Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity.     

首发精神分裂症患者及其一级亲属返回抑制对照研究

目的：探讨首发精神分裂症患者及其一级亲属注意返回抑制特点。方法将31例首发精神分裂症患者设为患者组,29名健康一级亲属设为亲属组,30名健康志愿者设为对照组。分别对3组被试进行注意返回抑制测试。结果3组不同线索开始呈现到靶子的时间间隔水平靶子同侧反应时间均显著长于异侧反应时间（P＜0．01）,均存在返回抑制;3组所有线索开始呈现到靶子的时间间隔水平靶子同侧与异侧反应时间依次为：患者组＞亲属组＞对照组。结论首发精神分裂症患者及其一级亲属存在返回抑制功能障碍,这可能是精神分裂症的遗传易感性指标。     

Electrocardiographic changes in acute perimyocarditis

Pericarditis and myocarditis are characterised by electrocardiographic changes and elevated cardiac enzymes, respectively, and patients with perimyocarditis often complain of chest discomfort. These findings are nonspecific and often lead to diagnostic difficulties, as ST-elevation myocardial infarction commonly presents in a similar fashion. Clinical differentiation between perimyocarditis and myocardial infarction are especially important because adverse side effects can occur if reperfusion therapy is administered for a patient with acute pericarditis or if a diagnosis of acute myocardial infarction is missed. We herein describe a case of perimyocarditis with ST elevation and raised cardiac markers, which led to two emergency coronary angiographies that were subsequently found to be normal. We include the three serial electrocardiographies (ECGs) performed to show the characteristic features of perimyocarditis and further discuss the importance of identifying typical and atypical ECG features of pericarditis.     

Plasma α1-antitrypsin: A Neglected Predictor of Angiographic Severity in Patients with Stable Angina Pectoris

Background:

As an acute phase protein, α1-antitrypsin (AAT) has been extensively studied in acute coronary syndrome, but it is unclear whether a relationship exists between AAT and stable angina pectoris (SAP). The purpose of the present study was to investigate the association between AAT plasma levels and SAP.

Methods:

Overall, 103 SAP patients diagnosed by coronary angiography and clinical manifestations and 118 control subjects matched for age and gender were enrolled in this case-control study. Plasma levels of AAT, high-sensitivity C-reactive protein (hsCRP), lipid profiles and other clinical parameters were assayed for all participants. The severity of coronary lesions was evaluated based on the Gensini score (GS) assessed by coronary angiography.

Results:

Positively correlated with the GS (r = 0.564, P < 0.001), the plasma AAT level in the SAP group was significantly higher than that in the control group (142.08 ± 19.61 mg/dl vs. 125.50 ± 19.67 mg/dl, P < 0.001). The plasma AAT level was an independent predictor for both SAP (odds ratio [OR] = 1.037, 95% confidence interval [CI]: 1.020–1.054, P < 0.001) and a high GS (OR = 1.087, 95% CI: 1.051–1.124, P < 0.001) in a multivariate logistic regression model. In the receiver operating characteristic curve analysis, plasma AAT level was found to have a larger area under the curve (AUC) for predicting a high GS (AUC = 0.858, 95% CI: 0.788–0.929, P < 0.001) than that of hsCRP (AUC = 0.665, 95% CI: 0.557–0.773, P = 0.006; Z = 2.9363, P < 0.001), with an optimal cut-off value of 137.85 mg/dl (sensitivity: 94.3%, specificity: 68.2%).

Conclusions:

Plasma AAT levels correlate with both the presence and severity of coronary stenosis in patients with SAP, suggesting that it could be a potential predictive marker of severe stenosis in SAP patients.     

Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris

Background: To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. Methods: 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors. Flow cytometry analysis was applied to all 200 patients to measure the quantity of natural killer cells. Results: In myocardial infarction group, the mRNA expressions of six inhibitory receptors KIR2DL2, KIR3DL3, CD94, NKG2A, KLRB1, KLRG1, and eight activating receptors KIR2DS3, KIR2DS5, NKp30, NTB-A, CRACC, CD2, CD7 and CD96 were significantly down-regulated (P<0.05) compared with both angina patients and the controls. There was no statistical difference in receptor expressions between angina patients and control group. The quantity of natural killer cells was significantly decreased in both infarction and angina patients compared with normal range (P<0.001). Conclusions: The significant mRNAs down-regulation of several receptors in myocardial infarction group and reduction in the quantity of natural killer cells in both myocardial infarction and angina patients showed a quantitative loss and dysfunction of natural killer cells in myocardial infarction patients.     

肿瘤坏死因子α促进烧伤后蛋白高分解代谢的潜在机制

骨骼肌蛋白高分解代谢导致的骨骼肌消耗是一种常见的骨骼肌病变,在肿瘤、慢性肾病、脓毒症及烧伤患者中较为常见。研究发现肿瘤坏死因子α(TNF-α)是骨骼肌高分解代谢的重要调控因子,骨骼肌细胞凋亡可能是骨骼肌蛋白高分解代谢的重要机制之一,而TNF-α又可诱导骨骼肌细胞凋亡。本文将简要介绍TNF-α通过介导骨骼肌细胞凋亡而参与烧伤后骨骼肌蛋白高分解代谢的潜在机制。     

内镜下射频消融术治疗胃低级别上皮内瘤变的临床研究

目的通过临床大样本研究,进一步明确内镜下射频消融术(RFA)治疗胃低级别上皮内瘤变(LGIN)的有效性及安全性。 方法回顾性选择2014年10月至2019年12月经解放军总医院消化内镜中心术前筛查的175例患者证实为胃LGIN的255例病变纳入研究,并进行内镜下RFA,关注其围手术期并发症发生情况,术后采用Wong-Baker面部表情量表进行疼痛评分,并追踪其复查随访结果。 结果255例病变均成功完成内镜下RFA,术中无明显并发症发生;术后3个月、6个月、1年、2年、3年的治愈率分别为91.3%、90.8%、89.4%、88.2%、86.5%,术后腹痛为主要并发症。 结论内镜下RFA是治疗胃LGIN的一种安全有效、操作简便、可门诊治疗的新方法,具有良好的临床应用前景。     

Prognostic impact of stress echocardiography with discordant stress electrocardiography in patients with suspected coronary artery disease

INTRODUCTIONDuring stress echocardiography, the echocardiologist routinely collects both echocardiographic images and stress electrocardiogram (ECG) concurrently. The managing physician faces a dilemma when the stress ECG and stress echocardiography results are discordant; for example, when a patient has negative stress echocardiography but positive stress ECG. We therefore sought to evaluate the prognostic value of stress echocardiography in relation to concordant or discordant stress ECG findings in our local Singapore setting, which has a well-defined Southeast Asian population.METHODSThis was a retrospective observational study of all patients who underwent stress echocardiography in 2012 at Changi General Hospital, Singapore. All study patients were followed up for 18 months via electronic medical records.RESULTSThere was no difference in the major adverse cardiovascular events (MACE) outcome of patients with normal stress echocardiography and normal stress ECG (reference group) as compared with patients with normal stress echocardiography but positive (discordant) stress ECG (odds ratio 2.02, 95% confidence interval 0.82‑4.98; p = 0.125).CONCLUSIONThis study will help to reassure cardiologists that discordant results (negative stress echocardiography but positive stress ECG) do not portend a higher risk of MACE when compared to concordant results (i.e. both stress echocardiography and stress ECG are negative).     

The HIV‐1 gp41 ectodomain is cleaved by matriptase to produce a chemotactic peptide that acts through FPR2

Several aspects of HIV‐1 virulence and pathogenesis are mediated by the envelope protein gp41. Additionally, peptides derived from the gp41 ectodomain have been shown to induce chemotaxis in monocytes and neutrophils. Whereas this chemotactic activity has been reported, it is not known how these peptides could be produced under biological conditions. The heptad repeat 1 (HR1) region of gp41 is exposed to the extracellular environment and could therefore be susceptible to proteolytic processing into smaller peptides. Matriptase is a serine protease expressed at the surface of most epithelia, including the prostate and mucosal surfaces. Here, we present evidence that matriptase efficiently cleaves the HR1 portion of gp41 into a 22‐residue chemotactic peptide MAT‐1, the sequence of which is highly conserved across HIV‐1 clades. We found that MAT‐1 induced migration of primary neutrophils and monocytes, the latter of which act as a cellular reservoir of HIV during early stage infection. We then used formyl peptide receptor 1 (FPR1) and FPR2 inhibitors, along with HEK 293 cells, to demonstrate that MAT‐1 can induce chemotaxis specifically using FPR2, a receptor found on the surface of monocytes, macrophages and neutrophils. These findings are the first to identify a proteolytic cleavage product of gp41 with chemotactic activity and highlight a potential role for matriptase in HIV‐1 transmission and infection at epithelial surfaces and within tissue reservoirs of HIV‐1.