Interspecies plasmid transfer appears rare in sequential infections with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae

From a cohort of 1836 Swedish patients infected with ESBL-producing Enterobacteriaceae (EPE) during 2004–2014, 513 patients with recurrent EPE infection were identified. Only in 14 of the 513 patients was a change of species (ESBL-E. coli to ESBL-K. pneumoniae or vice versa) found between the index and subsequent infection. Eleven sequential urine isolates from 5 of the 14 patients were available for further analysis of possible transfer of ESBL-carrying plasmids. The plasmid content was studied using optical DNA mapping (ODM), PCR-based replicon typing, and ESBL gene sequencing. ODM allowed us to directly compare whole plasmids between isolates and found similar ESBL-carrying plasmids in 3 out of the 5 patients. The ODM results and the rarity in shift of species between ESBL-E. coli and ESBL-K. pneumoniae imply that in recurrent EPE infections interspecies plasmid transfer is uncommon.     

基于3D Slicer应用程序构建大鼠小脑外形微细结构信息数据库

目的:建立大鼠小脑外形三维重构的可视化数据集,为小脑中央核团的三维重建摸索一个可行的方案。方法:实验于2003-03/2005-05在首都医科大学解剖教研室实验室完成。取SD大鼠5只,麻醉后处死取小脑,固定后进行冰冻连续切片、贴片,后经尼氏染色,用扫描仪对各切片进行投射扫描,图像大小为(1868×1491),获取原始图像数据库,并通过首都医科大学生物工程学院开发的配准软件及图像处理软件photoshop7.0对数据库中的数据进行半自动配准及人工分割,应用哈佛大学开发的图像处理专业软件3DSlicer对分割后的数据库进行三维重建。并应用牙科Cad-cam仪器对小脑外形进行扫描,获取完整的小脑外形图像。结果:①小脑尼氏染色获得的原始图像共159张,图像边缘清晰,可见深染的皮质和浅染的白质部分,白质间的小脑中央核深染,边界清晰。②共获得159个小脑外形的三维表面模型数据库(.vtk文件)。在3DSlicer应用程序上可选择小脑外形的三维表面模型数据进行三维显示,并构建了它们的动画显示文件(.gif),使用WindowsMediaPlayer应用软件即可以播放;与应用牙科Cad-cam仪器对小脑表面扫描获取的小脑表面的图像比较,信息更饱满,图像更真实,层次感强。结论:通过切片、配准、分割等方法获得了大鼠小脑外形微细结构信息的数据库,此法更适用于组织微细结构的三维重建。     

Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease

Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL- 1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.     

Guiding catheter-assisted renal artery angioplasty.

A guiding catheter was used in seven patients who underwent balloon dilation of nine renal arteries. The advantages of using a guiding catheter for renal angioplasty are analogous to the benefits obtained with a coronary angioplasty guiding catheter used in coronary angioplasty. The guiding catheter provides back-up support to cross lesions and allows selective contrast visualization of the lesion before, during, and after dilation. It is also possible, when using a guiding catheter, to measure pressure gradients across lesions without having to recross the lesion which may help to ensure that adequate dilation of the stenosis has been accomplished.     

Levels of elastase activity in bronchoalveolar lavage fluids of healthy smokers and nonsmokers

Elastase activity was measured in concentrated, cell-free bronchoalveolar lavage (BAL), using the synthetic substrate butyloxycarbonyl-L-alanyl-L-alanyl-L-prolyl-L-valyl-amino-methylcoumarin. The BAL fluids obtained from young, asymptomatic smokers with normal urine desmosine concentrations 1 h after they had smoked 2 cigarettes showed significant increases in elastase levels compared with those in nonsmoking control subjects [nanomoles substrate hydrolyzed (3 h) per milligram lavage albumin = mean 2.7 +/- 1.9 SD (11 smokers) versus 0.5 +/- 0.4 (11 nonsmokers), p less than 0.01]. Repeated BAL samples were obtained at later times from one smoker with a high initial enzyme value and from one nonsmoking control subject. Elastase activity varied over time, but both subjects consistently remained within their respective group ranges. Inhibition studies on pooled BAL from smokers showed that the elastase activity present had properties of both serine and metalloenzymes, suggesting that neutrophils and/or monocytes (serine enzyme) as well as macrophages (metalloenzyme) contributed to the observed activity. Lung lavage cells obtained from 2 of the smokers and 2 of the nonsmokers were stained with both a chromogenic substrate and by indirect immunofluorescence for the serine enzyme. Positively stained neutrophils were readily found in smokers' lavages, but no, or only rare, positive mononuclear cells could be identified. By contrast, peripheral blood mononuclear cells from all 4 subjects stained positively with either method. These results show that some asymptomatic smokers have significantly more elastase activity in their bronchopulmonary secretions than do nonsmokers (as measured with a low molecular weight synthetic substrate). Furthermore, the enzyme activity recovered in smokers' BAL appears to be derived mainly from neutrophils (serine enzyme) and macrophages (metalloenzyme), rather than from monocytes.     

Acute leukemia in idiopathic sideroblastic anemia: response to combination chemotherapy

Three patients with idiopathic sideroblastic anemia of variable duration developed acute leukemia. In two the leukemia was morphologically and histochemically myeloblastic, in one lymphoblastic. With combination chemotherapy remission was achieved in all three. The remission inductions were complicated by long periods of bone marrow suppression and the duration of remissions was brief (3, 2 and 3 months). Survival after diagnosis was 13, 10 and 9 mo, respectively. The ring sideroblast abnormality persisted during the leukemic and remission phases and transfusion requirements remained unaltered in the two patients with transfusion dependent anemia throughout their courses.     

Towards a combined prognostic index for survival in HIV infection: the role of ‘non‐HIV’ biomarkers

Background

As those with HIV infection live longer, ‘non‐AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non‐HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).

Methods

Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV‐infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS‐defining conditions); ‘non‐HIV’ biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data.

Results

Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle‐aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and ‘non‐HIV’ markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68–0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30‐day C statistic 0.86, 95% confidence interval (CI) 0.80–0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72–0.74). Results were robust to adjustment for missing data.

Conclusions

When added to HIV biomarkers, ‘non‐HIV’ biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.