Rainer Mattern

Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans.

Abstract Extracellular heme derived from hemoglobin following hemorrhage or released from dying cells induces the expression of heme oxygenase-1 (HO-1, HSP-32) which metabolizes heme to the gaseous mediator carbon monoxide (CO), iron (Fe) and biliverdin. Biliverdin and its product bilirubin are powerful antioxidants. Thus, expression of HO-1 is considered to be a protective mechanism against oxidative stress and has been described in microglia, astrocytes and neurons following distinct experimental models of pathological alterations to the brain such as subarachnoidal hemorrhage, ischemia and traumatic brain injury (TBI) and in human neurodegenerative diseases. We have now analyzed the expression of HO-1 in human brains following TBI (n = 28; survival times: few minutes up to 6 months) and focal cerebral infarctions (FCI; n = 17; survival time: < 1 day up to months) by ¶immunohistochemistry. Follwing TBI, accumulation of ¶HO-1+ microglia/macrophages at the hemorrhagic lesion was detected as early as 6 h post trauma and was still pronounced after 6 months. In contrast, after FCI HO-1+ microglia/macrophages accumulated within focal hemorrhages only and were absent in non-hemorrhagic regions. Further, HO-1 was weakly expressed in astrocytes in the perifocal penumbra. In contrast to experimental data derived from rat focal ischemia, these results indicate a prolonged HO-1 expression in humans after brain injury.

CD14 expression by activated parenchymal microglia/macrophages and infiltrating monocytes following human traumatic brain injury.

Abstract. The immune response in the central nervous system (CNS) is under tight control of regulatory mechanisms, resulting in the establishment of immune privilege. CNS injury induces an acute inflammatory reaction, composed mainly of invading leukocytes and activated microglial cells/macrophages. The generation of this robust immune response requires binding of receptors such as CD14, a pattern recognition receptor of the immune system. CD14, a surface molecule of monocytic cells, is up-regulated after monocyte stimulation and is involved in cellular activation. To examine CD14 expression in human brain lesions we investigated sections of brains obtained at autopsy from 25 cases following closed traumatic brain injury (TBI) and 5 control brains by immunohistochemistry. Detection of CD14 in controls demonstrated constitutive expression by perivascular cells, but not in parenchymal microglial cells, equivalent to known expression pattern of ED2 in rats. Following TBI, numbers of CD14+ cells in perivascular spaces and in the brain parenchyma increased in parallel within 1–2xa0days, both at the lesion and in adjacent perilesional areas. The number of CD14+ cells in perivascular spaces and in the brain parenchyma reached maximum levels within 4–8xa0days and remained elevated until weeks after trauma. In contrast to activated parenchymal microglia/macrophages, resting parenchymal microglial cells lacked CD14. Thus, early CD14 expression constitutes an essential part of the acute inflammatory CNS response following trauma.

Detection of gunshot residues in routine CTs

Abstract The forensic assessment of non-fatal gunshot wounds often proves to be difficult as wounds have usually been cleaned and protected with a sterile bandage by the time of the examination. The aim of our investigation was to test the possible application of computed tomography (CT) for the forensic assessment. Doing so raised the questions whether gunshot residues in the soft tissues, detected by means of 3-dimensional CT, can be used as evidence of a close-range shot and whether conclusions can be drawn pertaining to the range of the shot or the type of bullet used based on the distribution of the radiologically detectable material? In this experimental study 39 shots were fired at fresh pig skin and it was possible to distinguish shots fired from distances of more than 10 cm and contact shots independent of the type of bullet. For unjacketed lead bullets, radiopaque material could be seen in the depth of the entrance wound for firing distances up to 10 cm. In individual cases, CT data and the 3-D reconstruction could provide valuable information in the forensic assessment of patients with gunshot wounds.

Estimation of sex on the basis of radiographs of the calcaneus

Lateral and anteroposterior radiographs of the ankles of 800 Central Europeans aged 20 to 79 were analyzed with regard to sexual dimorphism. All the distances, but not the angles, of the calcaneus were much larger in males than in females. Approximately 80% of the study sample could be sexed correctly by classifying all specimens greater than 86.0 mm in length as male and those less than 86.0 mm as female. The prevalence of os tibiale externum was 8.0 and 2.6% and the prevalence of plantar heel spur was 16.3 and 6.5% (increasing with age) for males and females, respectively, being significantly more frequent in females. On the other hand, the bone island frequencies were 9.1% in males and 4.8% in females. Our study suggests that radiographs of the ankle are a convenient, rapid, cheap and non-invasive means for estimating sex.

Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose

The postmortem distribution of morphine and its metabolites was investigated in four cases of heroin overdose to evaluate some of the factors that influence intravasal blood concentrations. Variables included were the chemical stability of morphine conjugates, hemoconcentration, incomplete distribution of the drug and diffusion processes. Blood samples from different sampling sites including the aorta, the infra- and suprarenal portion of the inferior vena cava, the superior vena cava, the femoral and subclavian veins, and the right and left ventricles were examined for morphine, morphine-3-glucuronide and morphine-6-glucuronide, hematocrit and water content. Drug concentrations were determined by HPLC based on the native fluorescence of the analytes. Morphine glucuronides proved to be stable for a time period of 72 h. The water content ranged from 65 to 83% and hematocrit values from 25 to 75%, and were seen as contributory factors to the dramatic differences observed for drug concentrations from different sampling sites. The differences could neither be attributed to incomplete distribution during life-time nor to a diffusion process following the different distribution volumes of morphine and its conjugates. A definite relationship between the ratio of the molar concentrations of morphine and its glucuronides, as assessed in pharmacokinetical studies after morphine dosing, could not be established. For a better understanding more cases and changes over time and tissue concentrations should be analysed.

QUANTIFICATION OF SIDE IMPACT RESPONSES AND INJURIES

Side impacts have been shown to produce a large portion of both serious and fatal injuries within the total automotive crash problem. These injuries are produced as a result of the rapid changes in velocity an automobile occupants body experiences during a crash. Any improvement to the side impact problem will be brought about by means which will ultimately modify the occupants rapid body motions to such a degree that they will no longer produce injuries of serious consequence. Accurate knowledge of both the bodys motion and resulting injuries under a variety of impact conditions is needed to achieve this goal. Possession of this knowledge will then permit development of accurate anthropomorphic test devices and injury criteria which can be used to create effective injury countermeasures in vehicles.

Comparison Between Child Cadavers and Child Dummy by Using Child Restraint Systems in Simulated Collisions

At present, numerous restraint systems for children applied in vehicles are in general considered for the use on the back seats. Up to now, only impact tests with dummies and animals have been carried through by these systems. Out of the great number of children, seats and belts we used a system (deformable safety impact table combined with a lap-belt) which has been investigated by us during frontal impacts utilizing two dummies and four cadavers of children in the age of 2 5 up to 11 years having body weights of 16 up to 31 kg. The tests have been conducted on the deceleration-sled track at the Institute of Legal Medicine of the University Heidelberg. Impact velocities of 30 km/h and 40 km/h at a medium deceleration of 20g have been chosen. None of the test sugjects showed injuries to the inner organs; however, numerous muscular hemorrhages as well as hemorrhages of discs and ligaments were noticed. The HIC values lay between 100 and 500; accelerations in x-direction up to 44g and in z- direction up to 85g occurred at the head. Lap-belt forces of 160 up to 400 daN were measured. A weak point of the investigated system is that the childs movements are considerably limited, a factor also noticed in other child restraint systems; however, the protective function proved to be an advantage. The movements during the impact, pictured by high-speed cameras, essentially differ from those of adults wearing 3-point belts. The maximum flexion of the vertebral column is, due to the system, located in the transition of the thoracic to the lumbar vertebral column and the flexion angles amounted about 90 degrees. As expected were the maximum head displacements in relation to a sled-fixed axis dependent on the impact velocity and the body height, and ranged between 50 cm (crash velocity 30 km/h, body height 97 cm) and 90 cm (crash velocity 40 km/h, body height 139 cm). The movement will be analyzed; the anatomical and mechanical causes are going to be investigated. Finally, the results will be compared with similar dummy tests investigated by use. Due to these differences in the dummy and cadaver behavior, the necessity is pointed out to examine all restraint systems by cadaver tests. /Author/

A preliminary study on the stability of benzodiazepines in blood and plasma stored at 4° C

Abstract An approach to determine the stability of benzodiazepines and some of their metabolites (n = 13) by means of a routinely applied gas chromatographic method using electron capture detection was made in this preliminary study. Validation data of the method are given. Spiked blood and plasma samples were stored at 4°u2002C and analysed at selected times up to 240 days. The concentrations of all analytes had decreased to at least 60% of the original levels at the end of the observation period. A clear pattern of breakdown could not be established. The data obtained suggest that results from long-term stored samples should be interpreted cautiously. Further investigations concerning the stability of drugs in blood and plasma samples, additional methods of identification and determination as well as the establishment of optimal storage conditions seem necessary.

Driving-related risks and impact of methylphenidate treatment on driving in adults with attention-deficit/hyperactivity disorder (ADHD)

Summary.This study assesses driving behaviour and history of driving outcomes through a semi-structured interview in 27 clinically referred German adults with ADHD and 27 age-, gender- and education-matched non-ADHD controls. In nineteen of the ADHD-subjects a test battery of driving-related cognitive measures was performed (ART 2020) and re-assessed after at least six weeks of treatment with methylphenidate (n = 9) or after a six-week medication free period (n = 10).ADHD-subjects drove significantly more kilometres per year, were more often registered by traffic authorities and fined more frequently, were involved in more accidents and described their driving style as more insecure and hectic than controls. A high-risk driving group was delineated with 3–6 accidents per ADHD-subject. All results were controlled for intercorrelations with driving experience. Methylphenidate treatment resulted in improved information processing, e.g., better visu-motor coordination under high-stress conditions, improved visual orientation and sustained visual attention compared to baseline and our untreated control group.

Human Response to and Injury from Lateral Impact

Lateral impacts have been shown to produce a large portion of both serious and fatal injuries within the total automotive crash problem. These injuries are produced as a result of the rapid changes in velocity that an automobile occupants body experiences during a crash. In an effort to understand the mechanisms of these injuries, an experimental program using human surrogates (cadavers) was initiated. Initial impact velocity and compliance of the lateral impacting surface were the primary test features that were controlled, while age of the test specimen was varied to assess its influence on the injury outcome. Instrumentation consisted of 24 accelerometer channels on the subjects along with contact forces measured on the wall both at the thoracic and pelvic level. The individual responses and resulting injuries sustained by 11 new subjects tested at the University of Heidelberg are presented in detail. An examination of the relationship between forces applied and responses observed in the thorax is discussed. The average injuries for different sled test conditions are presented based on a total of 42 cadaver tests (11 of which are the ones discussed above). The comparison of rigid wall and padded wall sled tests is made based on these average injuries. For the covering abstract of the conference see HS-036 716. (Author/TRRL)