Staphylococcal Esx Proteins Modulate Apoptosis and Release of Intracellular Staphylococcus aureus during Infection in Epithelial Cells

The opportunistic pathogen Staphylococcus aureus is one of the major causes of health care-associated infections. S. aureus is primarily an extracellular pathogen, but it was recently reported to invade and replicate in several host cell types. The ability of S. aureus to persist within cells has been implicated in resistance to antimicrobials and recurrent infections. However, few staphylococcal proteins that mediate intracellular survival have been identified. Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system (Ess), are important during intracellular S. aureus infection. The Esx proteins are required for staphylococcal virulence, but their functions during infection are unclear. While isogenic S. aureus esxA and esxB mutants were not defective for epithelial cell invasion in vitro, a significant increase in early/late apoptosis was observed in esxA mutant-infected cells compared to wild-type-infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the protein also resulted in a significant increase of epithelial cell apoptosis. Furthermore, cells transfected with esxA showed an increased protection from apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced increased apoptosis but, remarkably, was unable to escape from cells as efficiently as the single mutants or the wild type. Thus, using in vitro models of intracellular staphylococcal infection, we demonstrate that EsxA interferes with host cell apoptotic pathways and, together with EsxB, mediates the release of S. aureus from the host cell.     

Post-marketing surveillance study of the safety and efficacy of sildenafil prescribed in primary care to erectile dysfunction patients

In order to investigate the safety and efficacy of sildenafil prescribed in primary care, a post-marketing surveillance study was undertaken. A total of 651 men with erectile dysfunction (ED) were enrolled from 31 family physicians in Korea from December 1999 to July 2002. Patients were regularly followed up to ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled, 572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458 (80.1%) of 572 patients reported improved erectile function with sildenafil. Hypertension, diabetes and low-dose sildenafil were associated with poor efficacy. A total of 71 adverse events were reported among 56 patients (8.6%), with the most frequent being hot flushes (5.6%), followed by headache (2.6%), palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients (1.0%) discontinued sildenafil as a direct result of adverse events. These results suggest that sildenafil prescribed by primary care physicians was well tolerated and improved erectile function in patients with ED.     

Low-density lipoprotein cholesterol level in patients with acute myocardial infarction having percutaneous coronary intervention (the cholesterol paradox)

The relation between low-density lipoprotein (LDL) cholesterol levels and clinical outcomes after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has not been described. A total of 9,571 eligible patients (mean age 62.6 ± 12.5 years, 6,967 men) who underwent PCI with a final diagnosis of AMI from the Korea Acute Myocardial Infarction Registry (KAMIR) were divided into 5 groups according to LDL cholesterol level: < 70, 70 to 99, 100 to 129, 130 to 159, and ≥ 160 mg/dl. Clinical outcomes in hospital and 1 and 12 months after PCI in patients with AMI were examined. Age and co-morbidities decreased as LDL cholesterol increased. Patients with higher LDL cholesterol levels had favorable hemodynamic status and laboratory findings. Lifesaving medications, including lipid-lowering drugs, were underused in patients with lower LDL cholesterol levels. Clinical outcomes in hospital and 1 and 12 months after PCI showed better results as LDL cholesterol increased, except for patients with LDL cholesterol levels ≥ 160 mg/dl. In a Cox proportional-hazards model, LDL cholesterol level was not an independent predictor of mortality at 12 months, after adjusting for clinical characteristics including demographics and biologic data. In conclusion, the cholesterol paradox in patients with AMI is related to confounding by baseline characteristics associated with survival. More intensive treatment including lipid-lowering therapy for AMI in patients with lower LDL cholesterol level may result in better clinical outcomes.     

High body mass index and dietary pattern are associated with childhood asthma

The increasing prevalence of asthma has coincided with an increase of body mass index (BMI) in both children and adults. We investigated the relationship between BMI and the symptom prevalence of asthma and the possible influences of dietary pattern. This was a community-based, cross-sectional study of 24,260 school children aged 6-12 years. Prevalences of asthma and potential confounding factors were assessed using a Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire which was completed by parents. We analyzed the relationship between BMI and symptoms of asthma and the possible influences of dietary pattern. A significant positive association between high BMI and previous 12-month prevalence of wheeze remained in boys (adjusted odds ratio, 1.610; 95% confidence interval, 1.274-2.033) but not in girls. In addition, there were significant associations between high BMI and lifetime prevalence of wheeze, previous 12-month wheeze, exercise-induced wheeze, diagnosis, and treatment of asthma. There were significant associations between high BMI and previous 12-month wheeze regardless of breast-milk feeding or whole-milk feeding. Frequent intake of fresh seafood, fresh fruits, and vegetables was associated with reduced prevalence of current asthma symptoms and was also associated with decreased BMI. These results indicate that BMI may be an independent risk factor for the development of asthma symptoms in boys. Intake of fresh seafood, fresh fruit, and vegetables, which may be associated with decreased BMI, may contribute to protect against the development of asthma symptoms in Korean elementary schoolchildren.     

Clinical benefit of low molecular weight heparin for ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitor

The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH.     

Intraoperative radiofrequency ablation with or without tumorectomy for hepatocellular carcinoma in locations difficult for a percutaneous approach

BACKGROUND:Although hepatic resection is widely accepted as a proper modality for treating hepatocellular carcinoma(HCC),a majority of patients are unable to undergo surgical resection due to various tumor and patient factors.Radiofrequency ablation(RFA)has mostly been used as a therapeutic alternative to resection for treating HCC.The objective of this study was to evaluate the results of intraoperative RFA for HCCs in locations difficult for a percutaneous approach.METHODS:Eight patients(male,seven;age,49...