INTRODUÇÃO: Existem várias doenças que evoluem com hipertensão pulmonar (HP), entre elas a Hipertensão Arterial Pulmonar Idiopática (HAPI) e a Esquistossomose. Acredita-se que um dos principais fatores desencadeantes da HP esteja relacionado com a disfunção endotelial. OBJETIVOS: 1. Avaliar a disfunção endotelial de pacientes com HAPI e esquistossomóticos com e sem HAP usando os marcadores plasmáticos Endotelina-1, Selectina E, VEGF, PDGFAB e PDGF-BB; 2.Avaliar se pacientes com HAP associada à esquistossomose possuem o mesmo grau de disfunção endotelial que pacientes com esquistossomose sem HAP. METODOLOGIA: Foram formados 4 grupos distintos: Controle (n=13), HAPI (n=11), pacientes com esquistossomose e HP (ESQ+HP) (n=13) e pacientes com esquistossomose sem HP (ESQ)(n=13). Os pacientes foram submetidos a avaliação clínica (caracterizados quanto a gravidade), funcional (realizaram ecocardiograma com medida de pressão sistólica de ventrículo direito, ultrassonografia abdominal quando indicada e exames para excluir outras doenças) e laboratorial (entre eles, contagem de leucócitos, plaquetas e dosagem de BNP). A avaliação hemodinâmica foi realizada nos pacientes com HP. Para a análise da disfunção endotelial, foram coletados 40 mL de sangue de todos os indivíduos para a dosagem de Endotelina-1, Selectina E, VEGF, PDGF-AB e PDGF-BB. RESULTADOS: Observou-se que os grupos não se diferiram quanto a idade, houve um predomínio do sexo feminino e os grupos controle e ESQ apresentaram valores de PSVD menores do que os grupos com HP (controles: 23,4±4,6, ESQ: 29,5±8,5, HAPI: 79,8±26,4 e ESQ+HP: 75,2±15,3 mmHg). As medidas hemodinâmicas foram semelhantes em ambos os grupos com HAP. Quanto aos marcadores da função endotelial, o grupo controle apresentou valores séricos de PDGF-BB mais aumentados (8,9±4,8x 103 pg/mL, p<0,001) que os grupos HAPI, ESQ+HP, ESQ (3,7±2,1; 5,2±3 ; 2,4±1,7 x 103 pg/mL, respectivamente). O grupo HAPI apresentou valores mais elevados de Selectina E (61,5±24,2 x 103 pg/mL) que os grupos controle, ESQ+HP e ESQ (14,5±12,2; 23,9±15,3; 21,4±18 x 103 pg/mL, respectivamente, p=0,005). Os valores séricos de PDGF-AB do grupo controle foram mais elevados que no grupo ESQ (p=0,006). Não foram encontradas diferenças significantes nos valores séricos de Endotelina-1 entre os grupos (p=0,281). Em relação ao VEGF, os pacientes com HAPI apresentaram valores séricos similares ao grupo ESQ+HP e mais elevados que o grupo controle e ESQ (p=0,002). O ponto de corte da dosagem da selectina E (43.806 pg/mL) para diferenciar pacientes com HAPI dos pacientes com ESQ+HP apresentou uma sensibilidade de 91% e a especificidade de 89%. O PDGF-BB apresentou uma boa acurácia para distinguir o grupo controle dos demais, com uma sensibilidade de 77% e uma especificidade de 83%. Além disso, a Selectina E apresentou uma forte correlação com o níveis séricos de BNP (r=0,74, p=0,006). O número de leucócitos e de plaquetas foram diferentes entre os três grupos do estudo. Pacientes com HAPI tinham maior número de leucócitos e plaquetas quando comparados com esquistossomóticos. CONCLUSÕES: 1.Pacientes com HAPI apresentaram valores séricos mais elevados de Selectina E do que pacientes com esquistossomose e controles; 2.Pacientes portadores de esquistossomose com e sem HP apresentaram os mesmos valores séricos dos marcadores de disfunção endotelial / INTRODUCTION: There are several diseases that cause Pulmonary hypertension (PH), such as Idiopathic Pulmonary Arterial Hypertension and Schistosomiasis. The mechanisms that lead to PH are thought to be related to endothelial dysfunction. OBJECTIVES: To evaluate endothelial dysfunction, using plasma markers such as Endothelin-1(ET-1), E-Selectin, VEGF, PDGF-AB and -BB, in patients with idiopathic pulmonary arterial hypertension (IPAH) and schistosomiasis patients with or without PH; and to evaluate if schistosomiasis groups have endothelial dysfunction in the same degree. METHODOLOGY: Patients were divided in 4 different groups: Patients with IPAH (n=11), Patients with PH associated to Schistosomiasis (SchPH)(n=13), Patients with Schistosomiasis without PH (Sch)(n=13) and Controls(n=13). PAH patients were classified according to severity. All groups were submitted to echocardiography and right ventricule systolic pressure(RVSP) was measured. Abdominal ultrassonography was used to rule in or rule out schistosomiasis diagnosis. PH patients went through haemodynamics evaluation and all patients had laboratorial assessment (leucocytes and platelet count and BNP levels) Soluble adhesion molecules such as E-Selectin, VEGF, PDGF-AB, PDGF-BB e ET-1 were determined by ELISA. Leucocytes and platelet counts as well as BNP levels were also evaluated. Results: Subjects did not differ according to age and there was a higher proportion of female patients. Controls and Sch subjects had lower RVSP compared to PH groups (Sch: 23.4±4.6, controls: 29.5±8.5, IPAH: 79.8±26.4 and Sch+HP: 75.2±15.3 mmHg). Haemodynamics data did not differ in PH patients. In IPAH group, E-selectin was elevated (61.5±24,2x103pg/mL) compared to controls, Sch+HP and Sch (14.5±12.2; 23.9±15.3; 21.4±18 x103pg/mL, respectively, p=0,005). PDGF-BB was decreased in IPAH, Sch+HP, Sch (3.7±2.1; 5.2±3; 2.4±1.7x103pg/mL, respectively) compared to controls (8.9±4.8x 103 pg/mL, p<0.001). PDGF-AB was elevated in controls (25.6±8.6x103pg/mL) when compared to Sch (11.4±8.6 x103pg/mL)(p=0.006). There were no differences in ET-1 levels within groups. In relation to VEGF, IPAH group had higher levels compared to controls and Sch (96,6±68,2, 38,4±28, 37,±19,2 pg/mL, respectively) (p=0,002). Based on ROC curve, E-selectin cutoff value of 43.806 pg/mL showed a sensitivity of 91% and a specificity of 89% to distinguish IPAH patients from other groups and PDGF-BB had a good accuracy to differentiate controls with a sensitivity of 77% and a specificity of 83%. Furthermore, E-selectin had a strong correlation with BNP levels (r=0,74, p=0,006). The number of leucocytes and platelets were different within groups. IPAH patients had the highest, and Sch group had the lowest blood cells and platelets count. Conclusions: 1. IPAH patients had higher levels of serum E-selectin and VEGF and controls had higher levels of PDGF-BB and AB; 2. Schistosomiasis patients with or without PH had the same levels of endothelial dysfunction serum markers

by Wu Che-yuen Justin. / "September 2000 (amendment)." / Thesis (M.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 237-267). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-23Bitstream added on 2014-06-13T19:07:28Z : No. of bitstreams: 1 barrach_rh_me_botfm.pdf: 1289263 bytes, checksum: 490cd4fe7ff6848d99b4260ebbae5f93 (MD5) / A cavidade oral é um local potencial de complicações em pacientes imunossuprimidos podendo ser um importante local de agentes causadores de infecções sistêmicas, o que pode contribuir para a perda do transplante de célulastronco hematopoéticas, ou mesmo para o óbito do paciente. OBJETIVOS: Apresentar um modelo de avaliação para identificação de potenciais riscos das doenças orais em pacientes imunossuprimidos antes e após transplante de célulastronco hematopoéticas. O presente estudo é clínico, prospectivo, com modelo de coorte temporal longitudinal, realizado no período de julho de 2007 a dezembro de 2008 no Hospital Amaral Carvalho em Jaú/SP. Foram incluídos 65 pacientes divididos em 2 grupos de acordo com o tipo de transplante (alogênico e autológo), maiores de 18 anos, de ambos os sexos, portadores de doenças hematológicas malignas ou não, e que se submeteram ao transplante de células-tronco hematopoéticas no período acima citado. Foram feitas 3 avaliações odontológicas: no período pré-transplante (momento 1), uma semana após a infusão das célulastronco (momento 2) e cem dias pós-transplante (momento 3). Os dados de cada momento foram correlacionados de acordo com a pontuação obtida e os indivíduos foram classificados como grau de risco leve, moderado, grave e gravíssimo no momento 1 e graus de toxicidade leve, moderado, grave e gravíssimo nos momentos 2 e 3 para as complicações clínicas da cavidade oral. As alterações patológicas da boca mais frequentes foram as gengivites, pericoronarite de 3º molar e próteses nos três momentos. Porém, nos momentos 2 e 3 a principal causa do aumento da toxicidade associada a imunossupressão foi a mucosite. Mesmo em indivíduos classificados com grau leve, quando tinham mucosite em graus variados o período de internação hospitalar era maior o mesmo ocorrendo para as recidivas e óbitos... / Oral cavity is a potential site for complications in immunosuppressed patients and it can be an important center of causative agents of systemic infections, which can contribute to the loss of hematopoietic stem cell transplantation, or even to patient’s death. To present an assessment model for identifying the potential risks of oral diseases in immunosuppressed patients, before and after the hematopoietic stem cell transplantation. This is a clinical, prospective study with model of longitudinal temporal cohort performed from July/2007 to December/2008, at the Amaral Carvalho Hospital, Jau, São Paulo. The sample comprised 65 patients who were divided into 2 groups according to transplant type (allogenous and autologous), older than 18 years old, both sexes, with or without malignant hematopoietic diseases, and who undergone hematopoietic stem cell transplantation during the aforementioned period. Three dental assessments were executed: at pretransplantation (Time 1), at one week after stem cell infusion (Time 2), and at 100-day post-transplantation (Time 3). Data of each time were correlated according to the score obtained, and the individuals were classified in: mild, moderate, severe, and very severe risk groups at Time 1; and, in mild, moderate, severe and very severe toxicity levels at Time 2 and 3, regarding to clinical complications of oral cavity. The most frequent pathological conditions were: gingivitis, pericoronaritis due to third molar, and presence of prosthesis, at three times. However, at Time 2 and 3, the main cause of the increase of toxicity associated to immunosuppression was mucositis. Even when mild-risk individuals exhibited mucositis at several levels, the hospital stay length was higher, as well as the relapses and deaths. In the identification of oral diseases in patients who will undergo hematopoietic stem cell transplantation, mucositis accounted... (Complete abstract click electronic access below)

The clinical needs of patients with epilepsy are often unmet for the following reasons: (1) the clinical diagnosis of epilepsy in a hospital setting is challenging and there is a lack of longitudinal data from the time-point of initial triage to help clinicians go through the diagnostic process; (2) epilepsy patients who develop refractory illness may encounter problems of localization and lateralization of their seizure foci and (3) the technology required in the delineation of epileptogenic zones and functional cortices may not be accurate enough to support the clinicians in their diagnoses. / The current thesis begins with the exploration of the epidemiology of suspected seizure patients in a hospital setting where patients with first seizure, epilepsy and non-epileptic events may present at the same point-of-care entry. We designed a longitudinal, prospective study examining patients presenting with “seizure-specific“ and “non-specific“ labels. Among 531 patients with “seizure-specific“ labels, 27(5%) had non-epileptic events and among 1170 patients with “non-specific“ labels, 58(5%) had a first seizure or epilepsy. In particular, first seizure patients were prone to misdiagnosis as up to 22% of these patients had an initial “non-specific“ label. Components of evaluation contributing to revision of diagnosis included retrieval of witness accounts, epileptiform discharges on electroencephalogram(EEG), short-term monitoring of patients with acute symptomatic seizures and panel discussion of cases. These may represent the first step towards a multimodal investigation of patients with epilepsy. / In the second part of the current thesis, we examined the prognosis of first acute symptomatic seizures (ASS), an important component of the seizure diagnosis under the hospital setting. We challenged the traditional school of thought that “ASS are not necessarily considered epilepsy as their potential to generate unprovoked seizure is low“. By following 105 patients with ASS, we found that first ASS was associated with status epilepticus (29.5%), multiple-onset (>1 seizure within 24h on day of presentation, 35.2%) and multiple aetiologies (22.9%) with a mortality of 30% at 2 years by the Kaplan-Meier method. By using seizure recurrences in the setting of a persisting or re-emerging acute symptomatic cause, we were able to demonstrate a risk of recurrence following an ASS of 32% at 2 years with epileptiform EEG being an independent predictor2. This information sheds light onto the fact that even ASS can be “refractory insofar as the acute symptomatic cause takes a long time to treat, is prone to re-emergence, or is irreversible. This may be seen as the second step towards a multimodal investigation of patients with epilepsy. / In the next part of the current thesis, focus was placed on the refractory epilepsy patients. A formal treatise on a specific modality of investigation, namely video electroencephalogram (VEEG) was presented. The clinical appearance of patients at the time of seizure was known as semiology, and this was systematically explored in a cohort of patients undergoing VEEG. By carefully examining the localizing value (which cerebral lobe) and the lateralizing value (which side) of the semiology, we discovered a new set of semiology which might point towards an epileptic focus in the medial aspect of the frontal lobe. The gold standard for seizure localization was used in this study in the assembly of the cohort. Only patients with an Engel Class I outcome, seizure localization by analysis of resection margins and/or intracranial implantation were selected. The first part of study involved 152 patients who underwent frontal lobe surgery and the second part involved 253 patients with non-frontal lobe surgery. All habitual seizures were analyzed by VEEG using a semiology checklist of 47 items during the early (electrographic onset to 10s) and late phase (rest of episode). Localization semiology was analyzed by Chi-square test with Bonferroni correction and cluster analysis when occurrence exceeded 10% in at least 1 region. Ictal body turning along the horizontal body axis was a statistically significant localizing semiology for the mesial frontal region (57%) from the first part of study. In the second part, we found that ictal body turning along the horizontal axis and semiology with physiological movement together gave a positive predictive value of 85.7%. This modality of investigation may serve as clinicians’ hypothesis towards the localization of epileptic foci. / Electroencephalography (EEG) forms an essential part of the multi-modal investigation of epilepsy. Modern-day EEGs are performed with surface electrodes attached to the scalp to capture the electrographic information at the time of seizure but this can be hindered by muscle artifacts which decrease the localizing power of the EEG. We began with the exploration of the “hypersynchronous states of intracranial EEG in which no muscle artifact would be present. A total of 100 focal onset seizure episodes were analyzed from 60 patients undergoing intracranial implantation4. A multivariate method was used computing the eigenvalue spectrum of the zero-lag correlation matrix of a short sliding window. We showed that there were clearly observable and statistically significant changes of the correlation structure of focal onset seizures. These changes indicated that the zero-lag correlation of multi-channel EEG either remained approximately unchanged, or especially in the case of secondary generalization, decreased during the first half of seizures. The correlation then gradually increased again before the seizures terminated. This development was qualitatively independent of the anatomical location of the seizure onset zone and it appeared to be a generic property of focal onset seizures. We concluded that the de-correlation of EEG activity was due to the different propagation times of locally synchronous ictal discharges from the seizure onset zone to other brain areas and the increase of correlation during the second half of the seizures may be causally related to seizure termination. / In the next part of our multimodal investigations, focus was made on how to use applied mathematics in procuring an accurate EEG interpretation from surface EEG. A mathematical model known as discrete wavelet transform (DWT) is a powerful tool which may help denoise the ictal EEG. It can be coupled with an absolute slope method as described in the last part of the thesis which enhances the determination of ictal foci. Twelve patients achieving Engel Class I/IIa outcome following temporal lobe surgery at 1 year were selected for EEG analysis5. The EEG signals were denoised with DWT, followed by computing the normalized absolute slopes and spatial interpolation of scalp topography associated to detection of local maxima. For localization, the region with the highest normalized absolute slopes at the time when epileptiform activities were registered (>2.5 times standard deviation) was designated as the region of onset. For lateralization, the cerebral hemisphere with the first emergence of normalized absolute slopes >2.5 times the standard deviation was considered the side of onset. As comparison, all the EEG episodes were reviewed by two neurologists blinded to clinical information to determine the localization and lateralization of seizure onset by visual analysis. The wavelet and absolute slope method improved the diagnostic accuracy for localization from 64% (16/25) to 84% (21/25). Similarly, the wavelet and absolute slope method improved the diagnostic accuracy for lateralization from 48% (12/25) to 92% (23/25). The comparison between the wavelet/absolute slope method and the visual analysis showed statistical significance for lateralization (p=0.0026, McNemar test). It was conceivable that coupling DWT with the absolute slope method helps clinicians achieve a better EEG diagnostic accuracy. / To conclude, findings of the present thesis open up an area of neuroscience to researchers and biomedical engineers in relation to multi-modal investigations of epilepsy patients, which may play an essential role in fostering our understanding of the epileptic brain, through which more accurate and precise treatment may be delivered to patients with epilepsy. / Leung, Ho Wan Howan. / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 172-185). / Chapter Chapter 1 --- Understanding first seizures and epilepsy / Introduction- epilepsy, past and present --- p.(Page 17) / The burden of epilepsy --- p.(Page 19) / From first seizures --- p.(Page 19) / Scrutiny of clinical first seizure studies --- p.(Page 21) / Symptomatology of first seizures --- p.(Page 22) / Prognosis of first seizures --- p.(Page 23) / The question of managing first seizures --- p.(Page 29) / From first seizure onto refractory seizures --- p.(Page 30) / From drugs to surgery --- p.(Page 32) / Chapter Chapter 2 --- A treatise on epilepsy from the local perspective of Hong Kong / Local epidemiological data --- p.(Page 34) / Use of antiepileptic agents in Hong Kong --- p.(Page 36) / Epilepsy surgery in Hong Kong --- p.(Page 37) / Chapter Chapter 3 --- What are multi-modal investigations? / Semiology as a modality of investigation --- p.(Page 41) / Electroencephalography as a modality of investigation --- p.(Page 44) / Neuroimaging as a modality of investigation --- p.(Page 53) / Additional modalities of neuroimaging --- p.(Page 56) / Methods of ascertaining the functional areas of the cerebral cortex --- p.(Page 63) / The scientific future of multi-modal investigations in Hong Kong --- p.(Page 66) / Chapter Chapter 4 --- The triage of patients before multi-modal investigations can be applied / Method --- p.(Page 70) / Setting and patients --- p.(Page 70) / Results --- p.(Page 73) / Exploring how diagnoses were revised --- p.(Page 75) / Completeness of patient inclusion --- p.(Page 77) / Thematic considerations of current study --- p.(Page 77) / Chapter Chapter 5 --- Consideration of a special category in the process of triage / Patient cohort --- p.(Page 81) / Definitions --- p.(Page 82) / Statistical analysis --- p.(Page 87) / Results --- p.(Page 88) / Demographics and clinical profile --- p.(Page 86) / Mortality --- p.(Page 92) / Seizure recurrence using acute symptomatic seizure as outcome --- p.(Page 93) / Seizure recurrence using unprovoked seizure as outcome --- p.(Page 96) / Risk factors for recurrence --- p.(Page 96) / Progressive symptomatic seizures as a separate category --- p.(Page 97) / Thematic considerations of current study --- p.(Page 97) / Chapter Chapter 6 --- Analyzing semiology with video monitoring as multi-modal investigation / Study part I --- p.(Page 103) / Study part II --- p.(Page 107) / Results --- p.(Page 108) / Semiology in the early phase of seizures --- p.(Page 108) / Semiology in the late phase of seizures --- p.(Page 109) / Cluster analysis of mesial frontal lobe epilepsy syndrome --- p.(Page 110) / Clinical utility of ictal body turning along the horizontal axis --- p.(Page 111) / Thematic considerations of current study --- p.(Page 111) / Chapter Chapter 7 --- Applying mathematical models in the analysis of electroencephalogram / Methods --- p.(Page 118) / Results --- p.(Page 126) / Discussion --- p.(Page 132) / An unanswered question in epileptology --- p.(Page 135) / Chapter Chapter 8 --- Wavelet theories in the analysis of electroencephalogram / Methods --- p.(Page 141) / Results --- p.(Page 150) / Localization --- p.(Page 151) / Lateralization --- p.(Page 154) / Discussion --- p.(Page 156) / Study by Battiston et al --- p.(Page 157) / Study by Ursino et al --- p.(Page 158) / Study by Senhadji et al --- p.(Page 158) / Thematic considerations including limitations --- p.(Page 162) / Chapter Chapter 9 --- Strengths and limitations of current thesis / General --- p.(Page 163) / Specific --- p.(Page 164) / Chapter Chapter 10 --- Conclusions and future research directions --- p.(Page 166)

Research interest in cerebral small vessel disease, which is manifested as lacunar infarct and white matter changes, has surged in the last decade. Small vessel disease has been increasingly recognized via neuroimaging to be highly prevalent among the elderly and more importantly; it is associated with cognitive impairment. Since the population worldwide is ageing, the cognitive burden associated with small vessel disease is foreseen to rise. This burden will be particularly great in China where the population is vast. However, data of cognitive impairment related to small vessel disease among Chinese is scarce. / The methods and results of these studies will be presented in the thesis. In brief, the author concluded that (1) among Chinese stroke patients with relevant subcortical lacunar infarct, underlying intracranial large artery disease should be looked for before attributing that the lacunar infarct is due to small vessel disease because of its not uncommon association with lacunar infarcts among Chinese; (2) half of the patients with stroke associated with small vessel disease complain of varying severity levels of cognitive impairment 3 months poststroke and executive dysfunction also affects functional activities; (3) thalamic lacunar infarct and left frontal lobe atrophy have small yet significant influences on cognitive performances; (4) cerebral atrophy predicts prestroke cognitive impairment; and (5) Chinese frontal assessment battery is a moderately valid, while executive clock drawing test is not a valid test in the evaluation of executive dysfunction among Chinese with small vessel disease. / This thesis aimed to present studies that were conducted by the author among Chinese stroke patients on this particular field. The aims of the studies were to evaluate the (1) frequency of relevant intracranial large artery disease among Chinese stroke patients having subcortical lacunar infarcts; (2) frequency and impact of cognitive impairment after stroke associated with small vessel disease; (3) neuroimaging determinants of cognitive performances after stroke associated with small vessel disease; (4) determinants of prestroke cognitive impairment in stroke associated with small vessel disease; and the (5) validity of frontal assessment battery and executive clock drawing test in assessing executive dysfunction among Chinese patients with small vessel disease. / Mok Chung Tong Vincent. / "April 2005." / Adviser: Lawrence Ka Sing Wong. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3695. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 180-197). / 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. / School code: 1307.

Qiao, Mu. / "June 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 190-209). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

by Joseph Jao Yiu Sung. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (p. 201-220). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Fang Yujing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 148-182). / Abstracts in English and Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Overview of the study --- p.1 / Chapter 1.2 --- Overview of Hypertension --- p.4 / Chapter 1.3 --- Overview of Obesity-Related Hypertension --- p.9 / Chapter 1.3.1 --- Body fat distribution --- p.11 / Chapter 1.3.2 --- Insulin resistance and Hyperinsulinaemia --- p.12 / Chapter 1.3.3 --- Sympathetic nervous system activity --- p.13 / Chapter 1.3.4 --- Genetics of Obesity --- p.15 / Chapter 1.3.4.1 --- Brown adipose tissue (BAT) --- p.15 / Chapter 1.3.4.2 --- Uncoupling protein --- p.16 / Chapter 1.3.4.3 --- Uncoupling Protein 1 Gene --- p.17 / Chapter 1.3.4.4 --- Association of the UCP1 Polymorphism and Weight Gain in Obesity --- p.18 / Chapter 1.4 --- Overview of Genetics of Hypertension --- p.19 / Chapter 1.4.1 --- The Renin-Angiotensin System --- p.19 / Chapter 1.4.1.1 --- Functions of Renin-Angiotensin System --- p.20 / Chapter 1.4.1.2 --- The Renin-Angiotensin System and Hypertension --- p.21 / Chapter 1.4.2 --- Renin --- p.22 / Chapter 1.4.3 --- Angiotensinogen --- p.25 / Chapter 1.4.4 --- Angiotensin-Converting Enzyme (ACE) --- p.29 / Chapter 1.4.4.1 --- Angiotensin-Converting Enzyme Gene --- p.29 / Chapter 1.4.4.2 --- Association of the ACE I/D Polymorphism with Hypertension --- p.30 / Chapter 1.4.4.3 --- Association of the ACE I/D Polymorphism with Other disease --- p.32 / Chapter 1.4.5 --- The Angiotensin II Receptor --- p.35 / Chapter 1.4.5.1 --- Type 1 Angiotensin II Receptor --- p.35 / Chapter 1.4.5.2 --- The Type 1 Angiotensin Receptor Gene --- p.36 / Chapter 1.4.6 --- Dopamine --- p.39 / Chapter 1.4.6.1 --- Dopamine Receptors --- p.42 / Chapter 1.4.6.2 --- The Dopamine D2 Receptor Gene --- p.45 / Chapter 2 --- Aims --- p.47 / Chapter 3 --- Materials and methodology --- p.48 / Chapter 3.1 --- Patient recruitment protocol --- p.48 / Chapter 3.2 --- Subjects --- p.49 / Chapter 3.2.1 --- Classification of Hypertension --- p.50 / Chapter 3.2.2 --- Definition of Dyslipidaemia --- p.51 / Chapter 3.2.3 --- Classification of Diabetes Mellitus --- p.52 / Chapter 3.2.4 --- Definition of Obesity --- p.53 / Chapter 3.2.5 --- Exclusion Criteria --- p.54 / Chapter 3.3 --- Routine Assessment --- p.54 / Chapter 3.3.1 --- Blood Pressure --- p.54 / Chapter 3.3.2 --- Measurements of obesity --- p.55 / Chapter 3.3.2.1 --- Body mass index --- p.55 / Chapter 3.3.2.2 --- Waist to hip ratio --- p.55 / Chapter 3.3.2.3 --- Skin-Fold Thickness --- p.55 / Chapter 3.3.2.4 --- Skinfold Percentage Fat --- p.56 / Chapter 3.3.3 --- Biochemical measurements --- p.56 / Chapter 3.3.3.1 --- Assays measuring biochemical factors from plasma --- p.57 / Chapter 3.3.3.1.1 --- Plasma electrolytes --- p.57 / Chapter 3.3.3.1.2 --- Plasma urate --- p.57 / Chapter 3.3.3.1.3 --- Plasma creatinine --- p.57 / Chapter 3.3.3.1.4 --- Fasting plasma glucose --- p.57 / Chapter 3.3.3.1.5 --- Fasting plasma cholesterol --- p.57 / Chapter 3.3.3.1.6 --- Fasting plasma triglyceride --- p.58 / Chapter 3.3.3.2 --- Assays measuring biochemical factors from urine --- p.58 / Chapter 3.3.3.2.1 --- Urinary electrolytes --- p.58 / Chapter 3.3.3.2.2 --- Urinary creatinine --- p.58 / Chapter 3.3.3.2.3 --- Urinary albumin concentration --- p.58 / Chapter 3.4 --- Extraction of DNA from blood specimen --- p.59 / Chapter 3.5 --- Polymerase Chain Amplification protocols --- p.60 / Chapter 3.5.1 --- Uncoupling protein 1 gene polymorphism --- p.60 / Chapter 3.5.2 --- Angiotensin-Converting Enzyme insertion-deletion polymorphism --- p.62 / Chapter 3.5.3 --- Angiotensin type 1 receptor gene A1166C polymorphism --- p.64 / Chapter 3.5.4 --- Dopamine D2 receptor TaqI polymorphism --- p.66 / Chapter 3.5.5 --- Dopamine D2 receptor TaqI polymorphism --- p.66 / Chapter 3.6 --- Statistical analysis --- p.68 / Chapter 3.6.1 --- Paired sample T test --- p.68 / Chapter 3.6.2 --- Conditional Logistic Regression --- p.68 / Chapter 3.6.3 --- Linkage analysis --- p.69 / Chapter 3.6.3.1 --- Allelic frequency and genotypic distribution --- p.69 / Chapter 3.6.3.2 --- Hardy- Weinberg equilibrium --- p.69 / Chapter 3.6.3.3 --- Parametric analysis --- p.71 / Chapter 3.6.3.4 --- Nonparametric analysis --- p.71 / Chapter 3.6.3.4.1 --- The affected sib pair (ASP) method --- p.74 / Chapter 3.6.3.4.2 --- The affected pedigree member (APM) method of linkage analysis --- p.76 / Chapter 3.6.3.4.3 --- Quantitative traits linkage analysis --- p.79 / Chapter 4 --- Results --- p.81 / Chapter 4.1 --- Description of the characteristics of in siblings --- p.81 / Chapter 4.1.1 --- Siblings and sib-pairs --- p.81 / Chapter 4.1.2 --- Demographic characteristics --- p.81 / Chapter 4.1.3 --- Relationship to age and gender --- p.83 / Chapter 4.1.3.1 --- Hypertension versus age and gender --- p.83 / Chapter 4.1.3.2 --- Central obesity versus age and gender --- p.83 / Chapter 4.1.3.3 --- General obesity versus age and gender --- p.84 / Chapter 4.1.3.4 --- Hypertension-central obesity versus age and gender --- p.84 / Chapter 4.1.3.5 --- Hypertension- general obesity versus age and gender --- p.85 / Chapter 4.1.4 --- Relationship to anthropometric indices --- p.85 / Chapter 4.1.4.1 --- Large proportion of obesity --- p.85 / Chapter 4.1.4.2 --- Hypertension versus anthropometric indices --- p.86 / Chapter 4.1.5 --- Relationship to biochemistry indices --- p.87 / Chapter 4.1.5.1 --- Large proportion of dyslipidaemia --- p.87 / Chapter 4.2 --- Association between disease traits and covariates in discordant sib pairs --- p.87 / Chapter 4.2.1 --- Association between blood pressure and covariates in discordant sib-pairs --- p.87 / Chapter 4.2.2 --- Association between general obesity and covariates in discordant sib-pairs --- p.89 / Chapter 4.2.3 --- Association between obesity related hypertension and covariates in combined discordant sib-pairs --- p.91 / Chapter 4.3 --- Description of the analysis of the polymorphisms of 4 genes which might be related to hypertension and obesity --- p.93 / Chapter 4.3.1 --- The uncoupling protein 1 gene --- p.93 / Chapter 4.3.1.1 --- Comparison of A-G polymorphism in terms of hypertension or obesity --- p.94 / Chapter 4.3.1.2 --- Comparison of A-G polymorphism in terms of HT and obesity --- p.97 / Chapter 4.3.1.3 --- Comparison of characteristics among different genotypes --- p.99 / Chapter 4.3.2 --- The angiotensin-converting enzyme gene --- p.99 / Chapter 4.3.2.1 --- Comparison of the ACE I/D polymorphism in terms of HT --- p.100 / Chapter 4.3.2.2 --- Comparison of characteristics among different genotypes --- p.101 / Chapter 4.3.3 --- The angiotensin type 1 receptor gene --- p.104 / Chapter 4.3.3.1 --- Comparison of the A T1R A1166C polymorphism in terms of HT --- p.104 / Chapter 4.3.3.2 --- Comparison of characteristics among different genotypes --- p.105 / Chapter 4.3.4 --- The Dopamine D2 receptor gene --- p.105 / Chapter 4.3.4.1 --- Comparison of the DRD2 gene TaqI polymorphism in terms of HT --- p.106 / Chapter 4.3.4.2 --- Comparison of the DRD2 gene TaqI polymorphism in terms of general obesity or central obesity --- p.108 / Chapter 4.3.4.3 --- Comparison of the DRD2 gene TaqI polymorphism in terms of general obesity/central obesity and HT --- p.110 / Chapter 4.4 --- Sib pair linkage analysis --- p.113 / Chapter 4.4.1 --- Linkage between each gene and hypertension in our data --- p.114 / Chapter 4.4.1.1 --- Genetic linkage of the marker near the UCP1 gene locus to hypertension --- p.114 / Chapter 4.4.1.2 --- Genetic linkage of the angiotens in-converting enzyme gene locus to hypertension --- p.116 / Chapter 4.4.1.3 --- Genetic linkage of the angiotensin type 1 (AT1) receptor gene locus to hypertension --- p.117 / Chapter 4.4.1.4 --- Genetic linkage of the dopamine D2 receptor gene locus to hypertension --- p.118 / Chapter 4.4.2 --- Linkage between each gene locus and obesity in Hong Kong hypertensive Chinese families --- p.120 / Chapter 4.4.2.1 --- Genetic linkage of the uncoupling protein 1 gene locus to obesity with hypertensive family history --- p.120 / Chapter 4.4.2.2 --- Genetic linkage of the angiotens in-converting enzyme gene locus to obesity with hypertensive family history --- p.123 / Chapter 4.4.2.3 --- Genetic linkage of the angiotensin type 1 receptor gene locus to obesity with hypertensive family history --- p.124 / Chapter 4.4.2.4 --- Genetic linkage of the dopamine D2 gene locus to obesity --- p.127 / Chapter 5 --- Discussion --- p.129 / Chapter 5.1 --- Age-related anomalies --- p.129 / Chapter 5.2 --- Gender-related anomalies --- p.129 / Chapter 5.3 --- Obesity- related hypertension --- p.130 / Chapter 5.4 --- Abnormal biochemical parameters in hypertension --- p.131 / Chapter 5.5 --- Genetic parameters involved in the pathogenesis of hypertension and obesity. --- p.132 / Chapter 5.6 --- The uncoupling protein gene --- p.132 / Chapter 5.6.1 --- Higher frequency in central obese males --- p.132 / Chapter 5.6.2 --- Linkage of systolic blood pressure with G allele --- p.134 / Chapter 5.6.3 --- Metabolic link --- p.135 / Chapter 5.7 --- The angiotensin-converting enzyme gene --- p.137 / Chapter 5.7.1 --- The ACE D allele and hypertension in previous studies --- p.137 / Chapter 5.7.2 --- Positive role of the ACE DD genotype found in our data --- p.139 / Chapter 5.8 --- Angiotensin II type 1 receptor gene --- p.141 / Chapter 5.8.1 --- No linkage with HT --- p.141 / Chapter 5.9 --- Dopamine D2 gene --- p.143 / Chapter 5.9.1 --- Dopamine and obesity --- p.143 / Chapter 5.9.2 --- Linkage with obese and HT --- p.144 / Chapter 5.10 --- Summary of the study --- p.146 / Chapter 5.11 --- Possible further developments in this study --- p.146 / Chapter 6 --- References --- p.148

No description available.

This thesis deals with quantifying the costs of treatment of disease, which is by experts described as pandemic of the 21st century, diabetes. In the Czech Republic, the costs of treatment represents more than 6 % of total health expenditures and its quantity is growing, as well as the number of patients. The main goal is to determine costs of treatment for the 1st and the 2nd type of diabetes and the post-treatment complications associated with this disease using up-to-date statistical data and methodology called Pilot analysis of pharmacoeconomic aspects of diabetes mellitus treatment. This thesis also evaluates the change in regulation announcement in the CR and the Czech Republic's approach to diabetes as an incurable disease.