Neonatal Group B Streptococcal bacteraemia in India: ten years'experience

Group B Streptococcus (GBS) is an infrequent cause of neonatal septicaemia in many developing countries. In a perinatal centre in India with 60,119 live births between 1988 and 1997, GBS was isolated from blood cultures of 10 babies. Thus the incidence of GBS bacteraemia was 0.17 per 1000 live births. Lethargy, respiratory distress and poor perfusion were the presenting features in eight symptomatic babies. Two babies had meningitis, three required ventilatory support and one died. There were no cases of late onset disease. The low incidence could be due to the low rate of colonisation and high prevalence of protective antibody in the mothers.     

Incidence and Significance of Chronotropic Incompetence in Patients with Indications for Primary Pacemaker Implantation or Pacemaker Replacement

This prospective study was undertaken to evaluate the incidence and significance of chronotropic incompetence in 211 patients [age 71.1 6 10.6 years (mean 6 SD)] by means of maximum exercise test in order to determine the indication for rate-responsive pacing before primary pacemaker implantation (147 patients) or pacemaker replacement (64 patients). There were 112 (53%) patients with second- or third-degree AV block, 63 (30%) with sick sinus syndrome, and 36 (17%) with chronic atrial fibrillation. Chronotropic incompetence was defined as maximum heart rate lower than age-adjusted norm calculated by the formula: 0.7x(220 - age) and its significance as the difference between the two rates. The overall incidence of chronotropic incompetence was 42%. The incidence was significantly higher in patients with atrial fibrillation (67%, P<0.0005) and sick sinus syndrome (49%, P<0.012) than in those with AV block (30%). The mean difference between maximum heart rate and the age-adjusted norm was 18% (range 2%-63%). The mean difference was significantly higher in patients with atrial fibrillation (27%, range 8-63%) than in those with sick sinus syndrome (19%, range 2%-45%, P<0.01), or with AV block (12%, range 6%-26%, P<0.000001). The rate-responsive pacemakers were implanted in 44% of 211 patients studied and in 43% of 196 patients excluded from the study due to the apparent (contra)indication of rate-responsive pacing (NS). Thus, chronotropic incompetence seems to be common in the pacemaker patient population. The highest incidence and significance was found in patients with chronic atrial fibrillation. Systematic evaluation of chronotropic competence can double the rate of implantation of rate-responsive pacemakers; however, further studies are needed to clarify relation between the significance of chronotropic incompetence and functional benefit of rate-responsive pacing.     

ANTI-DNA AUTOANTIBODIES STIMULATE THE RELEASE OF INTERLEUKIN-1 AND INTERLEUKIN-6 FROM ENDOTHELIAL CELLS

The pathogenetic mechanism of vasculitis in systemic lupus erythematosus (SLE) remains a subject of debate. Evidence for a direct pathogenetic role of anti-double-stranded DNA antibodies (anti-dsDNA) is not strong. Supernatant concentrations of interleukin-1β and interleukin-6, and mRNAs encoding for interleukin-1 α and interleukin-1 receptor-1 were determined in cultured human umbilical vein endothelial cells (HUVEC), incubated with control IgG ( n =18), anti-dsDNA ( n =18), or IgG from the same lupus patient depleted of anti-dsDNA by affinity chromatography (anti-dsDNA-dep-IgG). Compared with control IgG, there was a significant increase of supernatant interleukin-1β and interleukin-1α mRNA in endothelial cells incubated with anti-dsDNA. The supernatant interleukin-1β and interleukin-6, and mRNAs encoding for interleukin-1α and interleukin-1 receptor-1, were significantly elevated in endothelial cells incubated with anti-dsDNA, compared with those incubated with anti-dsDNA-dep-IgG. Pretreating HUVEC with native DNA before incubating with anti-dsDNA did not result in an additive effect. These in vitro studies suggest that anti-dsDNA plays an important pathogenetic role in inducing inflammatory injury of vascular endothelium in SLE.     

Electrocardiographic markers of cardiac resynchronization therapy response: delayed time to intrinsicoid deflection onset in lateral leads

Cardiac resynchronization therapy(CRT)has emerged as an important intervention for patients with heart failure(HF)with reduced ejection fraction and delayed ventricular activation.In these patients,CRT has demonstrated to improve quality of life,promote reverse left ventricular(LV)remodeling,reduce HF hospitalizations,and extend survival.However,despite advancements in our understanding of CRT,a significant number of patients do not respond to this therapy.Several invasive and non-invasive parameters have been assessed to predict response to CRT,but the electrocardiogram(ECG)has remained as the prevailing screening method albeit with limitations.Ideally,an accurate,simple,and reproducible ECG marker or set of markers would dramatically overcome the current limitations.We describe the clinical utility of an old ECG parameter that can estimate ventricular activation delay:the onset to intrinsicoid deflection(ID).Based on the concept of direct measurement of ventricular activation time(intrinsic deflection onset),time to ID onset measures on the surface ECG the time that the electrical activation time takes to reach the area subtended by the corresponding surface ECG lead.Based on this principle,the time to ID on the lateral leads can estimate the delay activation to the lateral LV wall and can be used as a predictor for CRT response,particularly in patients with non-specific intraventricular conduction delay or in patients with left bundle branch block and QRS<150 ms.The aim of this review is to present the current evidence and potential use of this ECG parameter to estimate LV activation and predict CRT response.     

金藤清痹颗粒治疗急性痛风性关节炎的作用机制研究

目的 应用网络药理学分析金藤清痹颗粒治疗急性痛风性关节炎（acute gouty arthritis，AGA）的作用机制，并建立AGA大鼠模型进行验证。方法 在清热解毒、活血止痛治法指导下，通过TCMSP数据库搜集金藤清痹颗粒的活性成分及靶点，利用GeneCards、NCBI数据库等搜集AGA相关靶点，与金藤清痹颗粒作用靶点整合后，构建共有靶点蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络和“金藤清痹颗粒-中药-活性成分-靶点-AGA”网络，并进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。雄性SD大鼠随机分为空白组、模型组、秋水仙碱（0.3 mg/kg）组和金藤清痹颗粒低、中、高剂量（1.05、2.10、4.20 g/kg）组，每组6只，踝关节注射单钠尿酸盐（monosodium urate，MSU）晶体建立AGA大鼠模型。采用游标卡尺测量大鼠踝关节直径，计算踝关节肿胀度；采用全自动生化仪检测血清尿酸（serum uric acid，SUA）、C反应蛋白（C-reactive protein，CRP）水平；采用苏木素-伊红（HE）染色观察踝关节组织病理变化；采用qRT-PCR、ELISA和Western blotting检测踝关节组织及血清中关键靶点和信号通路的表达。结果 共检索到金藤清痹颗粒110种活性成分、212个作用靶点，272个AGA治疗靶点，共有靶点29个，关键靶点有白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子（tumor necrosis factor，TNF）及IL-6，涉及TNF信号通路、IL-17信号通路和NOD样受体信号通路等。大鼠踝关节注射MSU晶体后明显肿胀（P<0.01），SUA及CRP显著升高（P<0.05、0.01），滑膜组织增生明显、结构紊乱，有大量炎症细胞浸润，NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）、NIMA相关蛋白激酶7（NIMA-related kinases 7，NEK7）、凋亡相关斑点样蛋白（apoptosis-associated speck-like protein containing a CARD，ASC）、半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1，Caspase-1）、消皮素D（gasdermin D，GSDMD）、IL-18、IL-1β、IL-6及TNF-α表达水平明显升高（P<0.01）；秋水仙碱或金藤清痹颗粒治疗后，有效缓解踝关节肿胀（P<0.05、0.01），SUA及CRP均显著降低（P<0.05、0.01），关节滑膜增生、炎症细胞浸润均得到改善，同时显著抑制IL-1β、TNF-α及IL-6等靶点和NOD样受体信号通路的表达（P<0.05、0.01）。结论 金藤清痹颗粒对AGA大鼠具有明显的保护作用，其机制可能与抑制NOD样受体信号通路的异常激活，降低炎症因子水平，改善关节滑膜增生、炎症细胞浸润有关。     

The erroneous perception of a clinical sign: Cholestasis preceding sepsis mimicking hepatitis in an adolescent patient

Jaundice should be considered as a first clinical sign preceding severe invasive bacterial infection or sepsis in patients of all ages including childhood and adolescence. Early laboratory investigations and MR imaging studies for osteomyelitis or myositis are paramount to avoid progression to life‐threatening sepsis and significant morbidity and mortality.     

生物碱类天然药物抗痛风作用及作用机制的研究进展

痛风是由于机体嘌呤代谢异常和(或)尿酸排泄障碍所致的一组异质性疾病。生物碱是一类含有氮的有机化合物,广泛存在于植物中,用于痛风等多种疾病引起的炎症反应。通过查阅国内外最新相关文献报道,对生物碱抗痛风作用及作用机制的研究进展进行综述,以期为生物碱的进一步研究和临床应用提供科学依据和理论指导。