During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain omega-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.

Our data suggest that cEPC enumeration in peripheral blood of septic patients might be a valuable marker to assess the clinical outcome in these patients.

The presence of perceptual sensitization and related brain responses was examined in 14 chronic low back pain (CLBP) patients and 13 healthy controls comparable in age and sex. Multichannel EEG recordings and pain ratings were obtained during the presentation of 800 painful electrical intramuscular and intracutaneous stimuli each to the left m. erector spinae and the left m. extensor digitorum. Perception and pain thresholds were not significantly different between the two groups, though patients showed significantly more perceptual sensitization. Across all stimulation conditions, a larger EEG component 80 milliseconds after stimulation was observed in the CLBP group. No significant group differences were found for the N150. The component 260 milliseconds after stimulus onset was significantly smaller in the CLBP group. N80, N150, and perceptual sensitization were significantly positively correlated. These results indicate enhanced perceptual sensitization and enhanced processing of the sensory-discriminative aspect of pain, as expressed in the N80 component, in CLBP patients. This may be one neurophysiologic basis of sensitization and the chronicity process. The lower P260 component in the patients may be explained in terms of tonic pain inhibiting phasic pain or may be related to the affective distress observed in this patient group.

Mean and local cerebral blood flows were lower during sevoflurane than during isoflurane anesthesia. This difference cannot be explained by differing changes in glucose utilization because glucose utilization was decreased to the same extent in both groups.

Induction, emergence and recovery characteristics were compared during sevoflurane or halothane anaesthetic in a large (428) multicentre, international study of children undergoing elective inpatient surgical procedures. Two hundred and fourteen children in each group underwent inhalation induction with nitrous oxide/oxygen and sevoflurane or halothane. Incremental doses of either study drug were added until loss of eyelash reflex was achieved. Steady state concentrations of anaesthesia were maintained until the end of surgery when anaesthetic agents were terminated simultaneously. Time variables were recorded for induction, emergence and the first need for analgesia in the recovery room. In addition, in 86 of the children in both groups, venous blood samples were drawn for plasma fluoride levels during and after surgery. There was a trend toward smoother induction (induction of anaesthesia without coughing, breath holding, excitement laryngospasm, bronchospasm, increased secretion, and vomiting) in the sevoflurane group with faster induction (2.1 min vs 2.9 min, P = 0.037) and rapid emergence times (10.3 min vs 13.9 min, P = 0.003). Among the children given sevoflurane, 2% developed bradycardia compared with 11% in the halothane group. Postoperatively, 46% of the children in the halothane group developed nausea and or vomiting versus 31% in the sevoflurane group (P = 0.002). Two children in the halothane group developed cardiac dysrhythmia and were dropped from the study. In addition, a child in the halothane group developed malignant hyperthermia, received dantrolene, and had an uneventful recovery. Mean maximum inorganic fluoride concentration was 18.3 microM.l-1. The fluoride concentrations peaked within one h of termination of sevoflurane anaesthetic and returned rapidly to baseline within 48 h. This study suggests that sevoflurane may be the drug of choice for the anaesthetic management of children.

In the present study, the sensitivity of LMVEC and human umbilical vein endothelial cells (HUVEC) to lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was compared. To this end, the production of the CC- (MCP-1), CXC- (IL-8, ENA-78, Groalpha, NAP-2, GCP-2) and CX3C (fractalkine) chemokines was studied. A low basal production of these chemokines was observed in both cell types. TNF-alpha, IL-1 and LPS up-regulated all chemokines tested. IFN-gamma however was only able to up-regulate MCP-1 production. LMVEC were more sensitive to IL-1 and LPS compared with HUVEC, since LMVEC produced significantly more MCP-1, ENA-78 and Groalpha (P < 0. 01) under these conditions. Maximal production of MCP-1 in LMVEC was achieved with TNF-alpha (28.4 ng/ml, P < 0.01), whereas IL-1 was the most potent stimulator of ENA-78 (2.78 ng/ml, P < 0.001) and Groalpha (29.2 ng/ml, P < 0.001). IL-8 production in LMVEC cells was maximal after LPS stimulation (28.4 ng/ml), but lower than on HUVEC (P < 0.01). LPS, TNF-alpha and IL-1 stimulation strongly up-regulated all chemokine mRNA. No quantitative differences in mRNA expression between LMVEC and HUVEC were detected for MCP-1 and Groalpha after LPS stimulation. mRNA expression of ENA-78, GCP-2, CX3C and NAP-2 was however higher in LMVEC under LPS stimulation. In contrast, IL-8 mRNA was slightly more expressed in HUVEC under these conditions. These results further support the hypothesis that the microvascular lung endothelium plays an active role in the induction and perpetuation of acute lung injury.

Whether the increase in cerebral blood flow measured after hemodilution is mediated by a decrease in blood viscosity or in oxygen delivery to the brain is debated. In the present study, blood was replaced by an oxygen-carrying blood substitute, ultrapurified, polymerized, bovine hemoglobin (UPBHB). In contrast to normal blood, UPBHB yields a constant and defined viscosity in the brain circulation, since its viscosity is not dependent on the shear rate. CBF was determined after blood exchange with UPBHB in one group of conscious rats (UPBHB group) and in another group of blood-exchanged conscious rats in which viscosity was increased fourfold by the addition of 2% polyvinylpyrrolidone (PVP), mw 750,000 (UPBHB-PVP group). Local CBF (LCBF) was measured in 34 brain structures by means of the quantitative iodo(14C)antipyrine method. After blood replacement, systemic parameters such as cardiac index, arterial blood pressure, blood gases, and acid-base status were not different between the UPBHB and the UPBHB-PVP groups. In particular, arterial oxygen content was similar in both groups. Compared with a control group without blood exchange, LCBF was increased after blood exchange in the different brain structures by 60-102% (UPBHB group) and by 33-101% (UPBHB-PVP group). Mean CBF was increased by 77% in the UPBHB group and by 69% in the UPBHB-PVP group. No significant differences were observed in the values of LCBF or mean CBF between the UPBHB group and the UPBHB-PVP group. The results show that a fourfold variation in the viscosity of a Newtonian blood substitute does not result in differences in CBF values.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and microcirculatory effects of autologous whole blood resuscitation after 4-h hemorrhagic shock with a mean arterial pressure (MAP) level of 40 mmHg were investigated in 63 conscious Syrian golden hamsters. Microcirculation of skeletal skin muscle and subcutaneous connective tissue was visualized in a dorsal skinfold. Shed blood was retransfused within 30 min after 4 h. Animals were grouped into survivors in good (SG) and poor condition (SP) and nonsurvivors (NS) according to 24-h outcome after resuscitation and studied before shock, during shock (60, 120, and 240 min), and 30 min and 24 h after resuscitation. Microvascular and interstitial[Formula: see text] values were determined by phosphorescence decay. Shock caused a significant increase of arterial[Formula: see text] and decrease of[Formula: see text], pH, and base excess. In the microcirculation, there was a significant decrease in blood flow (Q˙B), functional capillary density (FCD; capillaries with red blood cell flow), and interstitial [Formula: see text][1.8 ± 0.8 mmHg (SG), 1.3 ± 1.3 mmHg (SP), and 0.9 ± 1.1 mmHg (NS) vs. 23.0 ± 6.1 mmHg at control]. Blood resuscitation caused immediate MAP recompensation in all animals, whereas metabolic acidosis, hyperventilation, and a significant interstitial [Formula: see text] decrease (40–60% of control) persisted. In NS (44.4% of the animals), systemic and microcirculatory alterations were significantly more severe both in shock and after resuscitation than in survivors. Whereas in SG (31.8% of the animals) there was only a slight (15–30%) but still significant impairment of microscopic tissue perfusion (Q˙B, FCD) and oxygenation at 24 h, SP (23.8% of the animals) showed severe metabolic acidosis and substantial decreases (≥50%) of FCD and interstitial[Formula: see text]. FCD, interstitial[Formula: see text], and metabolic state were the main determinants of shock outcome.