Key issues in advanced bleeding care in trauma.

The incidence of hemostatic abnormalities in the early hours after traumatic incident is high and represents an independent predictor of mortality. Key factors in the development of traumatic coagulopathy include the severity of injury, hypothermia, acidosis, hemorrhagic shock, hemodilution, clotting factor consumption, and fibrinolysis. Assessment of bleeding includes evaluation of the mechanism of injury, vital signs, biochemistry, detection of external and internal bleeding sources, injuries found upon secondary investigation, and response to treatment.

Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation.

Background: Neuroprotective strategies for prevention of the neuropathological sequelae of traumatic brain injury (TBI) have largely failed in translation to clinical treatment. Thus, there is a substantial need for further understanding the molecular mechanisms and pathways which lead to secondary neuronal cell death in the injured brain. The intracerebral activation of the complement cascade was shown to mediate inflammation and tissue destruction after TBI.

[Role of gene therapy in trauma and orthopedic surgery].

Modern molecular and genetic technologies enable the modification of a cellular genome through transfer of specific genes. The various procedures alter specific cell functions, which allow the transfected cell to produce any encoded transgene information. The transfected cell then synthesizes proteins that are normally not produced or only in very small amounts.

The role of the complement system in CNS inflammatory diseases.

Complement is an important component of both the innate and adaptive immune response that contributes to host defense in a variety of mechanisms, including inflammation, phagocytosis and cell lysis. Complement proteins are produced by all cell types in the CNS, and the same effector functions that protect the host from pathogens can mediate inflammation and tissue destruction in CNS diseases, leading to neurological deficits or even death. In the last 10 years, the development of complement inhibitors and a variety of animal models for CNS diseases has revealed that targeted inhibition of complement offers significant therapeutic potential.

Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury.

The complement system represents an important mediator of neuroinflammation in traumatic brain injury. We have previously shown that transgenic mice with central nervous system-targeted overexpression of Crry, a potent murine complement inhibitor at the level of C3 convertases, are protected from complement-mediated neuropathological sequelae in brain-injured mice. This knowledge was expanded in the present study to a pharmacological approach by the use of a recombinant Crry molecule (termed Crry-Ig) which was recently made available in a chimeric form fused to the non-complement fixing mouse IgG1 Fc region.

Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young people in industrialized countries. Although various anti-inflammatory and antiapoptotic modalities have shown neuroprotective effects in experimental models of TBI, to date, no specific pharmacological agent aimed at blocking the progression of secondary brain damage has been approved for clinical use. Erythropoietin (Epo) belongs to the cytokine superfamily and has traditionally been viewed as a hematopoiesis-regulating hormone.

[Current concepts of polytrauma management: from ATLS to "damage control"].

In recent years, the implementation of standardized protocols for polytrauma management has led to a significant improvement in trauma care as well as to a decrease in post-traumatic morbidity and mortality. As such, the "Advanced Trauma Life Support" (ATLS) protocol of the American College of Surgeons for the acute management of severely injured patients has been established as a gold standard in most European countries since the 1990s. Continuative concepts to the ATLS program include the "Definitive Surgical Trauma Care" (DSTC) algorithm and the concept of "damage control" surgery for polytraumatized patients with immediate life-threatening injuries.

[Traumatic brain injury: impact on timing and modality of fracture care].

Traumatic brain injury (TBI) represents the major "killing factor" after trauma in young individuals. Those patients who survive the initial injury are highly susceptible to secondary insults to the injured brain which are mainly caused by hypotension and/or hypoxia in the early resuscitative period. Furthermore, a potent inflammatory cascade is initiated within the injured brain which leads to the development of brain edema and delayed neuronal cell death.

[Emergency management of thoracic trauma].

Thoracic injuries are a major cause of mortality during the "golden hour" of trauma. Many patients with chest trauma die after reaching the hospital. Less than 10% of all blunt thoracic injuries require a thoracotomy, and many potentially life-threatening conditions can be relieved by simple procedures, such as chest tube insertion.

IL-18: a key player in neuroinflammation and neurodegeneration?

Interleukin (IL)-18 is a potent inflammatory cytokine of the IL-1 family. It is synthesized as an inactive precursor (pro-IL-18), which is cleaved into its functionally active form by caspase-1. Resident cells of the CNS express IL-18 and caspase-1 constitutively, thus providing a local IL-18-dependent immune response.

Closed head injury--an inflammatory disease?

Closed head injury (CHI) remains the leading cause of death and persisting neurological impairment in young individuals in industrialized nations. Research efforts in the past years have brought evidence that the intracranial inflammatory response in the injured brain contributes to the neuropathological sequelae which are, in large part, responsible for the adverse outcome after head injury. The presence of hypoxia and hypotension in the early resuscitative period of brain-injured patients further aggravates the inflammatory response in the brain due to ischemia/reperfusion-mediated injuries.

Ultrasonography as a reliable diagnostic tool in old quadriceps tendon ruptures: a prospective multicentre study.

Quadriceps tendon rupture is an uncommon injury. In the majority of cases, predispositions as recurrent microtrauma or degenerative changes are present. The diagnosis of acute quadriceps tendon ruptures can usually be made by clinical examination.

[The role of whole body spiral CT in the primary work-up of polytrauma patients--comparison with conventional radiography and abdominal sonography].

Purpose: To evaluate the role of routine "whole body spiral CT"in the primary work-up of polytrauma patients for injuries of the thorax, abdomen and spine, and to compare the results with those of conventional radiography of the chest and spine and abdominal ultrasound.

Materials And Methods: Fifty consecutive polytrauma patients underwent contrast-enhanced single slice spiral CT (5 mm collimation) from the vertex to the floor of the pelvis as part of the primary work-up after emergency room admission. Overlapping high resolution sections and sagittal reformations of the spine were obtained.

Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: a clinical and experimental study in head-injured patients and in a murine model of closed head injury.

Tumor necrosis factor (TNF) and interleukin-(IL)-18 are important mediators of neuroinflammation after closed head injury (CHI). Both mediators have been previously found to be significantly elevated in the intracranial compartment after brain injury, both in patients as well as in experimental model systems. However, the interrelation and regulation of these crucial cytokines within the injured brain has not yet been investigated.

Predictive value of complement activation fragments C3a and sC5b-9 for development of severe disease in patients with acute pancreatitis.

Background: Complement activation has been shown to occur in patients with acute pancreatitis. However, the diagnostic potential of complement activation products in plasma for predicting severe disease remains unclear to date.

Methods: The daily levels of the complement anaphylatoxin C3a and the soluble terminal complement complex sC5b-9 were determined by ELISA in plasma of patients with mild (n = 16) or severe (n = 14) acute pancreatitis during the first week after onset of symptoms, and in healthy control subjects (n = 14).

Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice.

The role of intracerebral complement activation after traumatic brain injury remains unclear. In this study, the authors demonstrate that transgenic mice with astrocyte-targeted expression of the soluble complement inhibitor sCrry have a significantly reduced neurologic impairment and improved blood-brain barrier function after closed head injury compared with wild-type C57BL/6 littermates. This work further implicates the complement system as a participant in secondary progression of brain damage after head trauma and provides a strong rationale for future studies of posttraumatic pharmacologic complement inhibition.

Incidence and management of biliary pancreatitis in cholecystectomized patients. Results of a 7-year study.

Data are lacking concerning the frequency of biliary acute pancreatitis in the postcholecystectomy patient. The aim of this study was to identify patients at risk for biliary pancreatitis after cholecystectomy and to describe the therapeutic management of these patients, based on an analysis of 278 unselected patients with acute pancreatitis during a 7-year period. A biliary etiology was presumed in the presence of laboratory findings of cholestasis that could not be explained by another disease, together with the absence of any other known etiology of acute pancreatitis.

Cefepime tissue penetration in experimental acute pancreatitis.

Introduction: Antibiotic treatment represents a cornerstone in the management of severe acute pancreatitis. However, different antibiotic substances are currently used. In this study, we analyzed penetration of cefepime into pancreatic tissue in two models of acute pancreatitis.

Inflammatory response in acute traumatic brain injury: a double-edged sword.

Inflammation is an important part of the pathophysiology of traumatic brain injury. Although the central nervous system differs from the other organs because of the almost complete isolation from the blood stream mediated by the blood-brain barrier, the main steps characterizing the immune activation within the brain follow a scenario similar to that in other organs. The key players in these processes are the numerous immune mediators released within minutes of the primary injury.

Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury.

Proinflammatory cytokines are important mediators of neuroinflammation after traumatic brain injury. The role of interleukin (IL)-18, a new member of the IL-1 family, in brain trauma has not been reported to date. The authors investigated the posttraumatic release of IL-18 in murine brains following experimental closed head injury (CHI) and in CSF of CHI patients.

1alpha,25-dihydroxyvitamin D3 shows strong and additive immunomodulatory effects with cyclosporine A in rat renal allotransplants.

Background: Vitamin D3 and its metabolites have long been found to exert immunosuppressive effects both in vivo and in vitro. The present study investigated the effect of 1alpha,25-dihydroxycholecalciferol (1,25DHC) on vascularized renal allografts in rats.

Methods: Three days prior to transplantation, two groups of animals were subjected to 1,25DHC (1 microg/kg/day IP) and a low calcium diet, which was continued until the end of the experiments.

1 alpha,25-Dihydroxycholecalciferol reduces rejection and improves survival in rat liver allografts.

Vitamin D(3) affects the immuno response and improves experimental autoimmune diseases. We investigated the effect of 1,25-dihydroxycholecalciferol (1,25[OH](2)D(3)) Rocaltrol as a single immunosuppressive agent and in combination with low-dose cyclosporin A (CsA) in vascularized liver allografts in rats in a high-responder strain combination (ACI-->Lewis). Recipients were placed on a low-calcium diet 7 days before transplantation and were treated with 0.

Role of cerebral inflammation after traumatic brain injury: a revisited concept.

Neuroinflammation occuring after traumatic brain injury (TBI) is a complex phenomenon comprising distinct cellular and molecular events involving the injured as well as the healthy cerebral tissue. Although immunoactivation only represents a one of the many cascades initiated in the pathophysiology of TBI, the exact function of each mediator, activated cell types or pathophysiological mechanism, needs to be further elucidated. It is widely accepted that inflammatory events display dual and opposing roles promoting, on the one hand, the repair of the injured tissue and, on the other hand, causing additional brain damage mediated by the numerous neurotoxic substances released.

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.

Regulation of chemokines and chemokine receptors after experimental closed head injury.

The expression of the chemokines macrophage inflammatory protein (MIP)-2 and MIP-1alpha and of their receptors CXCR2 and CCR5 was assessed in wild type (WT) and TNF/lymphotoxin-alpha knockout (TNF/LT-alpha-/-) mice subjected to closed head injury (CHI). At 4 h after trauma intracerebral MIP-2 and MIP-1alpha levels were increased in both groups with MIP-2 concentrations being significantly higher in WT than in TNF/LT-alpha-/- animals (p < 0.05).