Distinct pharmacologic substrate in lidocaine-sensitive, repetitive atrial tachycardia

Lidocaine-sensitive, repetitive atrial tachycardia is an uncommon arrhythmia. The electrophysiologic substrate is still unknown, and the pharmacologic responses have not been fully explored. The aim of this study was to investigate the effects of intravenous adenosine and verapamil in patients with lidocaine-sensitive atrial tachycardia. In 9 patients with repetitive uniform atrial tachycardia, the response to intravenous adenosine (12 mg), lidocaine (1 mg/kg body weight), and verapamil (10 mg) were sequentially investigated. Simultaneous 12-lead electrocardiogram (ECG) was recorded at baseline and continuously monitored thereafter. Tracings were obtained at regularly timed intervals right after the administration of each drug to evaluate changes in the arrhythmia characteristics. Repetitive atrial tachycardia was abolished by intravenous lidocaine in the 9 patients within the first 2 minutes after the end of injection. Adenosine suppressed the arrhythmia in 2 patients and shortened the runs of atrial ectopic activity in 1 patient, while verapamil was effective in 2 patients, 1 of them insensitive to adenosine and the other 1 sensitive to this agent. In 5 patients, the arrhythmia was abolished by radiofrequency ablation at different sites of the right atrium. Lidocaine-sensitive atrial tachycardia may eventually be also suppressed by adenosine and/or verapamil. This suggests that this enigmatic arrhythmia may be caused by different underlying electrophysiologic substrates and that at least in some cases, delayed afterdepolarizations seem to play a determining role.     

Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac β andrenergic receptors

BACKGROUND: The mechanisms underlying inappropriate sinus tachycardia are not fully known. An autonomic imbalance seems to play a role, but no attempts have been made to investigate a relationship between this arrhythmia and the antiautonomic membrane receptor antibodies found in other heart disorders and arrhythmias. OBJECTIVE: The purpose of this study was to investigate the prevalence and the functional and biochemical effects of circulating antiautonomic receptor antibodies in patients with inappropriate sinus tachycardia. METHODS: We studied 21 patients with inappropriate sinus tachycardia and 15 healthy volunteers. The chronotropic effects of the IgG fractions (also of affinity-purified anti-beta1 adrenergic receptor antibodies in selected cases) were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The effects of the IgG fractions from five patients and five healthy volunteers on cAMP production were evaluated in COS-7 cells transfected with genes encoding for beta1 or beta2 adrenergic receptor. RESULTS: The IgG fractions from patients with inappropriate sinus tachycardia exerted a positive chronotropic action with a high prevalence of anti-beta receptor antibodies (52%) and induced a clear-cut and long lasting increment of cAMP. No anti-M2 cholinergic receptor antibodies were found. The IgG fractions from healthy volunteers did not contain antiautonomic receptor antibodies. CONCLUSIONS: Our results suggest, for the first time, a link between inappropriate sinus tachycardia and circulating anti-beta adrenergic receptor antibodies that induce a persistent increment in cAMP production. This finding offers new insight into the physiopathology of inappropriate sinus tachycardia with potential therapeutic consequences.     

In Silico Modeling of the Molecular Structure and Binding of Leukotriene A4 into Leukotriene A4 Hydrolase

A combined molecular docking and molecular structure in silico analysis on the substrate and product of leukotriene A4 hydrolase (LTA4H) was performed. The molecular structures of the substrate leukotriene A4 (LTA4) and product leukotirene B4 (LTB4) were studied through density functional theory (DFT) calculations at the B3LYP/6‐31 + G(d) level of theory in both gas and condensed phases. The whole LTB4 molecule was divided into three fragments (hydrophobic tail, triene motif, and a polar acidic group) that were subjected to a full conformational study employing the most stable conformations of them to build conformers of the complete molecule and geometry optimize further. LTA4 conformers’ structures were modeled from the LTB4 minimum energy conformers. Both protonated and deprotonated species of LTA4 and LTB4 were analyzed according to pKa values found in the literature. Finally, a binding model of LTA4 with LTA4 hydrolase is proposed according to docking results that show intermolecular interactions that position the protonated and deprotonated ligand in the active site, in excellent agreement with the model suggested from LTA4H‐inhibitors crystallographic data.     

Epidemiology,antibiotic therapy and clinical outcomes of healthcare-associated pneumonia in critically ill patients: a Spanish cohort study

Purpose

Information about healthcare-associated pneumonia (HCAP) in critically ill patients is scarce.

Methods

This prospective study compared clinical presentation, outcomes, microbial etiology, and treatment of HCAP, community-acquired pneumonia (CAP), and immunocompromised patients (ICP) with severe pneumonia admitted to 34 Spanish ICUs.

Results

A total of 726 patients with pneumonia (449 CAP, 133 HCAP, and 144 ICP) were recruited during 1 year from April 2011. HCAP patients had more comorbidities and worse clinical status (Barthel score). HCAP and ICP patients needed mechanical ventilation and tracheotomy more frequently than CAP patients. Streptococcus pneumoniae was the most frequent pathogen in all three groups (CAP, 34.2 %; HCAP, 19.5 %; ICP, 23.4 %; p = 0.001). The overall incidence of Gram-negative pathogens, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa was low, but higher in HCAP and ICP patients than CAP. Empirical treatment was in line with CAP guidelines in 73.5 % of patients with CAP, in 45.5 % of those with HCAP, and in 40 % of those with ICP. The incidence of inappropriate empirical antibiotic therapy was 6.5 % in CAP, 14.4 % in HCAP, and 21.8 % in ICP (p < 0.001). Mortality was highest in ICP (38.6 %) and did not differ between CAP (18.4 %) and HCAP (21.2 %).

Conclusions

HCAP accounts for one-fifth of cases of severe pneumonia in patients admitted to Spanish ICUs. The empirical antibiotic therapy recommended for CAP would be appropriate for 90 % of patients with HCAP in our population, and consequently the decision to include coverage of multidrug-resistant pathogens for HCAP should be cautiously judged in order to prevent the overuse of antimicrobials.     

An electro- and vectorcardiographic study of ventricular activation in scleroderma]

Electrical ventricular activation was studied by means of electrocardiogram and vectorcardiogram in 62 patients, 55 women and 7 men, affected by systemic sclerosis of average disease duration of 10.3 years. 45% of the patients showed the "diffused form" of the disease and 55% the "limited form". The vectorcardiogram showed some alterations of the ventricular activation in 55% of the recorded cases. The previous electrocardiogram found only 18%. The alterations, which are more frequent in the diffuse form than in the limited one, are the presence of loss of forces in septal, lateral or inferior or combined areas and intraventricular conduction disorders as complete and incomplete right bundle branch block, left anterior subdivision block, left posterior subdivision block, or combination between incomplete right bundle branch block and left anterior or posterior subdivision block. The vectorcardiogram was more sensitive than the electrocardiogram in showing loss of forces, also in patients with the limited form of systemic sclerosis, when the electrocardiogram was normal. Moreover the vectorcardiogram is helpful to identify left posterior subdivision block. The vectorcardiographic investigation seems to be a useful complement of the electrocardiogram especially for the identification of cases with myocardial involvement that is clinically silent.     

Interview‐based Qualitative Research in Emergency Care Part II: Data Collection,Analysis and Results Reporting

Qualitative methods are increasingly being used in emergency care research. Rigorous qualitative methods can play a critical role in advancing the emergency care research agenda by allowing investigators to generate hypotheses, gain an in‐depth understanding of health problems or specific populations, create expert consensus, and develop new intervention and dissemination strategies. In Part I of this two‐article series, we provided an introduction to general principles of applied qualitative health research and examples of its common use in emergency care research, describing study designs and data collection methods most relevant to our field (observation, individual interviews, and focus groups). Here in Part II of this series, we outline the specific steps necessary to conduct a valid and reliable qualitative research project, with a focus on interview‐based studies. These elements include building the research team, preparing data collection guides, defining and obtaining an adequate sample, collecting and organizing qualitative data, and coding and analyzing the data. We also discuss potential ethical considerations unique to qualitative research as it relates to emergency care research.     

The use of 3′-deoxy-3′-18F-fluorothymidine (FLT) PET in the assessment of long-term survival in breast cancer patients treated with neoadjuvant chemotherapy

Annals of Nuclear Medicine - To assess the role of serial FLT-PET scans during early neoadjuvant treatment as a prognostic marker of response to treatment and survival. This study is a prospective...