Hyperthyroidism-induced left ventricular diastolic dysfunction: implication in hyperthyroidism-related heart failure

Background Heart failure occurs in 6% of hyperthyroid patients. Nonetheless, only half of those with hyperthyroidism‐related heart failure have impaired left ventricular (LV) systolic function. Thus, diastolic dysfunction may play an important role in the pathogenesis. Methods and results We performed serial echocardiographic examinations in 70 consecutive patients with hyperthyroidism (39 ± 2 years, 47 women) to determine their diastolic function and repeated the examinations 6 months after achieving a euthyroid state. All patients had normal LV systolic function, but diastolic dysfunction was detected in 22 cases (mild: 3, moderate: 15 and severe: 4). The prevalence of diastolic dysfunction increased with age from 17·9% in patients <40 years to 100% in those >60 years. Increasing age was the only independent predictor for diastolic dysfunction in hyperthyroid patients. After achievement of a euthyroid state, most patients (16/22, 72%) had completely normalized diastolic function: 100% of patients <40 years, 33·3% of those ≥60 years. Further analyses revealed significant age‐related differences in the cardiovascular response to hyperthyroidism. Among patients <40 years, hyperthyroidism resulted in a marked reduction in total peripheral vascular resistance, increased cardiac output and enhanced diastolic function as determined by E’. No such significant change in total peripheral vascular resistance or cardiac output was observed in hyperthyroid patients ≥40 years. In addition, hyperthyroidism was associated with reduced E’, signifying diastolic dysfunction in older hyperthyroid patients. Conclusion Hyperthyroidism is associated with diastolic dysfunction, particularly in older patients. It is partly reversible following achievement of a euthyroid state.     

The virology and developments toward control of human enterovirus 71

Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae family, was first recognized as a dermotrophic virus that usually cause mild, self-limiting hand-foot-and-mouth disease (HFMD). However, EV71 infection can sometimes induce a variety of severe neurological complications and even death. Current large outbreaks of EV71 make this virus being a major public health issue. Intense effort has been made to address its underlying pathogenesis and to develop effective means for combating EV71 infections. Here, we aimed to provide an overview of cellular mechanisms underlying EV71 infection and to assess potential agents for prevention and treatment of EV71 infections.     

Revisit complexation between DNA and polyethylenimine — Effect of length of free polycationic chains on gene transfection

Our revisit of the complexation between DNA and polyethylenimine (PEI) by using a combination of laser light scattering and gel electrophoresis confirms that nearly all the DNA chains are complexed with PEI to form polyplexes when the molar ratio of nitrogen from PEI to phosphate from DNA (N:P) reaches ~ 3, irrespective of the PEI chain length and solvent. Each solution mixture with N:P > 3 contains two kinds of PEI chains: bound to DNA and free in the solution. It has been shown that it is those free PEI chains that play a vital role in promoting the gene transfection. The effects of the length of the bound and free chains on the gene transfection were respectively studied. Both short and long PEI chains are capable of condensing DNA completely at N:P ~ 3 but long ones are ~ 10²-fold more effective in the gene transfection, apparently due to their fast endocytosis and intracellular trafficking. The cellular uptake kinetics studied by flow cytometry reveals that long free chains increase the uptake rate constant of the DNA/PEI complexes. In the intracellular pathway, they are able to prevent the development of the later endolysosomes, and facilitate the subsequent release of the polyplexes from the endosomes. Our result shows that the “proton sponge” effect is not dominant because the shut-down of the proton pump only partially attenuates the transfection efficiency. A possible mechanism is speculated and presented.     

The association between serum adhesion molecules and outcome in acute spontaneous intracerebral hemorrhage

Introduction  

Serum concentrations of adhesion molecules may be connected to the pathogenesis of secondary brain injury after spontaneous intracerebral hemorrhage (ICH). This study posits the hypothesis that levels of adhesion molecules substantially increase after ICH and are decreased thereafter, and that they can predict treatment outcomes.     

Amyloid plaque imaging from IMPY/SPECT to AV-45/PET

The formation and deposition of β-amyloid (Aβ) plaques are the earliest pathological changes in Alzheimer's disease (AD). Molecular imaging of Aβ plaques could serve as a surrogate marker in early diagnosis and neuropathogenesis studies of AD. Several radionuclide labeled ligands have recently been developed for noninvasive visualization of Aβ plaques in the brains of AD patients using single photon emission computed tomography or positron emission tomography (PET). There has been rapid progress in the field of imaging for plaque pathology. AV-45 was the first plaque imaging agent to enter multi-center, investigational new drug clinical trials in the US, and has now been studied in dozens of trials with more than 1,000 subjects ranging from cognitively normal individuals to those with AD dementia. "Imaging to autopsy" phase III studies further confirmed and validated the specific imaging signal correlated to the plaque burden in living subjects. With these promising and confirmed characteristics of AV-45, the Alzheimer's Disease Neuroimaging Initiative (ADNI) under common consensus decided on AV-45 as the emerging standard PET imaging agent for evaluating the progression of plaque pathology in patients with AD or mild cognition impairment, and even healthy controls. With the wide availability of AV-45 for plaque imaging, the ultimate goal of the ADNI is global clinical trials for disease detection and progression. This review presents recent experience with Aβ-targeting radiotracers at Chang Gung University and Chang Gung Memorial Hospital.     

The prognostic value of atrial fibrillation on 30-day clinical outcome in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

This study evaluated the association between atrial fibrillation (AF) and 30-day clinical outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Between January 2005 and October 2009, 783 consecutive patients with acute STEMI undergoing primary PCI were enrolled. Of these patients, 85 (10.9%) with AF during admission were categorized into group 1, while the remaining 698 (89.1%) with sinus rhythm during admission served as group 2. The results demonstrated that the incidence of advanced Killip score (defined as ≥ score 3) and advanced congestive heart failure (defined as ≥ NYHA class 3) were significantly higher, whereas the left ventricular ejection fraction (LVEF) was notably lower in group 1 than in group 2 (all P < 0.003). Additionally, the normal blood flow in the infarct-related artery was notably lower in group 1 than in group 2 (P = 0.003). Moreover, the incidences of new-onset stroke and 30-day mortality were remarkably higher in group 1 than in group 2 (all P < 0.003). Furthermore, Kaplan-Meier analysis demonstrated that the 30-day survival rate was markedly lower in AF patients than in those with sinus rhythm. However, multivariate stepwise Cox regression analysis demonstrated that the advanced Killip score and low LVEF were significantly and independently predictive of 30-day mortality (all P < 0.004). In conclusion, AF was significantly associated with 30-day mortality.     

Perfusion-like template and standardized normalization-based brain image analysis using 18F-florbetapir (AV-45/Amyvid) PET

Purpose

Amyloid positron emission tomography (PET) is an important noninvasive method for detecting amyloid burden in Alzheimer’s disease (AD) patients. As amyloid PET images have limited anatomical information, magnetic resonance (MR) imaging is usually acquired to perform reliable spatial normalization needed for large-scale analysis. This work proposed and evaluated the performance of new MR-free spatial normalization methods using a perfusion-like template for amyloid PET imaging.

Methods

Amyloid PET and MR images were collected in 35 subjects (cohort 1: 8 AD patients and 6 controls; cohort 2: 15 AD patients and 6 controls). Three ligand-related templates (AD, control, mixed group) and a perfusion-like template (pAV-45) from early time frames of amyloid PET images were constructed from cohort 1. The variations of ¹⁸F-AV-45 standardized uptake value ratios (SUVRs) among AD patients, controls, and all subjects were tested with repeated two-way (template × brain region) analysis of variance (ANOVA) in cohort 2. ¹⁸F-AV-45 SUVRs by region of interest analysis and voxelwise analysis between MR-based and MR-free approaches were compared and correlated to clinical and image parameters. Effect size (group mean SUVR difference between AD and control/standard deviation) was also evaluated for each template method.

Results

Significantly different ¹⁸F-AV-45 SUVRs between MR-free spatial normalization and MR-based reference images were found among AD patients, controls, and all subjects by the effect of template and brain regions. The highest correlation (r=0.991) of ¹⁸F-AV-45 SUVR to MR-based reference was found in the pAV-45 group. The SUVR percentage difference to MR-based reference showed the least variation and bias (control: ?1.31±3.47 %; AD: ?0.36±2.50 %) in the pAV-45 group as well. The voxelwise analysis showed the smallest t statistic value in pAV-45 followed by mixed, control, and AD groups when compared to MR-based reference images. Moreover, an overall larger effect size but compatible to that of MR-based reference result was observed in the pAV-45 group as compared to those of the other MR-free template.

Conclusion

The novel MR-free template based on the early-phase perfusion images pAV-45 approach for amyloid imaging showed significantly better performance in quantitation accuracy, effect size, and stability when compared with other MR-free PET templates and thus has potential for large-scale clinical applications.