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.     

Whole body MR imaging in ankylosing spondylitis: a descriptive pilot study in patients with suspected early and active confirmed ankylosing spondylitis

Background  

Ankylosing spondylitis is a chronic inflammatory rheumatic disorder which usually begins in early adulthood. The diagnosis is often delayed by many years. MR imaging has become the preferred imaging method for detection of early inflammation of the axial skeleton in ankylosing spondylitis.     

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.     

慢性低氧时小鼠肺组织低氧诱导因子-1α的表达

目的：研究低氧时小鼠肺组织中低氧诱导因子-1α(HIF-k)表达的变化。方法：实验用雄性小鼠，低氧仓浓度分别为10％、7％、5％。用免疫荧光组织化学技术及共聚焦显微术，检测小鼠在低氧条件下肺组织中HIF-1α表达的变化。结果：正常组小鼠肺组织HIF-1α无表达，低氧组HIF-1α表达增加，且随低氧时间的延长及低氧强度的增加而增强。结论：低氧可诱导小鼠肺组织中HIF-1α的表达增强，(HIF-k)可能参与肺组织细胞凋亡的发生。