PubMed Health⌕ Search

Biomedical subjects

Thomas Kossmann

Publications and source records attributed to Thomas Kossmann.

At least 19 recordsLinked to original sources
PubMed2006

Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration.

Cerebral inflammation and apoptotic cell death are two processes implicated in the progressive tissue damage that occurs following traumatic brain injury (TBI), and strategies to inhibit one or both of these pathways are being investigated as potential therapies for TBI patients. The tetracycline derivative minocycline was therapeutically effective in various models of central nervous system injury and disease, via mechanisms involving suppression of inflammation and apoptosis. We therefore investigated the effect of minocycline in TBI using a closed head injury model. Following TBI, mice were treated with minocycline or vehicle, and the effect on neurological outcome, lesion volume, inflammation and apoptosis was evaluated for up to 7 days. Our results show that while minocycline decreases lesion volume and improves neurological outcome at 1 day post-trauma, this response is not maintained at 4 days. The early beneficial effect is likely not due to anti-apoptotic mechanisms, as the density of apoptotic cells is not affected at either time-point. However, protection by minocycline is associated with a selective anti-inflammatory response, in that microglial activation and interleukin-1beta expression are reduced, while neutrophil infiltration and expression of multiple cytokines are not affected. These findings demonstrate that further studies on minocycline in TBI are necessary in order to consider it as a novel therapy for brain-injured patients.

Animals↗
PubMed2006

Activin a release into cerebrospinal fluid in a subset of patients with severe traumatic brain injury.

Activin A is a member of the transforming growth factor-beta superfamily and has been demonstrated to be elevated during inflammation and to have neuroprotective properties following neural insults. In this study, we examined whether traumatic brain injury (TBI) induced a response in activin A or in the concentrations of its binding protein, follistatin. Thirty-nine patients with severe TBI had daily, matched cerebrospinal fluid (CSF) and serum samples collected post-TBI and these were assayed for activin A and follistatin using specific immunoassays. Concentrations of both molecules were assessed relative to a variety of clinical parameters, such as the Glasgow Coma Score, computer tomography classification of TBI, measurement of injury markers, cell metabolism and membrane breakdown products. In about half of the patients, there was a notable increase in CSF activin A concentrations in the first few days post-TBI. There were only minor perturbations in either serum activin or in either CSF or serum follistatin concentrations. The CSF activin A response was not related to any of the common TBI indices, but was strongly correlated with two common markers of brain damage, neuronal specific enolase and S100-beta. Further, activin A levels were also associated with indices of metabolism, such as lactate and pyruvate, excitotoxicity (glutamate) and membrane lipid breakdown products such as glycerol. In one of the two patients who developed a CSF infection, activin A concentrations in CSF became markedly elevated. Thus, some TBI patients have an early release of activin A into the CSF that may result from activation of inflammatory and/or neuroprotective pathways.

Activins↗
PubMed2006

Cervical spine clearance in unconscious traumatic brain injury patients: dynamic flexion-extension fluoroscopy versus computed tomography with three-dimensional reconstruction.

BACKGROUND: An optimal protocol for clearing the cervical spine in unconscious patients with traumatic brain injury remains controversial. Protocols include plain radiographs and computed tomography (CT), and ligamentous injury may be identified with flexion-extension radiographs. We questioned whether cervical CT with three-dimensional (3D) reconstructions may obviate the need for flexion-extension radiology in the detection of occult ligamentous injury. METHODS: Between July 1999 and November 2001, 276 unconscious traumatic brain injured patients admitted to The Alfred Hospital received cervical spine plain radiographs, CT with 3D reconstructions, and dynamic flexion-extension X-ray studies with fluoroscopy as part of a routine protocol. These patients were identified from a prospective intensive care unit database and all radiology reports were reviewed. RESULTS: Dynamic flexion-extension X-ray studies with fluoroscopy identified no new fractures or instability; there were no instances of true-positive results. Dynamic flexion-extension was true-negative in 260 of 276 (94%) patients, falsely positive in six patients (2.2%) and falsely negative in one (0.4%) patient. In nine patients, dynamic flexion-extension was inadequate. CONCLUSION: Dynamic flexion-extension X-ray studies with fluoroscopy delayed cervical spine clearance and were almost always reported as normal. In a cervical spine clearance protocol for unconscious traumatic brain injury patients, dynamic flexion-extension X-ray studies with fluoroscopy did not identify any patients with cervical fracture or instability not already identified by plain radiographs and fine-cut CT (C0 to T2) with 3D reconstructions.

Algorithms↗
PubMed2006

Current controversies in the management of patients with severe traumatic brain injury.

BACKGROUND: Traumatic brain injury is a major cause of mortality and morbidity, particularly among young men. The efficacy and safety of most of the interventions used in the management of patients with traumatic brain injury remain unproven. Examples include the 'cerebral perfusion pressure-targeted' and 'volume-targeted' management strategies for optimizing cerebrovascular haemodynamics and specific interventions, such as hyperventilation, osmotherapy, cerebrospinal fluid drainage, barbiturates, decompressive craniectomy, therapeutic hypothermia, normobaric hyperoxia and hyperbaric oxygen therapy. METHODS: A review of the literature was performed to examine the evidence base behind each intervention. RESULTS: There is no class I evidence to support the routine use of any of the therapies examined. CONCLUSION: Well-designed, large, randomized controlled trials are needed to determine therapies that are safe and effective from those that are ineffective or harmful.

Barbiturates↗
PubMed2006

Trauma reception and resuscitation.

The hospital reception phase of major trauma management requires a great number of expedient decisions. However, despite widely taught programmes advocating a standardized, algorithmic approach to decision-making, there is an ongoing rate of human errors contributing to adverse outcomes. It is now time for a fundamental change in our approach to trauma resuscitation. Point-of-care computer technology linked to real-time decision-making and trauma team coordination may achieve error reduction through standardized decision-making and a corresponding reduction in preventable mortality and morbidity.

Algorithms↗
PubMed2005

The evolution of an integrated State Trauma System in Victoria, Australia.

The incidence of major trauma and associated fatalities in the State of Victoria, Australia, have declined over 20 years following the successful implementation of strategies to modify environmental and behavioural factors that contribute to motor vehicle injuries. However, several system deficiencies in the management of major trauma patients had remained unresolved. To investigate these shortfalls the State Government of Victoria established a task force in 1997 to review trauma and emergency services. The task force adopted the principle of "the right patient to the right hospital in the shortest time" and in 2000 began to deploy an integrated State Trauma System. Implementation of such a system required the designation of specific hospitals of various levels to care for trauma patients; the concentration of trauma expertise at these centres; integration and coordination between the service providers; development of agreed triage and transfer protocols and improved education, training and research programs. A statewide major trauma database was established to enable system monitoring and facilitate further enhancements. The Victorian experience with the development of an integrated trauma system should aid in the development of similar systems nationally and internationally and is described in this paper.

Ambulances↗
PubMed2005

Cervical spine assessment in the unconscious trauma patient: a major trauma service's experience with passive flexion-extension radiography.

BACKGROUND: There is no consensus on the most appropriate method of cervical spine assessment in unconscious trauma patients. Passive flexion-extension imaging is one option for further investigating unconscious patients whose plain cervical radiographs are normal. This study examines the usefulness of this passive imaging in investigating for occult cervical injury. METHODS: All unconscious patients admitted to The Alfred Trauma Intensive Care Unit over 1 year (January 1-December 31, 1998), who could not be clinically assessed within 48 hours in regard to their cervical spine, were identified. Results of passive flexion-extension radiography were compared with final injury status and clinical outcome as determined by retrospective review of the imaging reports, radiographic films, and case notes. RESULTS: One hundred twenty-three patients with normal three-view plain radiographs proceeded to passive functional investigation. These were false-negative in four of the seven patients with cervical spine injuries at presentation. No patients suffered any adverse neurologic events from their delayed diagnoses or from the flexion-extension procedure. CONCLUSION: Passive flexion-extension imaging has inadequate sensitivity for detecting occult cervical spine injuries. Although no patients suffered adverse neurologic complications, the potential for devastating consequences from missed cervical injury has resulted in the removal of passive flexion-extension imaging from the screening protocol.

Adult↗
PubMed2005

Determinants of quality of life and role-related disability after injury: impact of acute psychological responses.

BACKGROUND: The factors that determine quality of life (QOL) and disability after traumatic injury are poorly understood. This study identified the unique contributions that characteristics about the injury/hospital admission and acute psychological adjustment make in determining 12-month role-related disability and QOL. METHODS: Consecutive admissions (n = 363) to a Level I trauma service were assessed just before discharge and followed up at 12 months. Structural equational modeling was used to examine the relationships between the acute factors and 12-month outcomes. RESULTS: Characteristics of the individual's injuries measured in the acute setting significantly predicted 12-month disability but only indirectly predicted 12-month QOL. An individual's acute psychological response directly predicted both the level of disability and QOL at 12 months. CONCLUSIONS: Both characteristics about an individual's injury and acute psychological responses play important roles in determining later QOL and role-related disability outcomes. Trauma care systems must consider both physical and psychological injury to offer effective and comprehensive healthcare management.

Adult↗
PubMed2005

The trauma registry as a statewide quality improvement tool.

BACKGROUND: Trauma registries have been developed to describe the pattern of trauma and trauma workload, provide data for research, and to demonstrate changes in patient outcomes. Quality improvement using trauma registries at a system-wide level has been difficult to achieve. In Victoria, Australia, a statewide trauma system and trauma registry has been established to monitor and feedback the process of management and outcomes of major trauma patients across all healthcare providers. METHODS: The development and implementation of the Victorian State Trauma Registry (VSTR), including its role as a quality monitoring tool and results from the first 2 years of operation, are provided. RESULTS: More than 80% of major trauma patients are being managed at major trauma services and standardized death rates are comparable with international standards. Quality indicators identify some areas for improvement. CONCLUSION: VSTR data indicate that the statewide trauma system is working well and provides a method for ongoing monitoring and trauma care feedback.

Adolescent↗
PubMed2004

Damage control surgery for spine trauma.

The concept of "damage control" surgery was originally developed for massive abdominal trauma and also successfully applied to the management of lone bone injuries. More recently this has been extended to severely injured patients with spine injuries. This paper provided an overview of how damage control principles can be applied to multitrauma patients with spine injuries, to patients with isolated spine injuries and to spine injuries with and without neurology. The role of neuroimaging in acute spine trauma and controversies in the pharmaceutical approach to spine injuries are discussed. Additional prospective controlled trials are required to delineate the role and timing of damage control surgery in acute spine injury. With improved neuroimaging early spinal damage control surgery will be formally established in the management of spine trauma.

Diagnostic Imaging↗
PubMed2004

The chemokine fractalkine in patients with severe traumatic brain injury and a mouse model of closed head injury.

The potential role of the chemokine Fractalkine (CX3CL1) in the pathophysiology of traumatic brain injury (TBI) was investigated in patients with head trauma and in mice after experimental cortical contusion. In control individuals, soluble (s)Fractalkine was present at low concentrations in cerebrospinal fluid (CSF) (12.6 to 57.3 pg/mL) but at much higher levels in serum (21,288 to 74,548 pg/mL). Elevation of sFractalkine in CSF of TBI patients was observed during the whole study period (means: 29.92 to 535.33 pg/mL), whereas serum levels remained within normal ranges (means: 3,100 to 59,159 pg/mL). Based on these differences, a possible passage of sFractalkine from blood to CSF was supported by the strong correlation between blood-brain barrier dysfunction (according to the CSF-/serum-albumin quotient) and sFractalkine concentrations in CSF (R = 0.706; P < 0.01). In the brain of mice subjected to closed head injury, neither Fractalkine protein nor mRNA were found to be augmented; however, Fractalkine receptor (CX3CR1) mRNA steadily increased peaking at 1 week postinjury (P < 0.05, one-way analysis of variance). This possibly implies the receptor to be the key factor determining the action of constitutively expressed Fractalkine. Altogether, these data suggest that the Fractalkine-CX3CR1 protein system may be involved in the inflammatory response to TBI, particularly for the accumulation of leukocytes in the injured parenchyma.

Adolescent↗
PubMed2004

Complications of intercostal catheter insertion using EMST techniques for chest trauma.

BACKGROUND: The purpose of the present study was to determine the complication rates associated with intercostal catheter insertion (ICI) performed using Early Management of Severe Trauma (EMST) guidelines on trauma patients admitted through The Alfred Trauma Centre. METHODS: The Alfred Trauma Registry identified demographic and clinical data for patients who underwent ICI in the Alfred hospital following admission for trauma. The medical histories were subsequently reviewed for complications resulting from ICI. RESULTS: There were 211 ICI performed on 173 trauma patients at The Alfred Trauma Centre between July 2001 and June 2002. The mean injury severity score was 34. Mean age was 38 (range 15-82 years), with 77% of the patients being men. Chest injury was the result of blunt trauma in 90.2% and penetrating trauma in 9.8%. ICI occurred in the Trauma Centre (84%), operating theatre (6%), intensive care unit (9%) and in the general ward (1%). Eighty per cent of patients had a unilateral ICI. The indications for ICI were pneumothorax (45.7%), haemothorax (15.0%), haemopneumothorax (28.3%) and tension pneumothorax (7.5%). There were no insertional and 11 (5.2%) positional complications. The infection rate was 2.4% comprising two superficial and three deep (empyema thoraces) infections. No statistically significant association was found between infective complications and age, injury severity score (ISS), haemothorax, penetrating trauma, prehospital needle thoracostomy and time to ICI. There was no mortality arising from ICI complications. CONCLUSION: Intercostal catheter insertion for chest trauma performed in accordance with EMST guidelines has a low complication rate. Prehospital prophylactic chest decompression for ventilated patients with chest trauma, using a lateral rather than an anterior approach, may decrease the incidence of untreated tension pneumothorax.

Adolescent↗
PubMed2004

Methicillin-resistant Staphylococcus aureus and beyond: what's new in the world of the golden staph?

Methicillin-resistant Staphylococcus aureus (MRSA) continues to plague our hospitals. With the appearance of isolates that are resistant to vancomycin, now, more than ever, we must direct our efforts to controlling its development and spread. New antimicrobials have become available for treatment, but may only be a short-term answer. Our efforts towards control must be directed towards infection control measures such as improved hand hygiene with user-friendly products, such as alcohol-based hand disinfectants. Intranasal mupirocin may have a place in prevention of surgical site infection, although this role has not yet been clearly defined. Other areas where MRSA control may be effected include prudent controlled use of antibiotics, including surgical prophylaxis.

Humans↗
PubMed2003

Atlanto-occipital dislocation: four case reports of survival in adults and review of the literature.

Traumatic atlanto-occipital dislocation (AOD) is a rare cervical spine injury and in most cases fatal. Consequently, relatively few case reports of adult patients surviving this injury appeared in the literature. We retrospectively report four patients who survived AOD injury and were treated at our institution. A young man fell from height and a woman was injured in a traffic accident. Both patients survived the injury but died later in the hospital. The third patient had a motorcycle accident and survived with incomplete paraplegia. The last patient, a man involved in a working accident, survived without neurological deficit of the upper extremities. Rigid posterior fixation and complete reduction of the dislocation were applied in last two cases using Cervifix together with a cancellous bone grafting. Previously reported cases of patients surviving AOD are reviewed, and clinical features and operative stabilisation procedures are discussed.

Adult↗
PubMed2003

Cytomegalovirus production by infected astrocytes correlates with transforming growth factor-beta release.

Cytomegalovirus (CMV) encephalitis is well documented in immunosuppressed persons, but its pathogenesis has received little investigative attention. The examination of brain tissue from 2 patients with acquired immunodeficiency syndrome who had CMV encephalitis showed colocalization of CMV inclusions and transforming growth factor (TGF)-beta in cells that contained astrocyte-specific glial filaments. To investigate the relationship between CMV and TGF-beta in the brain, an ex vivo murine model of CMV-infected astrocytes was established. Cultures of primary murine (strain FVB/N) astrocytes inoculated with murine (Smith strain) CMV expressed, over time, increasing amounts of infectious CMV in parallel with increasing levels of TGF-beta mRNA and peptide. Astrocyte release of CMV declined in the presence of antibody to TGF-beta and increased substantially after the addition of exogenous TGF-beta. These findings suggest that CMV infection of astrocytes induces the production of TGF-beta, which in turn enhances productive CMV expression.

AIDS-Related Opportunistic Infections↗