Background-We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome. Methods and Results-Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell-derived IL-10 and interferon-␥ were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients' leukocytes and that an immunosuppressive activity was also present in their plasma. Conclusions-Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis. (Circulation. 2002;106:562-568.)
These data suggest that early application of standard continuous venovenous hemofiltration is deleterious in severe sepsis and septic shock. This study does not rule out an effect of high-volume hemofiltration (>35 mL/kg/hr) on the course of sepsis.
Low molecular weight heparins are as effective as unfractionated heparin in deep-vein thrombosis (DVT) prophylaxis for major surgery. However, there is no evidence nor consensus for prophylaxis in medical patients. We compared the efficacy and safety of nadroparin calcium (nadroparin) with placebo in medical patients at high risk of DVT. A total of 223 patients mechanically ventilated for acute, decompensated chronic obstructive pulmonary disease, were randomized to treatment with subcutaneous nadroparin adjusted for body weight (0.4 ml, i.e., 3,800 AXa IU, or 0.6 ml, i.e., 5,700 AXa IU) or placebo. The average duration of treatment was 11 d. The incidence of DVT in patients receiving nadroparin was significantly lower than that in patients receiving placebo (15.5 versus 28.2%; p = 0.045). Although the incidence of adverse events was high in both groups, there were no significant differences between nadroparin and placebo for total adverse events (46.3 versus 39.8%; p = 0.33), serious adverse events (25.0 versus 19.5%; p = 0.32), or those resulting in early permanent discontinuation of treatment (12.0 versus 8.8%; p = 0.44). The most common adverse event was hemorrhage. There was the same number of deaths in both treatment groups. Subcutaneous nadroparin resulted in 45% decrease in incidence of DVT compared with placebo.
Physiological and behavioural measures of stress in caged hens on a commercial farm were compared between White Leghorn and brown Hyline strains, and between three tiers of cages. Blood and faecal samples were collected from undisturbed birds for corticosterone measurements. Plasma corticosterone responses to a stressor were measured by the collection of blood samples after 15, 30, and 60 min of a handling stressor. Tonic immobility and novel object tests were used to measure fear behaviour. Plasma corticosterone in undisturbed hens and faecal corticosterone did not differ between White Leghorn and brown Hyline hens, whereas the plasma corticosterone response to a handling stressor was greater in White Leghorns. The duration of tonic immobility, latency to first head movement and number of head movements in tonic immobility tests were greater in white than brown birds, whereas the number of inductions was less for tonic immobility tests. There were no differences between the strains in their responses to a novel object. There were no differences between tiers in plasma corticosterone or corticosterone responses or tonic immobility responses, and no consistent differences in responses of birds to a novel object. This is the first study in which plasma and faecal corticosterone concentrations and fear behaviour have been measured together in laying hens, and the first description of plasma corticosterone responses to handling over 60 min for caged laying hens on a commercial farm. The study has shown the value of measuring endocrine and behavioural variables together to provide objective data on characteristics of different strains of hens.
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