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An analysis of the determinants of peripheral conduit arterial stiffness in children and teenagers in health and diseaseCheung, Yiu-fai, 張耀輝 January 2004 (has links)
published_or_final_version / abstract / toc / Medicine / Master / Doctor of Medicine
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Using heterogeneous, longitudinal EHR data for risk assessment and early detection of cardiovascular diseaseBhave, Shreyas Abhay January 2024 (has links)
Cardiovascular disease (CVD) affects millions of people and is a leading cause of death worldwide. CVD consists of a broad set of conditions including structural heart disease, coronary artery disease and stroke. Risk for each of these conditions accumulates over long periods of time depending on several risk factors. In order to reduce morbidity and mortality due to CVD, preventative treatments administered prior to first CVD event are critical. According to clinical guidelines, such treatments should be guided by an individual’s total risk within a window of time. A related objective is secondary prevention, or early detection, wherein the aim is to identify and mitigate the impact of a disease that has already taken effect. With the widespread adoption of electronic health records (EHRs), there is tremendous opportunity to build better methods for risk assessment and early detection.
However, existing methods which use EHRs are limited in several ways: (1) they do not leverage the full longitudinal history of patients, (2) they use a limited feature set or specific data modalities, and (3) they are rarely validated in broader populations and across different institutions. In this dissertation, I address each of these limitations. In Aim 1, I explore the challenge of handling longitudinal, irregularly sampled clinical data, proposing discriminative and generative approaches to model this data. In Aim 2, I develop a multimodal approach for the early detection of structural heart disease.
Finally, in Aim 3, I study how different feature inclusion choices affect the transportability of deep risk assessment models of coronary artery disease across institutions. Collectively, this dissertation contributes important insights towards building better approaches for risk assessment and early detection of CVD using EHR data and systematically assessing their transportability across institutions and populations.
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The gender difference and association between social position and cardiovascular risk factors in Hong KongNg, Kuen-to., 伍權韜. January 2007 (has links)
published_or_final_version / Community Medicine / Master / Master of Public Health
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Markers of glycaemia and risk of cardiovascular diseaseKhan, Hassan January 2014 (has links)
No description available.
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Investigating the cholesterol-independent (pleiotropic) effects of selected hypolipidaemic agents in functional and dysfunctional endothelial cellsWestcott, Corli 03 1900 (has links)
Thesis (DScMedSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Vascular endothelium forms the first line of defence against harmful stimuli in the circulation.
Endothelial dysfunction is a valuable predictor of cardiovascular disease and therapies aimed at
improving endothelial function are therefore needed. The anti-dyslipidaemic agents, simvastatin
and fenofibrate, are known for their beneficial effects on lipid parameters, however additional
pleiotropic effects have been shown for both. These include improved endothelial function due
to increased levels of nitric oxide (NO), as well as anti-oxidant and anti-inflammatory actions. NO
is produced by the enzyme, nitric oxide synthase (NOS), which exists in the endothelial NOS
(eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS) isoforms. Most studies investigating the
endothelial effects of simvastatin and fenofibrate are performed on macrovascular-derived
endothelial cells, and there is a lack of data on endothelial cells (ECs) from the microcirculation,
particularly the cardiac microvessels.
This dissertation aimed to investigate and elucidate mechanisms underlying the pleiotropic
effects of simvastatin and fenofibrate on ECs and vascular tissue using in vitro, ex vivo and in vivo
experimental models. In vitro investigations included flow cytometry-based intracellular
measurements of NO, as well as different types of reactive oxygen species (ROS) and cell viability
parameters. Signalling pathways involved with these changes were measured by western blot
analyses of the expression and phosphorylation of critical proteins involved in vascular function.
Results on cardiac microvascular ECs (CMECs) demonstrated that fenofibrate (50 μM) exerted a
potent, increasing effect on NO production after short periods (1 and 4 hour treatments), but
after 24 hours the effects were less robust. Exhaustive investigations suggested that the NOincreasing
effects of fenofibrate in baseline CMECs were NOS-independent, a novel finding as far
as we are aware. Fenofibrate’s ability to protect ECs against injury was demonstrated when
CMECs incubated with the pro-inflammatory cytokine, TNF-α, were pre-treated with fenofibrate,
resulting in increased NO and improved cell viability parameters. Simvastatin (1 μM) increased
NO to a lesser extent in baseline CMECs, and resulted in increased apoptosis and necrosis.
Following the cell studies, their effects on vascular reactivity was measured by aortic ring
isometric tension studies. The effects of acutely administered fenofibrate to pre-contracted
aortic rings were investigated, and results showed a modest, but significant NOS-dependent
vasodilatory response. Next, an in vivo model of Wistar rats treated with simvastatin (0.5
mg/kg/day) and fenofibrate (100 mg/kg/day) for 6 weeks was established. Data showed that
neither drug was able to improve aortic ring contraction and dilation above baseline values. Both
drug treatments increased iNOS expression, which is usually associated with harmful actions.
However, in our hands, increased iNOS expression was associated with a beneficial anticontractile
response in the simvastatin-treated animals. Fenofibrate treatment increased NO
bioavailability in the blood of these animals.
In conclusion, fenofibrate showed endothelio-protective pleiotropic effects with regards to NO
production after short treatment periods in CMECs. These effects were mediated via a NOSindependent
mechanism, a novel finding. Fenofibrate pre-treatment was also protective against
the harmful effects of TNF-α. Simvastatin did not show pronounced pleiotropic effects in vitro
or in vivo on endothelial function. / AFRIKAANSE OPSOMMING: Die vaskulêre endoteellaag is die eerste linie van verdediging teen skadelike stimuli in die
bloedsirkulasie. Endoteeldisfunksie is ‘n waardevolle voorspeller van kardiovaskulêre siektes en
enige terapeutiese behandeling wat kan bydra tot verbeterde endoteelfunksie is belangrik.
Simvastatien en fenofibraat word as anti-dislipidemiese middels voorgeskryf en hoewel hulle
primêr gebruik word om cholesterolvlakke te verbeter, toon hulle ook pleiotropiese (cholesterolonafhanklike)
eienskappe. Dit sluit in bevordering van endoteelfunksie (via verhoogde
stikstofoksied (NO) produksie), asook anti-oksidant en anti-inflammatoriese effekte. NO word
vervaardig deur die ensiem, stikstofoksiedsintase (NOS) wat voorkom in drie isovorme: endoteelafgeleide
NOS (eNOS), induseerbare NOS (iNOS) en neuronale NOS (nNOS). Die meerderheid
studies wat pleiotropiese effekte van simvastatien en fenofibraat ondersoek, gebruik
endoteelselle van makrovaskulêre bloedvate, wat beteken daar is ‘n tekort aan data aangaande
endoteelselle vanaf mikrovaskulêre vate, veral kardiale mikrovaskulêre vate (CMECs).
Hierdie proefskrif het dit ten doel gehad om meganismes betrokke by die pleiotropiese effekte
van simvastatien en fenofibraat te ondersoek deur van in vitro, ex vivo en in vivo modelle gebruik
te maak. Die in vitro ondersoeke het gefokus op vloeisitometrie-gebaseerde metings van
intrasellulêre NO, reaktiewe suurstof-radikale (ROS) en sellewensvatbaarheid. Seintransduksie
paaie betrokke by hierdie veranderinge was bepaal deur proteienuitdrukking en -fosforilasie
vlakke te meet van belangrike proteïene, met behulp van die Western-blot tegniek.
Resultate van die CMEC eksperimente het getoon dat fenofibraat (50 μM) ‘n kragtige en
verhogende effek op NO produksie uitgeoefen het na kort behandelingstye (1 en 4 ure), maar na
24 uur was hierdie effek minder uitgesproke. Uitvoerige ondersoeke het getoon dat fenofibraat
se basislyn effekte op CMECs deur NOS-onafhanklike meganismes teweeggebring is, en sover ons
kennis strek, is dit ‘n nuwe bevinding. Fenofibraat se endoteel-beskermende effekte kon ook
aangetoon word deur CMECs vir een uur te behandel voor byvoeging van die pro-inflammatories
sitokien, tumor nekrose faktor alpha (TNF-α), wat gelei het tot verhoogde NO vlakke en
verbeterde seloorlewing. Simvastatien (1 μM) het tot ‘n mindere mate NO produksie verhoog in
CMECs, tesame met pro-apoptotiese en -nekrotiese effekte.
Vervolgens was die effekte op vaskulêre reaktiwiteit geëvalueer d.m.v. isometriese
spanningsondersoeke. Akute effekte van fenofibraat is gemeet deur byvoeging daarvan tot ‘n
vooraf saamgetrekte aorta-ring, wat tot matige, maar beduidende NOS-afhanklike verslapping
gelei het. Hierna is ‘n in vivo model opgestel deur Wistar rotte vir ses weke met 0.5 mg/kg/dag
simvastatien of 100 mg/kg/dag fenofibraat te behandel. Resultate toon dat geen van die
behandelings basislyn kontraksie of verslapping van aorta ringe kon verbeter nie. Beide
behandelings het tot verhoogde iNOS uitdrukking gelei, wat gewoonlik met nadelige effekte
geassosieer word, maar in ons studies was dit met voordelige, anti-kontraktiele effekte in aortaringe
van simvastatien-behandelde rotte geassosieer. Fenofibraat behandeling het die NObiobeskikbaarheid
in die rotte se bloed verhoog.
Ten slotte, fenofibraat het met endoteel-beskermende, pleiotropiese effekte op endoteelselle
gepaard gegaan, veral t.o.v. NO-produksie na akute middeltoediening in die CMECs. Die
meganisme was ‘n NOS-onafkanklike proses, wat ‘n nuwe bevinding is. Fenofibraat prebehandeling
het teen die skadelike effekte van TNF-α beskerm. Geen uitgesproke pleiotropiese
effekte is in vitro of in vivo gevind met simvastatien behandeling nie.
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Postmenopausal hormone replacement therapy and its effects on lipoprotein metabolism, oxidation and bone related biochemcialvariablesTing, Kuei-fu, Lily. January 2000 (has links)
published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy
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Age of menarche and cardiovascular risk in China: the Guangzhou Biobank Cohort studyHeys, Michelle. January 2007 (has links)
published_or_final_version / Community Medicine / Master / Master of Public Health
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Educational attainment and cardiovascular disease related mortality: a retrospective cohort evaluation ofChinese elderly population in Hong Kong陸坡, Luke, Baw D. January 2008 (has links)
published_or_final_version / Community Medicine / Master / Master of Public Health
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Relationships among patient characteristics, care processes, and outcomes for patients in coronary care units (CCUs)Chao, Shir-Ley January 1988 (has links)
The purpose of this research was to describe the relationships among patient characteristics, care processes, and care outcomes for patients in a coronary care unit (CCU). The sample consisted of 179 CCU patients. Data collectors reviewed charts and retrieved the chart information needed to measure the operational variables of APACHE II score (Acute Physiology and Chronic Health Evaluation II), years of age, CCU length of stay, nurse to patient ratio, and mortality. Descriptive statistics were used to analyze the demographic data of the patient characteristics. Correlational statistics were used to analyze the five operational variables in the "CCU Patient Outcomes Model." Pearson correlations revealed significant positive relationships between APACHE II score and age and nurse to patient ratio. Point Biserial correlations revealed significant positive relationships between mortality and APACHE II score and nurse to patient ratio. Patient characteristics were related to care processes. Patient characteristics and care processes were related to patient outcomes.
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Synthesis and new reactions of allenyl carbonyls: studies towards the total synthesis of anti-thrombotic natural products Vitisinol D and CUnknown Date (has links)
We report here the development of new and more general synthetic pathways for the preparation of allenyl and alkynyl carbonyls. These highly dense functionalized compounds were utilized as key intermediates for the synthesis of [3.2.1] and [3.3.1] bicyclic framework, the motifs found in many natural products. A convenient method described for the dehydration of ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method involves the formation of a vinyl triflate monoanion intermediate that leads to the selective formation of alkynes or allenes depending on additives and conditions used. Product outcomes appear to be a function of unique monoand dianion mechanisms which are described. Our design of a Morita-Baylis-Hilman (MBH) reaction to include a fast silyl 1,3- Brook rearrangement has enabled the first ever anion-catalysis. This new reaction makes possible the addition of both aliphatic and aromatic aldehydes to s ilylallenes leading to carbinol allenoates. These new MBH reactions products allow for a fasttracked synthesis of [3.2.1] bisoxa-bicycles which make up the framework of many biologically active natural products including Vitisinol D. The development of cyclic addition of hydrazine nitrogen to unactivated alkynes catalyzed by non-metals is reported. Starting from readily accessible silyl allenyl esters, alkynyl hydrazines are prepared in one step and subsequently undergo unprecedented cyclization reactions in the presence of ammonium and phosphonium catalysts leading to dehydro-azaproline products. These heterocycles were also produced in high enantiomeric excesses using chiral ammonium phase transfer catalysts via a kinetic resolution pathway. / The racemic synthesis of fully functionalized bicyclic core of Vitisinol D was achieved using allenyl ester as a key intermediate. The required electron withdrawing group (EWG) at the position was screened for better addition followed by the compatibility towards successive transformation and, finally, the ease of removal. A reductive aldol method to transform lactone-enol to the desired [3.2.1] bicycle was extensively studied to understand the stereoelectronic requirements for the formation of such bicyclic structures. Due to the necessity of selective protection and deprotection of many phenolic and aliphatic hydroxyls as well as ester groups, orthogonal protecting groups were established accordingly. / by Pradip Maity. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.
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