Isolated Rheumatic Tricuspid Stenosis with Reverse Lutembacher's Physiology

Tricuspid valve dysfunction occurs frequently in patients with rheumatic heart disease and is usually manifested as functional or organic tricuspid regurgitation. Rheumatic tricuspid stenosis is less common and occurs characteristically in the presence of concomitant mitral valve disease. In this report, we describe the clinical and echocardiographic findings in a patient with isolated rheumatic tricuspid stenosis and a right-to-left shunt across the interatrial septum, likely as a result of a patent foramen ovale, resulting in central cyanosis. This case illustrates an interesting association of tricuspid stenosis and an interatrial right-to-left shunt suggestive of a reverse Lutembacher's physiology.     

Effects of Oxytocin on Attention to Emotional Faces in Healthy Volunteers and Highly Socially Anxious Males

Background:

Evidence suggests that individuals with social anxiety demonstrate vigilance to social threat, whilst the peptide hormone oxytocin is widely accepted as supporting affiliative behaviour in humans.

Methods:

This study investigated whether oxytocin can affect attentional bias in social anxiety. In a double-blind, randomized, placebo-controlled, within-group study design, 26 healthy and 16 highly socially anxious (HSA) male volunteers (within the HSA group, 10 were diagnosed with generalized social anxiety disorder) were administered 24 IU of oxytocin or placebo to investigate attentional processing in social anxiety. Attentional bias was assessed using the dot-probe paradigm with angry, fearful, happy and neutral face stimuli.

Results:

In the baseline placebo condition, the HSA group showed greater attentional bias for emotional faces than healthy individuals. Oxytocin reduced the difference between HSA and non-socially anxious individuals in attentional bias for emotional faces. Moreover, it appeared to normalize attentional bias in HSA individuals to levels seen in the healthy population in the baseline condition. The biological mechanisms by which oxytocin may be exerting these effects are discussed.

Conclusions:

These results, coupled with previous research, could indicate a potential therapeutic use of this hormone in treatment for social anxiety.     

Identifying Patients with Group 3 Pulmonary Hypertension Associated with COPD or ILD Using an Administrative Claims Database

Lung - Group 3 pulmonary hypertension (PH) describes a subpopulation of patients with PH due to chronic lung disease and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and...     

Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial

STUDY OBJECTIVES: The primary objective was to determine the safety and tolerability of repeated doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding the complete human CFTR cDNA. Secondary objectives included evaluation of pulmonary function assessed by spirometry, lung abnormalities by high-resolution CT (HRCT), airway cytokines, vector shedding, serum neutralizing antibody to AAV serotype 2 (AAV2), and gene transfer and expression in a subset of subjects undergoing bronchoscopy with bronchial brushings. DESIGN: Randomized, double-blind, placebo-controlled, phase II trial. SETTING: Eight cystic fibrosis (CF) centers in the United States. SUBJECTS: CF patients with mild lung disease, defined as FEV(1) > or =60% predicted. INTERVENTIONS: Subjects were randomized to inhale three aerosolized doses of 1 x 10(13) deoxyribonuclease-resistant particles of tgAAVCF or matching placebo at 30-day intervals using the Pari LC Plus nebulizer (PARI; Richmond, VA). Measurements and results: Of 42 subjects randomized, 20 subjects received at least one dose of tgAAVCF and 17 subjects received placebo. No difference in the pattern of adverse events or laboratory abnormalities was noted between the two treatment groups. Improvements in induced-sputum interleukin-8 (p = 0.03) and FEV(1) (p = 0.04) were observed at day 14 and day 30, respectively, in the group receiving tgAAVCF when compared to those receiving placebo. No significant differences in HRCT scans were noted. Vector shedding in sputum was observed at low levels up to 90 days after the third dose of vector. All subjects receiving tgAAVCF exhibited an increase (by at least fourfold) in serum AAV2-neutralizing antibodies and detectable levels in BAL fluid from five of six treated subjects undergoing BAL. Gene transfer but not gene expression was detected in a subset of six tgAAVCF subjects who underwent bronchoscopy. CONCLUSIONS: Repeat doses of aerosolized tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease.     

Phospholamban gene ablation improves calcium transients but not cardiac function in a heart failure model

Decreased amplitude and slower kinetics of cardiomyocyte intracellular calcium (Ca(i)(2+)) transients may underlie the diminished cardiac function observed in heart failure. These alterations occur in humans and animals with heart failure, including the TNF1.6 mouse model, in which heart failure arises from cardiac-specific overexpression of tumor necrosis factor alpha (TNF alpha). OBJECTIVE: Since ablation of phospholamban expression (PLBKO) removes inhibition of the sarcoplasmic reticulum (SR) Ca(2+) pump, enhances SR Ca(2+) uptake and increases contractility, we assessed whether ablation of phospholamban expression could improve cardiac function, limit remodeling, and improve survival in the TNF1.6 model of heart failure. METHODS: We bred PLBKO with TNF1.6 mice and characterized the progeny for survival, cardiac function (echocardiography), cardiac remodeling (hypertrophy, dilation, fibrosis), and Ca(2+)(i) transients and contractile function of isolated cardiomyocytes. RESULTS: PLB ablation did not improve survival, cardiac function, or limit cardiac chamber dilation and hypertrophy in TNF1.6 mice (TKO mice). However, contractile function and Ca(2+)(i) transients (amplitude and kinetics) of isolated TKO cardiomyocytes were markedly enhanced. This discordance between unimproved cardiac function, and enhanced Ca(2+)(i) cycling and cardiomyocyte contractile parameters may arise from a continued overexpression of collagen and decreased expression of gap junction proteins (connexin 43) in response to chronic TNF alpha stimulation. CONCLUSIONS: Enhancement of intrinsic cardiomyocyte Ca(2+)(i) cycling and contractile function may not be sufficient to overcome several parallel pathophysiologic processes present in the failing heart.