RF ablation in a patient with recurrent post-infarction ventricular tachycardia requiring multiple cardioverter-defibrillator interventions

A case of a 51 year old patient with a history of myocardial infarction (MI) and recurrent ventricular tachycardia (VT) is presented. Three months after MI the patient underwent coronary angioplasty and one year later received prophylactic implantable cardioverter-defibrillator (ICD) due to complex ventricular arrhythmias, detected on Holter ECG monitoring, and depressed left ventricular ejection fraction. Later on the patient started to experience palpitations and ICD shocks during physical activity (cycling). Interrogation of the ICD memory showed appropriate shocks due to slow (160 betas/min) VT. The device was reprogrammed and new antitachycardia pacing (ATP) algorithms were enabled, however, it occurred proarrhythmic due to the ATP-induced acceleration of VT rate. Finally, in April 2005 he received 37 appropriate ICD shocks during a few hours. The patient was selected for RF ablation and underwent successful procedure with the use of the electro-anatomical CARTO mapping system.     

LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-alpha

The deleterious effects of lipopolysaccharide (LPS) during endotoxic shock are associated with the secretion of tumor necrosis factor (TNF) and the production of nitric oxide (NO), both predominantly released by tissue macrophages. We analyzed the mechanism by which LPS induces apoptosis in bone marrow-derived macrophages (BMDM). LPS-induced apoptosis reached a plateau at about 6 hours of stimulation, whereas the production of NO by the inducible NO-synthase (iNOS) required between 12 and 24 hours. Furthermore, LPS-induced early apoptosis was only moderately reduced in the presence of an inhibitor of iNOS or when using macrophages from iNOS -/-mice. In contrast, early apoptosis was paralleled by the rapid secretion of TNF and was almost absent in macrophages from mice deficient for one (p55) or both (p55 and p75) TNF-receptors. During the late phase of apoptosis (12-24 hours) NO significantly contributed to the death of macrophages even in the absence of TNF-receptor signaling. NO-mediated cell death, but not apoptosis induced by TNF, correlated with the induction of p53 and Bax genes. Thus, LPS-induced apoptosis results from 2 independent mechanisms: first and predominantly, through the autocrine secretion of TNF-alpha (early apoptotic events), and second, through the production of NO (late phase of apoptosis). (Blood. 2000;95:3823-3831)     

Gab1, SHP2, and protein kinase A are crucial for the activation of the endothelial NO synthase by fluid shear stress

Fluid shear stress enhances NO production in endothelial cells by a mechanism involving the activation of the phosphatidylinositol 3-kinase and the phosphorylation of the endothelial NO synthase (eNOS). We investigated the role of the scaffolding protein Gab1 and the tyrosine phosphatase SHP2 in this signal transduction cascade in cultured and native endothelial cells. Fluid shear stress elicited the phosphorylation and activation of Akt and eNOS as well as the tyrosine phosphorylation of Gab1 and its association with the p85 subunit of phosphatidylinositol 3-kinase and SHP2. Overexpression of a Gab1 mutant lacking the pleckstrin homology domain abrogated the shear stress-induced phosphorylation of Akt but failed to affect the phosphorylation or activity of eNOS. The latter response, however, was sensitive to a protein kinase A (PKA) inhibitor. Mutation of Gab1 Tyr627 to phenylalanine (YF-Gab1) to prevent the binding of SHP2 completely prevented the shear stress-induced phosphorylation of eNOS, leaving the Akt response intact. A dominant-negative SHP2 mutant prevented the activation of PKA and phosphorylation of eNOS without affecting that of Akt. Moreover, shear stress elicited the formation of a signalosome complex including eNOS, Gab1, SHP2 and the catalytic subunit of PKA. In isolated murine carotid arteries, flow-induced vasodilatation was prevented by a PKA inhibitor as well as by overexpression of either the YF-Gab1 or the dominant-negative SHP2 mutant. Thus, the shear stress-induced activation of eNOS depends on Gab1 and SHP2, which, in turn, regulate the phosphorylation and activity of eNOS by a PKA-dependent but Akt-independent mechanism.     

Pulmonary Aspergillosis: Spectrum of Disease

Aspergillus species are ubiquitous in the environment. Aspergillosis is acquired by inhalation of Aspergillus spores. In normal hosts, spore inhalation rarely causes lung disease. Pulmonary Aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive Aspergillosis to Aspergillus bronchitis. Invasive Aspergillosis usually occurs in severely immunocompromised patients, typically in neutropenic but also in non-neutropenic patients. Chronic pulmonary Aspergillosis affects patients with chronic structural lung disease such as COPD or previous mycobacterial lung disease, but without other significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such as bronchiectasis. Allergic bronchopulmonary Aspergillosis affects patients with bronchial asthma or cystic fibrosis, and is due to an allergic response to Aspergillus.     

Brain age estimation reveals older adults’ accelerated senescence after traumatic brain injury

GeroScience - Adults aged 60 and over are most vulnerable to mild traumatic brain injury (mTBI). Nevertheless, the extent to which chronological age (CA) at injury affects TBI-related brain aging...     

External Quality Assessment of Blood Glucose Monitors: Quality Control of Self-Monitoring of Blood Glucose: Why and How?

The control of analytical quality of self-monitoring of blood glucose (SMBG) is recommended as a routine procedure in diabetes management. This control procedure should be easily accessible to patients, convenient, not time-consuming, and provide a reliable assessment of glucose meter performance. Optimally it should be located in the diabetes outpatient clinic. Presently there are two approaches to carrying out SMBG quality control. The first is based on the comparison of results obtained by a controlled glucose meter and use of the laboratory method or point-of-care testing device as a surrogate reference analyzer. The second one is a traditionally organized external quality assessment scheme with use of a dedicated control material, which is distributed to all participants. The recommended allowable meter error in SMBG can be realistically set at 10%.