Biomedical subjects
Publications and source records attributed to E Neugebauer.
Explore the source record for details and available documents.
We determined concentrations of selected trace elements in livers, kidneys and blood samples from common eiders (Somateria mollissima borealis) from the eastern Canadian arctic during 1997 and 1998. Concentrations of total mercury and organic mercury were generally low in the livers of these birds (less than 6 and 4 microg g(-1) dry wt, respectively). Selenium ranged between 11-47 microg g(-1) in livers. Renal cadmium concentrations were among the highest ever published for this species (range: 47-281 microg g(-1)). The regressions of log-transformed concentrations of these trace elements in blood samples on those in liver or kidney were significant (all P-values < 0.05) and positive. However, except for organic mercury (R2 = 0.83), the co-efficients of determination were low to moderate (range of R2: 0.26-0.52), suggesting poor to moderate predictive capability. Furthermore, the relationships between total mercury in blood and liver changed between 1997 and 1998, suggesting that it would not be possible to predict consistently, concentrations of mercury in blood from those in liver based on samples taken in one year. Blood samples can be used to determine concentrations of these trace elements in common eiders (and probably other sea duck species as well). The use of blood samples is especially warranted when it is undesirable to kill the animal such as when working with rare or endangered sea duck species or when the objective is to relate trace element exposure to annual survival rates. However, the predictive equations developed here should not be used to predict expected concentrations in one type of tissue from those in the other.
The mechanisms underlying secondary cell death after traumatic brain injury (TBI) are poorly understood. Animal models of TBI recapitulate many clinical and pathologic aspects of human head injury, and the development of genetically engineered animals has offered the opportunity to investigate the specific molecular and cellular mechanisms associated with cell dysfunction and death after TBI, allowing for the evaluation of specific cause-effect relations and mechanistic hypotheses. This article represents a compendium of the current literature using genetically engineered mice in studies designed to better understand the posttraumatic inflammatory response, the mechanisms underlying DNA damage, repair, and cell death, and the link between TBI and neurodegenerative diseases.
BACKGROUND: Treatment with interferon-gamma (IFN-gamma), a key mediator for adequate forward-regulatory monocyte immune capability, has been advocated to overcome posttraumatic mononuclear leukocyte paralysis. Conversely, IFN-gamma also is a potent proinflammatory mediator contributing to capillary leakage in sepsis-driven organ failure. The objective of this investigation was to further define the potential of IFN-gamma as a modifier of monocyte activity before and after injury. METHODS: Whole blood samples from 19 patients (7 female and 12 male patients; age, 68 +/- 5 years) before and after cardiac surgery with extracorporeal circulation were incubated under continuous rotation with lipopolysaccharide for 12 hours in the presence or absence of human recombinant IFN-gamma. Pro- and anti-inflammatory cytokines were determined in the plasma. RESULTS: Lipopolysaccharide-induced release of tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-1Ra, and prostaglandin E2 was clearly augmented with IFN-gamma most strikingly postoperatively (p < 0.05). There was no effect on IL-1beta, neopterin, and soluble tumor necrosis factor-R release. CONCLUSION: Thus there is a wide spectrum of IFN-gamma activity on monocyte activation including anti-inflammatory properties. Since cellular preactivation facilitates monocyte reactivity toward IFN-gamma, we conclude that exogenous administration should be effective but must be carried out with great caution in patients with profound inflammation.
This prospective, multi-center, observational study of 2069 multiple trauma patients evaluated the prognostic significance of the posttrauma base deficit (BD) on hospital and intensive care unit (ICU) admission to hemodynamic changes, volume and transfusion requirements, lactate and coagulation, as well as mortality. Furthermore, the importance of the BD development throughout a patient's course of critical illness from the time of injury to ICU admission is analyzed as a prognostic factor for fatal outcome. The data were obtained by the trauma registry of the 'Deutsche Gesellschaft für Unfallchirurgie.' The patients were subdivided into five categories of increasing BD values on hospital and ICU admission: Category I, BD < or = -2; Category II, -2 < BD < or = 2; Category III, 2 < BD < or = 6; Category IV, 6 < BD < or = 10; and Category V, BD > 10. A statistical analysis was performed by means of the ANOVA and chi-square tests. In 1264 (61.1%) of 2069 multiple trauma patients (age 39 +/- 19 years, 70.0% males, injury severity score 22 +/- 13, 18.6% mortality), the BD was documented on hospital and in 1536 (74.2%) patients on ICU admission. At both points in time, an increase in the BD category was associated with a significant decrease in systolic blood pressure and prothrombin time as well as increases in heart rate, lactate level and mortality (P < 0.0001). Also transfusion requirements (Category I: 4.5 +/- 7.7 and Category V: 13.7 +/- 13.0 packed red blood cells) increased significantly on hospital admission (P < 0.0001) with a worsening in the BD category. Mortality increased significantly (P < 0.0001) with a worsening of BD from hospital to ICU admission (from a mortality of 13% in patients with a hospital and an ICU admission BD of <6 to 45% in patients with a hospital and an ICU admission BD of >6). These data show that the base deficit is an early available important indicator to identify trauma patients with hemodynamic instability, high transfusion requirements, metabolic and coagulatory decompensation, as well as a high probability of death. The base deficit development may help to guide an early and aggressive therapy for the trauma/hemorrhage induced tissue hypoxia.
The process of care of a severely injured patient from the site of the accident up to rehabilitation is complex and the result may be influenced by many factors. The outcome of the patient is determined by the primary injury caused by the accident but also by the secondary injury which is influenced by the quality of the diagnostic and therapeutic procedures. Different studies observed a negative correlation between the duration of diagnostic procedures in the initial phase in the emergency room and the outcome of the patient. It could be shown that a standardized documentation of emergency room procedures and the discussion of the resulting data in quality circles contributed to an improved survival of patients. Beside these internal quality circles the trauma registry of the German Trauma Society provides the possibility of external comparison.
PURPOSE: Cyclosporin A (CsA) is widely used in clinical situations to attenuate graft rejection following organ and central nervous system transplantation. Previous studies demonstrated that CsA administration is neuroprotective in models of traumatic brain injury (TBI). However, no studies, to date, have evaluated the influence of post-injury CsA administration on behavioral recovery after TBI. METHODS: Rats (n = 33) were anesthetized and subjected to severe, lateral fluid percussion brain injury. Fifteen minutes thereafter, animals were randomized to receive the first of 28 daily injections of either CsA (10 mg/kg, ip) or saline. Sham-operated animals (n = 14) were anesthetized and surgically prepared without injury and treated daily either with CsA or saline. Motor and sensorimotor functions were assessed at one day before and two days after injury, and weekly thereafter up to 4 wks post-injury. Cognition was assessed at 1 and 4 wks post-injury using a Morris Water Maze test. RESULTS: Injured animals showed significant impairments in motor, sensorimotor and cognitive function over the 4-week post-injury period. Injured animals treated with CsA showed a significant improvement in motor function assessed using a composite neuroscore (at day 28) and in sensorimotor function assessed using a sticky paper test (at days 2, 14, and 28) (p < 0.05, when compared to vehicle treated, injured animals). No beneficial effects on cognitive function were observed following CSA administration. CONCLUSION: These data suggest that daily post-injury treatment with CsA improves certain aspects of motor and sensorimotor function following experimental TBI.
We report here the isolation of human zinc finger 2 (HZF2), a putative zinc-finger transcription factor, by motif-directed differential display of mRNA extracted from histamine-stimulated human vein endothelial cells. The expression of HZF2 mRNA in venous endothelial cells was verified by Northern blot analysis, which also revealed an enrichment of HZF2 mRNA in lymphocytes and monocytes. Histamine induced a time- and concentration-dependent upregulation of HZF2 level with a 6-fold peak increase of mRNA at 30 min. HZF2 upregulation was abolished by different NOS isozyme inhibitors. Guanylate cyclase inhibition resulted in a significant decrease of HZF2 expression. These observations indicate HZF2 as a potentially interesting new target for studies concerning rapid NO-mediated gene regulation.
Explore the source record for details and available documents.
Here we report the isolation of a cDNA encoding the complete human rab18 protein from histamine-stimulated endothelial cells using differential display. The amino acid sequence showed 98% homology with the previously isolated mouse rab18 protein, which is implicated in apical/basolateral endocytosis. Northern blot analysis revealed two transcripts (2.5 kb and 1 kb) ubiquitously expressed in all examined organs, as well as in human umbilical vein endothelial and aortic cells. In blood cells rab18 transcripts were hardly detectable. The histamine-induced time-dependent increase of rab18 mRNA expression in human umbilical vein endothelial cells and peripheral blood mononuclear cells indicates for the first time a link between receptor-mediated signal transduction and the regulation of rab gene expression. This finding might also imply a role for rab proteins in inflammation.
Explore the source record for details and available documents.
INTRODUCTION: Sufficient pain treatment is part of surgical therapy. One popular method of pain control is patient-controlled analgesia (PCA), which allows the patients to apply small doses of analgesics intravenously via a pump. Patient involvement in PCA requires an exact assessment of the patient's expectations as to the treatment of pain. METHODS: In a prospective study the patient's expectations of pain therapy were observed with respect to their disease and the actual intensity of pain during activities measured with a visual analogue scale (VAS). Fifty-three patients were involved, using a pain questionnaire. Healthy nursing staff (n = 44) served as a control group. RESULTS: Patients with benign (n = 29) or malignant (n = 24) disease showed no significant difference in the VAS scores accepted from patients as aim of successful pain therapy (25 points in the conservatively treated group and 27 points in the group of the operatively treated patients with malignant disease, 21 points in the operatively treated group with benign disease, and 18 points in the group suffering from chronic pain of benign causes). The aims for pain therapy showed no correlation with the actually felt pain intensity during movement. The control group of healthy nursing staff felt less actual pain during movement, but their expectations for sufficient pain treatment were not significantly different from the study patients (VAS 25.4 points).
Isolated severe head trauma (SHT) or SHT in combination with multiple injuries are important factors for the prognosis of morbidity and mortality in patients suffering from the consequences of accidents. The prognosis mainly depends on the presence of primary mechanic brain injury and the development of secondary brain damage. Causes for the development of secondary brain damage are the intracranial space demand after traumatic injury and edema formation which may result in iscemia, as well as inflammatory processes. Both isolated SHT and polytrauma with or without brain damage may result in a systemic inflammatory response syndrome (SIRS) due to the synthesis of cytokines and other inflammatory mediators which may cause a single or multiple organ failure (MOF). Often the organism is able to survive isolated traumatic injuries and functional disturbances, but in combination or cumulation they may be lethal. The hypermetabolism after SHT is often regarded as an interaction between the central nervous system and the whole organism by the activation of the neuroendocrine axis. In contrast to the consequences of SHT for the whole organism, multiple injuries after polytrauma may affect brain functions, such as the shock dependent disturbance of the brain perfusion accompanied by brain hypoxia which may lead to an aggravated prognosis. Moreover, coagulation, metabolism and fracture healing are influenced by the onset of SIRS as well. Our knowledge about the bidirectional inflammatory interaction between brain and whole organism is still limited. In this context, the effects of secondary surgical interventions which may additionally, stress a traumatized body have to be considered and are the subject for actual clinical discussions and experimental studies. This article tries to summarize some important aspects on this topic.
BACKGROUND: The expansion of the laparoscopic techniques to the critically ill patient is currently under debate. In order to evaluate the potential risks of performing laparoscopy in a body with signs of sepsis, the effects of the pneumoperitoneum were studied in a porcine model of mild endotoxemia. METHODS: Twenty-eight pigs were separated into four groups of seven animals: untreated control (C), 2 microg/kg/h endotoxin (E), endotoxin and a pneumoperitoneum (3 h, 15 mmHg) with CO2 (EC) or with helium (EH). Hemodynamic and homeostatic variables were studied for a period of 5.5 h. Primary endpoints were arterial and mucosal pH and the ATP content of the bowel wall. Statistical evaluation was performed using analysis of variance and the Bonferroni test. RESULTS: Endotoxin infusion induced characteristic symptoms of early sepsis: increase of arterial CO2, pulmonary arterial, portal venous, and pulmonary artery wedge pressure, and decrease of arterial pressure, cardiac output, arterial and mucosal pH. An additional pneumoperitoneum led to aggravation of all criteria with significant alterations in arterial and mucosal pH, arterial CO2, wedge and portal venous pressure. The most striking derangement of mean values was observed for mucosal pH (EC: 7.40, EH: 7.54) and arterial pH (EC: 7.15, EH: 7.18). In group EC, two animals died in septic shock. CONCLUSION: Applying a pneumoperitoneum during an ongoing sepsis significantly deteriorates hemodynamic and homeostatic variables, thus enhancing the risk of severe complications.
BACKGROUND: Ideally, a consensus panel combines expert knowledge with external evidence derived from the literature. To date, many consensus conferences do not use a structured approach to search the literature, but simply compile an add-on reference list from all papers cited by the panelists. This study examined how well such panelists retrieved the relevant literature. METHODS: We used the reference lists of nine surgeons who took part in a consensus conference on common bile duct stones. We included all papers that were referred to as randomized controlled trials (RCTs). We then compared this list with a database search in order to calculate sensitivity and specificity. RESULTS: The nine experts cited between 35 and 518 papers, but only eight papers on average were RCTs. Of the 49 papers that the experts believed to be RCTs, only 23 actually were RCTs. The sensitivity resp. specificity for correctly identifying an RCT was 0.21 (95% Cl, 0.11-0.30) resp. 0.80 (95% Cl; 0.64-0.95). RCTs that included the word "randomized" in their title were significantly more likely to be identified (relative risk, 1.31; 95% Cl, 1.18-1.45). CONCLUSION: Our data indicate that consensus panelists usually do not perform systematic literature searches, but simply use their favorite papers to back up their arguments. Because this may lead to a biased selection of the evidence base on which the consensus statements are founded, a systematic search of all relevant articles should become a mandatory task in any consensus or guideline process.
Due to its opsonizing role, plasma fibronectin (pFN) binds to circulating degradation products deriving from collagenous structures and mediates their elimination by the reticuloendothelial system (RES). In septic shock, an overflow of this material may lead to a lack of pFN and an impaired RES activity. In fact, low pFN levels have been reported to correlate with unfavorable clinical outcome. However, dysfunction of the RES is also caused by other shock related factors, and death from septic shock also has been observed in the presence of normal FN levels. To investigate the involvement of opsonic FN in the progression of sepsis, we discriminated between biologically active FN and FN bound to gelatin-like material in pigs developing a hyperdynamic endotoxic shock. All FN determinations were performed with the immunochemical assay. Discrimination between free FN and complexed FN was achieved by separation on gelatin sepharose. A continuous decrease of total FN and free FN was observed in the septic group reaching 57% and 50% of the initial level at the end of the 5-h observation period, respectively. However, a significant difference was not detected before both the microcirculatory and macrocirculatory alterations indicative of hyperdynamic endotoxic shock were completely established. Complexed FN was increased slightly in both groups without any group specific differences. We conclude that the FN-mediated opsonization of circulating gelatine-like material does not play a critical role in early circulatory shock.
The present study evaluated behavioral and histopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor necrosis factor [TNF(-/-)] and their wild-type (wt) littermates. Mice were subjected to CCI brain injury [TNF(-/-), n = 10; wt, n = 10] or served as uninjured controls [TNF(-/-), n = 10; wt, n = 10] and were evaluated for deficits in memory retention at 7 days postinjury. Although both brain-injured wt and TNF(-/-) mice exhibited significant memory dysfunction compared to uninjured controls (P < 0.02), the deficits in memory retention in injured TNF(-/-) mice were significantly less severe than in injured wt mice (P < 0.02). A second group of mice was subjected to CCI brain injury [TNF(-/-), n = 20; wt, n = 20] or served as uninjured controls [TNF(-/-), n = 15; wt, n = 15] and were evaluated over a 4-week period for neurological motor function. In the acute posttraumatic period (48 h postinjury), brain-injured TNF(-/-) mice were significantly less impaired than injured wt mice on composite neuroscore (P < 0.001), rotarod (P < 0.05), and beam balance (P < 0. 02) tests. However, wt mice recovered from brain injury by 2-3 weeks postinjury, whereas TNF(-/-) mice continued to demonstrate persistent motor deficits up to 4 weeks postinjury. Histopathological analysis at 2 and 4 weeks postinjury revealed that brain-injured TNF(-/-) mice had significantly more cortical tissue loss than wt mice (P < 0.02). Our results suggest that although the presence of TNF in the acute posttraumatic period may be deleterious, this cytokine may play a role in facilitating long-term behavioral recovery and histological repair after brain injury.
In this prospective clinical study we examined the intravenous application of salmon-calcitonin in eight patients with severe phantom limb pain (Visual Analogue Scale = 50-100). The patients presented at the Acute Pain Service (APS) section of the Second Department of Surgery, University of Cologne. Six of eight patients (75%) had no phantom limb pain after 10 days of intravenous treatment with salmon-calcitonin (maximum of five cycles of calcitonin infusion). Systematic follow-up examinations after 3, 6 and 12 months showed long-term success. Patient satisfaction was examined with a numeric rating scale (NRS 1-6) between the single infusion cycles. When patient satisfaction was low, the physician modified the time period or drug dosage between infusions. This study shows good or excellent results in patient satisfaction for six of eight patients (75%). A prospective randomized trial is required to verify the excellent results of intravenous salmon-calcitonin in a larger population. Alternative pharmacological and operative treatments of phantom limb pain are critically reviewed and assessed.