Thesis (M.S.)--Brigham Young University. Dept. of Mechanical Engineering, 2003. / Includes bibliographical references (p. 105-107).

published_or_final_version / abstract / toc / Surgery / Doctoral / Doctor of Philosophy

Theoretical Foundations Catheter ablation is an intervention focused on targeted removal of or damage to an area that causes arrhythmias. This intervention began to be performed at the turn of the 1980s and 1990s because it had been found that treatment with antiarrhythmic drugs was expensive and the drugs had to be taken throughout patients' lives. Thanks to its high success rate and low risk of complications, it has been used in the treatment of supraventricular tachyarrhythmias. At present, the success rate is around 75 %, and the intervention sometimes needs to be repeated to achieve its desired effect. Objectives of the thesis The first objective was to find out whether patients with a history of catheter ablation changed their personal and professional lives. The second objective was to map out which areas of the patients' live were affected most by the catheter ablation treatment. The third objective was to find out about differences in the patients' lives before and after catheter ablation. Research questions V1: In what areas are the patients' lives limited most? V2: What changes have occurred in their lives after catheter ablation? Methodology The research part of the thesis was carried out using a qualitative survey conducted by means of semi-structured interviews with patients suffering from arrhythmias. The total of 9 respondents, 5 males and 4 females, were interviewed. The information obtained was processed using programme Atlas.ti. The results are presented as networks created in this programme. Results The research questions can be answered using the data obtained from the respondents suffering from arrhythmias. The first research question was aimed at finding out in what areas the patients' lives were limited most. It was found out, through the semi-structured interviews, that the most limited area was personal life, in which arrhythmia caused most difficulties to the respondents during sports activities. Because of their health problems, most of the respondents limited their sports activities or abandoned them altogether in favour of their health. Other problems are caused during physical strain and under physical load. That was also the thing that the addressed respondents preferred to avoid. The respondents are also limited in the performance of their work, when the main cause of their problems is psychological stress, mental stress resulting in arrhythmia symptoms in the respective respondents. The second research question examined what changes occurred in their lives after catheter ablation. The changes that occurred related to the care of the family and the household in which they are able to engage in multiple activities. The respondents were able to pay more attention to their families by whom they are encouraged in the treatment. There was an overall improvement in their health, enabling better integration into everyday life. The most frequently mentioned area of changes was sport. During the period after catheter ablation, the respondents began to return gradually to their hobbies. Conclusion The thesis describes the restrictions that arrhythmia caused to the respondents and also the changes that have occurred in the individual respondents after catheter ablation treatment. The results can be used in practice in the education of patients who wait for the catheter ablation treatment and in subsequent measures using the prepared mind maps.

Marfan's syndrome is a common connective tissue disease with different musculoskeletal, ophthalmic and cardiac manifestations. Marfan's patients carry increased risk for cardiac arrhythmias. Only three cases of atrial flutter in Marfan's patients are described in the literature. We report a fourth case of a young Marfan's patient who presents with typical atrial flutter after motor vehicle accident. After electrical cardioversion, sinus rhythm was restored but he had recurrent atrial flutter on follow up. The patient then underwent electrophysiological study and successful radiofrequency catheter ablation of the flutter circuit. Since discharge, the patient has had no documented arrhythmias on follow up.

Jin, Dawei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 83-93). / Abstracts in English and Chinese. / ABSTRACT (IN CHINESE) --- p.ii / ABSTRACT (IN ENGLISH) --- p.iv / ACKNOWLEDGEMENTS --- p.vii / CONTENTS --- p.ix / LIST OF TABLES --- p.vxiii / LIST OF FIGURES --- p.xiv / LIST OF ABBREVIATIONS --- p.xvi / Chapter CHAPTER I --- INTRODUCTION --- p.1 / Chapter 1.1 --- Biology of C. albicans --- p.2 / Chapter 1.1.1 --- Taxonomy --- p.2 / Chapter 1.1.2 --- Basic cell biology --- p.2 / Chapter 1.1.2.1 --- Cell cycle and phenotypic switch --- p.2 / Chapter 1.1.2.2 --- Cell wall --- p.3 / Chapter 1.1.3 --- "Morphological, culture and biochemical characteristics" --- p.4 / Chapter 1.1.4 --- Genomics --- p.5 / Chapter 1.1.5 --- Pathogenecity --- p.6 / Chapter 1.2 --- Catheter-related bloodstream infections (CRBSI) caused by C. albicans --- p.7 / Chapter 1.2.1 --- Intravenous catheter type --- p.7 / Chapter 1.2.2 --- Epidemiology of CRBSI caused by C. albicans --- p.8 / Chapter 1.2.3 --- Pathogenesis of intravascular catheter-related infections --- p.9 / Chapter 1.2.4 --- Diagnosis of catheter-related infections --- p.10 / Chapter 1.2.5 --- Prevention and control --- p.11 / Chapter 1.3 --- Mechanism of C. albicans adhesion to catheters --- p.12 / Chapter 1.3.1 --- The definition of microbial adhesion --- p.12 / Chapter 1.3.2 --- Relationship between microbial adhesion and biofilm formation --- p.12 / Chapter 1.4 --- Agglutinin-like sequence (ALS) gene family of C. albicans --- p.14 / Chapter 1.4.1 --- Members of ALS gene family --- p.14 / Chapter 1.4.2 --- Chromosomal location of ALS genes --- p.14 / Chapter 1.4.3 --- ALS gene organization --- p.14 / Chapter 1.4.3.1 --- Three-domain structure of ALS genes --- p.15 / Chapter 1.4.3.2 --- Characterization of ALS genes. --- p.15 / Chapter 1.4.4 --- ALS gene allelic variation --- p.17 / Chapter 1.5 --- Experimental models for catheter adhesion study of C. albicans --- p.17 / Chapter 1.5.1 --- "Static adhesion model for C, albicans" --- p.18 / Chapter 1.5.1.1 --- Advantage of static adhesion model --- p.19 / Chapter 1.5.1.2 --- Limitation of static adhesion model --- p.19 / Chapter 1.5.2 --- Dynamic adhesion model for C. albicans --- p.19 / Chapter 1.5.2.1 --- Advantage of dynamic adhesion model --- p.20 / Chapter 1.5.2.2 --- Limitation of dynamic adhesion model --- p.20 / Chapter 1.5.3 --- Quantification methods of adherent cells --- p.21 / Chapter 1.5.4 --- ALS gene expression study in the in vitro model --- p.22 / Chapter 1.6 --- Aim of study --- p.22 / Chapter CHAPTER II --- MATERIALS & METHODS --- p.24 / Chapter 2.1 --- Strains used in this study --- p.25 / Chapter 2.2 --- Design of an in vitro dynamic adhesion model for C. albicans --- p.26 / Chapter 2.2.1 --- Flask --- p.26 / Chapter 2.2.2 --- Peristaltic pump --- p.26 / Chapter 2.2.3 --- Glass tube and vascular catheters. --- p.27 / Chapter 2.2.4 --- Sterility check of in vitro dynamic adhesion model --- p.27 / Chapter 2.3 --- Construction of C. albicans growth curve --- p.27 / Chapter 2.4 --- Measurement of C. albicans adhesion to catheters --- p.29 / Chapter 2.5 --- Detection of C. albicans ALS genes --- p.30 / Chapter 2.5.1 --- DNA extraction of C. albicans --- p.30 / Chapter 2.5.2 --- ALS primers design --- p.31 / Chapter 2.5.3 --- PCR reaction --- p.32 / Chapter 2.5.4 --- Gel electrophoresis --- p.32 / Chapter 2.5.5 --- Purification of PCR products --- p.33 / Chapter 2.6 --- Construction of E. coli plasmid containing gene --- p.34 / Chapter 2.6.1 --- Ligation using the pGEM®-T Easy Vector --- p.34 / Chapter 2.6.2 --- Preparation of E. coli DH5a electro-competent cells --- p.35 / Chapter 2.6.3 --- Clean up of DNA ligation reaction for electro-transformation --- p.36 / Chapter 2.6.4 --- Electro-transformation of E. coli DH5a electro-competent cells --- p.37 / Chapter 2.6.5 --- Blue / white screening for positive transformation of E. coli DH5a. --- p.37 / Chapter 2.6.6 --- Extraction of plasmid containing ALS1 gene --- p.39 / Chapter 2.6.7 --- Plasmid validation by PCR and gel electrophoresis --- p.39 / Chapter 2.6.8 --- Serial dilution of plasmid solutions for ALS1 standard curve construction --- p.40 / Chapter 2.7 --- C. albicans ALS1 gene expression in dynamic adhesion model --- p.41 / Chapter 2.7.1 --- Design of real-time PCR primers specific for C. albicans ALS1 --- p.41 / Chapter 2.7.2 --- Validation of primers specificity --- p.42 / Chapter 2.7.3 --- RNA extraction of C. albicans cells adhered on catheters --- p.43 / Chapter 2.7.4 --- Complementary DNA (cDNA) synthesis --- p.45 / Chapter 2.7.5 --- Quantitative real-time RT-PCR --- p.46 / Chapter 2.8 --- Statistical analyses --- p.48 / Chapter CHAPTER III --- RESULTS --- p.49 / Chapter 3.1. --- Validation of the in vitro dynamic adhesion model for C. albicans --- p.50 / Chapter 3.2. --- C. albicans growth curve construction --- p.50 / Chapter 3.3. --- Measurement of C. albicans adhesion on catheters --- p.50 / Chapter 3.4. --- Detection of C. albicans SC5314 ALS genes --- p.52 / Chapter 3.5. --- Validation of E. coli plasmid containing ALS1 gene --- p.54 / Chapter 3.6. --- C. albicans ALS 1 gene expression in dynamic adhesion model --- p.54 / Chapter 3.6.1. --- Specificity validation of ALS1 real-time primers --- p.55 / Chapter 3.6.2. --- Quantitative real-time RT-PCR --- p.55 / Chapter CHAPTER IV --- DISCUSSION --- p.57 / Chapter 4.1 --- Experimental design of the in vitro dynamic adhesion model --- p.58 / Chapter 4.1.1 --- Advantages of this in vitro dynamic adhesion model --- p.58 / Chapter 4.1.2 --- Limitation of this in vitro dynamic adhesion model --- p.58 / Chapter 4.1.3 --- Catheter arrangement inside the glass tube --- p.60 / Chapter 4.1.4 --- Reproducibility of experiments in the model --- p.62 / Chapter 4.1.5 --- Identification of potential contamination in the model --- p.63 / Chapter 4.1.6 --- Advantages of removing method for C. albicans adherent cells --- p.64 / Chapter 4.1.7 --- Limitation of removing method for C. albicans adherent cells --- p.64 / Chapter 4.1.8 --- Limitation of statistical analysis --- p.66 / Chapter 4.1.9 --- Primers design --- p.67 / Chapter 4.1.9.1 --- Primers of C. albicans ALS gene detection --- p.67 / Chapter 4.1.9.2 --- Validation of ALS 1 real-time primers specificity --- p.69 / Chapter 4.2 --- C. albicans adhesion to catheters --- p.70 / Chapter 4.2.1 --- Theoretical explanation of C. albicans adhesion to different catheters --- p.71 / Chapter 4.3 --- C. albicans ALS gene expression --- p.74 / Chapter 4.3.1 --- Functions of Als proteins --- p.75 / Chapter 4.3.1.1 --- Adhesive functions --- p.75 / Chapter 4.3.1.2 --- Other functions in C. albicans pathogenesis --- p.75 / Chapter 4.3.2 --- Analysis of ALS1 gene expression pattern in the in vitro model --- p.76 / Chapter 4.4 --- Clinical application of our study --- p.78 / Chapter 4.5 --- Future study --- p.80 / Chapter 4.6 --- Conclusion --- p.81 / REFERENCES --- p.83

Introdução: Na última década, desde a descrição inicial da ablação das veias pulmonares, a ablação por cateter da fibrilação atrial (FA) tem evoluído consideravelmente em eficácia e segurança, consolidando-se como opção terapêutica em pacientes selecionados com FA. No entanto, a ablação da FA é um procedimento complexo e não isento de riscos. Ainda que seja uma complicação rara, o desenvolvimento de fístulas átrio-esofágicas (FAE) é a segunda complicação responsável por morte relacionada ao procedimento e responde por 16% dos casos de morte após ablação de FA. Consensos atuais não orientam recomendações definitivas para prevenção de lesões esofágicas, consideradas lesões precursoras de FAE. O objetivo deste trabalho foi comparar a incidência de lesões esofageanas e periesofageanas por ecoendoscopia após ablação de fibrilação atrial, utilizando diferentes estratégias de proteção esofágica durante as aplicações de radiofrequência na parede posterior do átrio esquerdo. Método: No período de outubro/2012 a julho/2014, foram estudados 45 pacientes submetidos à ablação percutânea de FA, portadores de FA paroxística ou persistente há menos de um ano. Todos os pacientes foram submetidos a ablação circunferencial com isolamento elétrico das veias pulmonares, com cateter de ablação 8 mm. Antes do procedimento, os pacientes foram randomizados para uma de três estratégias de proteção esofágica durante as aplicações de radiofrequência na parede posterior do átrio esquerdo para ablação da FA: Grupo I - aplicações limite fixo e de baixa energia, 30 W; Grupo II - aplicações com energia limitada pela temperatura esofágica; GIII - aplicações com limite fixo de energia durante resfriamento esofágico contínuo. A pesquisa de lesões esofágicas/periesofágicas foi feita por ecoendoscopia realizada em até 48 horas após a ablação. Resultados: As características basais foram similares nos três grupos, não sendo encontradas diferenças significativas entre as variáveis clínicas, laboratoriais, ecocardiográficas ou ecoendoscópicas prévias, com exceção da distância átrio-esofágica pré-ablação medida pela ecoendoscopia, que foi menor no Grupo III (GI = 3,9 mm +- 0,4; GII = 3,9 mm +- 0,5; GIII = 3,4 mm +- 0,4, p = 0.002). Nas ecoendoscopias pós-ablação de FA, foram encontradas 04 lesões esofágicas/periesofágicas: duas úlceras de parede esofágica e dois casos de edemas de mediastino periesofágico. Todos os casos de lesões esofágicas/periesofágicas ocorreram no grupo de resfriamento esofágico, G III (p= 0,008). A comparação das características clínicas dos pacientes que apresentaram lesões esofágicas/periesofágicas com os que não apresentaram essas alterações, pela análise bivariada, mostrou que foram similares nos dois grupos, exceto pelos valores médios de proteína C reativa (PCR) após a ablação de fibrilação atrial, que foram significativamente maiores no grupo com lesões (Grupo sem lesões: PCR = 0,82 mg/dl; Grupo com lesões: PCR = 2,12 mg/dl, p < 0,001). A comparação dos parâmetros das ablações por regiões das veias abordadas, quanto ao tempo das aplicações de radiofrequência, a potência e a temperatura do cateter de ablação, identificou que os pacientes que apresentaram lesões esofágicas/periesofágicas tiveram maiores valores de média de potência nas aplicações realizadas na parede posterior das veias pulmonares esquerdas, que os pacientes que não tiveram lesões (Grupo sem lesões esofágicas: potência média cateter = 37,7 w; Grupo com lesões esofágicas: potência média do cateter = 48,8 w, p = 0.013). A incidência de recorrência de arritmia após um único procedimento de ablação de Fibrilação Atrial, em seguimento clínico de 11 +- 5 meses, foi de 7 casos (15.6%), sem diferença significativa entre os grupos (GI = 26,7%, GII = 13,3% e GIII = 6,7%, p = 0,305). A incidência de complicações maiores relacionadas aos procedimentos de ablação realizados foi de 2,2% (um caso de congestão pulmonar no segundo dia após o procedimento, resolvido com uso de diuréticos). Conclusão: O uso da estratégia de resfriamento esofágico durante ablação de FA foi ineficaz como estratégia preventiva de lesões esofágicas/periesofágicas na população estudada, quando comparada às estratégias de aplicações de radiofrequência com baixa energia ou de energia limitada pela temperatura esofágica / Introduction: In the last decade, since the initial description of the ablation of pulmonary veins, the atrial fibrillation (AF) catheter ablation has evolved significantly in terms of efficacy and safety, consolidating itself as the therapeutic choice for AF selected patients. However, AF ablation is a complex procedure not without risks. Despite being a rare complication, the development of atrialesophageal fistulas (AEFs) ranks second in terms of procedure-related deaths, accounting for 16% of all post-AF ablation losses of life. Current consensus is not dispositive with regards to directives for the prevention of esophageal lesions, which come first and lead to AEFs. The objective of this work is to compare the incidence of esophageal and periesophageal lesions post-AF ablation, given use of different esophageal protection strategies during the radiofrequency applications on the left-atrium posterior wall. Method: From October 2012 through July 2014, 45 patients submitted to AF percutaneous ablation were studied. All of them were bearers of paroxistic or persistent AF for less than one year, and all of them were submitted to 8mm-catheter, pulmonary vein electric-shielding circumferential ablation. Before the procedure, patients were randomly assigned to one of three esophageal lesion protection strategies: Group I - 30w, low energy, fixed limited applications; Group II - energy applications limited by esophageal temperature; and Group III - fixed limit energy applications during continuous esophageal cooling. The survey for esophageal/periesophageal lesions was carried by means of esophageal endoscopy combined with radial ultrasound performed within 48 hours post ablation. Results: Baseline characteristics were even across groups; no significant differences in clinical, laboratorial, ecocardiographic or endoscopic variables were found, except for pre-ablation distance between posterior left atrium wall and the esophagus as measured by radial ultrasound endoscopic, smaller in Group III (GI = 3,9 mm +- 0,4; GII = 3,9 mm +- 0,5; GIII = 3,4 mm +- 0,4, p = 0.002). Post FA-ablation endoscopies revealed the existence of 4 counts of esophageal/periesophageal lesions: 2 esophageal wall ulcer and 2 periesophageal mediastin edema. All cases of esophageal/periesophageal lesions occurred in the esophageal cooling group (GIII) (p=0.008). Bivariate analysis on the clinical characteristics of patients that presented esophageal/periesophageal lesions showed no significant difference from those in the lesion-free group, except for average values for post ablation reactive-C protein (RCP), significantly greater in the lesion group (2.12 mg/dl vs. 0.82 mg/dl for the lesion-free group, p < 0.001). Ablation parameter comparison by approached vein region revealed that patients with post ablation lesions had received higher-powered applications in their posterior wall left pulmonary veins (average catheter power = 48.8 w vs. 37.7 w for lesion-free group, p=0.013). After a 11 +- 5 month clinical following, arrhythmia recurrence post a single AF ablation procedure added to 7 cases (15.6%), and no significant difference among the three different groups was found (GI = 26.7%, GII = 13.3% e GIII = 6.7%, p = 0.305). Incidence of major complications related to the ablation procedures reached 2.2% (one case of pulmonary congestion occurring in the second day post procedure, and resolved with the use of diuretics). Conclusion: The use of esophageal cooling during AF ablation was an ineffective strategy to prevent esophageal/periesophageal lesions in the studied population when compared to low-energy radiofrequency or energy limited by esophageal temperature lesion prevention strategies

A elevada prevalência da hipertensão arterial sistêmica e as reduzidas taxas de controle tensional obtidas com o tratamento farmacológico despertaram interesse por estratégias alternativas. A denervação simpática renal percutânea surgiu como perspectiva no tratamento de pacientes com hipertensão arterial resistente. As vantagens do cateter irrigado nas ablações cardíacas fomentaram a hipótese de que esse também poderia ser benéfico no contexto da denervação renal. Objetivos: Avaliar a factibilidade e a segurança da denervação simpática renal com cateter irrigado em pacientes com hipertensão arterial resistente. Métodos: O objetivo primário do estudo foi a análise de segurança do procedimento avaliada pela: 1) quantificação de eventos adversos vasculares (em sítio de punção e artéria renal) periprocedimento; 2) Comprometimento da função renal durante o seguimento; 3) ocorrência de estenose/aneurisma da artéria renal, seis meses após a intervenção. Os objetivos secundários foram avaliar: 1) o efeito da denervação renal no comportamento da pressão arterial (aferida em consultório e na MAPA) e no número de anti-hipertensivos, seis meses após a intervenção; 2) o efeito do procedimento na qualidade de vida, aos três meses de seguimento. As variáveis contínuas, ao longo do tempo, foram comparadas utilizando-se os testes t de Student pareado ou Wilcoxon. Para a análise dos dados, utilizaram-se os programas SPSS e STATA11 SE. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: Vinte pacientes (idade 50 ± 9,8 anos, 75% mulheres) foram submetidos à denervação renal. As médias das pressões arteriais sistólica e diastólica aferidas no consultório foram de 194,8 ± 36,5mmHg e 112 ± 16,8mmHg, respectivamente. As médias das pressões arteriais sistólica e diastólica aferidas na MAPA foram de 168,4 ± 22,2mmHg e 101,3 ± 19,1mmHg, respectivamente. O número médio de antihipertensivos foi de 7,1 ± 1,5. O procedimento foi realizado sem complicações em 95% dos casos. Em um caso, houve dissecção da artéria renal por trauma mecânico causado pela bainha introdutora. Não foram observadas complicações relacionadas à punção femoral ou elevação dos níveis séricos de creatinina no seguimento. Após seis meses, todos os pacientes foram submetidos à avaliação da integridade vascular. Houve um caso de estenose significativa em artéria renal esquerda, sem repercussão clínica. Ao final de seis meses, observou-se redução de 29,7 ± 33,1mmHg na PAS (p = 0,001) e 14,6 ± 18,9mmHg na PAD (p = 0,003) aferida em consultório, respectivamente. A redução na média da PAS e da PAD, aferida na MAPA, foi de 17,4 ± 33,4mmHg (p = 0,03) e 10,0 ± 21,3mmHg (p = 0,05), respectivamente. Em média, houve redução de 2,6 ± 2,0 anti-hipertensivos (p < 0,01). Antes do procedimento, o valor médio atribuído ao estado de saúde foi de 37,5 ± 22,7 e aumentou para 70,5 ± 20,9 (p = 0,01), três meses após a intervenção. Pacientes que experimentaram redução no número de anti-hipertensivos relataram melhora do estado de saúde. Conclusões: A denervação simpática renal com cateter irrigado é factível e segura. Hipertensos resistentes têm baixos escores do estado de saúde e de qualidade de vida. Os resultados sugerem que esse procedimento reduz os valores pressóricos e melhora a qualidade de vida, na maioria dos pacientes. / The high prevalence of hypertension and reduced blood pressure control obtained with pharmacological treatment aroused interest in alternative therapies. Percutaneous renal sympathetic denervation has emerged as an alternative in the treatment of resistant hypertension. The benefits of irrigated catheter in cardiac ablations fostered the hypothesis that these catheters may also be beneficial for renal denervation. Objectives: To evaluate the feasibility and safety of renal sympathetic enervation for resistant hypertension using an irrigated catheter. Methods: The primary endpoint was the safety of the procedure by means of: 1) periprocedural adverse vascular (puncture site and renal artery) events; 2) changes on renal function during follow-up; 3) evidence of renal artery stenosis/aneurysm at 6 months post-intervention. Secondary objectives were to assess the effects of renal denervation on: 1) blood pressure (difference on office and ABPM between baseline and 6 months of follow-up); 2) number of antihypertensive drugs (difference between baseline and 6 months post-intervention); 3) quality of life (comparison between baseline and 3 months). Continuous variables were compared using the paired Student t test or Wilcoxon test. Data was examined using the SPSS software and STATA11 SE. P values < 0.05 were considered statistically significant. Results: 20 patients (age 50 ± 9.8 years, 75% female) underwent renal denervation. Mean office systolic and diastolic blood pressure was 194.8 ± 36.5mmHg and 112.0 ± 16.8mmHg, respectively. Mean blood pressure on 24 hour ABPM was 168.4 ± 22.2mmHg e 101.3 ± 19.1mmHg, respectively. The mean number of anti-hypertensive drugs was 7.1 ± 1.5; 95% of cases were performed without complications. In one patient, there was a renal artery dissection by mechanical trauma caused by the sheath, resulting in stent implantation. There were no complications related to femoral puncture or elevation of creatinine values during the follow up. All patients were evaluated for vascular integrity at 6months. In one patient, significant left renal artery stenosis was diagnosed. At 6 months, office systolic and diastolic blood pressure reduced 29.7 ± 33.1mmHg (p = 0.001) and 14.6 ± 18.9mmHg (p = 0.003) respectively; Systolic and diastolic blood pressure on ABPM reduced 17.4 ± 33.4mmHg (p = 0.03) and 10.0 ± 21.3mmHg (p = 0.05), respectively. On average, there was a reduction of 2.6 ± 2.0 (p < 0.01) antihypertensive drugs. Before the procedure, the average value attributed to health status was 37.5 ± 22.7 and improved significantly at 3 months (70.5 ± 20.9, p = 0.01). Patients who experienced a reduction in the number of antihypertensive drugs reported improved health status. Conclusions: Renal sympathetic denervation with irrigated catheter is feasible and safe. Hypertensive patients have low quality of life scores. Comparison to post-renal denervation results showed a reduction in blood pressure and better quality of life in most patients.

INTRODUÇÃO: Os tumores renais pequenos e localizados são hoje diagnosticados mais frequentemente graças ao uso mais intenso dos métodos de imagem, o que favorece técnicas de tratamento menos traumáticas e igualmente eficazes. Dentre as técnicas minimamente invasivas, uma alternativa atraente é a radiofrequência (RF) por ser eficiente, de baixo custo e fácil aplicação. OBJETIVO: Avaliar métodos de aprimoramento da aplicação da RF para promover lesão celular renal de forma mais eficiente, obtendo lesões maiores, utilizando diferentes temperaturas e, em seguida, administrar drogas vasoativas para comparar o tamanho das lesões. Objetivou-se avaliar também se há remanescência de células viáveis na área abrangida pela lesão. MATERIAL E MÉTODO: O estudo foi realizado na Divisão de Clínica Urológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre janeiro de 2005 e dezembro de 2008. Inicialmente, 16 cães (Grupo A) foram submetidos a RF no parênquima renal com diferentes temperaturas: 80, 90 e 100 graus centígrados. Para comparar os resultados, foi analisado o tamanho das lesões nas diferentes temperaturas por medida da profundidade e da largura, correlacionadas com a impedância. Em seguida, usando a temperatura de 90 oC, 14 cães foram submetidos a RF com injeção dos dois diferentes agentes vasoativos: como vasoconstritor, a adrenalina (Grupo B), versus a prostaglandina E1 (Grupo C) como vasodilatador. Após 14 dias, os animais foram submetidos a nefrectomia para avaliação das lesões e a sacrifício. RESULTADOS: Houve diferença estatisticamente significante na profundidade (p < 0,001) e largura (p < 0,001) da lesão entre as três temperaturas (80, 90 e 100 oC), sendo que há um pico no tamanho das lesões renais na temperatura de 90 oC. Foi observada diferença estatisticamente significante da impedância entre as três temperaturas estudadas (p < 0,001), e se observou resultado mais favorável a 90 oC (menor impedância) e similar entre as temperaturas de 80 e 100 oC. A segunda etapa do estudo demonstrou que o uso da prostaglandina E1 resultou em lesões significativamente mais profundas e mais largas que o uso da adrenalina e também que a resistência tecidual foi menor com a prostaglandina E1. CONCLUSÕES: A temperatura de 90 oC foi mais eficiente para provocar destruição celular com a RF por produzir lesões mais extensas na largura e profundidade, quando comparada com as temperaturas de 80o e 100 oC (p < 0,001). A impedância também foi menor com 90 oC (p < 0,001). Observou-se que as lesões produzidas sem drogas não apresentaram diferença significante comparado com o uso de prostaglandina E1. Porém, o uso de adrenalina promoveu lesões menores (p < 0,001) quando comparada com os dois outros grupos. Não foram observadas células viáveis na análise microscópica dentro dos limites atingidos pela RF em ambos os experimentos / INTRODUCTION: Small, localized renal tumors are diagnosed more frequently nowadays due to the more intense use of imaging methods, which favor less traumatic but equally efficacious treatment techniques. Among the minimally invasive techniques, an attractive alternative is that of radiofrequency (RF), as it is efficient, and easily applicable. OBJECTIVE: To assess methods for the improvement of the application of RF, for the more efficient promotion of the renal cell lesion, to obtain larger lesions, making use of various temperatures and then administering vasoactive drugs to compare the size of the lesions produced, and also to assess the existence of remaining viable cells in the area affected by the lesion. MATERIAL AND METHOD: The study was undertaken at the Urological Clinical Division of the Hospital das Clínicas of the Medical School of the University of São Paulo, between January 2005 and December 2008. Initially, 16 dogs (Group A) underwent RF of the renal parenchyma at various temperatures: 80, 90 and 100 degrees centigrade. For the comparison of the results, the size of the lesions at the various temperatures was analyzed by the measurement of their depth and width, correlated with the impedance. Then, using a temperature of 90 oC, 14 dogs were submitted to RF with an injection of one of the two different vasoactive agents: adrenaline, vasoconstrictor (Group B), versus with E1 prostaglandin, vasodilator (Group C). After 14 days, the animals underwent nephrectomy for the assessment of the lesions, and then were sacrificed. RESULTS: It was observed that, with the application of RF at the temperatures of 80, 90 and 100 oC, there was a statistically significant difference in the depth (p < 0.001) and width (p < 0.001) of the lesions as between the three temperatures, with a peak in the size of the renal lesions at 90 oC. A statistically significant difference in impedance was observed as between the three temperatures studied (p < 0.001), the most favorable result occurring at 90 oC (least impedance) and similar ones occurring between the temperatures of 80 and 100 oC. The second phase of the study demonstrated that the use of the prostaglandin E1 gave rise to significantly deeper and wider lesions than did the use of adrenaline and also that the tissue resistance was less than with the prostaglandin E1. CONCLUSIONS: It was observed that the temperature of 90oC was more efficient in provoking cell destruction with RF as it produced more extensive lesions both in width and depth than those at the temperatures of 80o and 100 oC (p < 0.001). The impedance was also less at 90 oC (p < 0.001). It was observed that the lesions produced without drugs presented no significant difference with the use of prostaglandin. However, the use of adrenaline provoked smaller lesions (p < 0.001) than did the other two (technical) groups. No viable cells were observed by microscopic analysis within the limits attained by the RF, in either of the experiments

Introduction: Radiofrequency ablation (RFA) is a popular method of treating unresectable liver tumours by the use of a high frequency, alternating electrical current that heats and destroys tumour cells. The size of the ablation is limited by localised charring of adjacent tissue that prevents further conduction of the radiofrequency current. In the clinical setting, this results in increased rates of local recurrence in tumours that are greater than 3 cm in diameter as multiple, overlapping ablations need to be performed to treat the one tumour. To overcome this problem, a modified form of RFA called Bimodal Electric Tissue Ablation (BETA) has been created. BETA adds a direct electrical current to the alternating radiofrequency current, thus establishing its bimodal character. When direct currents are used in biological tissues, water is transferred from anode to cathode by a process called electro-osmosis. By attaching the cathode to the radiofrequency electrode, water is attracted to the area thus preventing tissue desiccation and charring. The BETA circuit has been constructed and tested using a porcine model. The aims of the studies are to confirm that larger ablations can be produced with the BETA system and that it is safe to use in an animal model. Three studies have been performed to test these aims in porcine liver. Methods: The first study was designed to compare sizes of the ablation produced between standard RFA and the BETA circuit. This was followed by a long-term study to assess associated changes to liver function and pathological changes within the liver as well as identifying any other treatment related morbidity. The third study assessed the difference in ablation size and safety aspects when the positive electrode of the direct current circuitry was moved from small surface area under the skin to a large surface area on the skin. Results: Ablations with significantly larger diameters are created with the BETA circuit using a multi-tine needle (49.55 mm versus 27.78 mm, p<0.001). This finding was confirmed in the third experiment using a straight needle (25 mm versus 15.33 mm, p<0.001). Ablations produced by the BETA circuit induce coagulative necrosis within the treated liver and the injury heals by fibrosis in a manner similar to other thermal therapies. Significant rises in some serum liver enzymes are seen within 24 hours of treatment but these return to normal within 4 days. An electrolytic type injury can be produced at the site of the positive electrode. By increasing the surface area of this electrode, the risk of tissue damage is decreased but ablations are significantly smaller (18 mm versus 25 mm, p<0.001). Conclusions: The BETA circuit consistently produces significantly larger ablations than RFA. The treatment appears safe but positioning of the positive electrode of the direct current requires careful consideration. Injuries produced behave like other thermal therapies with coagulative necrosis followed by fibrotic healing. As larger ablations are consistently produced, it is hypothesised that with further refinements, tumours greater than 3 cm in diameter could be treated with lower rates of recurrence. / Thesis (M.S.) -- University of Adelaide, School of Medicine, 2008

Bedingt durch die zunehmende Prävalenz der Rhythmusstörung Vorhofflimmern mit den assoziierten Morbiditäts- und Mortalitätsrisiken ist die Entwicklung und Etablierung kurativer Therapieverfahren von klinischem und wissenschaftlichem Interesse. Entsprechend dem pathophysiologischen Verständnis der Arrhythmie-induzierenden Triggeraktivität und des Arrhythmie-erhaltenden Flimmersubstrat mit der vorrangigen anatomisch-strukturellen Lokalisation beider Entitäten im Übergangsbereich der großen Pulmonalvenentrichter in den posterioren linken Vorhof wurden katheterinterventionelle Ablationskonzepte als potentiell kurative Therapien entwickelt. Limitationen der praktischen Umsetzung theoretischer Linienkonzepte ergeben sich aus komplexen anatomischen Gegebenheiten und instabilen Zugangsbedingungen infolge Atmung und kardialer Mobilität. Aufbauend auf non-fluoroskopischen Navigationssystemen wurden Verfahren für vollständig Modell-integrierte Ansätze der Ablationslinienplatzierung entwickelt, bei denen Planung, Durchführung und Validierung der Ablation an anatomisch korrekten dreidimensionalen CT-Modellen des linken Vorhofes erfolgen. Zur Verbesserung instabiler Zugangsbedingungen wurden Verfahren der Katheternavigation mittels steuerbaren Schleusensystemen eingeführt und in entsprechenden Studien mit klinischen Endpunkten validiert. Zu objektivierbaren Erfassung von Energietransfer und myokardialer Läsionsbildung während der Ablation wurden katheterinterventionelle Kontakttechnologien, die auf der Messung lokaler komplexer Impedanzen zwischen Katheter und Gewebe beruhen, in der ersten klinischen Anwendung erprobt und validiert. Mit diesen technologischen Entwicklungen gelangen eine zunehmend akkuratere klinische Umsetzung theoretischer Ablationskonzepte und damit eine Etablierung des Therapiekonzeptes als klinisches Standardverfahren. Eine zur Abschätzung des Nutzen/Risiko-Profils nötige detaillierte Komplikationsanalyse stellte die Ösophagusverletzung als schwerste Komplikation heraus, die mit 0,3% selten auftrat, aber für nahezu alle langfristigen Folgeschäden verantwortlich war. Entwicklungen zur periprozeduralen Visualisierung des Ösophagus mit paralleler intraösophagealer Temperaturmessung sind Ansätze zur Vermeidung dieser Komplikation in der Zukunft. Bedingt durch das Auftreten und die postinterventionelle Zunahme asymptomatischer Flimmerrezidive ist die Frage eines objektiven Vorhofflimmermonitorings von entscheidender Bedeutung für die Beurteilung der Effektivität der Ablation sowie weitergehende klinische und wissenschaftliche Fragestellungen; wie die Indikation zur Antikoagulation oder den Vergleich von Rhythmus- und Frequenzkontrolle. 7-Tage-LzEKGs und transtelephonische EKGs wurden als Standard zum Monitoring innerhalb klinischer Vorhofflimmerstudien etabliert. Entwicklungen im Bereich implantierbarer kontinuierlicher Rhythmusmonitore werden in Zukunft das Netz zur Erfassung asymptomatischen Vorhofflimmerns weiter verdichten.