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Supplementary Figures 1-6 from A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes

The Ca2+-regulated calcineurin/nuclear factor of activated T cells (NFAT) cascade controls alternative pathways of T-cell activation and peripheral tolerance. Here, we describe reduction of NFATc2 mRNA expression in the lungs of patients with bronchial adenocarcinoma. In a murine model of bronchoalveolar adenocarcinoma, mice lacking NFATc2 developed more and larger solid tumors than wild-type littermates. The extent of central tumor necrosis was decreased in the tumors in NFATc2(−/−) mice, and this finding was associated with reduced tumor necrosis factor-α and interleukin-2 (IL-2) production by CD8+ T cells. Adoptive transfer of CD8+ T cells of NFATc2(−/−) mice induced transforming growth factor-β1 in the airways of recipient mice, thus supporting CD4+CD25+Foxp-3+glucocorticoid-induced tumor necrosis factor receptor (GITR)+ regulatory T (Treg) cell survival. Finally, engagement of GITR in NFATc2(−/−) mice induced IFN-γ levels in the airways, reversed the suppression by Treg cells, and costimulated effector CD4+CD25+ (IL-2Rα) and memory CD4+CD127+ (IL-7Rα) T cells, resulting in abrogation of carcinoma progression. Agonistic signaling through GITR, in the absence of NFATc2, thus emerges as a novel possible strategy for the treatment of human bronchial adenocarcinoma in the absence of NFATc2 by enhancing IL-2Rα+ effector and IL-7Rα+ memory-expressing T cells. [Cancer Res 2009;69(7):3069–76]

Supplementary Figure Legends 1-6 from A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes

Verletzungen der zentroaxialen (inneren) Hirnstrukturen sind ein nicht seltener Begleitbefund schwerer stumpfer Schadel-Hirn-Traumen (SHT) und werden seit Einfuhrung der Computer- (CT-) und Magnetresonanztomographie- (MRT-)Diagnostik in klinischen Studien haufig aufgefuhrt. Soweit sie Bestandteil einer disseminierten/diffusen allgemeinen Hirnschadigung sind, die auch unmittelbar lebensnotwendige Zentren betreffen kann, kommt ihnen klinisch keine herausragende Bedeutung zu. Das andert sich, wenn sie Quelle relevanter Blutungen in das Ventrikelsystem werden. Vorgelegt werden die Daten einer 676 Falle betreffenden makroskopischen neurophathologischen Untersuchung formalinfixierter Gehirne bei Todesfallen Erwachsener infolge stumpfer SHT der haufigsten Ursachen. Eine Beteiligung zentraler ventrikelnaher Hirnstrukturen war in 91 Fallen (13,5%) festzustellen. In 5 Fallen war es aus solchen zu Ventrikeltamponaden gekommen, allerdings nur in Fallen, in denen daneben weitere lebensbedrohliche intrakranielle Verletzungen erlitten worden waren. Isolierte innere Hirnverletzungen mit relevanten Folgen sind nach Angaben in der Literatur und auch dem eigenen Material Raritaten, die dann allerdings wegen der notwendigen Abgrenzung von Spontanblutungen erhebliche gutachtliche Schwierigkeiten bereiten. Dies wird an 2 Todesfallen mit erfolgter morphologischer Untersuchung und einem Gutachtenfall ohne Autopsiebefunde erlautert.

Die vorgestellte Auswertung umfasst 119 Falle von raumfordernden Subduralhamatomen (SDH), getrennt nach ihren Blutungsquellen: 45 aus Kortikalarterien, 29 aus Bruckenvenen und 45 aus Contrecoup-Verletzungen. Ziel der Untersuchung war es, Unterschiede und Gemeinsamkeiten hinsichtlich Einflussfaktoren, Verletzungsmustern und biomechanischen Komponenten zu erarbeiten. Alkoholismus und akute Alkoholisierung zum Zeitpunkt des Geschehens waren wie das Vorliegen einer Hirnatrophie in allen Gruppen annahernd gleich. Unterschiede fanden sich bei der Lokalisation von Kopfhautverletzungen; hierbei wiesen vaskulare Blutungsquellen haufiger exzentrische Gesichtsverletzungen und Contrecoup-Lasionen exzentrische Verletzungen der behaarten Kopfhaut auf. Hinsichtlich biomechanischer Komponenten konnten Contrecoup-Herde am ehesten einem Kontakttrauma mit fuhrend translatorischer Komponente zugeordnet werden. Dagegen war bei vaskularen Blutungsquellen und hier besonders bei denen aus Rindenarterien ein Nonkontakttrauma mit rotatorischer Komponente fuhrend. Von mitunter forensischer Bedeutung war die oft nur geringe Auspragung oder – bei SDH aus Rindenarterien in immerhin 2 Fallen – das vollstandige Fehlen von Hautverletzungen, die als Beleg fur eine traumatische Einwirkung angesehen werden und deren Richtung klaren helfen konnen.

In recent years, cardiopulmonary resuscitation (CPR) has been discussed as a cause of petechial hemorrhage in eyelids and conjunctivae, which could be of substantial significance to forensic expertises in cases of suspected strangulation. In the reported series or case observations, the combination of CPR and petechiae seemed to be sufficient to explain such a causal connection. Nearly all presented cases were victims for which the mechanisms resulting in death were themselves well-known causes explaining the development of such petechiae; and said mechanisms can frequently be observed in victims that did not receive CPR. An earlier, also retrospective, analysis of a series of forensic autopsies did not confirm CPR as a significant cause of conjunctival petechiae. Now we present the result of a prospective examination of 196 resuscitations of adult patients with separate assessment of petechiae being present even prior to resuscitation. Petechiae were present in 12 cases - but in eight of them prior to resuscitation already. Three other persons with petechiae found only after CPR were in the group of successfully resuscitated persons and exhibited petechiae hours after CPR during therapy in intensive care units - during a phase of ongoing cardiac insufficiency, which obviously caused them. The only case with petechiae observed neither immediately prior to nor after unsuccessful resuscitation, but during a follow-up examination one day later, needs to be discussed. It is not interpreted as reliable evidence for the causality of CPR though. Our interpretation of reports in literature as well as our experiences confirm the absence of actual proof of petechiae being generated by CPR and in the presence of generally significant doubts of this relation.

This review surveys subdural hematomas, including general knowledge presented in the literature as well as own experiences. Main topics are: frequency, causes, types, clinical symptoms, development, risk factors, prognosis of subdural hematomas and injured structures predominantly responsible for such bleedings. Focal points of the presentation are forensic aspects, not clinically important details. Generally, a reduction of the diagnosis as “subdural hematoma” seems to be problematic. Firstly a subdivision in “hematomas in patients with relevant injuries of the cerebral tissue” (like contrecoup-lesion) and “... without cerebral injury” (pure, respectively isolated) is necessary, because the predominant causes of such cases differ, and (forensic) experiences with one of these classes cannot be completely transferred to the other. Secondly, in pure subdural hematomas the source of bleeding, i.e. the type of injured vessel should be characterized - if ever possible. Ruptures of cerebral bridging veins are generally looked at as traumatically caused. In contrast, following clinical literature hemorrhages from cortical arteries sometimes occur spontaneously. This aspect seems to be not sufficiently discussed in forensic literature. An excursion to traumatic subdural hygromas rounds off this presentation.

In a series of 93 unselected forensic autopsies of adults the following volumes were measured: skull volume by filling a sac of synthetic material with water, placed intracranially, after removal of the brain and brain volume by its water displacement. Objective was to demonstrate if generally is there a relation between reduced difference of skull volume minus cerebral volume ("reserve volume"=RV, predominantly identical with cerebrospinal fluid compartment) and the presence of pressure marks (grooves) on the basis of temporal lobes (uncal grooves) and cerebellum (cerebellar cone). These alterations in post-mortem examination were usually regarded as signs of increased intracranial pressure during life. The obtained data were presented in diagrams. Most of the intracranial volumes were in the range 1200-1600 ml and brain volumes in the range 1200-1500 ml. The actual brain volume can be estimated by the multiplication brain weight *0.957. The RV in most cases was situated between 25 and 150 ml, corresponding 2-10% of the cranial cavity--increasing with increasing age of the persons. Clear uncal grooves (less distinct: cerebellar grooves) relate to significant decrease of the RV and the conclusion seems acceptable that this is indicative for intracranial displacement during life and is therefore an indirect sign of - at least local - brain swelling and increased intracranial pressure. However, to provide a well-founded basis for such a conclusion in a case under investigation a (semi quantitative) graduation of the intensity of such actual grooves seems to be recommendable.

Petechial hemorrhages or ecchymoses in the skin of the face and/or in eyelids and/or conjunctivae are one important feature in postmortem diagnosis of lethal strangulation. On the other hand, petechial bleedings can occur in various causes of death, especially in cases of neck or thoracic compression, they can occur in acute cardiac failure, as a result of blood or skin diseases or as a postmortem phenomenon. The focus of this investigation (retrospective study of 279 corpses, found initially in a prone position or some other face down position) was to analyse the frequency of postmortem (hypostatic) hemorrhages and factors which may influence their development. Petechial hemorrhages in livor mortis in the skin of the trunk and extremities were found in 110 cases (39%). The frequency ranged from 41% in the side position and 44% in the kneeling position to 50% in the prone position. Increasing intensity of livor mortis resulted in an increasing frequency of hemorrhages, up to 59%. In cases with a body-mass-index (BMI) of more than 26 the frequency of hemorrhages increased up to 64%. In cases without livor mortis when the corpses were found as well as in cases with complete movement of livor mortis after turning the corpses, no hemorrhages were found. If hypostasis was partly or completely fixed, the rate of hemorrhages increased up to 50%, without additional increase in longer postmortem intervals. Obviously postmortem petechiae develop neither very soon nor days after death, but within a period of several hours after death.

Bei der forensischen Untersuchung todlicher Subarachnoidalblutungen geht es mitunter um die Abgrenzung zwischen einer Spontanblutung und einem traumatischen Geschehen. Dies ist erst nach einer Identifizierung der Blutungsquelle und der Art der Gefaslasion moglich. Die konventionellen Nachweismethoden einer Aneurysmaruptur basieren auf einer zeitraubenden Praparation des Circulus arteriosus Willisii. Dabei konnen praparationsbedingte Artefakte in Form von Gefaseinrissen entstehen; trotz aller Muhe werden die Blutungsquellen so auch nicht in jedem Fall gefunden. Eine einfache rontgenologische Darstellungsmethode mit Einfuhren eines Kontrastmittels in die A. vertebralis und A. carotis interna wahrend der Obduktion kann fruhzeitig die Rupturstelle anzeigen. Unterschiedliche Rontgenbefunde von traumatischer und spontaner Subarachnoidalblutung konnen (bei bisher nur sehr begrenzter Erfahrung) sogar einen Hinweis auf die Art der Gefaslasion geben. In jedem Fall wurde bei uns eine gezielte Untersuchung der geschadigten Gefasregion erleichtert.

Suicides by ligature strangulation are rare events. In Berlin (3.5 million inhabitants; ca. 500 suicides per year) approximately one case per year occurs. Here, we present the main findings of 19 cases investigated between 1978 and 1998, compared to 47 cases of homicidal ligature strangulation. Two of the 19 suicidal victims had single fractures of the upper thyroid horns and one victim a fracture of a lower thyroid horn; other types of laryngohyoid injuries were not observed. In the homicidal series, the laryngohyoid structures were unaffected in 26 cases (12 of these victims were children or adolescents), single thyroid horn fractures were present in three cases and more significant injuries in 18 cases. Macroscopic bleedings of the laryngeal muscles were found in 12 victims of the homicidal group and in none of the suicidal. Bleedings in the neck muscles seldom occurred in suicides. According to these findings, the laryngohyoid injuries can be helpful in the differentiation of suicide from homicide, if more than a single thyroid horn fracture or a laryngeal soft tissue trauma is present.

The problems of assessment of aspiration (foreign bodies, stomach contents, food material) in forensic practical work are well-known, especially if 'suffocation due to aspiration' is considered to be the cause of death (or a concurrent cause of death). In the last 4 years (1998-2001) in the Department of Legal Medicine of the Free University, Berlin, 14 deaths with massive aspirations were investigated. The lethal aspiration cases consisted of seven men and five women between 55 and 91 years old, as well as two children (boy 6 years and girl 19 months old). All but one of the victims had severe neurological alterations (dementia, apoplexia, sequelae of head injuries). In six cases the victims died during or a short time after a meal; they had been fed by the nursing staff, a family member or another caregiver. The witness statements pertaining to clinical symptoms or the course of events ranged from 'no symptoms' to intensive cyanosis, congestion and no clear reactions of distress.

Zusammenfassung Es werden die Standardmethode der Kehlkopfpraparation bei der forensischen Obduktion sowie deren Unzulanglichkeiten bei geringfugigen morphologischen Veranderungen und Verletzungen beschrieben. Ein detailliertes Untersuchungsprotokoll fur Routine- und forensisch relevante Falle wird vorgestellt. Diese Sektionstechniken sollen sicherstellen, dass Verletzungen am Schildknorpel, am Ringknorpel und am Zungenbein entdeckt, dass Einblutungen der kleinen Kehlkopfmuskeln gefunden, und Kapsel- oder Gelenkblutungen der Kehlkopfgelenke nicht ubersehen werden und dass artifizielle Verletzungen, die zu Missinterpretationen fuhren konnen, ausgeschlossen werden.

Vor dem Hintergrund der aktuellen Diskussionen in unserer Fachgesellschaft uber einen effektiven praktischen Studentenunterricht im Fach „Rechtsmedizin“ stellen wir den Ablauf unseres Kurses „Rechtsmedizin“ vor. Neben den Vorlesungen zur Rechtsmedizin und zur arztlichen Rechts- und Berufskunde, die sich am Gegenstandskatalog orientieren, konzentriert sich unser Kurs auf die arztliche Leichenschau sowie die forensische Verletzungskunde. Bei der Leichenschau lernen die Studierenden die korrekte Einordnung der Todesart sowie ihre arztlichen Pflichten im Zusammenhang mit den Bestattungsgesetzen. Bei der Verletzungskunde werden sie uber die richtige Befunderhebung und Dokumentation sowie Rekonstruktion von Verletzungsbefunden geschult. Jeder Studierende bekommt 28 Stunden im Kleingruppenunterricht, verteilt uber 12 Wochen. Der Kurs beinhaltet 12 Stunden im Horsaal, 7 Stunden praktischer Unterricht an der Leiche, 5 Stunden systematische Verletzungskunde im Seminarraum sowie ¶3 Stunden Prufungen und 1 Stunde ein freier Test uber Todesarten. Die Prufungen in der 3., 9. und 12. Woche haben sich als Wissenskontrollen bewahrt.

Fragestellung. Angesichts einer kontroversen Diskussion in der Literatur, ob lebensbedrohliche intrakranielle Verletzungen mit Subduralblutungen bei Sauglingen (im 1. Lebensjahr) durch sog. Bagatelltraumen moglich sind, sollte eine Ubersicht uber todliche Falle dieser Art gegeben werden. Inhalt der Untersuchung waren keine Falle mit Schadelbruch und fokalen Hirnverletzungen, sondern isolierte Subduralblutungen. Methodik. Auswertung der amtlichen Todesursachenstatistik von Berlin (1978–1998) sowie des Obduktionsmaterial des Instituts fur Rechtsmedizin der FU Berlin (1978–1999). Ergebnisse. In der amtlichen Todesursachenstatistik findet sich kein einziger Todesfall eines Sauglings, der als Folge eines unfallmasigen Sturzes aus geringer Fallhohe angesehen wurde. In unserem Institut wurden 21 todliche Kopftraumen bearbeitet, von denen 10 den oben genannten Kriterien entsprachen; in keinem war nachvollziehbar von einem Bagatelltrauma auszugehen. Schlussfolgerungen. Die Kombination mehrere/multiple Bruckenvenenrupturen, Ausbleiben einer raumfordernden Subduralblutung und Koma oder Todeseintritt ist mit der Annahme eines unfallmasigen Bagatelltraumas nicht vereinbar.

This article gives a short overview of medical education in Germany. The legal basis and organization of the medical studies program as well as the course in forensic medicine and the training duration for forensic pathologists are described.

A 62-year-old man with a long history of lung disease developed atelectasis of the right middle lung lobe, caused by a protrusion in the wall of the middle lobe bronchus. A biopsy was performed in the suspicious region. This was immediately followed by massive arterial bleeding into the airways and complicated by cardiac arrest soon after. The bleeding could not be controlled by nonsurgical treatment; the patient died 24 h after the complication because of pulmonary insufficiency. Autopsy revealed the bleeding to have been caused by a biopsy injury of a bronchial artery that had run superficially in the bronchial mucosa and had produced the intrabronchial protrusion. Several other abnormal intrabronchial arteries were found peripherally in this lung.

Experimental data and clinical as well as postmortem experiences have indicated that subdural hematomas are less frequent in acceleration injuries in traffic accidents compared to falls or assaults. The present report demonstrates that this does not hold true in the same way for bridging vein ruptures (one of the predominant causes for subdural bleedings). Ruptures of these vessels without subdural bleeding (SDB) are only seldom mentioned in the literature. However, if no SDB is present, no one will look for these structures. In our institute a systematic analysis of the bridging veins in all cases of lethal blunt head injury is made: prior to the careful morphological preparation we investigate these vessels by radiographic imaging after filling with contrast medium. 6 car passengers (age between 4 and 31 years) which suffered a lethal head injury were examined in the last year. 2 victims had impressed fractures with cerebral compression injuries. In 1 case the base of the skull was broken and in 3 cases no skull fracture was present; no serious focal brain injury had occurred in these 4 cases, but 3 victims had signs of diffuse brain injury. In 5 cases a direct impact of the head against the interior of the car was obvious. In 5 cases ruptures of several bridging veins could be demonstrated. In one case (survival for 3 days) a minor SDB (20 ml) was present and the ruptures had been closed by thrombosis; another victim died at the scene. The other 3 victims survived between 4 and 15 hours without developing SDB and without closing of the ruptures by thrombosis. This combination is surprising and shows that our knowledge concerning the relationship between bridging vein ruptures and SDB is restricted. The frequency of bridging vein lesions in severe head injuries is likely underestimated in the clinical as well as in the postmortem literature. A rapid increase of intracranial pressure after the accident resulting in a collapse of the cerebral circulation is probably responsible for the absence of the SDB in the presented cases.

To expand the passive safety of automobiles protecting traffic participants technological innovations were done in the last decades. Objective of our retrospective analysis was to examine if these technical modifications led to a clearly changed pattern of injuries of pedestrians whose death was caused by the accidents. Another reduction concerns the exclusion of injured car passengers – only pedestrians walking or standing at the moment of collision were included. We selected time intervals 1975–1985 and 1991–2004 (=years of construction of the involved passenger cars). The cars were classified depending on their frontal construction in types as presented by Schindler et al. [Schindler V, Kuhn M, Weber S, Siegler H, Heinrich T. Verletzungsmechanismen und Wirkabschatzungen der Fahrzegfrontgestaltung bei Pkw-Fusganger-Kollisionen. Abschlusbericht im Auftrag der Deutschen Versicherungswirtschaft e.V. TU-Berlin Fachgebiet Kraftfahrzeuge (GDV) 2004:36–40]. In both periods more than 90% of all cars were from the usual types small/medium/large class. Hundred and thirty-four autopsy records of such cases from Department of Forensic Medicine (Charite Berlin) data were analysed. The data included technical information of the accidents and vehicles and the external and internal injuries of the victims. The comparison of the two periods showed a decrease of serious head injuries and femoral fractures but an increase of chest-, abdominal and pelvic injuries. This situation could be explained by an increased occurrence of soft-face-constructions and changed front design of modern passenger cars, resulting in a favourable effects concerning head impact to the car during accident. Otherwise the same kinetic energy was transferred to the (complete) victim – but because of a displacement of main focus of impact the pattern of injuries modified (went distally).

Fragestellungen: Lassen sich neben dem bekannten Faktor „Todesursache“ weitere Faktoren ermitteln, die die Entstehung petechialer Blutaustritte im Kopfbereich begunstigen? Gehoren kardiopulmonale Reanimationsmasnahmen (REA) hierzu? Material, Methode: a) Auswertung von 473 fortlaufenden, fur die Fragestellung geeigneten Obduktionen eines Untersuchers. Ausgenommen blieben faulnisveranderte Leichen, Bauchlagefalle, Leichen mit gravierenden Gesichtsverletzungen durch Feuer oder stumpfe Gewalt und (mit Ausnahme von Ertrinkung) Erstickungs- sowie Strangulationsfalle; b) Analyse von 181 Herztodesfallen des Institutes (alle Untersucher). Ergebnisse: Petechien fanden sich in 13,3% aller Falle, mit deutlicher Abhangigkeit von der Todesursache: bis zu 31% bei Brandtodesfallen, Intensivpflegepatienten und kardialen Todesfallen. Bei im mittleren Lebensalter Verstorbenen waren Petechien deutlich haufiger (> 20%) als bei alten Personen (< 10%). Mit zunehmender Korpermasse stieg der Anteil an Fallen mit Petechien an und war bei extrem adiposen Personen wieder geringer. Auch mit Zunahme des Herzgewichtes stieg die Frequenz beobachteter Petechien. Vordergrundig scheint ein Zusammenhang zwischen REA und Petechien vorzuliegen: Bei Todesfallen ohne REA fanden sich petechiale Blutungen in 11%, bei REA in 19% (χ2: p < 0,05). Dieser (dann aber nicht mehr statistisch signifikante) Unterschied war jedoch nur bei solchen Todesursachen vorhanden, bei denen Petechien ohnedies haufig sind (insbesondere Koronartod), und auch nur bei jungeren, nicht jedoch bei alteren Personen. Bei vielen anderen Todesursachen bestand dagegen keine Differenz in der Inzidenz von Petechien mit bzw. ohne REA. Schlusfolgerung: Neben der Todesursache spielen weitere Faktoren (Alter, Korpermasse, moglicherweise auch das Herzgewicht) bei der Entstehung von Petechien eine Rolle. Reanimationsmasnahmen werden demgegenuber nicht als eigenstandiger Kausalfaktor fur die Entstehung petechialer Lid- und Konjunktivalblutungen angesehen.

Bei der Festnahme eines fluchtenden oder sich wehrenden Verdachtigen durch Polizeikrafte kann es zum Todeseintritt kommen. Es wird uber zwei solche akute Todeseintritte von Mannern berichtet. In beiden Fallen wurde trotz anfanglichen Verdachts auf einen direkten Zusammenhang des Todes mit polizeilichen Masnahmen (z. B. Halskompression bzw. „Schwitzkasten“; Brustkorbkompression) eine Cocainintoxikation diagnostiziert, die letztlich als Todesursache angenommen wurde. Als Vergleich wurden aus dem Obduktionsgut des Institutes 12 weitere Falle mit einer Mono-Intoxikation durch Cocain als Todesursache oder Nebenbefund ermittelt. 5 der 12 Falle gehen auf eine Schusverletzung zuruck, 4 wurden als Suizide eingestuft. Die Analyse last an eine erhohte Gewaltbereitschaft gegen sich oder andere Personen der unter dem Cocaineinflus stehenden Personen denken. In beiden Fallen trat ein Herzstillstand schlagartig und unerwartet fur alle Beteiligten auf, die aufgrund der intensiven Flucht- oder Widerstandsversuche der Tater keine Gefahr einer akut lebensbedrohlichen Situation sahen. Auf Falle dieser Art sollte bei der Ausbildung von Polizeikraften hingewiesen werden.

Vergleichsanalyse von Subduralhamatomen (SDH) mit bzw. ohne weitere Schadel-Hirnverletzungen. Methode, Untersuchungsgut: 166 todliche stumpfe Schadel-Hirn-Traumen (SHT) 1987–1997; ein Untersucher. Im Material enthalten waren 42 SDH bei starken Hirnkontusionen und 30 isolierte SDH. Resultate: Bei SHT mit eindeutiger Ursache und Verletzungsrichtung (Beispiel: Sturze aus dem Stand) hing die Haufigkeit eines SDH von der Richtung der Gewalteinwirkung ab: bei occipitalem Aufschlag lag in 12 von 38 Fallen ein SDH vor, bei lateralem in 12 von 17 und bei frontalem in 4 von 5 Fallen. Falle mit isoliertem SDH unterschieden sich deutlich von den mit Hirnverletzungen kombinierten SDH, u.a. durch die Verletzungsumstande, das Vorliegen von Schadelfrakturen, die Haufigkeit noch erfolgter Klinikeinlieferungen und Trepanationen sowie den Anteil chronischer Alkoholiker. Aufgrund von Befunden und Umstanden her „unverdachtige“ Sturzereignisse lagen 28 von 42 Fallen bei SDH mit Kontusion, aber nur 11 von 30 bei isoliertem SDH zugrunde; bei Fremdeinwirkungen waren dies 5/42 bzw. 8/30 Falle; nicht zwischen Unfall und Fremdeinwirkung zu unterscheiden war bei der ersten Gruppe nur ein Fall, beim isolierten SDH waren es 11 von 30. Schlussfolgerung: Das „isolierte SDH“ ist gutachtlich oft besonders problematisch, da hier haufig folgende Faktoren kombiniert sind: dubiose Umstande, verdachtige Verletzungen, aber keine vom Befund her allein beweiskraftige Rekonstruktion der Art der Einwirkung moglich. In diesen Fallen ist ein besonders vorsichtiges und aufwendiges praparatorisches Vorgehen bereits von der Entnahme des Gehirnes an notwendig, um uber den Nachweis der Blutungsquelle die Frage nach einer tatsachlich traumatischen Genese zuverlassig beantworten zu konnen.

Im Marz 1997 wurden alle 459 in Berlin praktizierenden Chirurgen und Orthopaden schriftlich nach ihren Erfahrungen mit atraumatischen und posttraumatischen HWS-Beschwerden befragt. Der Rucklauf betrug rund 25%. Bemerkenswerterweise beeinflusten personliche Unfallerfahrungen (als Fahrzeuginsasse) die Sichtweise der Arzte: von den 26 Arzten mit eigenen posttraumatischen HWS-Beschwerden hielten 54% eine solche Symptomatik fur traumaspezifisch, wahrend dies nur 35% der 40 Arzte mit Unfallen, aber ohne HWS-Beschwerden so sahen. 22% der Arzte ohne Unfallerfahrung gegenuber 62% der Arzte mit bezogen auf die HWS folgenlosem Unfall gaben an, materielle Begehrlichkeiten von Patienten wurden haufig in Symptomatik und Behandlung eine Rolle spielen. Angesichts seiner speziellen Beziehung zum Patienten sowie aufgrund der typischen Befundarmut des Beschwerdebildes hat es der behandelnde Arzt allerdings schwer, von ihm u. U. als uberzogen empfundenen Begehrlichkeiten entgegenzutreten.

Im Gegensatz zu vielen klinischen Angaben gibt es von pathologisch-anatomischer Seite keine uber bei verschiedenen postmortalen Fallgruppen beobachtete Fullungsvolumina der Gallenblase (GBV). Es sollte ein Vergleichsmaterial zu verstorbenen Krankenhaus- und vor allem Intensivpflegepatienten erarbeitet werden, bei denen abnorme GBV haufig sind. Basis waren 628 fur die Fragestellung geeignete Falle einer fortlaufenden Serie gerichtlicher Obduktionen 1988–1995. Das Untersuchungsgut war durch einen hohen Anteil geringen GBV charakterisiert: in 72% der Falle wurden 10 ml nicht uberschritten. Die Mittelwerte des GBV betrugen im Gesamtmaterial 11,8 ml (m: 12,9 ml; w: 9,6 ml). Ohne klaren Einflus waren eine blande Cholelithiasis sowie eine hohe Korpermasse (Body Mass Index). Mit zunehmendem postmortalen Intervall stieg der Anteil kaum gefullter GB etwas an. Die niedrigsten GBV fanden sich bei akuten Todesfallen (Koronartod: 8,7 ml; stumpfe Gewalt: 6,3 ml), deutlich hohere bei Intoxikationen (11,2 ml), ubrigen naturlichen Todesfallen (12,1 ml) und chronischen Alkoholikern (17,6 ml). Die GBV lagen deutlich unter den an Lebenden gewonnenen Volumina. Ein postmortaler Flussigkeitsverlust wird ebenso diskutiert wie eine von der Agonieform abhangige (Teil-)Entleerung im Todesgeschehen.

Reported is the case of a 36-year-old man with neurofibromatosis type 1 with lethal haemorrhage from rupture of the left common iliac artery. Histologically and immunohistochemically, no hints on angiodysplasia as a possible cause of bleeding were detected. Considering the literature and the histological findings in the area of rupture, a local weakness of the vascular wall caused by the neighbouring neurofibromatous proliferates was most probably the reason for bleeding.

Subdural hematomas (SDH) are a frequent autopsy finding in victims of closed head injuries. About 2/3 of the cases in our own massive SDH series had brain contusions as a cause of bleeding. In about 1/3 of the cases, SDH resulted from ruptured vessels of the brain surface in the absence of contusions. Our experience has shown that such an "isolated" SDH may be expected in about 5% of fatal blunt head injuries. A technique is presented to detect bridging vein leakage before there is any risk of artificial damage. After sawing through the skull in the fronto-occipital plane and cutting through the upper half of the brain together with the calvarium, approximately 5-10 ml of barium sulfate are instilled into the superior sagittal sinus by a balloon catheter at low pressure, and X-rays are taken. If there is extravasation, the rupture is visible before further preparation.

Report of a suicidal mono-intoxication with the class IC antiarrythmic drug propafenone. A 20-year-old female physician's assistant secretly ingested the substance (presumably 20 tablets per 300 mg) about 4-6 h before her death, and in the interim remained under the supervision of her physician. An ECG taken about 1/2-2 h after ingestion showed widening of the QRS complex and signs of an acute load of the right ventricle; the clinical symptoms were nausea, vomiting and hypotonia. After about 4 h without serious symptoms acute loss of consciousness and cardiac failure occurred, resuscitation efforts remained unsuccessful. At autopsy propafenone was found in blood (12 micrograms ml-1), liver (60 micrograms g-1) and cardiac muscle (11 micrograms g-1).

Vergleichende Untersuchung der Stauungsveranderungen am Kopf von 90 Opfern von Totungsdelikten mit Angriff gegen den Hals: petechiale Blutaustritte und allgemeine Blutstauung der Gesichtshaut. Der klinisch definierte Begriff „Zyanose” wird in der Regel nicht verwendet, ausgenommen bei sehr fruh nach dem Tod erfolgter Untersuchung der Leiche. Die Blutstauung der Gesichtshaut wurde in 3 Graden erfast (blas, mittel, stark gestaut). Im Hauptteil des Untersuchungsgutes (Rukkenlage, kein am Hals liegendes Strangwerkzeug, N=55) zeigte sich nach Erdrosseln haufiger ein blutgestautes Gesicht als beim Erwurgen. Entscheidende Faktoren fur das Auftreten dieses Befundes sind aber auch der Korperbau und die damit zusammenhangende Ausdehnung der Livores: Zunahme der Korperfulle ist verbunden mit einer Zunahme der Livores und dies mit einer solchen der Blutfulle auch der Gesichtshaut. Petechien waren mit Ausnahme von 3 Fallen vorhanden; davon wiesen 2 eine konkurrierende andere Todesursache auf. Bei Erwurgten (deren Gesicht in etwa 2/3 der Falle blas war) zeigte sich ein Uberwiegen stark entwickelter Petechien bei jungen und gering ausgepragter bei alten Personen. Beim Erdrosseln war die Intensitat von Petechien bei den mittleren und hoheren Altersgruppen starker als beim Wurgen; auch hier mit Trend zur geringeren Intensitat in hohem Alter. Vermutlich postmortale — oder von solchen nicht abgrenzbare — Blutaustritte (Vibices) waren bei wenige Stunden anhaltender Bauchlage (vollig um lagerbaren Livores) in keinem Fall, bei partiell fixierten in 2 von 9 und bei fixierten Livores in 5 von 6 Fallen vorhanden.

Autopsy findings and neuropathological examination of formalin-fixed brains in 676 deaths due to blunt head injury, here with special attention to injuries of the inner (periventricular) cerebral structures and haemorrhages into the ventricles. Intraventricular haemorrhage of any degree was present in 17.6%, considering only distinct and massive haemorrhage in 10% of all cases. Considering the types of trauma, the frequency was lowest in ground level falls and highest in traffic accidents (pedestrians with head contact to the car) - indicating a relation between the severity of impacts and the likelihood of ventricular haemorrhage. They predominantly resulted from periventricular injuries (27%) or retrograde expansions of infratentorial lesion with subarachnoid bleeding (19%), from massive contrecoup lesions (14%) or deep intracerebral ruptures (13%). In cases with predominant lesions of the cerebral surface the rate was lower than in those with more diffuse or internal damages. Injuries of the internal cerebral regions (away from cortex and subcortical white matter) were classified into those directly affecting the periventricular structures (9.1-13.5%; half of them affecting corpus callosum and/or fornix) and lesions of deep white matter or basal ganglia not adjoining the ventricular walls (4.0-5.9%). Intraventricular haemorrhage as well as injuries of the inner cerebral structures mostly are one element of a complex and severe blunt head injury. Solitary lesions - without other intracranial findings clearly indicating a trauma and therefore cases producing difficulties in forensic classification (spontaneous? traumatic?) - are rarities according to literature as well as our experiences.

Cell based therapy has become a new and attractive option for the treatment of cardiac disease and heart failure. Although it has been demonstrated in vitro and in vivo that differentiation of non-differentiated cells (progenitor cells) into cardiomyocytes is able even in adult hearts the potential use of such transdifferentiation processes is limited by the small number of cells that home and engraft in the myocardium and complete the transdifferentiation process. Therefore, cell recruitment to the damaged heart is a major challenge to improve any cell based therapy. This process requires homing and engraftment of stem or progenitor cells. Major strategies to improve stem or progenitor cell homing are based on an improvement of stem or progenitor cell mobilization from the bone marrow. Strategies that have been shown to be successful are those that use granulocyte colony-stimulating factor (G-CSF). But although cell mobilization was indeed successful no major impact on hemodynamics was found. Alternatives are therefore needed and experimental studies use parathyroid hormone, statins, erythropoietin, and others in addition to or as an alternative to G-CSF. Although each of these procedures does have an impact on cell mobilization and homing none of these studies has provided a direct evidence that a major improvement on top of standard pharmacological therapy can be expected from such strategies. In conclusion, improvement of stem cell homing is a major challenge in the development of successful cell based therapies but not yet improved to a clinical relevant status. The underlying concepts of different strategies will be discussed here.

To expand the passive safety of automobiles protecting traffic participants technological innovations were done in the last decades. Objective of our retrospective analysis was to examine if these technical modifications led to a clearly changed pattern of injuries of pedestrians whose death was caused by the accidents. Another reduction concerns the exclusion of injured car passengers--only pedestrians walking or standing at the moment of collision were included. We selected time intervals 1975-1985 and 1991-2004 (=years of construction of the involved passenger cars). The cars were classified depending on their frontal construction in types as presented by Schindler et al. [Schindler V, Kühn M, Weber S, Siegler H, Heinrich T. Verletzungsmechanismen und Wirkabschätzungen der Fahrzegfrontgestaltung bei Pkw-Fussgänger-Kollisionen. Abschlussbericht im Auftrag der Deutschen Versicherungswirtschaft e.V. TU-Berlin Fachgebiet Kraftfahrzeuge (GDV) 2004:36-40]. In both periods more than 90% of all cars were from the usual types small/medium/large class. Hundred and thirty-four autopsy records of such cases from Department of Forensic Medicine (Charité Berlin) data were analysed. The data included technical information of the accidents and vehicles and the external and internal injuries of the victims. The comparison of the two periods showed a decrease of serious head injuries and femoral fractures but an increase of chest-, abdominal and pelvic injuries. This situation could be explained by an increased occurrence of soft-face-constructions and changed front design of modern passenger cars, resulting in a favourable effects concerning head impact to the car during accident. Otherwise the same kinetic energy was transferred to the (complete) victim - but because of a displacement of main focus of impact the pattern of injuries modified (went distally).

OBJECTIVE: Although the literature concerning subdural hematomas (SDHs) is vast, few data are available as to the sources and related clinical differences of SDHs. Pure SDHs of arterial versus venous origin should be compared in terms of cause, size, space-occupying effect, and form. METHODS: We analyzed data from 46 patients who died as a result of pure SDHs. Twenty-three SDHs resulted from bridging vein ruptures and 23 from torn cortical arteries. We performed a morphometric analysis of the intracranial situation on the horizontal plane at the level of the greatest fronto-occipital diameter. We included in our analysis the clinical one-dimensional parameters (e.g., hematoma thickness, midline shift); the areas of the hemispheres, the SDHs, and their displacement; and the hematoma volume. RESULTS: Most of the investigated postmortem characteristics of both types of hematomas were similar, with the exception of the form and the midline shift. SDHs resulting from arterial ruptures (which are generally located in the temporoparietal region) differ in form from those caused by bridging vein ruptures (which typically rupture in the frontoparietal parasagittal region). CONCLUSION: The form difference allows the probable rupture site to be estimated; this observation might prove useful for clinical purposes.

Fractures of the upper thyroid horns are a frequent finding after a variety of neck injuries - resulting from a direct mechanical trauma, e.g. compression of the neck in manual strangulation or ligature strangulation, from blunt injuries (falls or blows against the neck), and sometimes from indirect trauma (whiplash-injuries). Although it is well known that thyroid horns can be broken with relatively little pressure, no quantitative data are available in the literature. In an experimental investigation, the isolated thyroid cartilage was prepared (divided into two parts, measured, X-rayed, photographed, embedded in paraplast) and clamped in a simple apparatus. Weight was applied on the upper thyroid horn (imitating pressure on the horns), beginning with 1 kg and gradually increased by increments of 250 g to a maximum of 8 kg, until an 'injury' occurred. In this study, 120 thyroid cartilages (77 men, 43 women, 16-95 years) were investigated. The location of the fractures was in nearly all cases the base of the horns. The mean weight resulting in an injury of the horn was 3 kg (men: 3.3 kg, women: 2.6 kg). The required weight was dependent on the degree of ossification. The highest rate of fractures was found in cases with incomplete ossification; in cases without ossification, specimens often remained macroscopically uninjured.

In the usual method of brain removal in forensic autopsies, the upper bridging veins were invariably torn. There are several types of head injuries, in which ruptures of these vessels are the predominant intracranial injury. For the past 5 years we have investigated nearly all cases of lethal head injuries by a simple X-ray method (axial X-ray after instillation of contrast material into the superior sagittal sinus). The evaluation of the 350 X-rays which were available until today can be summarized by the following statements. (a) Anatomy of the parasagittal bridging veins: regarding the numbers and diameters of the veins, we can separate cases with many bridging veins of small diameter from a group with few veins of a large diameter. (b) Causes of injury and direction of impact: bridging vein ruptures resulted more often from frontal than from occipital, parietal and lateral impacts and occurred in traffic accidents in the majority of our cases.

We compared the lungs of six drowned and six non-drowned persons over 70 to determine whether there is evidence of acute overinflation in drowning that can be distinguished from senile lung emphysema. All left lungs underwent intrathoracic formalin fixation to preserve their state of insufflation. To assess the effects of lung collapse, all right lungs were sectioned as usual and then immersed in formalin. After histological processing, microphotography and image processing of 12 specimens per corpse, 50 binary images of each specimen were measured by computerized morphometry. Intrathoracic fixation resulted in significantly less tissue area (and more airspace) in the left than in the right lungs of both groups. Comparing both groups' left lungs revealed that the interalveolar septa were thinner and the area occupied by connecting nodes smaller in drowning; these single nodes also tended to be smaller. There was a tendency for less alveolar tissue area per image in drowning than in control lungs and for narrow tissue structures to comprise a higher percentage of both the total tissue area and total tissue perimeter per image. We conclude that there is morphological evidence of acute overinflation even in senile lungs, but this is masked by postmortem lung collapse as suggested by the overlapping values of the right lungs. Support to the diagnosis of drowning among drowned elderly patients can only be available in lungs subjected to intrathoracic postmortem fixation.

congenital diaphragmatic hernia (CDH) in the prediction of neonatal survival. Methods: Between January 2006 and December 2009, the lung-tohead ratio was evaluated before and every two weeks after FETO in cases of severe isolated CDH (LHR

Case report on a suicide with a gas pistol loaded with 8 mm blank cartridges. A 58-year-old male shot himself in the right temple and then in the back of the neck. The contact shot wounds showed large wound cavities with interspersed powder particles. The soft tissues were injured solely by the pressure of the exploding powder. Death was due to an air/gas embolism in the right ventricle of the heart.

Hemorrhages of the tongue can be useful for the diagnosis in cases of lethal neck compression. The reported frequencies of tongue bleedings in the literature in cases of suicidal hanging range from 0 to 14% and in homicidal strangulation (str.) from 5 to 37%. This study gives a summary of the incidence and intensity of tongue bleedings in cases of homicidal str. by ligature, manual str., suicidal str. by ligature and suicidal hanging. In 25% of all homicides significant or massive hemorrhages of the tongue were detected. In contrast to this, in suicidal hanging the tongue was unaffected in 95%. The causes of massive hemorrhages here (2%) could be explained by an “abnormal” position of the loop.

In the last years, the discussion concerning the causes of infantile subdural hemorrhages became controversial. Many authors still suppose that child abuse is the predominant cause of such cases. On the other hand, reports presenting series of accidental cases were published, and the fear of an overdiagnosis of the shaken baby syndrome has been expressed. Our autopsy material concerning all lethal head injuries of infants and toddlers from 2 decades was reviewed. 17 of these 64 cases were characterized by the following: history of no trauma or only an insignificant event; children found dead or apnoic or in coma; no skull fractures; no focal brain injury; ruptures of several bridging veins but only minimal subdural bleeding. 11 victims were infants (1st year of life) and either 3 were 2 years resp. 3 - 6 years old; 50 % off all lethal head injuries of infants were of this type, while only 25 % resp. 10 % of the following age groups. None of these 17 cases was a result of a minor accident witnessed by unrelated persons. Abuse could be ascertained with a high degree of probability in most cases and remained quite likely in the others. Two different types of subdural hemorrhages should be kept from another: a) patients suffering a moderate head injury from a minor accident which results in a subdural bleeding (from a small intracranial lesion) often do not deteriorate soon after the impact, develop a hemorrhage of significant volume, respond well to therapy and have a good prognosis. b) cases with a history of no or only of an insignificant trauma, infants dead or nearly dead on clinical presentation, often a poor outcome in cases of survival. There is typically no significant subdural bleeding despite multiple bridging vein ruptures in the majority of these cases: the subdural hemorrhage is here only a visible sign of a much more serious and general cerebral alteration, resulting in a rapid increase of intracranial pressure (often complicated by respiratory arrest) which prevents a signifant bleeding into the subdural space. This combination of findings is typically found in victims of massive events (car occupants in high-velocity crashes) and not compatible with a supposition of a minor fall causing this.

The discussion concerning the causes of infantile subdural bleedings (SDB) has become quite controversial in recent years. The interpretation that most of these cases are the result of abuse, especially by the shaken baby syndrome (SBS), was doubted, and the role of accidental events was emphasized. Because of the lack of a reliable history and insignificant other findings, the conclusion of a SBS is not seldom drawn indirectly. In contrast to most other reports, the reliable demonstration of bridging vein (BV) ruptures is a standard element of postmortem diagnostics in our institute. In this way, a mechanical trauma can be identified as the cause of the child's death without any doubt, and if several BVs are torn, a trauma of significant degree can be concluded. Our methods of investigation are presented and typical examples are imaged. Furthermore, the occurrence of accidental and non-accidental lethal head injuries of infants and toddlers (up to 5 years old) in the city of Berlin has been analyzed, based on the official statistics of the causes of death in the city of Berlin (1978-1998) and the autopsy material of our institute (1978-1999). In this period, not a single death of a child due to an undoubted minor fall was recorded.

Recently the discussion concerning the causes of infantile subdural bleedings (SDB) has become quite controversial. The wide-spread interpretation that most of these cases are the result of abuse, especially by the shaken-baby-syndrome, was doubted, and the role of (even minor) accidental events was emphasized.This situation should be analyzed basing on the official statistics of the causes of death in the city of Berlin (1978-1998) and the autopsy material of our institute (1978-1999).In this period, approximately 440.000 children lived their first year of life in our city. Only 80 violent deaths of infants (up to 1 year old) were recorded in the official statistics, including 27 deaths due to blunt forces, with 24 lethal head injuries as the main group. Only two cases were attributed to "falls under unclear conditions"; all other accidental cases were the results of traffic accidents or falls from a height. No death due to an undoubted minor fall was recorded, nor was any in our autopsy material. We investigated 10 cases of infantile SDB, all without skull fractures and gross brain injuries. Only 1 victim had a SDB of a significant volume; in all other cases only small amounts of blood were present in the subdural space. Bridging vein ruptures were directly demonstrated in 8 cases and were bilaterally in most instances; recently their detection has been simplified by postmortem x-ray using contrast material. All 10 cases were interpreted as typical acceleration-deceleration injuries (as in shaking), although only in 2 cases a confession of this procedure could be obtained.Comparing cases of accidental and non-accidental SDB in the literature, infantile SDB obviously cannot be looked at as a homogeneous entity: two quite different types should be kept separate: the patients suffering from an accidental SDB due to a minor fall mostly do not deteriorate immediately after the trauma, develop SDB of some volume, up to a space-occupying mass lesion, and have often a good prognosis. A lethal outcome is extremely uncommon; we have not observed a single case of an infantile lethal SDB resulting from such a minor injury for more than 20 years. The source of the SDB in those cases currently is unknown in most instances. The second group of infantile SDB includes the well-known group of shaken-baby-syndrome: no adequate history, infants dead or nearly dead on clinical presentation, often a poor outcome if the event is survived, typically no significant volume of SDB, and--according to our experiences--in all cases BV ruptures. This combination of several BV ruptures with no significant subdural bleeding is not compatible with a supposition of a minor fall causing this.

Are any other factors besides the factor "cause of death" involved in the development of petechial hemorrhages (PET) of the head? The significance of the cause of death is well known, other factors have been rarely investigated in medical literature. Do they include cardiopulmonary resuscitation (CPR), as has been claimed in several forensic publications?(a) 473 consecutive autopsy cases (without strangulation) evaluated by one examiner, which were appropriate for this investigation; (b) analysis of 181 cardiac deaths (investigated by all physicians of our institute).Petechiae were found in 13.3% of all cases and were clearly dependent on the cause of death, up to 20% were found in burn victims, intensive-care patients and cardiac fatalities. Petechiae were more frequently observed in the middle age groups (20%) than in old persons (10%). The number of PET cases increased with body mass but was lower in extremely obese persons, a greater number of cases with PET was also observed with increasing heart weight. PET were observed in 11% of the deaths without CPR compared to 19% with CPR. This difference was predominantly caused by the subgroup "acute coronary death", especially if victims younger than 60 years were considered, whereas in many other causes of death no difference in the prevalence of PET with or without CPR could be observed.Besides the cause of death, other factors (age, body mass and possibly even heart weight) influence the development of petechiae. The hypothesis that CPR alone produces PET is not confirmed by our experience.

Report of two cases of lethal infantile subdural bleedings (SDB). Bridging vein (BV) ruptures were directly proven as the source of the (minimal) SDB by a postmortem X-ray. In the controversial discussion concerning the causes of infantile SDB, proof of the occurrence of several BV ruptures is seen as an important sign of a trauma of significant degree. Although infantile SDB undoubtedly can result from accidental as well as intentional injuries, and therefore, the SDB itself does not allow far-reaching conclusions as to the cause of injury, the presence of several BV ruptures combined with an SDB of insignificant volume, in an infant dead or in a deep coma on clinical presentation, is not compatible with the supposition of a minor fall as the cause. We have not observed such findings as the result of a minor accidental event for more than 15 years.