Stefan Pollak

Role for Reelin in the Development of Granule Cell Dispersion in Temporal Lobe Epilepsy

The reelin signaling pathway plays a crucial role during the development of laminated structures in the mammalian brain. Reelin, which is synthesized and secreted by Cajal–Retzius cells in the marginal zone of the neocortex and hippocampus, is proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin mRNA by hippocampal Cajal–Retzius cells correlates with the extent of migration defects in the dentate gyrus of patients with temporal lobe epilepsy. These results suggest that reelin is required for normal neuronal lamination in humans, and that deficient reelin expression may be involved in migration defects associated with temporal lobe epilepsy.

Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip.

Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extract Doloteffin, this postmarketing surveillance compared various disease-specific* and generic** measures of effect. We enrolled 250 patients suffering from nonspecific low back pain (Back group: n = 104) or osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin at a dose providing 60 mg harpagoside per day. The measures of effect on pain and disability included the percentage changes from baseline of established instruments (Arhus low back pain index*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain index*, three score index*, the patients global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their pain and any additional treatments for it. The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmed that several dimensions of effect were recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by 8. In multivariable analysis, the improvement tended to be more when the initial pain and disability score was more: older patients tended to improve less than younger, the hip group tended to improve convincingly more than the back group, whereas the improvement in the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantly more per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin. Between 50% and 70% of the patients benefitted from Doloteffin with few adverse effects. Thus, Doloteffin is well worth considering for osteoarthritic knee and hip pain and nonspecific low back pain.

Immunohistochemistry of catecholamines in the hypothalamic–pituitary–adrenal system with special regard to fatal hypothermia and hyperthermia

Catecholamines are involved in various stress responses. Previous studies have suggested applicability of the postmortem blood levels to investigations of physical stress responses or toxic/hyperthermic neuronal dysfunction during death process. The present study investigated cellular immunopositivity for adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) in the hypothalamus, adenohypophysis and adrenal medulla with special regard to fatal hypothermia (cold exposure) and hyperthermia (heat stroke) to examine forensic pathological significance. Medicolegal autopsy cases (n=290, within 3 days postmortem) were examined. The proportions of catecholamine (Adr, Nad and DA)-positive cells (% positivity) in each tissue were quantitatively estimated using immunostaining. Hyperthermia cases (n=12) showed a lower neuronal DA-immunopositivity in the hypothalamus than hypothermia cases (n=20), while Nad- and DA-immunopositivities in the adrenal medulla were higher for hyperthermia than for hypothermia. Rates of Nad-immunopositivity in the adrenal medulla were very low for hypothermia. No such difference between hypothermia and hyperthermia was seen in the adenohypophysis. In hypothermia cases, cellular Nad-immunopositivity in the adrenal medulla correlated with the Nad level in cerebrospinal fluid (r=0.591, p<0.01). These observations suggest a characteristic immunohistochemical pattern of systemic stress response to fatal hypothermia and hyperthermia, involving the hypothalamus and adrenal medulla.

Complex suicide versus complicated suicide

In complex suicides, two or more methods are applied either simultaneously or one after the other. The purpose of the present study was to distinguish such complex suicides in the proper sense from complicated suicides, which are characterized by an unintentional secondary traumatization following the original suicide method. The study material comprises 1217 suicides investigated at the Budapest Institute of Forensic Medicine in the period from 2004 to 2006. Among these, 4.43% (n=54) accounted for planned or unplanned complex suicides, whereas 0.49% (n=6) were categorized as complicated suicides. The latter group included four fatalities due to unintended falls from a height (for instance after breaking of the hanging noose), one death from electrocution and one case of drowning. The succession of a failed suicidal act and a secondary (unforeseen and therefore accidental) trauma with fatal outcome may cause problems in determining the manner and cause of death.

Diagnosis of a captive-bolt injury in a skull extremely destroyed by fire

The authors report on a combined suicide of a 71-year-old farmer who fired a shot to his forehead with a livestock stunner before burning himself. As the fire was fueled by a pile of firewood it burnt for many hours, thus, causing subtotal incineration of the body. The remaining bones were calcined and reduced to a residual mass of only 3 kg. In spite of the extreme destruction, a circular bone defect corresponding to the site where the captive-bolt had entered the skull could be identified in the frontal squama. The example of this suicide is used to illustrate the problems of distinguishing between mechanical and thermal fractures. As expected, the attempted isolation and amplification of both nuclear and mitochondrial DNA for the purpose of identification was not successful.

Skin tears away from the entrance wound in gunshots to the head

Abstract. The present investigation covers 116 contact shots to the head and shots into the mouth from the Freiburg forensic autopsy material including 20 gunshot wounds which showed stretchmark-like tears of the facial skin away from the entrance wound. In these cases the gunshot entrance wounds were localised either in the mouth, the forehead, or the submental region. The stretchmark-like tears were found in the region of the eyes and the nasolabial folds. Radial tears were seen on the lips and in the vicinity of the corners of the mouth, particularly in cases involving shots into the mouth. The stretchmark-like tears essentially followed the skin tension lines and the expression-related lines of the face. They were apparently caused by the subcutaneous or intraoral expansion of the muzzle gases and/or the radial forces of the bullet resulting in ballooning and overextension of the facial soft tissues. The weapons used were not only rifles and shotguns, but also revolvers and pistols.

Transorbital intracranial impalement injuries by wooden foreign bodies: clinical, radiological and forensic aspects.

Facial impalement injuries involve the danger of diagnostic pitfalls. Even if the penetrating object extends into the cranial cavity, the clinical symptoms and the radiological signs may be uncharacteristic. In order to illustrate the diagnostic problems, two cases of accidental impalement are reported. In both of them, a wooden foreign body penetrated via the orbita into the cranium and remained undetected at first. Imaging by CT and MRI is presented and compared with regard to the respective diagnostic validity of these methods. Due to its specific anatomic configuration, the orbita constitutes a predilective pathway for low-velocity foreign bodies entering the skull. Based on the clinical data and the radiological findings, transorbital impalement wounds inflicted by wooden objects are discussed under neurosurgical and medicolegal aspects.

Complex suicide by ethanol intoxication and inhalation of fire fumes in an old lady: Interdisciplinary elucidation including post-mortem analysis of congener alcohols

An 88-year-old woman committed suicide by drinking a toxic amount of highly concentrated alcohol and setting two rooms of her flat on fire. As there was not enough oxygen, the fire went out, however. At autopsy, no thermal lesions were found on the body, but soot depositions in the airways and a COHb value of 14% pointed to the inhalation of fire fumes. The ethanol concentration in femoral blood was 6.62 per mille. The gastric mucosa was fixed by the ingested alcohol and showed hardly any autolytic changes despite a post-mortem interval of five days. Congener analysis of the gastric contents and the femoral blood indicated the uptake of a fruit distillate or its foreshot.

Intracranial impalement with entrance site in the mandibular region: Postmortem elucidation of an accidental fall on a wooden plant stick

A 78-year-old woman with a history of transient ischemic attacks was found in the doorway of her house in a somnolent and unresponsive condition. In the right mandibular region, a small skin wound was localized, which was surgically treated. Six days after admission to the hospital, an exploratory craniotomy was performed because of abnormal CT findings. Apart from tissue lesions and hemorrhages a small bone fragment was detected in the right cerebral cortex, which was removed. After 11 days in hospital, the patient died from failure of central regulatory functions. At the forensic autopsy, a 15 cm long wound track running upward from the skin wound in the right mandibular region through the bony skull base to the right parietal lobe of the brain was noted. Apparently, the surgically removed bone fragment had been displaced from the right middle cranial fossa. The site of the incident in the deceaseds house was inspected again and a bamboo pole used to stabilize a potted plant standing on the floor was found and sent to the trace evidence laboratory. Analysis showed blood and tissue deposits from the victim. On the basis of all the findings and the circumstances of the case, a fatal impalement injury caused by an accidental fall could be assumed.

Pulmonary arteriovenous malformation causing sudden death due to spontaneous hemothorax

A sudden death due to hemothorax caused by spontaneous rupture of a congenital pulmonary arteriovenous malformation (AVM) is reported. A 44-year-old woman died unexpectedly with chest pain and dyspnea. The post-mortem examination revealed a massive right-sided hemothorax arising from a subpleural AVM of the upper lobe. There were multiple telangiectases in the tongue and the tonsils, as typically associated with Osler–Weber–Rendu disease (hereditary hemorrhagic telangiectasia, HHT). The post-mortem molecular genetic analysis proved the presence of a disease-causing mutation in the endoglin gene constituting a predisposition for pulmonary AVMs. According to the literature, almost half of the AVMs in the lung are seen in HHT patients. Based on the presented case and the relevant literature, the article addresses the forensic aspects of fatal hemothorax and the importance of detecting the source of bleeding.