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Edmund Neugebauer

Publications and source records attributed to Edmund Neugebauer.

16 recordsLinked to original sources
PubMed2007

Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients.

BACKGROUND: There is increasing evidence for acute traumatic coagulopathy occurring prior to emergency room (ER) admission but detailed information is lacking. PATIENTS AND METHODS: A retrospective analysis using the German Trauma Registry database including 17,200 multiple injured patients was conducted to determine (a) to what extent clinically relevant coagulopathy has already been established upon ER admission, and whether its presence was associated (b) with the amount of intravenous fluids (i.v.) administered pre-clinically, (c) with the magnitude of injury, and (d) with impaired outcome and mortality. Eight thousand seven hundred and twenty-four patients with complete data sets were screened. RESULTS: Coagulopathy upon ER admission as defined by prothrombin time test (Quick's value) <70% and/or platelets <100,000 microl(-1), was present in 34.2% of all patients. There was an increasing incidence for coagulopathy with increasing amounts of i.v. fluids administered pre-clinically. Coagulopathy was observed in >40% of patients with >2000 ml, in >50% with >3000 ml, and in >70% with >4000 ml administered. Ten percentage of patients presented with clotting disorders although pre-clinical resuscitation was limited to 500 ml of i.v. fluids maximum. The mean ISS score in the coagulopathy group was 30 (S.D. 15) versus 21 (S.D. 12) (p<0.001). Twenty-nine percentage of patients with coagulopathy developed multi organ failure (p<0.001). Early in-hospital mortality (<24h) was 13% in patients with coagulopathy (p<0.001) and overall in-hospital mortality totalled 28% (p<0.001). CONCLUSION: There is a high frequency of established coagulopathy in multiple injury upon ER admission. The presence of early traumatic coagulopathy was associated with the amount of intravenous fluids administered pre-clinically, magnitude of injury, and impaired outcome.

Adult↗
PubMed2006

Acute, transient hemorrhagic hypotension does not aggravate structural damage or neurologic motor deficits but delays the long-term cognitive recovery following mild to moderate traumatic brain injury.

OBJECTIVES: Posttraumatic hypotension is believed to increase morbidity and mortality in traumatically brain-injured patients. Using a clinically relevant model of combined traumatic brain injury with superimposed hemorrhagic hypotension in rats, the present study evaluated whether a reduction in mean arterial blood pressure aggravates regional brain edema formation, regional cell death, and neurologic motor/cognitive deficits associated with traumatic brain injury. DESIGN: Experimental prospective, randomized study in rodents. SETTING: Experimental laboratory at a university hospital. SUBJECTS: One hundred nineteen male Sprague-Dawley rats weighing 350-385 g. INTERVENTIONS: Experimental traumatic brain injury of mild to moderate severity was induced using the lateral fluid percussion brain injury model in anesthetized rats (n = 89). Following traumatic brain injury, in surviving animals one group of animals was subjected to pressure-controlled hemorrhagic hypotension, maintaining the mean arterial blood pressure at 50-60 mm Hg for 30 mins (n = 47). The animals were subsequently either resuscitated with lactated Ringer's solution (three times shed blood volume, n = 18) or left uncompensated (n = 29). Other groups of animals included those with isolated traumatic brain injury (n = 34), those with isolated hemorrhagic hypotension (n = 8), and sham-injured control animals receiving anesthesia and surgery alone (n = 22). MEASUREMENTS AND MAIN RESULTS: The withdrawal of 6-7 mL of arterial blood significantly reduced mean arterial blood pressure by 50% without decreasing arterial oxygen saturation or Pao2. Brain injury induced significant cerebral edema (p < .001) in vulnerable brain regions and cortical tissue loss (p < .01) compared with sham-injured animals. Neither regional brain edema formation at 24 hrs postinjury nor the extent of cortical tissue loss assessed at 7 days postinjury was significantly aggravated by superimposed hemorrhagic hypotension. Brain injury-induced neurologic deficits persisted up to 20 wks after injury and were also not aggravated by the hemorrhagic hypotension. Cognitive dysfunction persisted for up to 16 wks postinjury. The superimposition of hemorrhagic hypotension significantly delayed the time course of cognitive recovery. CONCLUSIONS: A single, acute hypotensive event lasting 30 mins did not aggravate the short- and long-term structural and motor deficits but delayed the speed of recovery of cognitive function associated with experimental traumatic brain injury.

Animals↗
PubMed2006

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. Priority in treating the bleeding trauma patient should be given to prevention of further bleeding, hypothermia, acidosis, coagulopathy, and maintenance of tissue oxygenation, achieved by careful physical handling, damage control surgery, analgesia, maintenance of normothermia, correction of coagulopathy, control of blood pH, and serum calcium. Priority during initial treatment is to restore tissue perfusion and achieve hemostasis in vital functions; other nonvital procedures may generally be delayed. This state-of-the-art review aims to address key issues in acute control of bleeding in the trauma patient.

Hemorrhage↗
PubMed2006

Neural differentiation of embryonic stem cells is induced by signalling from non-neural niche cells.

BACKGROUND/AIMS: Embryonic stem cell (ESC) transplantation offers new therapeutic strategies for neurodegenerative diseases and injury. However, the mechanisms underlying integration and differentiation of engrafted ESCs are poorly understood. This study elucidates the influence of exogenous signals on ESC differentiation using in vitro modelling of non-stem/stem cell interactions. METHODS: Murine ESCs were co-cultured with endothelial cells and astrocytes or conditioned medium obtained from endothelial or astrocyte cultures. After 7 days of co-culture isolated RNA was analysed using RT-PCR for the expression of pluripotency marker oct-4, neural progenitor marker nestin, and neurofilament (NFL), an early marker of neuronal lineage commitment. The presence of the glial cell surface marker A2B5 was determined in ESCs by flow cytometry. RESULTS: Neuronal differentiation was inhibited in ESCs when grown in close vicinity to cerebral endothelial or glial cells. Under these conditions, ESC differentiation was predominantly directed towards a glial fate. However, treatment of ESCs with endothelial cell- or astrocyte-conditioned medium promoted neuronal as well as glial differentiation. CONCLUSION: Our results indicate that ESC fate is determined by endothelial and glial cells that comprise the environmental niche of these stem cells in vivo. The direction of differentiation processes appears to be dependent on humoral factors secreted by adjacent cell lines.

Animals↗
PubMed2005

Newly born granule cells in the dentate gyrus rapidly extend axons into the hippocampal CA3 region following experimental brain injury.

We investigated whether new neurons generated in the adult rat brain following lateral fluid percussion traumatic brain injury (TBI) are capable of projecting axons along the mossy fiber pathway to the CA3 region of the hippocampus. Dividing cells were labeled by intraperitoneal injection of bromodeoxyuridine (BrdU) on the day of surgery/injury, and neurons that extended axons to the CA3 region were retrogradely labeled by fluorescent tracers (FluoSpheres), stereotactically injected into the CA3 region of both the ipsi- and contralateral hippocampus at 1 or 12 days following TBI (n = 12) or sham injury (n = 12) in anaesthetized rats. Animals (n = 6 injured and n = 6 sham-injured controls per time point) were sacrificed at either 3 or 14 days post-injury. Another group of animals (n = 3) was subjected to experimental TBI and BrdU administration and sacrificed 3 days after TBI to be processed for BrdU and immunohistochemistry for polysialylated neural cell adhesion molecule (PSA-NCAM), a growth-related protein normally observed during CNS development. A fivefold bilateral increase in the number of mitotically active (BrdU+) cells was noted within the dentate gyrus when compared to uninjured controls as early as 3 days following TBI. A subgroup of dividing cells was also immunoreactive for PSA-NCAM at 3 days following TBI. By 2 weeks post-injury the number of BrdU+ cells within the dentate gyrus was increased twofold compared to the uninjured counterparts and a proportion of these newly generated cells showed cytoplasmic staining for the fluorescent tracer. These findings document rapid neurogenesis following TBI and show, for the first time, that newly generated granule neurons are capable of extending projections along the hippocampal mossy fiber pathway in the acute post-traumatic period.

Animals↗
PubMed2005

Multimodal early onset stimulation combined with enriched environment is associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction after traumatic brain injury in rats.

This study was designed to determine whether exposure to multimodal early onset stimulation (MEOS) combined with environmental enrichment (EE) after traumatic brain injury (TBI) would improve neurological recovery and to elucidate its morphological correlates. Male Sprague-Dawley rats were subjected to lateral fluid percussion (LFP) brain injury or to sham operation. After LFP, one-third of the animals (injured and sham) were placed under conditions of standard housing (SH), one-third were kept in EE only, and one-third received EE + MEOS. Assessment of neuromotor function 24 h post-injury using a standardized composite neuroscore test revealed an identical pattern of neurological impairment in all animals subjected to LFP. Neuromotor dysfunction in SH animals remained on a similar level throughout the experiment, while improvements were noted in both other groups 7 days post-injury (dpi). On 15 dpi, reversal of neuromotor dysfunction was significantly better in EE + MEOS animals vs. SH- and EE-only groups. In parallel, the comparison of lesion volume in EE + MEOS- vs. EE-only vs. SH rats revealed that animals exposed to EE + MEOS had consistently the lowest values (mm3, mean +/- SD; n = 6 rats in each group) as measured in serial brain sections immunostained for neuron-specific enolase (5.2 +/- 3.4 < or = 5.5 +/- 4.1 < 9.5 +/- 1.9), caspase 3-active/C3A (5.9 +/- 4.0 < or = 6.4 +/- 3.9 < 10.3 +/- 1.8) and glial fibrillary acidic protein (6.0 +/- 3.4 < or = 6.5 +/- 4.3 < 10.7 +/- 1.2). This first report on the effect of EE + MEOS treatment strongly indicates that the combined exposure reduces CNS scar formation and reverses neuromotor deficits after TBI in rats.

Animals↗
PubMed2004

The capacity of alpha2-macroglobulin to inhibit an exogenous protease is significantly increased in critically ill and septic patients.

The image of alpha2-macroglobulin is based on a paradigm evolved in the 1970s. During this decade alpha2-macroglobulin was shown to irreversibly entrap and thereby inhibit a maximum of two proteases. Additional binding of nonproteolytic proteins, i.e., inflammatory mediators and growth factors, is dependent on the conformational status of alpha2-macroglobulin. It was our aim to clarify whether the interaction of nonproteolytic proteins with alpha2-macroglobulin during inflammatory conditions might also modulate the capacity of alpha2-macroglobulin to inhibit proteases. To explore this possibility, bromelain, an exogenous protease, was titrated against plasma of critically ill or septic patients, whose pathophysiological conditions are defined by a massive release of inflammatory mediators. The stoichiometry of bromelain inhibition by alpha2-macroglobulin was quantified by caseolytic activity assays. The maximal alpha2-macroglobulin/bromelain inhibition ratios were significantly increased (1:6 and 1:8 in the two patient groups, P < 0.01) as compared with control groups (1:2 with purified alpha2-macroglobulin and 1:4 in healthy volunteers). The increase of alpha2-macroglobulin inhibition capacity in patients was paralleled by the appearance of a large signal on Western blots, suggesting the formation of additional complexes. Our results demonstrate alpha2-macroglobulin to have more flexibility than had been thought, and it may thereby contribute to a shift in a 30-year-old paradigm.

Adult↗
PubMed2003

[The practice of evidence-based medicine in surgery--evidence and experience].

INTRODUCTION: The important role of technical expertise, experience and intuition in the operative specialties may hamper both clinical research and evidence-based medicine (EBM). We assessed whether the results of EBM practice projects actually varied between surgery and medicine. METHODS: EBM practice projects were identified through a search in Medline. We examined the proportion of questions, for which evidence was found and which led to a change in clinical management. At the same time, the proportion of randomised controlled trials (RCTs) in surgical (95) and general internal medicine (84) journals was compared. RESULTS: Of the 13 EBM practice projects identified, only two dealt with surgical patients. While the proportion of answerable questions was similarly high in all projects (61% to 96%), clinical impact was lower in surgical (9% and 18%) than in medical projects (20% to 48%). Compared to medical journals, surgical journals contained fewer RCTs (3.6% vs. 2.5%; p = 0.168). CONCLUSION: The clinical impact of EBM seems to be lower in the operative specialties. This is probably due to the slightly poorer quality of surgical studies or to the difficulties of applying research results in one's own practice.

Evidence-Based Medicine↗
PubMed2002

Revision of the multiple organ failure score.

BACKGROUND AND AIM: The multiple organ failure (MOF) score published by Goris et al. in 1985 was one of the first attempts to quantify severity of organ dysfunction and failure based on expert opinion in surgical intensive care unit patients. Fifteen years later a reassessment of this score is mandatory. PATIENTS AND METHODS: Daily MOF scores were documented in patients admitted to the surgical ICUs in Nijmegen (NL) and Cologne (D). Patients with an ICU stay < or = 3 days were excluded. Organ dysfunction (1 point) and organ failure (2 points) were recorded for the following organ systems: lung, heart, kidney, liver, blood, gastrointestinal tract (GI), and central nervous system (CNS). Maximum scores were computed, and logistic regression analysis was used to optimize point weights for each organ system. Predictive power was analyzed using receiver operating characteristic (ROC) curves. RESULTS: In all, 147 patients, mean age 56 years, were included with a total of 2,354 observation days. Hospital mortality was 30.6%. GI failure was present on only 3.3% of days, without impact on mortality. Valid evaluation of CNS was impossible in most cases due to sedation and ventilation. Reweighting of the score items revealed only marginal improvements in prediction. Mortality consistently increased with increase in number of failed organs. This phenomenon was even more pronounced in older patients, e.g., 55% mortality (age > or = 60) versus 0% (age < 60) with two failing organs. CONCLUSION: Due to problems in definition and assessment (reliability) CNS and GI should not be considered in future assessments of the MOF score. The original point weights in the remaining five organ systems provide a valid and reliable risk stratification, at least in surgical ICU patients.

Adult↗
PubMed2002

Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury.

OBJECTIVE: Using the neural stem cell (NSC) clone C17.2, we evaluated the ability of transplanted murine NSCs to attenuate cognitive and neurological motor deficits after traumatic brain injury. METHODS: Nonimmunosuppressed C57BL/6 mice (n = 65) were anesthetized and subjected to lateral controlled cortical impact brain injury (n = 52) or surgery without injury (sham operation group, n = 13). At 3 days postinjury, all brain-injured animals were reanesthetized and randomized to receive stereotactic injection of NSCs or control cells (human embryonic kidney cells) into the cortex-hippocampus interface in either the ipsilateral or the contralateral hemisphere. One group of animals (n = 7) was killed at either 1 or 3 weeks postinjury to assess NSC survival in the acute posttraumatic period. Motor function was evaluated at weekly intervals for 12 weeks in the remaining animals, and cognitive (i.e., learning) deficits were assessed at 3 and 12 weeks after transplantation. RESULTS: Brain-injured animals that received either ipsilateral or contralateral NSC transplants showed significantly improved motor function in selected tests as compared with human embryonic kidney cell-transplanted animals during the 12-week observation period. Cognitive dysfunction was unaffected by transplantation at either 3 or 12 weeks postinjury. Histological analyses showed that NSCs survive for as long as 13 weeks after transplantation and were detected in the hippocampus and/or cortical areas adjacent to the injury cavity. At 13 weeks, the NSCs transplanted ipsilateral to the impact site expressed neuronal (NeuN) or astrocytic (glial fibrillary acidic protein) markers but not markers of oligodendrocytes (2'3'cyclic nucleotide 3'-phosphodiesterase), whereas the contralaterally transplanted NSCs expressed neuronal but not glial markers (double-labeled immunofluorescence and confocal microscopy). CONCLUSION: These data suggest that transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after traumatic brain injury.

Animals↗
PubMed2002

Sepsis research in the next millennium: concentrate on the software rather than the hardware.

Today the basic principles of septic conditions are understood. Nevertheless, sepsis research has reached a critical point. To integrate our knowledge towards a consistent theory of the disease process and to derive effective therapies, new perspectives for future research that fit the complexity of the problem have to be found. We conducted a review of the literature concerning systemic inflammatory response syndrome (SIRS) and sepsis with particular reference to liver pathophysiology. And compared our findings with characteristic features of complex systems. The complexity of sepsis is broadly recognized. A review of the different aspects of liver inflammation during SIRS and sepsis, i.e. endotoxin challenge, cytokine induced dysfunction, the mechanisms of leukocyte transmigration, and hormonal and neuroendocrine regulatory mechanisms is given. Key aspects of complex systems, including parallelism, locality, emergence, and cross-scale interactions are introduced. We conclude that sepsis research needs new perspectives that allow us to handle the complex interactions occurring during the disease process. We propose to focus research on the interactions between the constituents of the system rather than only describing isolated aspects of the disease process. We also conclude that the ideas and techniques of non-linear systems theory are suitable tools for the analysis of complex and dynamic diseases like SIRS and sepsis.

Clinical Trials as Topic↗
PubMed1999

New perspectives in neurotrauma research.

Traumatic brain and spinal cord injuries are severe burdens for the patients, their relatives, the health care providers and society as a whole. Recent data demonstrate the magnitude of the problem: It is mostly a disease of the young gen-eration (age 20-45 years) with mortality rates for severe traumatic brain injury (TBI) between 40-50%. In approximately 60% of cases, multiple trauma is accompanied by head injury. The outcome of TBI is determined not only by the extent and severity of the primary insult, but also by the degree of secondary brain damage. In the subgroup of severe TBI (GCS</=8) only 25%t of patients showed a complete recovery or had minor neurological deficits; 15% resulted in a lifelong disability or even in a permanent vegetative state. Economically, the impact of TBI is enormous - estimates of the costs of TBI in the U.S. range from 4-15 billion dollars per year. Valid data for Germany are not yet available.

Journal Article↗
PubMed1999

Quality of Life after traumatic brain injury: A systematic review of the literature.

In modern industrial countries traumatic brain injury (TBI) is a common sequel after different kinds of accidents especially amongst young male adults. Apart from medical and economic consequences Quality of Life (QoL) after TBI becomes increasingly important in outcome assessment. Besides the classical domains of QoL (physical, psychological, social) cognitive impairments are playing an important role especially for TBI patients. In 1991 the Meran conference set important standards and formulated basic guidelines for defining and measuring QoL in surgery, but a special index for TBI patients has not yet been developed. Instead, QoL research concentrates on physical, medical, psychological and social problems only. Based on the existing QoL concept extended by the cognitive aspect it was the aim of this review to give an overview about the recent QoL research in TBI patients since 1991. Sixteen studies in TBI patients mentioning at least 2 domains of QoL (physical, psychological, social, cognitive) were published since 1991. Five of them considered all 4 domains of QoL. All studies except of one dealt with psychological and social problems. Only half of the studies considered cognitive impairments. Four studies tried to define QoL, but none of them included the cognitive component. There was no consensus regarding the definition and the choice of measurement instrument for QoL after TBI. This review of 16 studies considering outcome and QoL after TBI confirms that a homogenous and clinically relevant QoL concept for this group of patients is still missing. Further research in TBI patients should include all 4 domains of QoL.

Journal Article↗
PubMedDate not supplied

[Guideline: "Treatment of acute perioperative and posttraumatic pain". Updating from the S2- to the S3-level: a preliminary report].

The German guidelines for the treatment of acute perioperative and posttraumatic pain from 1999 have been revised during the last three years and will be published at the end of 2006 as a guideline on S3-level. 20 medical societies evaluate with the instruments of the centre of evidence based medicine of Oxford (CEBM) the available randomised controlled trials, systematic reviews and existing guidelines and consent in final Delphi rounds the detailed recommendations (grades A - C). Comprehensive information of the patients (pain level, therapeutic possibilities), measurement and documentation of pain, interdisciplinary management of therapy and complete consideration of all operative, pain therapeutic, medicinal, psychologic, physiotherapeutical and physical procedures are central aims of the actual guideline.

Acute Disease↗