Traumatic brain injuries induce a strong, locally restricted inflammatory response. Here we demonstrate that activated neutrophils infiltrate the site of tissue destruction and release large amounts of enzymatically active elastase, cathepsin G, and proteinase 3. High intracerebral protease concentrations were found to be accompanied by a reduced inhibitory potential at foci of inflammation. In 39 neurotrauma patients, a temporal correlation between the protease release from neutrophils and the solubilization of interleukin-2 (IL-2) receptor and IL-6 receptor ectodomains at sites of tissue destruction was observed, suggesting that neutrophil-derived proteases may play a crucial role in the cytokine receptor shedding at foci of inflammation. Under in vitro conditions, the cleavage of membrane-bound IL-2Ralpha was found to be predominantly catalyzed by elastase and, to a lesser extent, by proteinase 3. Cathepsin G was found to be incapable of solubilizing this receptor. In contrast, the cleavage of the IL-6R 80 kDa chain was catalyzed by cathepsin G but not by elastase or proteinase 3. The receptor fragments released by the action of these enzymes were found to retain their ligand-binding capacity. These results strongly suggest a pathophysiologic role of neutrophil-derived serine proteases, particularly in regulation of the expression of functional IL-2 and IL-6 receptors at foci of inflammation.
Thiopental and nitrous oxide have immunosuppressive activity. In contrast, sevoflurane may have a beneficial effect by alleviating the immunosuppressive effects of both substances.
Inadequate analgesia or anxiety may induce an increased stress response in patients undergoing carotid endarterectomy (CEA) under regional anesthesia (RA). Central alpha2 adrenoceptor agonists have significant sedative and analgesic properties, which may attenuate sympathoadrenal activation during CEA and improve the quality of RA. We randomly assigned 80 patients to 2 groups receiving either RA plus placebo (n = 40) or RA plus clonidine 1 microg/kg as the initial loading dose followed by 1 microg.kg(-1).h(-1) (n = 40). RA was performed as combined deep and superficial cervical plexus blockade. Hemodynamic and neurological variables were assessed before, during, and after CEA. Arterial blood samples were collected at defined time points for the determination of plasma concentrations of epinephrine, norepinephrine, cortisol, and creatinine kinase and creatinine kinase-MB. Throughout the study, all patients responded easily to neurological evaluations. Before and during clamping mean arterial blood pressure and heart rate were not different between the groups, but mean arterial blood pressure was lower in the clonidine group (P < 0.01) at skin closure and postoperatively in the intensive care unit. In the placebo group, cortisol, epinephrine, and norepinephrine plasma concentrations were increased significantly (P < 0.05) and more patients required antihypertensive treatment (P < 0.01). Postoperatively the incidence of hypertension (P < 0.001) and development of neurological deficits (P < 0.05) was significantly decreased in the clonidine group. We conclude that 1 microg.kg(-1).h(-1) clonidine suppresses the hyperadrenergic response to CEA without adverse effects on hemodynamics or clinical neurological monitoring.
Dreams and hallucinations under sedation or anesthesia have been well known phenomena since the introduction of anesthesia. Sexual hallucinations may lead to allegations of sexual molestation or assault by medical doctors or professional nursing staff. Hallucinations under the influence of sedative or hypnotic drugs may be very vivid and as misinterpreted as being real and it is therefore often difficult to disprove the resulting false allegations. In this report the terms drug-induced dreams and hallucinations are defined and the probable mechanism described. By a historical review and case reports the medicolegal consequences are demonstrated and procedures recommended to avoid allegations of sexual assault.
We report on two patients with schizoaffective psychosis, cancer, and pain. However, it is not possible to make somatic or psychic disturbances alone responsible for the pain. In patients with current schizoaffective disorders, only administration of a combination of psychopharmaceutical and opioid agents is successful.
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