Characterization of circulating Yersinia-specific immune complexes in patients with yersiniosis

The size of immune complexes (ICs) containing Yersinia enterocolitica antigens was studied by size exclusion high-pressure liquid chromatography and sucrose density gradient ultracentrifugation in sera of patients with recent yersiniosis. The ICs detected were relatively small, i.e., of equal size to or slightly larger than the corresponding anti-Yersinia antibodies. The size of the ICs was equal in the patients with Yersinia-triggered reactive arthritis and in those recovering without complications. No changes were observed during a follow-up. The equal size of ICs in the patients with and without arthritis also suggests that antigens and antibodies involved are similar in both patient groups. Taken together with our earlier findings indicating occurrence of high concentrations of Yersinia IgM ICs in the arthritic patients, the present results suggest that Yersinia--IgM ICs have a role in the pathogenesis of Yersinia-triggered reactive arthritis.     

Aven‐mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma

Conventional high‐grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis‐free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti‐apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G₂ cell‐cycle arrest; Chk1 protein levels were attenuated and ATR–Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven‐depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven‐controlled ATR–Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix‐embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR–Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

败血症病人死亡危险性预评估方法的探讨

目的:探索可早期预测严重败血症病人死亡的临床和实验室指标或系统模型。方法:对ICU连续收治的26例严重败血症病人行前瞻性观察28天,分析其死亡的相关临床和实验室指标。结果:共有14人(54％)死亡,多死于第1周内(74％)。根据循环中的细胞间粘附分子-1水平能早期预测其脏器衰竭和死亡。一些临床指标水平在死亡病人与生存病人之间差别较大,其中包括血总胆红素、pH值、红细胞压积、氧合指数、动静脉血氧差、四项SIRS指标和一些血流动力学指标等。结论:综合上述指标可以尝试建立起了一个能够早期评估病人死亡可能性的积分系统。     

耐一线药物及注射药物对耐多药结核病治疗效果的影响

背景和目的:最近的研究结果表明,对其他一线药物和注射类药物(如卡那霉素、卷曲霉素)等耐药是影响耐多药结核病(MDR-TB)患者治疗效果的独立危险因素.本研究旨在明确耐其他一线药物和注射类药物对韩国不合并人免疫缺陷病毒(HIV)感染的MDR-TB患者临床疗效的影响.方法:采用回顾性队列研究分析1996年1月至2005年12月首尔国家大学附属医院治疗的211例MDR-TB患者治疗效果,排除7例丢失和7例迁出,对197例患者进行了最终分析.     

Promoting shorter duration of ventilator treatment decreases the number of painful procedures in preterm infants

Aim:  To investigate whether promoting shorter ventilator treatment decreases the number of painful procedures and the use of analgesics in preterm infants.
Methods:  Retrospective patient chart review of all preterm infants in one Neonatal Intensive Care Unit (NICU) was carried out in 2000 (n = 240) and 2005 (n = 206). Between these cohorts, early nasal continuous positive airway pressure (nCPAP) application and early extubation policy were introduced.
Results:  Fewer infants were intubated (22 vs. 32%, p = 0.03), the duration of ventilator treatment decreased (6.7 SD 11.3 vs. 9.0 SD 11.1 days, p < 0.001) and nCPAP treatment became more common (41 vs. 25%, p < 0.001) in 2005 than in 2000. Similarly, the infants' exposure to painful procedures did not decrease significantly (61.9 SD 98.5 vs. 67.1 SD 104.3 procedures, p = 0.32) but the procedures related to respiratory support were fewer (45.2 SD 79.5 vs. 68.9 SD 91.1 procedures, p < 0.001) in 2005 than in 2000. In addition, the amount of pain medication used was significantly lower in 2005 than in 2000. One day on a ventilator included more painful procedures than a day on nCPAP (11.2 95% CI: 11.0–11.5 vs. 4.2 95% CI: 4.1–4.4 procedures, p < 0.001) during both study years.
Conclusion:  Early nCPAP and early extubation policies were successfully implemented in an NICU resulting in less invasive respiratory support. This was associated with fewer painful procedures and less pain medication in the preterm infants who required respiratory support. Despite this positive effect, the number of painful procedures in all preterm infants stayed at the same level. Our results provide further support for the use of nCPAP in preterm infants.     

Analysis of the relationship between age and treatment response in migraine

In migraine, headache severity varies with age. As a consequence, the effectiveness of medication may also depend on a patient's age. The purpose of this study was to assess the combined effect of age and drug treatment on headache characteristics. Using data from clinical trials of sumatriptan in adolescents and adults, we show how the interaction between age and drug exposure can be parameterised as a covariate on a Markov model that describes the decline of headache severity over three clinically defined stages (no relief, relief and pain-free status). The model explains important clinical observations: (i) the rates at which the pain relief and pain-free status were attained were found to be inversely related to age; (ii) in placebo-treated patients, the mean transit time from 'no relief' to 'relief' is 3 h for young adolescents and increases to 6 h for patients aged ≥ 30 years; and (iii) sumatriptan reduces the transit time to 2 h, irrespective of age. These findings indicate that the therapeutic gain over placebo increases with age. Prospective studies of antimigraine drugs should take this relationship into account when extrapolating efficacy data from adults to adolescents.     

Symptoms of ＂Heat＂ as a Pattern of Physiopathology

Objective： The guiding criteria are considered the backbone of Chinese medicine. They have previously been described as functional features （symptoms） leading to the overall assessment of human functions on the basis of a regulatory （cybernetic） model referring to the I Ging. Methods： The Heidelberg model can explain symptoms such as created by ＂heat＂ on a rational physiological level. Results ＆ Conclusion： The overall of physiological symptoms are shown as a schematic draft. The basis of ＂heat＂ is considered to be a general increase of microcirculation in the periphery. This leads to a couple of local pathophysiological consequences and sensations like 1） red tongue （the tongue is considered an embryological somatotopic system）. 2） Sensation of warmth （by increase of capillary flow）. 3） pre-inflammatory state, leading to pain modalities like ＂worse if pressed＂, as inflammations tend to be increasingly painful under pressure; 4） reddish skin, the mechanisms by which this is induced may include the release of substance P, therefore accompanied by burning sensation. Systemic pathophysiological consequences may include. Relative lack of fluid in the larger vessels, as fluid supplies peripheral capillary flow. This may lead to water saving mechanisms like thirst, dry mucosa with do, mouth, dry nose, dry lips, dry skin, and also dry stool, yellow and sparse urine.     

Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure

OBJECTIVES: We sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin. BACKGROUND: Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure. METHODS: A double-blind, placebo-controlled, randomized, multicenter, parallel-group study included 151 adult patients. Levosimendan was given as a 10-min intravenous bolus of 3, 6, 12, 24 or 36 microg/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 microg/kg/min, respectively. Dobutamine, for comparative purposes, was given as an open-label infusion (6 microg/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a > or =15% increase in stroke volume (SV) at 23 h to 24 h; 2) a > or =25% decrease in pulmonary capillary wedge pressure (PCWP) (and > or =4 mm Hg) at 23 h to 24 h; 3) a > or =40% increase in cardiac output (CO) (with change in heart rate [HR] <20%); 4) a > or =50% decrease in PCWP during two consecutive measurements. RESULTS: The response rate to levosimendan ranged from 50% at the lowest dose to 88% at the highest dose (compared with placebo 14%, dobutamine 70%). A dose-response relationship was demonstrated for levosimendan on increases in CO and SV, and reductions in PCWP during the infusion (for all, p< or =0.001). Headache (9%), nausea (5%) and hypotension (5%) were the most frequently reported adverse events at higher dosages. CONCLUSIONS: Dosing of levosimendan with a 10-min bolus of 6 to 24 microg/kg followed by an infusion of 0.05 to 0.2 microg/kg/min is well tolerated and leads to favorable hemodynamic effects.     

Rheological properties of three component creams containing sorbitan monoesters as surfactants

The objectives of the present study were (1) to evaluate the effect of formulation ingredients on the release rate of Ubiquinone from its adsorbing solid compact; and (2) to prepare and evaluate an optimized self-nanoemulsified tablet formulation. A three factor, three-level Box–Behnken design was used for the optimization procedure, with the amounts of copolyvidone (X₁), maltodextrin (X₂) and microcrystalline cellulose (X₃) as the independent variables. The response variable was cumulative percent of Ubiquinone emulsified in 45 min with constraints on weight, flowability index, tensile strength, friability and disintegration time of the dry powdered emulsion and the resultant compact. Based on the experimental design, different Ubiquinone release rates and profiles were obtained. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative percent emulsified in 45 min was Y₆=64.10−12.32X₁−4.36X₂−25.53X₃+6.99X₁X₂+3.97X₁X₃+9.70X₂X₃−8.98X₁²−16.22X₂²+17.10X₃². The optimization model predicted an 85.4% release with X₁, X₂ and X₃ levels of 66.6, 560.1 and 100, respectively. A new formulation was prepared according to these levels. The observed responses were in close agreement with the predicted values of the optimized formulation.