Identification of genetic variants that influence atherosclerosis in young persons

Atherosclerosis is widely accepted as a complex genetic phenotype and is the usual cause of cardiovascular disease, the world’s leading killer. Genetic factors have been proven to be important risk contributors for atherosclerosis and much work has been done to identify promising candidates that might play a role in the development of atherosclerosis. It is well known that many independent replications are needed to unequivocally establish a valid genotype-phenotype association across different populations before the findings are extended to clinical settings and to the expensive follow-up studies designed to identify causal genetic variants. Aiming to replicate the association with atherosclerosis in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we assessed the relationship of 32 atherosclerosis candidate SNPs to atherosclerosis in the PDAY cohort, consisting of AA and EA young people aged 15-34 years who died of non-medical causes. Two association studies, a whole sample study and a 1:1 matched case control study were performed by use of multiple linear regression and logistic regression analyses, respectively. For the whole sample association study, 32 SNPs among 2,650 individuals (1,369 AA and 1,281 EA) were tested for the association with six early atherosclerosis phenotypes: abdominal aorta fatty streaks, abdominal aorta raised lesions, right coronary artery fatty streaks, right coronary artery raised lesions, thoracic aorta fatty streaks, and thoracic aorta raised lesions. For the matched case-control association study, 337 case-control paired samples were included; cases were chosen with the highest total raised lesion scores from the studied population, while controls were randomly selected from individuals that had no raised lesions and matched to cases by age, gender and race. Sixteen SNPs in 13 genes were found to be significantly associated with atherosclerosis in at least one of the PDAY association studies. Among these 16 findings: eight SNPs (rs9579646, rs6053733, rs3849150, rs10499903, rs2148079, rs5073691, rs10116277, and rs17228212) successfully replicated previous results, six SNPs (rs17222814, rs10811661, rs7028570, rs7291467, rs16996148 and rs10401969) were reported as new findings exclusive to our study, the last two of the 16 SNPs, rs501120 and rs6922269, showed either intriguing or conflicting result. SNP rs17222814 in ALOX5AP and SNP rs3849150 in LRRC18 were consistently associated with atherosclerosis in both prior and the two PDAY association studies. SNP rs3849150 was also identified to be highly correlated with a non-synonymous coding SNP, rs17772611, which may damage the protein (polyphen score = 0.996), suggesting that SNP rs17772611 may be the causal functional variant.^ In conclusion, our study added more support for the association of these candidate genes with atherosclerosis. SNPs rs3849150 and rs17772611 of LRRC18, as well as SNP rs17222814 of ALOX5AP, were the most significant findings from our study, and may be ranked among the best for further study.^

William Osler: Original Papers 1898-1906

Part 1: 1898-1899 On Chronic Symmetrical Enlargement of the Salivary and Lachrymal Glands, 1898 Leprosy in the United States, with the Report of a Case, 1898 An Acute Myxaedematous Condition, with Tachycardia, Glycosuria, Melaena, Mania and Death, 1898 On some of the Intestinal Features of Typhoid Fever, 1898 Cerebro-Spinal Fever, 1898 The Arthritis of Cerebro-Spinal Fever, 1898 In Memoriam, William Pepper, 1899 After Twenty-Five Years, 1899 The Diagnosis of Typhoid Fever, 1899 Interstitial Processes in the Central Nervous System, 1899 Part 2: 1900 The Home Treatment of Consumption, 1900 On Splenic Anaemia, 1900 The Chronic Intermittent Fever of Endocarditis, 1900 A Case of Multiple Gangrene in Malarial Fever, 1900 Latent Cancer of the Stomach, 1900 On the Study of Tuberculosis, 1900 Fatal Angina Pectoris without Lesions of the Coronary Arteries of a Young Man, 1900 On the Advantages of a Trace of Albumin and a Few Casts in the Urine of Certain Men above Fifty Years of Age, 1900 Part 3: 1901-1902 Congenital Absence of the Abdominal Muscles with Distended Hypertrophied Urinary Bladder, 1901 Intermittent Claudication, 1902 On the Diagnosis of Bilateral Cystic Kidney, 1902 On Amebic Abscess of the Liver, 1902 Note on the Occurrence of Ascites in Solid Abdominal Tumors, 1902 Amebic Dysentery, 1902 Notes on Aneurism, 1902 William Beaumont; a Pioneer American Physiologist, 1902 Part 4: 1903 On the Educational Value of the Medical Society, 1903 On obliteration of the Superior Vena Cava,1903 Chronic Cyanosis, with Polycythemia and Enlarged Spleen: A New Clinical Entity, 1903 The Home and its Relation to the Tuberculosis Problem, 1903 Unity, Peace, and Concord, 1903 Typhoid Fever and Tuberculosis, 1903 Part 5: 1904-1906 Ochronosis, 1904 The “Phthisiologia” of Richard Morton, M.D., 1904 On the Surgical Importance of the Visceral Crises In the Erythema Group of Skin Diseases, 1904 Aneurysm of the Abdominal Aorta, 1905 Back Notes

Colonografia por tomografia computorizada : colonoscopia virtual a evidência actual

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2013

In vivo biocompatibility evaluation of composite polymeric materials for use in a novel artificial heart valve

A novel trileaflet polymer valve is a composite design of a biostable polymer poly(styrene-isobutylene-styrene) (SIBS) with a reinforcement polyethylene terephthalate (PET) fabric. Surface roughness and hydrophilicity vary with fabrication methods and influence leaflet biocompatibility. The purpose of this study was to investigate the biocompatibility of this composite material using both small animal (nonfunctional mode) and large animal (functional mode) models. Composite samples were manufactured using dip coating and solvent casting with different coating thickness (251μm and 50μm). Sample's surface was characterized through qualitative SEM observation and quantitative surface roughness analysis. A novel rat abdominal aorta model was developed to test the composite samples in a similar pulsatile flow condition as its intended use. The sample's tissue response was characterized by histological examination. Among the samples tested, the 25μm solvent-cast sample exhibited the smoothest surface and best biocompatibility in terms of tissue capsulation thickness, and was chosen as the method for fabrication of the SIBS valve. Phosphocholine was used to create a hydrophilic surface on selected composite samples, which resulted in improved blood compatibility. Four SIBS valves (two with phosphocholine modification) were implanted into sheep. Echocardiography, blood chemistry, and system pathology were conducted to evaluate the valve's performance and biocompatibility. No adverse response was identified following implantation. The average survival time was 76 days, and one sheep with the phosphocholine modified valve passed the FDA minimum requirement of 140 days with approximately 20 million cycles of valve activity. The explanted valves were observed under the aid of a dissection microscope, and evaluated via histology, SEM and X-ray. Surface cracks and calcified tissue deposition were found on the leaflets. In conclusion, we demonstrated the applicability of using a new rat abdominal aorta model for biocompatibility assessment of polymeric materials. A smooth and complete coating surface is essential for the biocompatibility of PET/SIBS composite, and surface modification using phosphocholine improves blood compatibility. Extrinsic calcification was identified on the leaflets and was associated with regions of surface cracks.

Testicular arteries systematization based on different levels of scrotal configuration in caprines

O objetivo deste trabalho foi analisar a distribuição dos vasos arteriais nos testículos em caprinos com diferentes graus de divisão escrotal. A configuração escrotal foi classificada da seguinte forma: Grupo I: constituído por caprinos com escroto único, Grupo II: com escroto separado até a metade do testículo e Grupo III: com separação escrotal estendendo-se além da metade do testículos. As artérias foram injetadas e coradas com solução de acetado de vinil, sendo os orgãos (30 pares) submetidos à corrossão para obtenção dos moldes vasculares. As artérias testiculares emergem da aorta abdominal, com trajeto retilíneo, atravessam o canal inguinal, apresentam-se espiraladas e envolvidas parcialmente pelo plexo pampiniforme. Próximo à extremidade caudada do testículo, dividem-se mais freqüentemente nos ramos cranial e caudal, os quais emitem vasos colaterais, de onde emergem ramos penetrantes. Os testículos dos animais com nível intermediário de divisão escrotal (Grupo II) apresentam menor quantidade destes ramos, sendo os quadrantes mais povoados o ventrolateral e o dorsolateral. Conclui-se que a origem, o trajeto e a distribuição das artérias testiculares não apresentam variações relacionadas ao grau de divisão escrotal em caprinos.

Ultrasonido a la cabecera del paciente, una herramienta diagnóstica de disección aórtica en el departamento de emergencias

El síndrome aórtico agudo puede presentarse como un cuadro clínico característico de una emergencia vascular, o por el contrario de una forma completamente atípica, donde el diagnóstico reta al médico de emergencias, llevando a errores fatales al pasar por alto el diagnóstico de esta entidad. Con el objetivo de mostrar la utilidad del ultrasonido realizado a la cabecera del paciente en el diagnóstico de disección aórtica, se describen 9 casos de pacientes que ingresaron al departamento de emergencias y que fueron diagnosticados con síndrome aórtico agudo, gracias a la valoración ultrasonográfica inicial realizada por residentes y Especialistas en Medicina de Emergencias en un hospital de Bogotá D.C., Colombia. Este reporte de casos muestra que el ultrasonido a la cabecera del paciente, es un método diagnóstico no invasivo, accesible y útil para la detección temprana de esta patología en los servicios de emergencias.

Left Ventricle Modification After Endovascular Aortic Repair

INTRODUCTION Endograft deployment is a well-known cause of arterial stiffness increase as well as arterial stiffness increase represent a recognized cardiovascular risk factor. A harmful effect on cardiac function induced by the endograft deployment should be investigated. Aim of this study was to evaluate the impact of endograft deployment on the arterial stiffness and cardiac geometry of patients treated for aortic aneurysm in order to detect modifications that could justify an increased cardiac mortality at follow-up. MATHERIALS AND METHODS Over a period of 3 years, patients undergoing elective EVAR for infrarenal aortic pathologies in two university centers in Emilia Romagna were examined. All patients underwent pre-operative and six-months post-operative Pulse Wave Velocity (PWV) examination using an ultrasound-based method performed by vascular surgeons together with trans-thoracic echocardiography examination in order to evaluate cardiac chambers geometry before and after the treatment. RESULTS 69 patients were enrolled. After 36 months, 36 patients (52%) completed the 6 months follow-up examination.The ultrasound-based carotid-femoral PWV measurements performed preoperatively and 6 months after the procedure revealed a significant postoperative increase of cf-PWV (11,6±3,6 m/sec vs 12,3±8 m/sec; p.value:0,037).Postoperative LVtdV (90±28,3 ml/m2 vs 99,1±29,7 ml/m2; p.value:0.031) LVtdVi (47,4±15,9 ml/m2 vs 51,9±14,9 ml/m2; p.value:0.050), IVStd (12±1,5 mm vs 12,1±1,3 mm; p.value:0,027) were significantly increased if compared with preoperative measures.Postoperative E/A (0,76±0,26 vs 0,6±0,67; p.value:0,011), E’ lateral (9,5±2,6 vs 7,9±2,6; p.value:0,024) and A’ septal (10,8±1,5 vs 8,9±2; p.value0,005) were significantly reduced if compared with preoperative measurements CONCLUSION The endovascular treatment of the abdominal aorta causes an immediate and significant increase of the aortic stiffness.This increase reflects negatively on patients’ cardiac geometry inducing left ventricle hypertrophy and mild diastolic disfunction after just 6 months from endograft’s implantation.Further investigations and long-term results are necessary to access if this negative remodeling could affect the cardiac outcome of patient treated using the endovascular approach.

Relações morfológicas entre a aorta torácica avaliada por ecocardiografia e a aorta abdominal estudada por ultrassonografia

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização em Ultrassonografia Cardiovascular.

O Eco-Doppler na Dissecção da Aorta Abdominal

Apresenta-se um caso clínico de dissecção da aorta abdominal - tipo B - diagnosticada por eco-Doppler e tomografia axial computorizada (TC). Discute-se o interesse do eco-Doppler no diagnóstico de dissecção da aorta abdominal e na avaliação do envolvimento arterial visceral. É ainda um método útil no follow-up dos doentes com terapêutica conservadora.

Cintilografia com MIBI-dipiridamol negativa em doença coronariana grave no pré-operatório de correção de aneurisma de aorta abdominal

Descreve-se o caso de um paciente de 73 anos, candidato à correção de aneurisma de aorta abdominal, sem anormalidades na primeira avaliação cardiológica. A cirurgia foi postergada para tratamento de epididimite. Duas semanas após, o paciente retornou ao hospital com dor torácica e a angiografia mostrou obstruções de duas coronárias, tratadas com sucesso por angioplastia transluminal percutânea com implante de stent. Após 45 dias, o paciente foi submetido à cirurgia para correção do aneurisma de aorta abdominal sob anestesia peridural e geral, evoluindo sem complicações.

Estudo prospectivo da morbi-mortalidade precoce e tardia da cirurgia do aneurisma da aorta abdominal

OBJETIVO: Avaliar, prospectivamente, a morbidade e mortalidade precoce e tardia de pacientes submetidos a correção cirúrgica eletiva de aneurisma de aorta abdominal infra-renal e determinar os preditores independentes de eventos cardiológicos. MÉTODOS: Estudados 130 pacientes durante seis anos consecutivos, submetidos a rotina de avaliação pré-operatória padronizada e cirúrgica, sempre pela mesma equipe clínica, cirúrgica e anestesiológica. RESULTADOS: A mortalidade hospitalar foi de 3,1% (4 pacientes), sendo a principal causa de óbito isquemia mesentérica, ocorrida em três pacientes. Houve 48 (37%) complicações não-operatórias, 8,5% consistiram em complicações cardíacas e 28,5% em complicações não cardíacas. As complicações pulmonares foram as mais comuns, ocorridas em 14 (10,8%) pacientes. A sobrevida no 1º, 3º e 6º ano pós-operatório foi, respectivamente, de 95%, 87% e 76%. As variáveis que se correlacionaram significativamente com a morbimortalidade foram preditor clínico, idade média de 70,5 anos, presença de insuficiência cardíaca e insuficiência renal crônica. Não foi identificado nenhum preditor de morbimortalidade tardia. CONCLUSÃO: Apesar de ser uma cirurgia considerada de alta complexidade, a mortalidade é baixa, as complicações cardíacas são de pequena monta e os pacientes apresentam boa evolução a longo prazo.

Supervivencia de los enfermos con aneurisma de aorta abdominal tratados con técnica endovascular

La reparació endovascular dels aneurismes d’aorta abdominal (AAA) és cada cop més usada, encara que només conta amb 15 anys des de l’inici amb una ràpida evolució. Davant la falta d’estudis amb resultats a més de 10 anys. L’objectiu del treball es analitzar prospectivament la supervivència dels 172 pacients tractats en nostre centre desde 06/1998 fins 01/2008, amb seguiment a 10 anys. S’obtingué una supervivència del 61% als 6 anys (error 5%), als 9 anys de 51% (error 7%), a 10 anys 47% (error 11%). La causa més freqüent de mort va ser per neoplàsia.

Resultats immediats de la reparacié endovascular dels aneurismes d'aorta abdominal amb coll aórtic no favorable.

Estudi retrospectiu de pacients tractats d'aneurisma d'aorta abdominal, mitjangant reparació endovascular. Període reclutament: 2006 a 201,2. Van ser dividits en dos grups depenen de les característiques anatómiques del coll aórtic proximal, considerant si eren o no favorables pel tractament endovascular. L'objectiu de l'estudi és avaluar els resultats immediats del tractament en funció de la morfologia del coll aórtic. 95 pacients van ser inclosos (62 favorable, 33 hostil). S'analitzen els motius per considerar el coll com hostil, aixícom els resultats d'aquestes técniques. Conclusió: el tractament endovascular és una técriica válida per aquest tipus pacient amb colls aórtics no favorables.