Dynamic resistance exercise is recommended in association to aerobic exercise for hypertensive patients. Blood pressure increase during this kind of exercise is mainly due to an increase in peripheral vascular resistance, however, an increase in cardiac output might also be involved. This blood pressure increase seems to be exacerbated in non-medicated hypertensives. Nevertheless, most of the hypertensives are taking medications, and some of them are receiving -blockers, which decreases cardiac output by the inhibition of sympathetic-induced increase on heart rate and cardiac contractility. Thus, -blockers might decrease blood pressure rise during resistance exercise which, to our knowledge, has not been studied yet. Hence, the aim of this study was to verify the effects of the selective -blocker atenolol on blood pressure increase during dynamic resistance exercise of different intensities. Ten essential hypertensives with systolic/diastolic blood pressures under placebo condition maintained among 140 and 160/90 and 105 mmHg were recruited. These volunteers were studied after 6 weeks of placebo and atenolol treatment, and they were blinded for the medication used. In each phase, the volunteers executed, in a random order, 3 protocols of knee extension exercise until fatigue: a) 1 set at 100% of 1 repetition maximum (1RM); b) 3 sets at 40% of 1RM; c) 3 sets at 80% of 1RM. Before, during and after the exercises, intra-arterial radial blood pressure was measured. Data were compared by paired student t-test and by two-way ANOVA for repeated measures. Newman-Keuls post-hoc test was applied when necessary. P&#8804;0.05 was considered as significant. Atenolol decreased the absolute value achieved by systolic blood pressure during the exercise performed at the 3 intensities (maximum values: 100% = 186&#177;4 vs. 215&#177;7, 80%= 224&#177;7 vs. 247&#177;9 e 40% = 223&#177;7 vs. 252&#177;16, mmHg, P&#8804;0.05). Moreover, atenolol also reduced systolic blood pressure increase in the first set of exercise at the 3 intensities (100% = +38&#177;5 vs. +54&#177;9; 80% = +68&#177;11 vs. +84&#177;13 e 40% = +69&#177;7 vs. +84&#177;14, mmHg, P&#8804;0.05). In regard to diastolic blood pressure, atenolol decreased its absolute values and its increase during exercise performed at 100% of 1RM (126&#177;6 vs. 145&#177;6 e +41&#177;6 vs. +52&#177;6, mmHg, P&#8804;0.05), but it did not change diastolic blood pressure at the other exercise intensities. In Conclusion, atenolol therapy was effective in reducing both, systolic blood pressure absolute values and increase during resistance exercise of different intensities in hypertensive subjects; given them some cardiovascular protection. This result enhances the belief that cardiac output increase is important for blood pressure enhancement during this kind of exercise

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This thesis encompasses the development and testing of an interstitial photodynamic therapy (iPDT) system for the treatment of prostate cancer. It begins with the optical characterization of a novel photosensitizer (SL-052) followed by a study of tissue optics as it applies to iPDT. The design and integration of a time-fractionated light delivery system with real-time spectral detection is then examined. An optical phantom test medium is formulated and in vitro system operation and testing is performed. Finally, in vivo experiments are performed on animal models with a focus on canine prostate iPDT. Unique optical results with dosimetric relevance are discovered and investigated. This includes metrics for optically measuring local in vivo SL-052 concentrations in real-time as well as novel oscillatory drug photobleaching and recovery behavior during time-fractionated light delivery. / Photonics and Plasmas

PhD Aims: The aim of our study was to evaluate an efficacy and safety of intra-arterial injection of bone marrow mononuclear cells (BMMCs) in patients with chronic critical limb ischemia (CLI) Methods.In average 400ml bone marrow blood was harvested from posterior iliac crests in 24 CLI patients. BMMCs were obtained from the blood by standard procedure used for bone marrow transplantation. After digital subtraction angiography was performed in each patient, BMMCs were injected into arteries of 28 limbs. Primary outcome was the efficacy of BMMCs injection measured as a successfull healing of limb defects, a change of Fontain ischemia grade and a rate of high limb amputations. Secondary outcomes were a safety of the BMMCs injections, changes in angiographic findings after BMMCs injections and changes in quality of life (questionnaire SF-36). Results: After one year follow-up all patients were alive and 2 patients have undergone high limb amputation. Out of 14 limb defects, eleven have been healed completely and the average Fontain ischemia grade has changed from baseline value of 3.5 to 2.0 after one year (P<0.0001). Angiographic findings have improved in all examined segments of limb vessels. One year after the procedure patients have reported significant improvement. Conclusion: The intra-arterial...