Brugada syndrome: from cell to bedside

Since its introduction as a new clinical entity in 1992, the Brugada syndrome has attracted great interest because of its high incidence in many parts of the world and its association with high risk for sudden death in infants, children, and young adults. Recent years have witnessed an exponential rise in the number of reported cases and a striking proliferation of articles serving to define the clinical, genetic, cellular, ionic, and molecular aspects of the disease. A consensus report published in 2002 delineated diagnostic criteria for the syndrome. A second consensus conference was held in September 2003. This review provides an in-depth overview of the clinical, genetic, molecular, and cellular aspects of the Brugada syndrome, incorporating the results of the two consensus conferences, and the numerous clinical and basic publications on the subject. The proposed terminology, diagnostic criteria, risk stratification schemes, and device and pharmacologic approach to therapy discussed are based on available clinical and basic studies and should be considered a work-in-progress that will without doubt require fine-tuning as confirmatory data from molecular studies and prospective trials become available.     

Coronary arterial remodeling: From bench to bedside

Coronary arterial remodeling describes changes of vessel size at the site of atherosclerotic lesions. Positive remodeling (expansion) of early lesions maintains lumen size despite plaque accumulation. In contrast, negative remodeling (shrinkage) contributes to luminal stenosis independent of plaque accumulation. Because of these adaptive changes, plaque progression/regression is not closely reflected in luminal size. Histologic studies have demonstrated that the pathophysiologic role of arterial remodeling is more complex than a mere compensatory process. Surprisingly, there is a consistent association between positive arterial remodeling, local inflammatory response, and plaque vulnerability. In vivo tomographic imaging techniques, in particular intravascular ultrasound, and potentially computed tomography and magnetic resonance imaging, allow the observation of remodeling in clinical settings. The integration of basic knowledge about arterial remodeling with clinical observations from in vivo imaging could lead to a better understanding of plaque progression, regression, and vulnerability and may eventually have implications for disease prevention.     

DPP-4抑制剂与血糖稳态——从基础到临床

2型糖尿病的一个特征就是α、β细胞激素均有分泌缺陷.胰升糖素样肽1(GLP-1)具有α、β细胞激素双重调节作用,是近年来新型降糖药物的研究热点.DPP-4抑制剂单药或联合用药可升高GLP-1水平,有效降低HbAlC,可成为不同病程2型糖尿病患者的用药选择.     

Brugada syndrome

The Brugada syndrome is a clinical-electrocardiographic diagnosis characterized by syncopal episodes or sudden death (caused by ventricular tachycardia and ventricular fibrillation) in patients with a structurally normal heart with a characteristic electrocardiographic pattern consisting of ST segment elevation in precordial leads (Vl-V3) and a morphology of the QRS complex resembling right bundle branch block (the latter can transiently disappear). Timely diagnosis and adequate treatment may essentially decrease mortality of this disease. In our review we have summarized results of recent studies of etiology, pathogenesis, clinical picture, diagnosis and treatment of the Brugada syndrome.     

Primary biliary cirrhosis: From bench to bedside

Primary biliary cirrhosis(PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient's genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed.     

Combination antifungal therapy: From bench to bedside

Invasive fungal infections are major causes of mortality in immunocompromised patients. Despite improved outcomes with new antifungals, there remains a pressing need to further improve outcomes, especially with invasive aspergillosis and other invasive mold infections. Combination antifungal therapy is an attractive option that offers the prospect for improved efficacy, decreased toxicity, reduced likelihood for the emergence of resistance, and shorter courses of therapy. The current available evidence regarding the role of combination antifungal therapy for invasive fungal infections is discussed in this article, including data from in vitro studies, animal models, and human clinical trials to try to clarify this important issue. Randomized, prospective clinical trials are urgently needed, especially for invasive aspergillosis.     

Brugada syndrome

Two siblings with features of Brugada syndrome are reported. One of them had permanent pacemaker implantation elsewhere where he was evaluated for recurrent syncope and diagnosed to have tri-fascicular block. He continued to have syncopal episodes and subsequently detected to have runs of polymorphic ventricular tachycardia picked up on a routine ECG. His sibling also was found to have features of Brugada syndrome.     

Brugada syndrome

Brugada syndrome (BrS) is, along with the long QT syndrome, one of the most frequently diagnosed inherited arrhythmogenic syndromes. It is a primary electric heart disease manifested by ST segment elevations in the right precordial leads. BrS is responsible for more than 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts. In 1998, the first mutations in the gene coding the structure of the cardiac sodium channel were identified in patients with BrS. Nowadays, several hundreds of mutations in at least 8 genes have been already associated with BrS. Functional consequences of many of these mutations on the molecular level have been revealed and, in some of them, even the consequences for the overall cardiac electrophysiology were suggested thank to the mathematical modelling. However, despite intense study of many scientific teams and formulation of several hypotheses, arrhythmogenic mechanisms in BrS have not been fully elucidated yet. This review provides a contemporary view of clinical symptoms, pathophysiology, diagnostics and therapy in BrS.     

Brugada syndrome

The Brugada syndrome is an autosomal dominant disease with incomplete penetrance that may cause syncope and sudden cardiac death in young individuals with a normal heart. It is characterized by an electrocardiographic pattern of complete or incomplete right bundle branch block and ST segment elevation in leads V1-V3. One of the genes linked to this syndrome is SCN5A, the gene encoding for the cardiac sodium channel. Mutations in SCN5A cause a functional reduction in the availability of cardiac sodium current in Brugada syndrome. However, only 20-25% of patients affected by this syndrome have mutations on this gene. A novel gene locus on chromosome 3, distinct from SCN5A, has been identified recently. The relative male preponderance of the phenotype, despite equal inheritance of the gene in males and females, has led to the speculation of a role for testosterone in the phenotype. The disease could manifest at first time as cardiac arrest without any previous symptom, and the electrocardiographic pattern could be intermittent, requiring a pharmacological challenge with Class I antiarrhythmic drugs to unmask ST elevation. Several conditions producing Brugada-like electrocardiographic patterns should be borne in mind and excluded while making a diagnosis of the Brugada syndrome. The management is difficult as pharmacological agents are not universally effective. The mode of treatment recommended by the majority of cardiac electrophysiologists is the implantation of a cardioverter defibrillator. Symptomatic patients with inducible ventricular arrhythmias and a positive family history should be considered for prophylactic implantation of a cardioverter defibrillator.