Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Reactive oxygen intermediates (ROI) contribute to neuronal injury in cerebral ischemia and trauma. In this study we explored the role of ROI in bacterial meningitis. Meningitis caused by group B streptococci in infant rats led to two distinct forms of neuronal injury, areas of necrosis in the cortex and neuronal loss in the dentate gyrus of the hippocampus, the latter showing evidence for apoptosis. Staining of brain sections with diaminobenzidine after perfusion with manganese buffer and measurement of lipid peroxidation products in brain homogenates both provided evidence that meningitis led to the generation of ROI. Treatment with the radical scavenger alpha-phenyl-tert-butyl nitrone (PBN) (100 mg/kg q8h i.p.) beginning at the time of infection completely abolished ROI detection and the increase in lipidperoxidation. Cerebral cortical perfusion was reduced in animals with meningitis to 37.5+/-21.0% of uninfected controls (P < 0.05), and PBN restored cortical perfusion to 72.0+/-8.1% of controls (P < 0.05 vs meningitis). PBN also completely prevented neuronal injury in the cortex and hippocampus, when started at the time of infection (P < 0.02), and significantly reduced both forms of injury, when started 18 h after infection together with antibiotics (P < 0.004 for cortex and P < 0.001 for hippocampus). These data indicate that the generation of ROI is a major contributor to cerebral ischemia and necrotic and apoptotic neuronal injury in this model of neonatal meningitis.

Validation and reclassification of MGAP and GAP in hospital settings using data from the Trauma Audit and Research Network.

BACKGROUND Recently, two simple clinical scores were published to predict survival in trauma patients. Both scores may successfully guide major trauma triage, but neither has been independently validated in a hospital setting. METHODS This is a cohort study with 30-day mortality as the primary outcome to validate two new trauma scores-Mechanism, Glasgow Coma Scale (GCS), Age, and Pressure (MGAP) score and GCS, Age and Pressure (GAP) score-using data from the UK Trauma Audit and Research Network. First, an assessment of discrimination, using the area under the receiver operating characteristic (ROC) curve, and calibration, comparing mortality rates with those originally published, were performed. Second, we calculated sensitivity, specificity, predictive values, and likelihood ratios for prognostic score performance. Third, we propose new cutoffs for the risk categories. RESULTS A total of 79,807 adult (≥16 years) major trauma patients (2000-2010) were included; 5,474 (6.9%) died. Mean (SD) age was 51.5 (22.4) years, median GCS score was 15 (interquartile range, 15-15), and median Injury Severity Score (ISS) was 9 (interquartile range, 9-16). More than 50% of the patients had a low-risk GAP or MGAP score (1% mortality). With regard to discrimination, areas under the ROC curve were 87.2% for GAP score (95% confidence interval, 86.7-87.7) and 86.8% for MGAP score (95% confidence interval, 86.2-87.3). With regard to calibration, 2,390 (3.3%), 1,900 (28.5%), and 1,184 (72.2%) patients died in the low, medium, and high GAP risk categories, respectively. In the low- and medium-risk groups, these were almost double the previously published rates. For MGAP, 1,861 (2.8%), 1,455 (15.2%), and 2,158 (58.6%) patients died in the low-, medium-, and high-risk categories, consonant with results originally published. Reclassifying score point cutoffs improved likelihood ratios, sensitivity and specificity, as well as areas under the ROC curve. CONCLUSION We found both scores to be valid triage tools to stratify emergency department patients, according to their risk of death. MGAP calibrated better, but GAP slightly improved discrimination. The newly proposed cutoffs better differentiate risk classification and may therefore facilitate hospital resource allocation. LEVEL OF EVIDENCE Prognostic study, level II.

Use of dextran sulfate in tourniquet-induced skeletal muscle reperfusion injury.

BACKGROUND Lower extremity ischemia-reperfusion injury (IRI)-prolonged ischemia and the subsequent restoration of circulation-may result from thrombotic occlusion, embolism, trauma, or tourniquet application in surgery. The aim of this study was to assess the effect of low-molecular-weight dextran sulfate (DXS) on skeletal muscle IRI. METHODS Rats were subjected to 3 h of ischemia and 2 or 24 h of reperfusion. To induce ischemia the femoral artery was clamped and a tourniquet placed under the maintenance of the venous return. DXS was injected systemically 10 min before reperfusion. Muscle and lung tissue samples were analyzed for deposition of immunoglobulin M (IgM), IgG, C1q, C3b/c, fibrin, and expression of vascular endothelial-cadherin and bradykinin receptors b1 and b2. RESULTS Antibody deposition in reperfused legs was reduced by DXS after 2 h (P < 0.001, IgM and IgG) and 24 h (P < 0.001, IgM), C3b/c deposition was reduced in muscle and lung tissue (P < 0.001), whereas C1q deposition was reduced only in muscle (P < 0.05). DXS reduced fibrin deposits in contralateral legs after 24 h of reperfusion but did not reduce edema in muscle and lung tissue or improve muscle viability. Bradykinin receptor b1 and vascular endothelial-cadherin expression were increased in lung tissue after 24 h of reperfusion in DXS-treated and non-treated rats but bradykinin receptor b2 was not affected by IRI. CONCLUSIONS In contrast to studies in myocardial infarction, DXS did not reduce IRI in this model. Neither edema formation nor viability was improved, whereas deposition of complement and coagulation components was significantly reduced. Our data suggest that skeletal muscle IRI may not be caused by the complement or coagulation alone, but the kinin system may play an important role.

Fall-related emergency department admission: fall environment and settings and related injury patterns in 6357 patients with special emphasis on the elderly

PRINCIPALS Throughout the world, falls are a major public health problem and a socioeconomic burden. Nevertheless there is little knowledge about how the injury types may be related to the aetiology and setting of the fall, especially in the elderly. We have therefore analysed all patients presenting with a fall to our Emergency Department (ED) over the past five years. METHODS Our retrospective data analysis comprised adult patients admitted to our Emergency Department between January 1, 2006, and December 31, 2010, in relation to a fall. RESULTS Of a total of 6357 patients 78% (n = 4957) patients were younger than 75 years. The main setting for falls was patients home (n = 2239, 35.3%). In contrast to the younger patients, the older population was predominantly female (56.3% versus 38.6%; P < 0.0001). Older patients were more likely to fall at home and suffer from medical conditions (all P < 0.0001). Injuries to the head (P < 0.0001) and to the lower extremity (P < 0.019) occurred predominantly in the older population. Age was the sole predictor for recurrent falls (OR 1.2, P < 0.0001). CONCLUSION Falls at home are the main class of falls for all age groups, particularly in the elderly. Fall prevention strategies must therefore target activities of daily living. Even though falls related to sports mostly take place in the younger cohort, a significant percentage of elderly patients present with falls related to sporting activity. Falls due to medical conditions were most likely to result in mild traumatic brain injury.

Injury severity and mortality of adult zebra crosswalk and non-zebra crosswalk road crossing accidents: a cross-sectional analysis

PRINCIPALS Over a million people worldwide die each year from road traffic injuries and more than 10 million sustain permanent disabilities. Many of these victims are pedestrians. The present retrospective study analyzes the severity and mortality of injuries suffered by adult pedestrians, depending on whether they used a zebra crosswalk. METHODS Our retrospective data analysis covered adult patients admitted to our emergency department (ED) between 1 January 2000 and 31 December 2012 after being hit by a vehicle while crossing the road as a pedestrian. Patients were identified by using a string term. Medical, police and ambulance records were reviewed for data extraction. RESULTS A total of 347 patients were eligible for study inclusion. Two hundred and three (203; 58.5%) patients were on a zebra crosswalk and 144 (41.5%) were not. The mean ISS (injury Severity Score) was 12.1 (SD 14.7, range 1-75). The vehicles were faster in non-zebra crosswalk accidents (47.7 km/n, versus 41.4 km/h, p<0.027). The mean ISS score was higher in patients with non-zebra crosswalk accidents; 14.4 (SD 16.5, range 1-75) versus 10.5 (SD13.14, range 1-75) (p<0.019). Zebra crosswalk accidents were associated with less risk of severe injury (OR 0.61, 95% CI 0.38-0.98, p<0.042). Accidents involving a truck were associated with increased risk of severe injury (OR 3.53, 95%CI 1.21-10.26, p<0.02). CONCLUSION Accidents on zebra crosswalks are more common than those not on zebra crosswalks. The injury severity of non-zebra crosswalk accidents is significantly higher than in patients with zebra crosswalk accidents. Accidents involving large vehicles are associated with increased risk of severe injury. Further prospective studies are needed, with detailed assessment of motor vehicle types and speed.

VIRTOPSY--scientific documentation, reconstruction and animation in forensic: individual and real 3D data based geo-metric approach including optical body/object surface and radiological CT/MRI scanning.

Until today, most of the documentation of forensic relevant medical findings is limited to traditional 2D photography, 2D conventional radiographs, sketches and verbal description. There are still some limitations of the classic documentation in forensic science especially if a 3D documentation is necessary. The goal of this paper is to demonstrate new 3D real data based geo-metric technology approaches. This paper present approaches to a 3D geo-metric documentation of injuries on the body surface and internal injuries in the living and deceased cases. Using modern imaging methods such as photogrammetry, optical surface and radiological CT/MRI scanning in combination it could be demonstrated that a real, full 3D data based individual documentation of the body surface and internal structures is possible in a non-invasive and non-destructive manner. Using the data merging/fusing and animation possibilities, it is possible to answer reconstructive questions of the dynamic development of patterned injuries (morphologic imprints) and to evaluate the possibility, that they are matchable or linkable to suspected injury-causing instruments. For the first time, to our knowledge, the method of optical and radiological 3D scanning was used to document the forensic relevant injuries of human body in combination with vehicle damages. By this complementary documentation approach, individual forensic real data based analysis and animation were possible linking body injuries to vehicle deformations or damages. These data allow conclusions to be drawn for automobile accident research, optimization of vehicle safety (pedestrian and passenger) and for further development of crash dummies. Real 3D data based documentation opens a new horizon for scientific reconstruction and animation by bringing added value and a real quality improvement in forensic science.

Visualization and quantification of air embolism structure by processing postmortem MSCT data.

Venous air embolism (VAE) is an often occurring forensic finding in cases of injury to the head and neck. Whenever found, it has to be appraised in its relation to the cause of death. While visualization and quantification is difficult at traditional autopsy, Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) offer a new potential in the diagnosis of VAE. This paper reports the findings of VAE in four cases of massive head injury examined postmortem by Multislice Computed Tomography (MSCT) prior to autopsy. MSCT data of the thorax were processed using 3D air structure reconstruction software to visualize air embolism within the vascular system. Quantification of VAE was done by multiplying air containing areas on axial 2D images by their reconstruction intervals and then by summarizing the air volumes. Excellent 3D visualization of the air within the vascular system was obtained in all cases, and the intravascular gas volume was quantified.

Range of Motion of the Upper Extremity in a Healthy Pediatric Population: Introduction to Normative Data.

Objective In the pediatric population traumatic injuries of the upper extremity are common. After therapy a decision has to be made if the mobility of the joint lies within a normal range. The purpose of this study was to give an introduction to normative data. We investigate if there is a significant difference in the range of motion (ROM) between male and female probands and furthermore, if an effect of the age can be detected. Methods We performed an institutional review board-approved study of healthy girls and boys aged between 2 and 16 years without any medical history of an upper extremity fracture. We investigated the active ROM of the elbow, wrist, metacarpophalangeal, and interphalangeal joints. Furthermore, age, handedness, weight, and height were recorded. A total of 171 adolescents with a mean age of 10.6 years were included and separated into four cohorts by age: 2 to 5, 6 to 10, 11 to 13, and 14 to 16 years. Results We found significant differences between the genders in the age group from 11 to 13 years for the flexion of the elbow, the pronation, the flexion of the interphalangeal joint of the thumb, as well as the flexion of the metacarpophalangeal joints of digitus II to V. Furthermore, a significant difference in the same joints except from the elbow flexion could be demonstrated between the genders. Conclusion Our study contributes normative data for upper extremity ROM in the pediatric population and presents a gender-related difference in certain joints. Clinical Relevance Normative data for the ROM of upper extremity joints in children is helpful for the evaluation of pediatric orthopedic patients and provides the framework for therapeutic resolution. Since a great number of traumatic injuries in children affect the upper extremity, this information may help the physician to estimate the impact of the injury and decide on the therapeutic management.

Successful transnasal delivery of stem cells in a rat model of perinatal hypoxic-ischemic brain injury

OBJECTIVE: New routes for cell transplantation into the brain need to be explored as intracerebral or intrathecal applications have a high risk to cause damage to the central nervous system. It has been hypothesized that transnasally administrated cells bypass the blood-brain barrier and migrate along the olfactory neural route into the brain and cerebrospinal fluid. Our goal is to confirm this hypothesis by transnasally administrating Wharton’s Jelly mesenchymal stem cells (WJ-MSC) and neural progenitor cells (NPC) to perinatal rats in a model of hypoxic-ischemic brain injury. STUDY DESIGN: Four-day-old Wistar rat pups, previously brain-damaged by combined hypoxic-ischemic and inflammatory insult, either received WJ-MSC or green fluorescent protein-expressing NPC: The heads of the rat pups were immobilized and 3 ml drops containing the cells (50’000 cells/ml) were placed on one nostril allowing it to be snorted. This procedure was repeated twice, alternating right to left nostril with an interval of one minute between administrations. The rat pups received a total of 600’000 cells. Animals were sacrificed 24h, 48h or 7 days after the application of the cells. Fixed brains were collected, embedded in paraffin and sectioned. RESULTS: Transplanted cells were found in the layers of the olfactory bulb (OB), the cerebral cortex, thalamus and the hippocampus. The amount of cells was highest in the OB. Animals treated with transnasally delivered stem cells showed significantly decreased gliosis compared to untreated animals. CONCLUSION: Our data show that transnasal delivery of WJ-MSC and NPC to the newborn brain after perinatal brain damage is successful. The cells not only migrate the brain, but also decrease scar formation and improve neurogenesis. Therefore, the non-invasive intranasal delivery of stem cells to the brain may be the preferred method for stem cell treatment of perinatal brain damage and should be preferred in future clinical trials.

Long-bone fractures in persons with spinal cord injury

STUDY DESIGN Retrospective data analysis. OBJECTIVES To document fracture characteristics, management and related complications in individuals with traumatic spinal cord injury (SCI). SETTING Rehabilitation centre for SCI individuals. METHOD Patients' records were reviewed. Patients with traumatic SCI and extremity fractures that had occurred after SCI were included. Patient characteristics, fractured bone, fracture localisation, severity and management (operative/conservative), and fracture-related complications were extracted. RESULTS A total of 156 long-bone fractures in 107 SCI patients (34 women and 73 men) were identified. The majority of patients were paraplegics (77.6%) and classified as American Spinal Injury Association Impairment Scale A (86.0%). Only the lower extremities were affected, whereby the femur (60.9% of all fractures) was fractured more frequently than the lower leg (39.1%). A total of 70 patients (65.4%) had one fracture, whereas 37 patients (34.6%) had two or more fractures. Simple or extraarticular fractures were most common (75.0%). Overall, 130 (83.3%) fractures were managed operatively. Approximately half of the femur fractures (48.2%) were treated with locking compression plates. In the lower leg, fractures were mainly managed with external fixation (48.8%). Conservative fracture management was applied in 16.7% of the cases and consisted of braces or a well-padded soft cast. Fracture-associated complications were present in 13.5% of the cases but did not differ significantly between operative (13.1%) and conservative (15.4%) fracture management. CONCLUSION SCI was associated with simple or extraarticular fractures of the distal femur and the lower leg. Fractures were mainly managed operatively with a low complication rate.

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair).

BACKGROUND Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). OBJECTIVES To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). METHODS The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. RESULTS AND CONCLUSIONS The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

AN OCCUPATIONAL INJURY MANAGEMENT INFORMATION SYSTEM FOR THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON

The purpose of this research and development project was to develop a method, a design, and a prototype for gathering, managing, and presenting data about occupational injuries.^ State-of-the-art systems analysis and design methodologies were applied to the long standing problem in the field of occupational safety and health of processing workplace injuries data into information for safety and health program management as well as preliminary research about accident etiologies. The top-down planning and bottom-up implementation approach was utilized to design an occupational injury management information system. A description of a managerial control system and a comprehensive system to integrate safety and health program management was provided.^ The project showed that current management information systems (MIS) theory and methods could be applied successfully to the problems of employee injury surveillance and control program performance evaluation. The model developed in the first section was applied at The University of Texas Health Science Center at Houston (UTHSCH).^ The system in current use at the UTHSCH was described and evaluated, and a prototype was developed for the UTHSCH. The prototype incorporated procedures for collecting, storing, and retrieving records of injuries and the procedures necessary to prepare reports, analyses, and graphics for management in the Health Science Center. Examples of reports, analyses, and graphics presenting UTHSCH and computer generated data were included.^ It was concluded that a pilot test of this MIS should be implemented and evaluated at the UTHSCH and other settings. Further research and development efforts for the total safety and health management information systems, control systems, component systems, and variable selection should be pursued. Finally, integration of the safety and health program MIS into the comprehensive or executive MIS was recommended. ^

The effect of alcohol consumption on mortality among idiosyncratic drug induced liver injury (IDILI) patients

Severe liver injury (SLI) due to drugs is a frequent cause of catastrophic illness and hospitalization. Due to significant morbidity, mortality, and excess medical care costs, this poses a challenge as a public health problem. The role of associated risk factors like alcohol consumption in contributing to the high mortality remains to be studied. This study was conducted to assess the impact of alcohol use on mortality in IDILI patients, while adjusting for age, gender, race/ethnicity, and education level. The data from this study indicate only a small excess risk of death among IDILI patients using alcohol, but the difference was not statistically significant. The major contribution of this study to the field of public health is that it excludes a large hazard of alcohol consumption on the mortality among idiosyncratic drug induced liver injury (IDILI) patients. ^

The genetic contribution of the major histocompatibility complex to bleomycin-induced lung injury

Pulmonary fibrosis (PF) is the result of a variety of environmental and cancer treatment related insults and is characterized by excessive deposition of collagen. Gas exchange in the alveoli is impaired as the normal lung becomes dense and collapsed leading to a loss of lung volume. It is now accepted that lung injury and fibrosis are in part genetically regulated. ^ Bleomycin is a chemotherapeutic agent used for testicular cancer and lymphomas that induces significant pulmonary toxicity. We delivered bleomycin to mice subcutaneously via a miniosmotic pump in order to elicit lung injury (LI) and quantified the %LI morphometrically using video imaging software. We previously identified a quantitative trait loci, Blmpf-1(LOD=17.4), in the Major Histocompatibility Complex (MHC), but the exact genetic components involved have remained unknown. ^ In the current studies, Blmpf-1 was narrowed to an interval spanning 31.9-32.9Mb on Chromosome 17 using MHC Congenic mice. This region includes the MHC Class II and III genes, and is flanked by the TNF-alpha super locus and MHC Class I genes. Knockout mice of MHC Class I genes (B2mko), MHC Class II genes (Cl2ko), and TNF-alpha (TNF-/-) and its receptors (p55-/-, p75-/-, and p55/p75-/-) were treated with bleomycin in order to ascertain the role of these genes in the pathogenesis of lung injury. ^ Cl2ko mice had significantly better survival and %LI when compared to treated background BL/6 (B6, P<.05). In contrast, B2mko showed no differences in survival or %LI compared to B6. This suggests that the MHC Class II locus contains susceptibility genes for bleomycin-induced lung injury. ^ TNF-alpha, a Class III gene, was examined and it was found that TNF-/- and p55-/- mice had higher %LI and lower survival when compared to B6 (P<.05). In contrast, p75-/- mice had significantly reduced %LI when compared to TNF-/-, p55-/-, and B6 mice as well as higher survival (P<.01). These data contradict the current paradigm that TNF-alpha is a profibrotic mediator of lung injury and suggest a novel and distinct role for the p55 and p75 receptors in mediating lung injury. ^

Sibling relationships in the family of a child with a burn injury

Purpose. Understanding siblings' experiences after a major childhood burn injury was the purpose of this mixed method, qualitative dominant study. The following research questions guided this project: How do siblings describe the impact of a major childhood burn injury experience? How do sibling relationship factors of warmth/closeness, relative status/power, conflict, and rivalry further clarify their relationship and their experience after a major burn injury? ^ Methods. A mixed method, qualitative dominant, design was implemented to understand the sibling experiences in a family with a child suffering from a major burn injury. Informants were selected from patients with childhood burn injuries attending the reconstructive clinic at a Gulf coast children's specialty hospital. The qualitative portion used the life story method, a narrative process, to portray the long-term impact on sibling relationships. A "case" represents a family unit and could be composed of one or multiple family members. Participants from 22 cases (N = 40 participants) were interviewed. Interviews were conducted in person and via telephone. The quantitative portion, or the embedded part of this mixed method design, used the Sibling Relationship Questionnaire Revised (SRQ-R) to conduct an additional structured interview and acquire scoring data. It was postulated that the SRQ-R would provide another perspective on the sibling experience and expand the qualitative data analysis. Thematic analysis was implemented on the qualitative interview data including the qualitative data from the interviews structured on the SRQ-R. Additionally, scores on the SRQ-R were tabulated to further describe the cases. ^ Results. The overall thematic pattern for the sibling relationship in families having a child with a major burn injury was that of normalization. Areas of normalization as well as the process of adjustment were the major themes. Areas of normalization were found in play and other activities, in school and work, and in family relations with their siblings and their parents. The process of adjustment in the sibling relationship was described as varied, involved school and work re-entry, and might even change their life perspective. Further analysis included an examination of the cases in which more than one person were interviewed and completed the SRQ-R. Participants from five ( n = 11) of six cases (n = 14), scored above 3.0 on the five-point scale on the Warmth/Closeness construct, indicating they perceived the sibling relationship as close. Five participants scored high on the Conflict construct and four participants scored high on the Rivalry construct. Finally, Relative Status/Power was low or negative in the six cases (n = 13). ^ Conclusions/implications. These findings suggest the importance of returning to normalcy for many of the families and the significance of sibling relationships on the process. Some of these families were able to use this major life event in a positive way to promote normalization. ^