Plasma tumor necrosis factor and mortality in critically ill septic patients

Tumor necrosis factor (TNF) cachectin has been implicated as an important host mediator responsible for shock and multiple organ failure (MOF) observed during sepsis. Using a sensitive enzyme-linked immunosorbent assay, we measured plasma TNF levels in 43 septic patients suffering from a broad range of diseases. Measurements were taken on the day that sepsis was diagnosed. Eleven patients had detectable TNF plasma levels ranging from 10 to 100 pg/ml (TNF-positive group); in 32 patients circulating TNF could not be detected (TNF-negative group). The groups did not differ significantly as to age, underlying disease, percentage positive bacteremia and bacteriologic profile, sepsis score, and extent of MOF. Eight (73%) of 11 TNF-positive patients died from sepsis during ICU stay, vs. 11 (34%) of 32 TNF-negative patients (p less than .05). This study demonstrates that sepsis is accompanied by detectable circulating TNF in 25% of the cases, and for these patients mortality is twice that for comparable TNF-negative patients.     

Toxicology of FK506 in the cynomolgus monkey: a clinical,biochemical, and histopathological study

We investigated clinical, biochemical, and histopathological parameters in FK506-treated cynomolgus monkeys. Eight monkeys given oral FK506, 1 (n = 4) or 10 (n = 4) mg/kg daily, survived the 90 days of treatment apparently in good health and without significant changes in biochemical and histopathological parameters, as did 2 control monkeys except one monkey on 10 mg/kg/day FK506 orally, who was found to have a malignant lymphoma. In contrast, monkeys given intramuscular FK506 1 mg/kg daily (n = 4) had to be sacrificed at day 20, 25, 32, and 47 because of severe illness. They showed abnormal biochemical parameters (increased serum urea and aspartate aminotransferase activity) and major histopathological changes in the kidney (mesangial cell proliferation and acute tubular necrosis), pancreas (depletion of beta cells), liver (steatosis), and heart (cardiomyopathy). Intramuscular administration of 1 mg/kg daily resulted in serum levels ranging from 10 to 15 ng/ml, while oral administration at a dose of 1 or 10 mg/kg daily resulted in equal or even higher serum levels (range 2–70 ng/ml). Thus, the height of the serum trough level of FK506 using the enzyme immunoassay is not related to the toxicity of FK506 in cynomolgus monkeys.     

A role for ELAM-1 in the pathogenesis of MOF during septic shock.

As a model for septic shock, LPS was infused into anesthetized Cynomolgus monkeys. Hematologic and metabolic parameters proved the induced shock response. The data presented show that administration of LPS to Cynomolgus monkeys induced a generalized inflammatory status, which was characterized by systemic release of the cytokines TNF and IL-6. Further it was demonstrated, using immune-histological methods, that a generalized expression in vivo of the endothelial leukocyte adhesion molecule (ELAM)-1 was induced on endothelial cells by LPS infusion. ELAM-1 expression was most pronounced on vasculature of lung tissue and skin. As shown in serial skin biopsies, ELAM-1 expression was induced rapidly: at 2 hr after the onset of LPS infusion, reaching maximum after 4 hr. The expression of ELAM-1 is considered to be of relevance for the mechanism which underlies the stasis of PMN in the tissues during septic shock.     

个体化下肢小腿假肢接受腔设计的生物力学评价技术研究

作为传递体重、固定假肢的部件 ,接受腔对于小腿假肢使用的舒适性和方便程度有决定性的作用。本研究建立了基于有限元应力分析的小腿假肢生物力学评价技术平台 ,实现了小腿残端 /接受腔 3D几何建模与信息交互、三维有限元自动建模及应力分析。 3D模型与信息交互的实现基于得到广泛支持的OpenGL技术 ,有限元模型的构建采用了专门针对小腿残端 /接受腔结构特点的自动建模方法 ,通过构建档案数据库系统作为整个系统的操作平台。该技术平台可与现有的CAD/CAM系统相结合 ,为接受腔的个体化设计提供生物力学定量化依据。其临床应用将改善传统的设计流程 ,提高设计效率。同时 ,它也是未来构建接受腔设计专家 /智能系统的基础。     

Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy

BACKGROUND: Endotoxin and its purified derivative LPS are important contaminants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable interindividual variability in LPS sensitivity. OBJECTIVE: The aim of the study was to relate the individual clinical responses to inhaled LPS with the inflammatory process and the atopic status. METHODS: Fifteen healthy subjects were challenged each week by inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic response was defined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selectin. The LPS-induced airway response was defined as the increase in airway responsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic status was defined as an increase in IgE or a positive skin prick test result. RESULTS: Subjects (n = 7) with a significant increase in body temperature had a larger increase in the systemic inflammatory response (blood neutrophilia; P <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P <.01). Subjects with a significant increase in airway responsiveness (n = 8) had an increase in the sputum concentration of eosinophil cationic protein (P <.01). The amplitude of the systemic response (increase in body temperature [P <.001], blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P <.01]) were inversely associated with the atopic status, suggesting a link between atopy and LPS responsiveness. CONCLUSIONS: The clinical response to LPS occurs systemically or locally and is associated with inflammation. The atopic status was inversely related to the systemic inflammation.     

Functional polymorphism of IgG FcRII (CD32) on human neutrophils.

In this study we demonstrate that Fc gamma RII on polymorphonuclear cells (PMN) (i) mediates binding of immune complexes, and (ii) is polymorphic, similar to the polymorphism described for monocytes and platelets. This was demonstrated in an adherence assay of PMN to activated human umbilical vein endothelial cells (HUVEC). Precoating of activated HUVEC with a mouse IgG1 monoclonal antibody (mAb) ENA1, which is highly reactive with activated HUVEC, caused an enhanced adhesion in 11 of 15 experiments using PMN from different donors. Enhanced adhesion of the PMN corresponded with expression of a high-responder (HR) Fc gamma RII on monocytes isolated from the same donor, as identified by anti-CD3-induced T-cell proliferation. These data led to the conclusion that Fc gamma RII on PMN is polymorphic. This conclusion was, furthermore, supported by immunofluorescence (IF) studies using a new mAb 41H16, which selectively reacts with the HR allotype of Fc gamma RII.     

Longitudinal Changes in Muscle Mass,Muscle Strength,and Physical Performance in Acutely Hospitalized Older Adults

ObjectivesAcute hospitalization may lead to a decrease in muscle measures, but limited studies are reporting on the changes after discharge. The aim of this study was to determine longitudinal changes in muscle mass, muscle strength, and physical performance in acutely hospitalized older adults from admission up to 3 months post-discharge.DesignA prospective observational cohort study was conducted.Setting and ParticipantsThis study included 401 participants aged ≥70 years who were acutely hospitalized in 6 hospitals. All variables were assessed at hospital admission, discharge, and 1 and 3 months post-discharge.MethodsMuscle mass in kilograms was assessed by multifrequency Bio-electrical Impedance Analysis (MF-BIA) (Bodystat; Quadscan 4000) and muscle strength by handgrip strength (JAMAR). Chair stand and gait speed test were assessed as part of the Short Physical Performance Battery (SPPB). Norm values were based on the consensus statement of the European Working Group on Sarcopenia in Older People.ResultsA total of 343 acute hospitalized older adults were included in the analyses with a mean (SD) age of 79.3 (6.6) years, 49.3% were women. From admission up to 3 months post-discharge, muscle mass (?0.1 kg/m²; P = .03) decreased significantly and muscle strength (?0.5 kg; P = .08) decreased nonsignificantly. The chair stand (+0.7 points; P < .001) and gait speed test (+0.9 points; P < .001) improved significantly up to 3 months post-discharge. At 3 months post-discharge, 80%, 18%, and 43% of the older adults scored below the cutoff points for muscle mass, muscle strength, and physical performance, respectively.Conclusions and ImplicationsPhysical performance improved during and after acute hospitalization, although muscle mass decreased, and muscle strength did not change. At 3 months post-discharge, muscle mass, muscle strength, and physical performance did not reach normative levels on a population level. Further research is needed to examine the role of exercise interventions for improving muscle measures and physical performance after hospitalization.     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

碱离子水饮用后血小板聚集率的的变化(附30例报告)

目的:报告30例饮用豪斯牌碱离子水前、后血小板聚集率的变化。方法:饮用碱离子水前、后(2～3月,>3～6月)作比浊法血小板聚集试验,以1分钟、5分钟及5分钟内最大聚集率(Max％)为指标,同时检测部分血粘度指标及凝血因子,并用自动生化仪检测血糖、血脂、主要电解质及部分肝、肾功能。结果:饮碱离子水后,血小板聚集率明显下降,而以疾病组(Max>80％)下降尤为明显,P均<0.001。饮碱离子水后血小板聚集率的下降,部分可能与损伤的血管内皮得到修复有关。主要电解质及部分肝、肾功能无明显异常改变。结论:由于心、脑血管血栓性疾病患者血小板聚集率多明显升高,饮碱离子水后血小板聚集率明显下降,且长期饮用对主要电解质及部分肝、肾功能无明显异常改变,作者认为碱离子水使用方例、安全、有效、价廉,因而对心、脑血管血栓性疾病防治方面可能是一种积极的辅助方法,值得临床进一步探索。