Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

大动脉闭塞性疾病是脑卒中常见病因，包括颅内外狭窄性血管病变。本研究旨在分析卒中患者颅内外大动脉狭窄斑块的血管造影特征以及相关治疗方案。进一步了解颅内斑块的形态学变化，以及颅外大动脉狭窄的血管造影特征和侧枝循环状态，对于研究其发病机制及临床治疗有指导意义。 / 研究目的 / 研究1：通过前瞻性纵向研究，利用三维旋转血管造影（3D-RA），探讨颅内斑块形态学变化。 / 研究2：通过病例对照研究分析症状性放射性闭塞性血管病变(ORV)的血管造影特征及侧枝循环状态。 / 研究3：通过病例对照研究分析放射性血管病变（RIV）患者进行颈动脉支架治疗（CAS）后血管造影特征及临床预后。 / 研究方法 / 研究1：24例颅内重度狭窄(>70%)的急性缺血性卒中患者，严格控制其危险因素，应用3D-RA研究其发病时及12个月后颅内斑块的形态学变化。 / 研究2：分析96例ORV以及115例非放疗所致严重颈动脉狭窄（>70%）的缺血性卒中患者血管造影特点，比较其病变分布，形态学改变及侧枝循环状态。 / 研究3：比较63例ORV以及87例动脉粥样硬化性颈动脉狭窄的卒中患者的血管造影及预后。主要终点事件包括短暂性脑缺血发作，卒中和死亡。次要终点事件为24个月时支架内再狭窄。 / 结果 / 研究1：颅内动脉粥样硬化性斑块的厚长比不能预测其稳定性。12个月的血管造影提示：13例（50%)斑块逆转；10例（38.5%)斑块无明显变化；3例（11.5%)斑块进展。 / 研究2：ORV更多累及颈总动脉，多见双侧颈动脉受累（54% vs 22%)或出现闭塞（30% vs 9%），常见椎动脉受累(28% vs 14%)（均P<0.05）。ORV常见代偿性软脑膜动脉、前后交通动脉开放，及逆向眼动脉血流。 / 研究3：两组间围手术期并发症，长期生存率和卒中复发率无统计学差异。 / 结论 / 研究1：3D-RA可评价颅内斑块形态学变化；颅内光滑斑块亦可为易损斑块。严格控制危险因素可能逆转斑块。 / 研究2： ORV患者更多见颈动脉及椎基底动脉狭窄-闭塞性病变，并伴随侧枝循环开放。侧枝循环代偿功能减退可能诱导ORV患者发生卒中。 / 研究3：RIV患者与对照组相比，CAS的耐受性和临床预后无明显差异。 / Large artery occlusive disease, encompassing stenosis in intracranial and extracranial vasculature, is the most common stroke subtype worldwide. In this thesis, we aimed to investigate angiographic plaque morphology and treatments in stroke patients attributed to intracranial and/or extracranial stenosis. A better understanding of intracranial plaque morphology, angiographic characteristics and collateral circulations of extracranial occlusive vasculopathy may help clarify pathogenesis and formulate treatment. / Objectives / Study 1: In this prospective longitudinal study, we investigated the intracranial plaque morphology of acute stroke patients by three-dimensional rotational angiography (3D-RA). / Study 2: We aimed to delineate the angiographic attributes and collateral circulations in symptomatic occlusive radiation vasculopathy (ORV) patients by a case-controlled study. / Study 3: We investigated the angiographic and clinical outcome of carotid artery stenting (CAS) in stroke patients attributed to ORV. / Methods / Study 1: Twenty-four patients with acute strokes attributed to a >70% intracranial stenosis were recruited to undergo 3D-RA at baseline and in 12 months after an intensive control of atherosclerotic risks. We described the degree of stenosis and morphology that might be associated with plaque vulnerability. / Study 2: We performed digital subtraction angiograms (DSA) in 96 patients who had first-ever ischemic strokes attributed to ORV, and 115 referent patients who had no radiotherapy (RT) but symptomatic high-grade (>70%) atherosclerotic carotid stenoses. We compared the lesions’ distribution, morphology, and the resultant alteration of collateral flows in both patient groups. / Study 3: We compared the angiographic and clinical outcome of CAS in 63 symtomatic ORV patients and 87 patients with spontaneous atheromatous carotid stenoses. Primary end-points were transient ischemic attack, stroke and death of all causes. Secondary end-point was instent restenosis in 24 months. / Results / Study 1: Inracranial atherosclerotic plaque is a dynamic lesion.Thickness-to-length ratio may not indicate plaque vulnerability. In 12-month angiogram, 13 patients (50%) had plaque regression, 10 (38.5%) had static plaque, and 3 (11.5%) had plaque progression. / Study 2: Compared with spontaneous atheromatous carotid disease, ORV lesions diffusely involved common carotid artery, and were more frequently bilateral (54% vs 22%), associated with complete occlusion in one or both carotid arteries (30% vs 9%), vertebral artery steno-occlusions (27% vs 14%) (all p<0.05). ORV patients showed more established collateral circulations through leptomeningeal arteries, anterior communicating artery, posterior communicating artery and retrograde flow in ophthalmic artery. / Study 3: We found no significant differences in the frequency of periprocedural complications, the rates of patient survival and stroke recurrence between ORV and control groups. / Conclusions / Study 1: Evaluation of intracranial plaque morphology is feasible with 3D-RA. Smooth plaques might also be vulnerable in intracranial vasculature. Intensive risk factor control may halt progression of intracranial plaques. / Study 2: ORV patients had more steno-occlusions over carotid and vertebral arteries amid mature collateral circulations at initial stroke presentation. Decompensation of collateral flows may precipitate stroke in ORV. / Study 3: The durability and clinical outcome of CAS in ORV patients were comparable to those in patients with spontaneous atherosclerotic carotid stenosis. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zou, Xinying. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 101-119). / Abstract also in Chinese. / ABSTRACT --- p.i / 摘要 --- p.vi / DECLARATION OF ORIGINALITY --- p.ix / ACKNOWLEDGEMENTS --- p.x / PUBLICATIONS AND PRESENTATIONS --- p.xii / LIST OF ABBREVIATIONS --- p.xiv / LIST OF TABLES --- p.xvii / LIST OF FIGURES --- p.xviii / TABLE OF CONTENTS --- p.xx / Chapter CHAPTER 1 --- INTRODUCTION AND LITERATURE REVIEW --- p.1 / Chapter 1.1 --- An overview of large artery occlusive disease in ischemic stroke --- p.1 / Chapter 1.2 --- Vulnerable plaque and plaque morphology in ischemic stroke --- p.3 / Chapter 1.2.1 --- Definition of vulnerable plaque and plaque morphology --- p.4 / Chapter 1.2.2 --- Imaging of vulnerable plaques --- p.5 / Chapter 1.2.3 --- Factors affecting plaque stability or arterial luminal narrowing --- p.7 / Chapter 1.2.3.1 --- Stenosis severity --- p.7 / Chapter 1.2.3.2 --- Thickness and length of plaque --- p.8 / Chapter 1.2.3.3 --- Mechanical stress, shear stress and hemodynamics on plaque stability --- p.9 / Chapter 1.2.3.4 --- Plaque eccentricity --- p.10 / Chapter 1.2.3.5 --- Plaque surface morphology --- p.11 / Chapter 1.2.4 --- Morphological characteristics of symptomatic plaque --- p.11 / Chapter 1.2.4.1 --- Carotid plaque morphology --- p.11 / Chapter 1.2.4.2 --- Intracranial plaque morphology --- p.12 / Chapter 1.2.5 --- Treatment of vulnerable intracranial stenosis --- p.12 / Chapter 1.3 --- Occlusive radiation vasculopathy (ORV) --- p.13 / Chapter 1.3.1 --- Epidemiology of ORV --- p.13 / Chapter 1.3.2 --- Pathogenesis and Pathophysiology of ORV --- p.14 / Chapter 1.3.3 --- Imaging and angiographic characteristics of ORV --- p.16 / Chapter 1.3.4 --- Collateralization in ORV --- p.18 / Chapter 1.3.5 --- Angioplasty and stenting for ORV --- p.19 / Chapter CHAPTER 2 --- OBJECTIVES --- p.22 / Chapter CHAPTER 3 --- RECRUITMENT OF STUDY PARTICIPANTS --- p.24 / Chapter CHAPTER 4 --- REGRESSION OF SYMPTOMATIC INTRACRANIAL PLAQUE BY INTENSIVE RISK FACTOR CONTROL: A LONGITUDIANL STUDY ON PLAQUE MORPHOLOGY BY 3D-ROTATIONAL ANGIOGRAPHY --- p.28 / Chapter 4.1. --- Background and objectives --- p.28 / Chapter 4.2 --- Methods --- p.32 / Chapter 4.2.1 --- Participants --- p.32 / Chapter 4.2.2 --- Risk factors and intensive control --- p.33 / Chapter 4.2.3 --- Evaluation of intracranial stenosis --- p.33 / Chapter 4.2.3.1 --- DSA and 3D-RA protocol --- p.33 / Chapter 4.2.3.2 --- Severity of stenosis --- p.34 / Chapter 4.2.3.3 --- Analysis of morphological characteristics on 3D-RA --- p.34 / Chapter 4.2.3.4 --- Plaque regression --- p.35 / Chapter 4.2.4 --- Statistical analysis --- p.36 / Chapter 4.3 --- Results --- p.36 / Chapter 4.4 --- Discussion --- p.54 / Chapter CHAPTER 5 --- ANGIOGRAPHY DISTINCTIONS AND COLLATERALIZATION IN SYMPTOMATIC CRANIO-CERVICAL OCCLUSIVE RADIATION VASCULOPATHY: A CASE-REFERENT STUDY --- p.58 / Chapter 5.1 --- Background and objectives --- p.58 / Chapter 5.2 --- Methods --- p.59 / Chapter 5.2.1 --- ORV and referent patients --- p.60 / Chapter 5.2.2 --- Evaluation of vascular lesions and collateral status --- p.61 / Chapter 5.2.3 --- Statistical analysis --- p.64 / Chapter 5.3 --- Results --- p.64 / Chapter 5.4 --- Discussion --- p.81 / Chapter CHAPTER 6 --- SAFETY AND CLINICAL OUTCOME OF CAROTID ARTERY STENTING IN STROKE PATIENTS WITH OCCLUSIVE RADIATION VASCULOPATHY --- p.86 / Chapter 6.1. --- Background and objectives --- p.86 / Chapter 6.2 --- Methods --- p.87 / Chapter 6.2.1 --- Participants --- p.87 / Chapter 6.2.2 --- Baseline clinical assessment --- p.87 / Chapter 6.2.3 --- Carotid artery stenting (CAS) --- p.88 / Chapter 6.2.4 --- Follow-up and end-points --- p.89 / Chapter 6.2.5 --- Statistical analysis --- p.89 / Chapter 6.3. --- Results --- p.90 / Chapter 6.4. --- Discussion --- p.96 / Chapter CHAPTER 7 --- CONCLUSIONS --- p.98 / REFERENCES --- p.101

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

Background Visual hallucinations (VH) are an important non-motor complication of Parkinson’s disease (PD) which carries a negative prognosis, but their biological basis is unclear. Multi-modal magnetic resonance imaging (MRI) can be used to evaluate structural and functional brain mechanisms underpinning VH in PD. Methods To assess cerebral microstructure and resting functional activities in patients with idiopathic PD and VH, I compared PD patients with VH (PDVH) and PD patients without VH (PDnonVH), while healthy controls (HC) were also recruited for comparison. Diffusion tensor imaging was used to calculate mean diffusivity (MD) and fractional anisotropy (FA). Structural MRI was used to calculate voxel-based intensity of grey matter (GM) and white matter (WM) across the entire brain and compared among groups. Furthermore, functional magnetic resonance imaging of the brain, acquired during rest, was processed to calculate the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) to inform a model of VH. In addition, hippocampal volume, shape, mean diffusivity and FC across the whole brain was further examined. Hippocampal dependent visual spatial memory performance was compared between groups, and predicted correlations with hippocampal microstructural indices and VH severity were tested. Results In the first study, PDVH had lower FA than both PDnonVH and HC in the right occipital lobe and left parietal lobe, but increased FA in the right infero-medial fronto-occipital fasciculus and posterior inferior longitudinal fasciculus. Moreover, PDVH patients showed less GM volume compared to PDnonVH in the right lingual gyrus of the occipital lobe. In the second study, PDVH patients compared to non-hallucinators showed lower ALFF in occipital lobes, with greater ALFF in temporo-parietal region, limbic lobe and right cerebellum. The PDVH group also showed alteration in functional connectivity between occipital region and corticostriatal regions. Finally in the third study, although there were no gross hippocampal volume and shape differences across groups, individuals with PDVH had higher diffusivity in hippocampus than PDnonVH and HC. Both PD groups had significantly poorer visuospatial memory compared to HC. Poorer visuospatial memory was correlated with higher hippocampal diffusivity in HC and more severe VH in the PDVH group.FC between hippocampus and primary visual cortex, dorsal/ventral visual pathways was also lower in PDVH than other groups, whereas FC between hippocampus and default mode network regions was greater in PDVH group compared to others. Conclusion Compared to PDnonVH groups, the PDVH group had multiple structural deficits in primary and associative visual cortices. In term of hemodynamic activity, the PDVH group had lower ALFF in occipital lobe, but greater ALFF in regions that comprise the dorsal visual pathway. Moreover, this lower ALFF in the primary visual cortex was accompanied by lower functional connectivity across components of the ventral/dorsal visual pathway in the PDVH group compared to the PDnonVH group. Moreover, evidence supporting a specific role for the hippocampus in PDVH was obtained. In the absence of gross macrostructural anomalies, hippocampal microstructure and functional connectivity was compromised in PDVH. I observed an association between visuospatial memory and hippocampal integrity and suggest that hippocampal pathology and consequent disruption in visuospatial memory plays a key contribution to VH in PD. Thus, in the PDVH group, "bottom-up" primary visual cortex and “top-down” visual association pathways and attentional networks appear to be disrupted. / published_or_final_version / Psychiatry / Doctoral / Doctor of Philosophy

No description available.

Wang, Hui Chuan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 184-202). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Thirty-two parkinsonians were compared to 32 age-, sex-, and education-matched healthy controls on measures of depression (Beck Inventory), dementia (Mattis Dementia Rating Scale), and primary and secondary memory components of Free Verbal Recall. Parkinsonians were found to be more depressed, with greater impairment of secondary memory. There were no significant group differences in primary memory or general cognitive functioning. Sub-groups of 41 parkinsonians (including the 32 patients described above) were used to compare the relative contributions of depression, age of onset, and general cognitive decline to the observed secondary memory deficit. Depressed parkinsonians demonstrated more impaired primary memory than did nondepressed parkinsonians, but did not account for the difference in secondary memory. Parkinsonians with later ages of onset demonstrated greater depression and cognitive decline over a shorter length of illness, and parkinsonians with greater cognitive decline performed more poorly on the measure of secondary memory. Comparisons of parkinsonians with predominant unilateral motor symptoms (either right or left) to those with equal bilateral symptoms revealed the bilateral group to be significantly older, with later ages of onset but no difference in length of illness. It is concluded that later age of onset is a critical factor that is more likely to be associated with depression and declines in cognitive functioning than is seen with earlier age of onset. The relationship between age of onset and cognitive decline is not accounted for by age alone, length of illness, nor by the interaction of age with parkinsonian symptoms. Furthermore, the presence of bilateral symptoms may serve as a marker for the cluster of symptoms associated with later ages of symptoms onset.

Apolipoprotein E (apoE) is a lipid transport protein which plays a key role in lipid metabolism. In addition to the well known polymorphic coding alleles epsilon2, epsilon3 and epsilon4, APOE promoter single nucleotide polymorphisms (SNPs) have also been reported to modify disease susceptibilities in humans. / In a case-control study involving 710 Chinese type 2 diabetes and 198 non-diabetic subjects, genotyping of three SNPs (-491A/T, -219G/T and +113G/C) within the APOE proximal promoter identified that -491A was associated with increased risk for type 2 diabetes in women (OR=2.44, 95%CI=1.15-5.19, p=0.017). However, the three tested SNPs were not associated with the risk of diabetic nephropathy (DN). Yeast one-hybrid screening of the human brain cDNA library using the polymorphic DNA sequences spanning the APOE promoter -491 site as the 'baits' identified one of the interacting transcription factors being the activating transcription factor 4 (ATF4). Electrophoretic-mobility-shift assay confirmed the physical interaction of the purified recombinant ATF4 protein and APOE promoter -491 A/T spanning region (-521 to -461). The binding of ATF4 to the -491T-containing sequence was stronger than that of the -491A-containing sequence. Chromatin immunoprecipitation (ChIP) assay further confirmed the interaction between ATF4 and APOE promoter -491-spanning region in vivo. The functional significance of APOE -491A/T polymorphism was supported by the dual-luciferase reporter assay showing that -491 A to T single nucleotide substitution significantly decreased the activity of the cloned APOE promoter (-1019 to +407) in human kidney (293), liver (WRL-68) and astrocyte (U-87) cell lines. Further analysis showed that ATF4 over-expression significantly down-regulated the activities of the cloned APOE promoter. The suppression of ATF4 on APOE promoter with -491A allelic form was significantly stronger than that with -491T allelic form in 293 cells (p&lt;0.05). Interestingly, overexpression of recombinant ATF4 stimulated endogenous APOE transcription by about 10% in WRL-68 cells. / In conclusion, APOE promoter -491A/T polymorphism modifies the risk of type 2 diabetes in Hong Kong Chinese women. The -491A/T polymorphism controls APOE promoter activity and is interactive with transcription factor ATF4. / My thesis project aimed at testing two hypotheses: (1) APOE promoter SNPs associate with the risks of type 2 diabetes and diabetic nephropathy, (2) APOE promoter SNPs modify transcriptional control of the gene. / Geng, Hua. / "September 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4559. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 140-151). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Background Patients infected with the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), have high rates of psychiatric morbidity. The effects of HIV on the Central Nervous System may lead to psychiatric morbidity even before the appearance of the full-blown AIDS syndrome. Sero-prevalence studies of patients with psychoses have found an estimated 5-20% to be HIV positive. However, sero-prevalence estimates vary from study to study due to the differences in sampling by geographic location, socio-economic class, race and ethnicity, and psychiatric-diagnostic composition. The Republic of South Africa has some of the highest prevalence rates in the world and research in this field is escalating rapidly. However research on HIV in patients with mental illness, particularly psychosis is very sparse. Aim of the study To determine the prevalence of HIV sero-positivity amongst patients admitted to Town Hill hospital presenting with first episode psychosis. Method All patients presenting to Town Hill hospital with first episode of psychotic symptoms were recruited to participate in the study. The treating doctor in collaboration with the multi-disciplinary team made the diagnosis of Psychosis. A total number of 63 patients participated in the study. Results. 23.8% of the patients tested positive for the human immunodeficiency virus. Conclusions. The prevalence of HIV sero-positivity is high amongst patients presenting with first episode psychosis. The HIV epidemic could have an important effect on the aetiology and clinical presentation of psychosis. Recommendations State mental health authorities should pursue the promotion of voluntary HIV testing programs, in patients presenting with first episode psychosis as soon as they are capable of giving informed consent. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2007.