永久起搏器在预防心房颤动中的作用

本文总结了用于预防和终止心房颤动的起搏器的类型。窦房结功能异常的病人,心室起搏与较高的心房颤动的发生率相关。有鉴于此,有心房颤动病史、因心动过缓而需要安装起搏器的病人,应该安装双腔或心房起搏生理性起搏器,而不应安装单腔的心室起搏器。     

Thrombopoietin primes human platelet aggregation induced by shear stress and by multiple agonists

Recombinant thrombopoietin has been reported to stimulate megakaryocytopoiesis and thrombopoiesis and it may be quite useful to treat patients with low platelet counts after chemotherapy. As little is known regarding the possible activation of platelets by thrombopoietin, we examined the effects of thrombopoietin on platelet aggregation induced by shear stress and various agonists in native plasma. Using hirudin as an anticoagulant, thrombopoietin (1 to 100 ng/mL) enhanced platelet aggregation induced by 2 micromol/L adenosine- diphosphate (ADP) in a dose dependent fashion. The enhancement was not affected by treatment of platelets with 1 mmol/L aspirin plus SQ-29548 (a thromboxane antagonist, 1 micromol/L) but was inhibited by a soluble form of the thrombopoietin receptor, suggesting that the enhancement was mediated by the specific receptors and does not require thromboxane production. Epinephrine (1 micromol/L), which does not induce platelet aggregation in hirudin platelet rich plasma (PRP), did so in the presence of thrombopoietin (10 ng/mL). Thrombopoietin (10 ng/mL) also enhanced or primed platelet aggregation induced by collagen (0.5 micron.mL),. thrombin, serotonin, and vasopressin. Thrombopoietin does not induce any rise in cytosolic ionized calcium concentration nor activation of protein kinase C, as estimated by phosphorylation of preckstrin, indicating that the priming effects of thrombopoietin does not require those processes. The ADP- or thrombin-induced rise in cytosolic ionized calcium concentration was not enhanced by thrombopoietin (100 ng/mL). Further, shear (ca. 90 dyn/cm2)-induced platelet aggregation was also potentiated by thrombopoietin. The priming effect on epinephrine-induced platelet aggregation in hirudin PRP was unique to thrombopoietin, with no effects seen using interleukin-6 (IL-6), IL-11, IL-3, erythropoietin, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, or c-kit ligand. These data indicate that monitoring of platelet functions may be necessary in the clinical trials of thrombopoietin.     

Emergence of fluoroquinolone‐resistant clonal group A: clonal analysis of Norwegian and Russian E. coli isolates

Strand L, Jenkins A, Grude N, Allum A‐G, Mykland H‐C, Nowrouzian FL, Kristiansen B‐E. Emergence of fluoroquinolone‐resistant clonal group A: clonal analysis of Norwegian and Russian E. coli isolates. APMIS 2010; 118: 571–77. We describe a study of urinary tract and intestinal isolates of Escherichia coli from Norway and Russia using automated ribotyping, single nucleotide polymorphism analysis for clonal group A (CgA) supplemented with phylogrouping, virulence gene profiling and resistance profiling. CgA comprised 19% of the Norwegian UTI isolates from 2001. Two highly multiresistant fluoroquinolone‐resistant CgA isolates were found. Ribotypes clustered into four major and six minor groups (ribogroups). Fluoroquinolone‐resistant isolates and phylogroups A and B1 were associated with ribogroup ^RA. Ribogroup ^RB predominated among Russian UTI isolates and was predominantly phylogroup A and depleted in P‐fimbriae. Ribogroup ^RC predominated among Norwegian UTI isolates and was rich in virulence factors (S‐fimbriae, haemagglutinin and haemolysin) and predominantly phylogroup B2 and D. Ribogroup ^RG was associated with CgA and predominantly phylogroup D. Ribogroups ^RD, ^RE and ^RF had too few members for statistical analysis. The correlation between ribotype and phylogenetic group was not as strong as reported in other studies.     

Live attenuated seasonal and pandemic influenza vaccine in school-age children: A randomized controlled trial

Background

The novel influenza A(H1N1pdm09) virus emerged in North America in early 2009 and rapidly spread worldwide. In this study we report the efficacy of the live attenuated monovalent H1N1pdm09 vaccine and 2009–10 seasonal influenza vaccine in a randomized double-blind placebo-controlled trial.

Methods

We enrolled 703 children aged 7–11. Each child was randomly allocated in the ratio 3:2 to receive one dose of live attenuated monovalent H1N1pdm09 vaccine or saline placebo between November 2009 and January 2010, followed after 3–10 weeks by independent random allocation to one dose of live attenuated trivalent 2009–10 seasonal influenza vaccine or saline placebo in the same ratio. Children were followed up through September 2010 with biweekly telephone calls and symptom diaries. Seasonal and pandemic influenza infections were confirmed by virologic testing of nose and throat swabs collected during acute respiratory illnesses.

Results

Overall, 30 children had confirmed influenza including 3 (0.43%) H1N1pdm09, 10 (1.4%) seasonal A(H3N2), and 17 (2.4%) influenza B. There were no significant differences in incidence rates of H1N1pdm09 or A(H3N2) between the four study arms, but receipt of the seasonal influenza vaccine was associated with a significant reduction in risk of influenza B (p < 0.01). Vaccine efficacy against confirmed H1N1pdm09 infection associated with receipt of the monovalent H1N1pdm09 vaccine was 65% (95% confidence interval, CI: −281%, 97%). Vaccine efficacies against confirmed seasonal influenza A(H3N2) and B infection associated with receipt of the seasonal influenza vaccine were 31% (95% CI: −138%, 80%) and 96% (95% CI: 67%, 99%) respectively.

Conclusions

Vaccine efficacy was consistent with other studies of the monovalent H1N1pdm09 vaccine and seasonal influenza vaccines. Our study was underpowered to provide precise estimates of vaccine efficacy due to low incidence of influenza A viruses during the study period.     

Long-term care cost drivers and expenditure projection to 2036 in Hong Kong

Background  

Hong Kong's rapidly ageing population, characterised by one of the longest life expectancies and the lowest fertility rate in the world, is likely to drive long-term care (LTC) expenditure higher. This study aims to identify key cost drivers and derive quantitative estimates of Hong Kong's LTC expenditure to 2036.     

白花丹参化学成分的研究

从白花丹参(Salvia miltiorrhiza f.alba)中分离出14个二萜醌类化合物,其中2个为新化合物,由光谱分析推定为1,2,15,16-四氢丹参醌(Ⅰ)和丹参醛(Ⅱ);另一个化合物Ⅲ与R₀-090680的结构相同。化合物Ⅰ和Ⅲ对淋巴白血病细胞P₃₈₈均有较强的抑制作用。     

Trends in treatment and overall survival among patients with proximal esophageal cancer

BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT) have been implemented. The trends in(non-)surgical treatment and its impact on overall survival(OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTS In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%,23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval(CI): 6.4-8.1] in 1989-1994 to 9.5 mo(95%CI: 8.1-10.8) in 2010-2014(logrank P 0.001). In non-metastatic disease, 5-year OS rates improved from 5%(95%CI: 3%-7%) in 1989-1994 to 13%(95%CI: 9%-17%) in 2010-2014(logrank P 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo(95%CI:2.5-5.1) in 1989-1994, and 5.1 mo(95%CI: 4.3-5.9) in 2010-2014(logrank P = 0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time.     

Targeting the ACE2-Ang-(1-7) pathway in cardiac fibroblasts to treat cardiac remodeling and heart failure

Fibroblasts play a pivotal role in cardiac remodeling and the development of heart failure through the deposition of extra-cellular matrix (ECM) proteins and also by affecting cardiomyocyte growth and function. The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system in health and disease and many of its effects involve cardiac fibroblasts. Levels of angiotensin II (Ang II), the main effector molecule of the RAS, are elevated in the failing heart and there is a substantial body of evidence indicating that this peptide contributes to changes in cardiac structure and function which ultimately lead to progressive worsening in heart failure. A pathway involving angiotensin converting enzyme 2 (ACE2) has the capacity to break down Ang II while generating angiotensin-(1-7) (Ang-(1-7)), a heptapeptide, which in contrast to Ang II, has cardioprotective and anti-remodeling effects. Many Ang-(1-7) actions involve cardiac fibroblasts and there is information indicating that it reduces collagen production and also may protect against cardiac hypertrophy. This report describes the effects of ACE2 and Ang-(1-7) that appear to be relevant in cardiac remodeling and heart failure and explores potential therapeutic strategies designed to increase ACE2 activity and Ang-(1-7) levels to treat these conditions. This article is part of a special issue entitled ‘‘Key Signaling Molecules in Hypertrophy and Heart Failure.’’     

Four and a half LIM protein 1 gene mutations cause four distinct human myopathies: a comprehensive review of the clinical, histological and pathological features

Mutations in the four and a half LIM protein 1 (FHL1) gene were recently identified as the cause of four distinct skeletal muscle diseases. Since the initial report outlining the first fhl1 mutation in 2008, over 25 different mutations have been identified in patients with reducing body myopathy, X-linked myopathy characterized by postural muscle atrophy, scapuloperoneal myopathy and Emery-Dreifuss muscular dystrophy. Reducing body myopathy was first described four decades ago, its underlying genetic cause was unknown until the discovery of fhl1 mutations. X-linked myopathy characterized by postural muscle atrophy is a novel disease where fhl1 mutations are the only cause. This review will profile each of the FHL1, with a comprehensive analysis of mutations, a comparison of the clinical and histopathological features and will present several hypotheses for the possible disease mechanism(s).