[Combined dorsal and palmar plate osteosynthesis for intraarticular distal radius fractures]. / Kombinierte dorsale und palmare Plattenosteosynthese bei distalen intraartikulären Radiusfrakturen.

BACKGROUND: Complex comminuted intraarticular fractures of the distal radius require anatomic restoration. In rare cases, this aim can only be achieved by a combined dorsal and volar plate fixation despite increasing experience with volar locking compression implants. This retrospective quality control study investigated functional, radiological and subjective outcomes of patients treated with this technique. METHODS: Between March 1999 and January 2003, 30 out of 360 patients who were operated on for an unstable distal radius fracture with complex C2/C3 type distal radius fractures at the Division of Trauma Surgery of the University Hospital Zurich, had been treated with a combined dorso-palmar plate fixation (dorsal two 1/4 tubular plates, volar 3.5 mm T-plate) and were included in this study (9 female, 21 male, mean age 52 years). Of the 30 patients 25 could be evaluated at an average of 29 months after injury. RESULTS: Anatomic reconstruction could not be achieved in all cases, 56% showed mild and 28% explicit signs of arthrosis. Flexion reached 66% and extension 75% of the contralateral wrist, whereas pronation reached 98% and supination 91%, respectively. Grip strength achieved 75% of that of the contralateral side and 10 patients (40%) developed a complex regional pain syndrome (CRPS). Return to work was possible 120 days after the injury. CONCLUSION: With the dorso-palmar plate fixation joint reconstruction in complex intraarticular distal radius fractures can be achieved with a satisfactory subjective, functional, and radiologic result, although additional soft tissue injury was caused by the bilateral approach. The patient has to be informed of the high rate of CRPS and the long period of disability.

Interactive visuo-haptic surgical planning tool for pelvic and acetabular fractures.

Treatment of pelvic and acetabular fractures still poses a major challenge to trauma surgeons. We present a tool for intervention planning for such injuries using patient-specific models built from Computed Tomography data. The presented tool has three main parts: (1) the virtual reduction of the bone fragments, (2) the virtual adaptation of the osteosynthesis implants and (3) Finite Element Analysis (FEA) for testing mechanical behavior of the resulting intervention plan. Our tool provides an intuitive visuo-hapic interface designed to be used by trauma surgeons. The type and size of the osteosynthesis material can be determined and measurements like distances and angles relative to landmarks can be taken. First results of prospectively planned interventions show an excellent correlation and a significant gain in operation time.

Systemic effects of severe trauma on the function and apoptosis of human skeletal cells.

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects. The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031). Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.

V.A.C. instillation: in vitro model. Part 1.

The reproducibility of a V.A.C. (Vacuum Assisted Closure) instillation system was investigated by means of an in vitro model. The relation between the volume of a delivered solution and its removal from the system was studied in foams of various size. The relationship of instillation time periods and the volume of delivered solution was determined.

Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood-brain barrier dysfunction and nerve growth factor production.

Interleukin (IL) 8 was measured in CSF of 14 patients with severe traumatic brain injury. IL-8 levels were significantly higher in CSF (up to 8,000 pg/ml) than serum (up to 2,400 pg/ml) (p < 0.05), suggesting intrathecal production. Maximal IL-8 values in CSF correlated with a severe dysfunction of the blood-brain barrier. Nerve growth factor (NGF) was detected in CSF of 7 of 14 patients (range of maximal NGF: 62-12,130 pg/ml). IL-8 concentrations were significantly higher in these patients than in those without NGF (p < 0.01). CSF containing high IL-8 (3,800-7,900 pg/ml) induced greater NGF production in cultured astrocytes (202-434 pg/ml) than samples with low IL-8 (600-1,000 pg/ml), which showed a smaller NGF increase (0-165 pg/ml). Anti-IL-8 antibodies strongly reduced (52-100%) the release of NGF in the group of high IL-8, whereas in the group with low IL-8, this effect was lower (0-52%). The inability of anti-IL-8 antibodies to inhibit the synthesis of NGF completely may depend on cytokines like tumor necrosis factor alpha and IL-6 found in these CSF samples, which may act in association with IL-8. Thus, IL-8 may represent a pivotal cytokine in the pathology of brain injury.

Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid.

Diffuse axonal injury is a frequent pathologic sequel of head trauma, which, despite its devastating consequences for the patients, remains to be fully elucidated. Here we studied the release of interleukin-6 (IL-6) into CSF and serum, as well as the expression of IL-6 messenger ribonucleic acid (mRNA) and protein in a weight drop model of axonal injury in the rat. The IL-6 activity was elevated in CSF within 1 hour and peaked between 2 and 4 hours, reaching maximal values of 82,108 pg/mL, and returned to control values after 24 hours. In serum, the levels of IL-6 remained below increased CSF levels and did not exceed 393 pg/mL. In situ hybridization demonstrated augmented IL-6 mRNA expression in several regions including cortical pyramidal cells, neurons in thalamic nuclei, and macrophages in the basal subarachnoid spaces. A weak constitutive expression of IL-6 protein was shown by immunohistochemical study in control brain. After injury, IL-6 increased at 1 hour and remained elevated through the first 24 hours, returning to normal afterward. Most cells producing IL-6 were cortical, thalamic, and hippocampal neurons as confirmed by staining for the neuronal marker NeuN. These results extend our previous studies showing IL-6 production in the cerebrospinal fluid of patients with severe head trauma and demonstrate that neurons are the main source of IL-6 after experimental axonal injury.

Experimental closed head injury: analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines.

Cytokines are important mediators of intracranial inflammation following traumatic brain injury (TBI). In the present study, the neurological impairment and mortality, blood-brain barrier (BBB) function, intracranial polymorphonuclear leukocyte (PMN) accumulation, and posttraumatic neuronal cell death were monitored in mice lacking the genes for tumor necrosis factor (TNF)/lymphotoxin-alpha (LT-alpha) (TNF/LT-alpha-/-) and interleukin-6 (IL-6) and in wild-type (WT) littermates subjected to experimental closed head injury (total n = 107). The posttraumatic mortality was significantly increased in TNF/LT-alpha-/- mice (40%; P < 0.02) compared with WT animals (10%). The IL-6-/- mice also showed a higher mortality (17%) than their WT littermates (5.6%), but the difference was not statistically significant (P > 0.05). The neurological severity score was similar among all groups from 1 to 72 hours after trauma, whereas at 7 days, the TNF/LT-alpha-/- mice showed a tendency toward better neurological recovery than their WT littermates. Interestingly, neither the degree of BBB dysfunction nor the number of infiltrating PMNs in the injured hemisphere was different between WT and cytokine-deficient mice. Furthermore, the analysis of brain sections by in situ DNA nick end labeling (TUNEL histochemistry) at 24 hours and 7 days after head injury revealed a similar extent of posttraumatic intracranial cell death in all animals. These results show that the pathophysiological sequelae of TBI are not significantly altered in mice lacking the genes for the proinflammatory cytokines TNF, LT-alpha, and IL-6. Nevertheless, the increased posttraumatic mortality in TNF/LT-alpha-deficient mice suggests a protective effect of these cytokines by mechanisms that have not been elucidated yet.

IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta1 and blood-brain barrier function.

Controlling the extent of inflammatory responses following brain injury may be beneficial since posttraumatic intracranial inflammation has been associated with adverse outcome. In order to elucidate the potential role of anti-inflammatory mediators, the production of interleukin-10 (IL-10) was monitored in paired cerebrospinal fluid (CSF) and serum of 28 patients with severe traumatic brain injury (TBI) and compared to control samples. The pattern of IL-10 was analyzed with respect to the patterns of IL-6, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in both fluids during a time period of up to 22 days. In parallel, the function/dysfunction of the blood-brain barrier (BBB) was monitored using the CSF-/serum-albumin quotient (Q(A)) and compared to intrathecal cytokine levels. Mean IL-10 concentration in CSF was elevated in 26 out of 28 TBI patients (range: 1.3-41.7 pg/ml) compared to controls (cut-off: 1.06 pg/ml), whereas only seven patients had elevated mean IL-10 concentration in serum (range: 5.4-23 pg/ml; cut-off: 5.14 pg/ml). The time course of IL-10 was similar in both fluids, showing a peak during the first days and a second, lower rise in the second week. Intrathecal IL-10 synthesis is hypothesized since CSF-IL-10 levels exceeded serum-IL-10 levels in most of the patients, IL-10-index (CSF/serum-IL-10/QA) was elevated in 23 individuals, and elevation of CSF-IL-10 showed to be independent from severe BBB dysfunction. Neither CSF nor serum IL-10 values correlated with the dysfunction of the BBB. IL-10, IL-6 and TGF-beta1 showed similar patterns in CSF over time, whereas rises of TNF-alpha corresponded to declines of IL-10 levels. Our results suggest that IL-10 is predominantly induced intrathecally after severe TBI where it may downregulate inflammatory events following traumatic brain damage.

Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice.

The anaphylatoxin C5a is a potent mediator of inflammation in the CNS. We analyzed the intracerebral expression of the C5a receptor (C5aR) in a model of closed head injury (CHI) in mice. Up-regulation of C5aR mRNA and protein expression was observed mainly on neurons in sham-operated and head-injured wild-type mice at 24 h. In contrast, in TNF/lymphotoxin-alpha knockout mice, the intracerebral C5aR expression remained at low constitutive levels after sham operation, whereas it strongly increased in response to trauma between 24 and 72 h. Interestingly, by 7 days after CHI, the intrathecal C5aR expression was clearly attenuated in the knockout animals. These data show that the posttraumatic neuronal expression of the C5aR is, at least in part, regulated by TNF and lymphotoxin-alpha at 7 days after trauma.

Detectable concentrations of Fas ligand in cerebrospinal fluid after severe head injury.

When the cell surface molecule Fas is triggered by its agonist Fas ligand the result is apoptosis of these cells and tissue destruction. To elucidate the pathophysiological relevance of Fas ligand in patients with cerebral oedema caused by trauma, we examined its concentrations in cerebrospinal fluid in 18 patients using specific ELISA. Serum and cerebrospinal fluid from healthy people and injured patients without head trauma did not contain detectable Fas ligand. In contrast, cerebrospinal fluid from patients with severe brain injury contained high concentrations of Fas ligand without detectable concentrations in serum. Soluble Fas ligand concentrations in cerebrospinal fluid correlated significantly with severity of brain injury. The Fas-Fas ligand-system may have a pivotal role in causing oedema and local tissue destruction in the brain after severe head injury.

Interleukin-18 plasma levels are increased in patients with sepsis compared to severely injured patients.

Interleukin-18 (IL-18) appears to play a critical role in cytokine-induced organ failure during endotoxemia in animal models. Therefore, plasma samples from patients with severe trauma and sepsis were examined for the presence of IL-18. Significantly elevated plasma IL-18 concentrations were found in patients with sepsis compared to severely injured patients and healthy humans. Septic patients who died and patients with septic shock exhibited higher levels of IL-18 than survivors and septic patients without shock. In addition, septic patients with gram-positive infections had significantly higher IL-18 plasma levels than patients with gram-negative infection. These findings were confirmed by whole blood assay from healthy humans where Staphylococcus aureus markedly (P < 0.05) increased the release of IL-18 in whole blood ex vivo, while endotoxin was ineffective. Although obtained from a small patient group, these results suggest that IL-18 production may discriminate between gram-positive and gram-negative sepsis, and that increased IL-18 appearance may be associated with an adverse outcome in septic patients.

Differential effect of caspase inhibition on proinflammatory cytokine release in septic patients.

The interleukins (IL)-1beta and IL-18 represent potent players in the proinflammatory cytokine cascade. Their activation is regulated predominantly through the IL-1-converting enzyme (ICE)/caspase-1. The role of caspases in the secretion of IL-1beta and IL-18, as well as in the release of the secondary-induced cytokines IL-12 and interferon (IFN)-gamma in whole blood from septic patients compared to healthy controls, was studied. Inhibition of caspase activity by Z-VAD significantly reduced lipopolysaccharide (LPS) and Staphylococcus aureus (SAC) induced release of mature IL-1beta in septic patients and controls. In contrast, in whole blood from septic patients significantly elevated basal level of IL-18 were found, which could neither be further increased by LPS or SAC, nor be inhibited by Z-VAD. Release of IL-12 p40 was significantly lower in septic patients compared to controls and was not affected by Z-VAD. Despite high levels of IL-18, IFN-gamma was not detected in whole blood from septic patients even after stimulation with SAC or LPS. Thus, during sepsis, caspases participate in the processing of IL-1beta, whereas maturation of IL-18 during sepsis appears to be independent of caspases. The lack of IFN-gamma release seen in septic patients could be attributed to low IL-12 release rather than to diminished IL-18 release.

Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.

Patients with severe traumatic brain injury (TBI) show a profound acute-phase response. Because interleukin-6 (IL-6) is an important mediator of these pathophysiological changes, IL-6 levels were monitored in the cerebrospinal fluid (CSF) and serum of 20 patients with severe isolated TBI. All patients received indwelling ventricular catheters for intracranial pressure monitoring and for release of CSF when intracranial pressure exceeded 15 mmHg. CSF and blood samples were drawn daily for up to 14 days. The CSF/serum albumin ratio (QA) served as a parameter of blood brain barrier dysfunction. Differential blood counts as well as the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and fibrinogen were recorded. IL-6 was detected in all CSF samples and reached values of up to 31,000 pg/mL, while serum levels remained significantly lower (alpha < or = .01) and never exceeded 1,100 pg/mL the entire study period. A correlation between CSF and serum IL-6 was found initially after the trauma and corresponded to a severe dysfunction of the blood brain barrier (r = .637, p = .001). Maximum IL-6 concentrations in serum correlated with peak levels of acute-phase proteins (C-reactive protein, alpha 1-antitrypsin, and fibrinogen). With regard to blood cell count, an initial leukocytosis combined with a borderline lymphocytopenia was observed. Thrombocytes decreased to a subnormal level during the first few days, but reached supranormal numbers by the end of the study period. Our results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI. Because cytokine concentrations are significantly lower in serum compared with CSF, we hypothesize that IL-6 produced in the central nervous system may play a role in initiating the acute-phase response.

Prone postioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS.

STUDY OBJECTIVES: Investigating the effect of low-volume pressure-limited ventilation and repeated prone positioning on the short-term course and outcome in patients with severe ARDS. SETTING: Level 1 trauma center of a university hospital. PATIENTS: Twenty-five patients suffering from ARDS with a lung injury score (LIS) > or = 2.5 admitted consecutively to our ICU from January 1992 to December 1994. METHODS: Mechanical ventilation with peak inspiratory pressure limitation to 35 mbar, irrespective of hypercapnia and prone positioning to achieve adequate oxygenation. SCORING AND MEASUREMENTS: Patient assessment with LIS, APACHE (acute physiology and chronic health evaluation) II score, injury severity score, and multiple organ failure score. Blood gas analyses and estimation of static compliance were repeated at least every 4 h during the treatment period. PaO2/FIO2 (fraction of inspired oxygen) ratio, alveolo-arterial oxygen difference, and intrapulmonary shunt were calculated according to standard equations. The best values taken from each 4-h period during the investigation were used to evaluate the best possible performance of the lung within this interval and to investigate the entire course. RESULTS: Mean predicted mortality based on the APACHE II score was 35.4+/-15.2%. Three of the 25 patients (12%) died. However, none was related to respiratory failure. No pneumothorax occurred. Sixteen patients, lacking any contraindication for prone positioning, responded positively to this change in position, each to a different individual degree. CONCLUSION: We assume that our low mortality in patients with severe ARDS might be due mainly to low-volume pressure-limited ventilation and prone positioning. This simple strategy seems to allow successful treatment for patients with severe ARDS.

Soluble ICAM-1 in CSF coincides with the extent of cerebral damage in patients with severe traumatic brain injury.

The intercellular adhesion molecule-1 (ICAM-1) expressed by endothelial cells is crucial in promoting adhesion and transmigration of circulating leukocytes across the blood-brain barrier (BBB). Migrated immunocompetent cells, in turn, release mediators that stimulate glial and endothelial cells to express ICAM-1 and release cytokines, possibly sustaining cerebral damage. Following activation, proteolytic cleavage of membrane-anchored ICAM-1 results in measurable levels of a soluble form, sICAM-1. The aims of this study were to investigate the changes of sICAM-1 levels in ventricular CSF and serum and to elucidate the influence of structural brain damage as estimated by computerized tomography (CT) as well as the extent of BBB dysfunction as calculated by the CSF/serum albumin ratio (QA) in patients with severe traumatic brain injury (TBI). All investigated parameters revealed two subgroups. Patients belonging to group A had sICAM-1 levels in CSF above normal range, presented marked cerebral damage and a disturbance of the BBB (range 0.6-24.7 ng/ml, n = 8). In contrast, patients belonging to group B had no elevation of sICAM-1 values in CSF (range 0.3-3.9 ng/ml, n = 5; p < 0.017) and showed minor cerebral damage with an intact BBB in most cases. In addition, overall analysis showed that sICAM-1 in CSF correlated with the extent of BBB damage as indicated by the QA (r = 0.76; p < 0.001). These results suggest that increased sICAM-1 levels in CSF might depict ongoing immunologic activation and that sICAM-1 correlates with the extent of tissue and BBB damage. The origin of soluble ICAM-1 in CSF and its pathophysiologic role after TBI remains to be clarified.

S-100 beta reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury.

It has been hypothesized that immunoactivation may contribute to brain damage and affect outcome after traumatic brain injury (TBI). In order to determine the role of inflammation after TBI, we studied the interrelationship of the immune mediators sICAM-1 and IL-6 with the levels of S-100beta and neuronal specific enolase (NSE), both recognized markers of brain damage. In addition, the extent and type of cerebral injury and the neurological outcome were related to these measured markers of injury. An evident elevation of S-100beta (range of means: 2.7-81.4 ng/mL) and NSE (range of means: 2.0-81.3 ng/mL) was observed in CSF of all 13 patients during the first 3 posttraumatic days and decreased over 2 weeks. In parallel, the production of sICAM-1 (range of means: 0.7-11.9 ng/mL) and IL-6 (range of means: 0.1-8.2 ng/mL) was also markedly enhanced in CSF. The CSF means of S-100beta and NSE per patient correlated with IL-6 (r = 0.60, p < 0.05; and r = 0.64, p < 0.05, respectively), whereas the corresponding means in serum showed a significant correlation only between NSE and IL-6 (r = 0.56, p < 0.05). Maximal CSF values of NSE and sICAM-1 correlated with each other (r = 0.57, p < 0.05). The contusion sizes assessed on the CT scans correlated with the means of S-100beta (r = 0.63, p < 0.05) and NSE (r = 0.71, p < 0.05) in CSF and with the mean of S-100beta in serum, although not statistically significant (r = 0.52, p = 0.06), but not with serum NSE. Interestingly, linear regression analysis demonstrated that means of S-100beta in CSF (r = 0.78, p = 0.002) and serum (r = 0.82, p < 0.001) correlated with the GOS. These results indicate that the elevation of these parameters in CSF depends on the extent of injury and that S-100beta may be a predictor of outcome after TBI, whereas NSE reflects better the inflammatory response.

TGF-beta is elevated in the CSF of patients with severe traumatic brain injuries and parallels blood-brain barrier function.

Traumatic brain injury (TBI) induces local and systemic immunologic changes, release of cytokines, and cell activation. Perpetuation of these cascades may contribute to secondary damage to the brain. Therefore, the ability of the antiinflammatory mediator transforming growth factor-beta (TGF-beta) to downregulate intrathecal immunoactivation may be of fundamental value for diminishing the incidence and extent of secondary insults. In this study, the release of TGF-beta into cerebrospinal fluid (CSF) and serum of 22 patients with severe TBI was analyzed with respect to the function of the blood-brain barrier (BBB) for 21 days. Levels of TGF-beta in CSF increased to their maximum on the first day (median, 1.26 ng/mL), thereafter decreasing gradually over time. Median TGF-beta values in serum always remained within the reference interval (6.5 to 71.5 ng/mL). Daily assessment of the CSF-serum albumin quotient (QA) and of the CSF-serum TGF-beta quotient (QTGF-beta) showed a strong correlation between maximal QTGF-beta and QA, indicating a passage of this cytokine from the periphery to the intrathecal compartment across the BBB. However, calculation of the TGF-beta index (QTGF-beta/Q(A)) suggested a cerebral production of TGF-beta in 9 of 22 patients. Levels of TGF-beta could not be correlated with extent of initial injury by computed tomography (CT), CD4/CD8 ratios, acute lung injury, or clinical outcome as rated by the Glasgow Outcome Scale (GOS). Although increased levels of TGF-beta in CSF seem to parallel BBB function, a partial intrathecal production is suggested, possibly modulated by elevation of interleukin-6 (IL-6). Thus, TGF-beta may function as a factor in the complex cytokine network following TBI, acting as an antiinflammatory and neuroprotective mediator.

Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury.

It has become evident in recent years that intracranial inflammation after traumatic brain injury (TBI) is, at least in part, mediated by activation of the complement system. However, most conclusions have been drawn from experimental studies, and the intrathecal activation of the complement cascade after TBI has not yet been demonstrated in humans. In the present study, we analyzed the levels of the soluble terminal complement complex sC5b-9 by ELISA in ventricular cerebrospinal fluid (CSF) of patients with severe TBI (n = 11) for up to 10 days after trauma. The mean sC5b-9 levels in CSF were significantly elevated in 10 of 11 TBI patients compared to control CSF from subjects without trauma or inflammatory neurological disease (n = 12; p < 0.001). In some patients, the maximal sC5b-9 concentrations were up to 1,800-fold higher than in control CSF. The analysis of the extent of posttraumatic blood-brain barrier (BBB) dysfunction, as determined by CSF/serum albumin quotient (Q(A)), revealed that patients with a moderate to severe BBB impairment (mean Q(A) > 0.01) had significantly higher intrathecal sC5b-9 levels as compared to patients with normal BBB function (mean Q(A) < 0.007; p < 0.0001). In addition, a significant correlation between the individual daily Q(A) values and the corresponding sC5b-9 CSF levels was detected in 8 of 11 patients (r = 0.72-0.998; p < 0.05). These data demonstrate for the first time that terminal pathway complement activation occurs after head injury and suggest a possible pathophysiological role of complement with regard to posttraumatic BBB dysfunction.

Markers for cell-mediated immune response are elevated in cerebrospinal fluid and serum after severe traumatic brain injury in humans.

The brain is believed to be an immunologically privileged organ, sheltered from the systemic immunological defense by the blood-brain barrier (BBB). However, there is increasing evidence for a marked inflammatory response in the brain after traumatic brain injury (TBI). Markers for cellular immune activation, neopterin, beta2-microglobulin (beta2M), and soluble interleukin-2 receptor (sIL-2R), were measured for up to 3 weeks in cerebrospinal fluid (CSF) and serum of 41 patients with severe TBI in order to elucidate the time course and the origin of the cellular immune response following TBI. Neopterin gradually increased during the first posttraumatic week in both CSF and serum. Concentrations in CSF were generally higher than in serum, suggesting intrathecal release of this marker. beta2M showed similar kinetics but with higher serum than CSF concentrations. Nonetheless, intrathecal release as assessed by the beta2M index could be postulated for most of the patients. The mean levels of sIL-2R in both CSF and serum were elevated during the whole study period, serum concentrations being up to 2 x 10(4) times higher than in CSF. No significant intrathecal production of sIL-2R could be detected. The present data shows that severe TBI leads to a marked cell-mediated immune response within the brain and in the systemic circulation. In the intrathecal compartment the activated cells appear to be predominantly of the macrophage/microglia lineage, while the immune activation in the systemic circulation seems to involve mainly T-lymphocytes.

Reduction by superoxide dismutase of leukocyte-endothelial adherence after liver transplantation.

One hour after orthotopic rat liver transplantation, hepatic microcirculation and adhesion characteristics of leukocytes to the endothelial wall were studied with intravital microscopy. Cold storage for 1 and 8 hours in Euro-Collins solution resulted in reduction of perfused sinusoids to 83% and 48% and a decrease of leukocyte velocity from 417 microns/sec in controls to 311 microns/sec and 269 microns/sec, respectively. Additionally, the number of permanently adherent leukocytes rose from 4% in controls to 33% and 43% after cold storage for 1 and 8 hours. Intravenous injection of the free radical scavenger human recombinant superoxide dismutase (40 mg/kg) during reperfusion resulted in marked improvement of the hepatic microcirculation after both 1 and 8 hours of cold storage (91% and 69% perfused sinusoids; 420 microns/sec and 350 microns/sec leukocyte velocity; p less than 0.05). Furthermore, the percentage of permanently adherent leukocytes decreased to 13% and 28% after 1 and 8 hours of cold ischemia, respectively. These results support the hypothesis that oxygen-derived free radicals contribute to leukocyte adherence and microcirculatory failure after cold liver ischemia and transplantation. Thus, application of oxygen free radical scavengers during liver transplantation procedures might be useful to improve graft function.