TRPC6 is altered in COVID-19 pneumonia.

In this Letter to the Editor supportive data were presented to a recent paper published in this journal reporting the involvement of TRP channels in COVID-19 pneumonia and its role for new therapies. Since gene expression of TRP channels was found in human lung tissues the protein was not being reported so far. TRP channels are supposed to be involved in the pulmonary inflammation and its symptoms such as fever, cough and others. Here, TRPC6 was investigated in tissues of normal human lungs and of SARS-Cov-2 infected lungs in a preliminary study. Tissue was obtained post mortem from anatomical body donations during dissections and during pathological dissections (13 normal, 4 COVID-19 pneumoniae) and processed for immunohistochemistry. In normal lungs TRPC6 was found in the ciliated epithelium, in the wall of larger lung vessels and in the alveolar septa. In COVID-19 pneumonia the distribution of TRPC6 was different. Inflammatory lesions, cellular infiltrates, hyaline membranes and fibrosis were labelled intensively as well as dilated capillaries. These observations are from four patients with COVID-19 pneumonia.The observations do not elucidate the molecular mechanisms but support the view that TRPC6 channels are involved in normal physiology of normal human lungs and in COVID-19 pneumonia. TRPC6 might aggravate SARS-2 induced inflammation and could be a target for inhibiting drugs.

Fatal anogenital exenteration of the intestine.

A case of a sadistically motivated homicide with extraordinary injuries is reported. A 32-year-old woman was naked with signs of severe blunt trauma and oral, vaginal and anal penetration. At the crime scene, the intestine lay next to the woman without connection to the body. During the trial before the criminal court, the perpetrator admitted fisting and inserting several objects into the vagina, anus and oral cavity. Moreover, after anal and vaginal insertion of the hands, large parts of the intestine were torn and pulled out through the anus and the vagina. The results of the forensic pathological examination and additional investigation are discussed and compared with the pertinent literature. This extraordinary case of a sadistically motivated homicide ended with a final judgment that is extremely rare in German jurisdiction.

Histological analysis of the structural composition of ankle ligaments.

BACKGROUND: Various ankle ligaments have different structural composition. The aim of this study was to analyze the morphological structure of ankle ligaments to further understand their function in ankle stability. METHODS: One hundred forty ligaments from 10 fresh-frozen cadaver ankle joints were dissected: the calcaneofibular, anterior, and posterior talofibular ligaments; the inferior extensor retinaculum, the talocalcaneal oblique ligament, the canalis tarsi ligament; the deltoid ligament; and the anterior tibiofibular ligament. Hematoxylin-eosin and Elastica van Gieson stains were used for determination of tissue morphology. RESULTS: Three different morphological compositions were identified: dense, mixed, and interlaced compositions. Densely packed ligaments, characterized by parallel bundles of collagen, were primarily seen in the lateral region, the canalis tarsi, and the anterior tibiofibular ligaments. Ligaments with mixed tight and loose parallel bundles of collagenous connective tissue were mainly found in the inferior extensor retinaculum and talocalcaneal oblique ligament. Densely packed and fiber-rich interlacing collagen was primarily seen in the areas of ligament insertion into bone of the deltoid ligament. CONCLUSIONS: Ligaments of the lateral region, the canalis tarsi, and the anterior tibiofibular ligaments have tightly packed, parallel collagen bundles and thus can resist high tensile forces. The mixed tight and loose, parallel oriented collagenous connective tissue of the inferior extensor retinaculum and the talocalcaneal oblique ligament support the dynamic positioning of the foot on the ground. The interlacing collagen bundles seen at the insertion of the deltoid ligament suggest that these insertion areas are susceptible to tension in a multitude of directions. CLINICAL RELEVANCE: The morphology and mechanical properties of ankle ligaments may provide an understanding of their response to the loads to which they are subjected.

Comparative analysis of inter- and intraligamentous distribution of sensory nerve endings in ankle ligaments: a cadaver study.

BACKGROUND: The aim of this study was to analyze the inter-, intraligamentous, and side-related patterns of sensory nerve endings in ankle ligaments. METHODS: A total of 140 ligaments from 10 cadaver feet were harvested. Lateral: calcaneofibular, anterior-, posterior talofibular; sinus tarsi: lateral- (IERL), intermediate-, medial-roots inferior extensor retinaculum, talocalcaneal oblique and canalis tarsi (CTL); medial: tibionavicular (TNL), tibiocalcaneal (TCL), superficial tibiotalar, anterior/posterior tibiotalar portions; syndesmosis: anterior tibiofibular. Following immunohistochemical staining, the innervation and vascularity was analyzed between ligaments of each anatomical complex, left/right feet, and within the 5 levels of each ligament. RESULTS: Significantly more free nerve endings were seen in all ligaments as compared to Ruffini, Pacini, Golgi-like, and unclassifiable corpuscles (P ≤ .005). The IERL had significantly more free nerve endings and blood vessels than the CTL (P ≤ .001). No significant differences were seen in the side-related distribution, except for Ruffini endings in right TCL (P = .016) and unclassifiable corpuscles in left TNL (P = .008). The intraligamentous analysis in general revealed no significant differences in mechanoreceptor distribution. CONCLUSIONS: The IERL at the entrance of the sinus tarsi contained more free nerve endings and blood vessels, as compared to the deeper situated CTL. Despite different biomechanical functions in the medial and lateral ligaments, the interligamentous distribution of sensory nerve endings was equal. CLINICAL RELEVANCE: The intrinsic innervation patterns of the ankle ligaments provides an understanding of their innate healing capacities following injury as well as the proprioception properties in postoperative rehabilitation.

Immunohistochemical analysis of sensory nerve endings in ankle ligaments: a cadaver study.

BACKGROUND: The aim of this study was to analyze the pattern and types of sensory nerve endings in ankle ligaments using immunohistochemical techniques, in order to gain more insight into functional ankle stability. METHODS: One hundred forty ligaments from 10 cadaver feet were included: the calcaneofibular and anterior/posterior talofibular ligaments from the lateral complex; inferior extensor retinaculum complex, talocalcaneal oblique and canalis tarsi ligaments from the sinus tarsi; deltoid ligament with its individual portions from the medial complex, and anterior tibiofibular ligament (ATiFL) from the syndesmosis. Mechanoreceptors were classified according to Freeman and Wyke [Acta Anat (Basel) 1967;68:321-333] after staining with hematoxylin-eosin, low-affinity neurotrophin receptor p75, protein gene product 9.5, and S-100 protein. RESULTS: Free nerve endings were the predominant sensory endings in all four complexes, with the greatest density in the lateral and medial complexes; followed by Ruffini endings, unclassifiable corpuscles, Pacini corpuscles, and Golgi-like endings. Ruffini endings were significantly more prevalent in the ATiFL than in the medial complex, and more common than Pacini corpuscles and Golgi-like endings in the lateral, medial, and sinus tarsi complexes. A greater number of blood vessels correlated with a greater number of free nerve endings. There was a negative correlation between the number of Ruffini endings, unclassifiable corpuscles, and age. CONCLUSIONS: Free nerve endings are the dominant mechanoreceptor type in the ankle ligaments, followed by Ruffini endings. The ligaments of the lateral and medial ankle complexes are more innervated than the sinus tarsi ligaments.

Indicators for acute hypoxia--an immunohistochemical investigation in cerebellar Purkinje-cells.

The Purkinje-cells (PCs) of the cerebellum are highly vulnerable to hypoxic/ischemic insult. Calbindin-D28k is a calcium-binding protein that is strongly expressed in PCs. Following hypoxia, a decrease in its concentration has been found in animal models before any morphological change of the PCs took place. Hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) are increasingly expressed in tissues that undergo durations of hypoxia, and also in brain tissues. We examine whether a change in expression of any of these factors, or a combination of alterations, is an indicator of acute hypoxia. We investigated the intensity of neuronal immunoreactivity of calbindin-D28k, HIF-1α and VEGF retrospectively in 141 samples of human cerebellar tissue obtained from autopsies performed at the Institute of Legal Medicine of Hanover Medical School in 2007 and 2008. Three groups were compared. The first group comprises individuals (n=48) who died due to acute hypoxia, such as drowning or asphyxia. The second is a control group comprising individuals who died due to heart failure (n=56), and the third group comprised individuals who died almost instantly of polytraumata (n=37). Our study finds a statistically significant decrease in the expression of calbindin-D28k (p<0.05) in PCs in the acute hypoxia group, relative to the control groups. No changes in the expression of HIF-1α or in the expression of VEGF were observed in any of the groups. Consequently HIF-1α and VEGF were not suitable indicators, whereas detection of a decreasing concentration of calbindin-D28k supports a diagnosis of acute hypoxia.

Fatal intoxication due to brucine.

A sensitive method for identifying and quantifying brucine by means of liquid chromatography-tandem mass spectrometry is presented in this article. Based on a solid-phase extraction for human serum, the validation indicated limits of detection and quantification of 0.12 and 0.23 ng/mL, respectively. In one case of lethal suicidal brucine monointoxication, brucine concentrations of 1.51 µg/mL, 1.69 µg/mL, 9.94 µg/mL, 16.4 µg/g, 0.99 µg/g, 0.75 µg/g, and 1.95 mg/g were determined in femoral blood, urine, bile collected from the gallbladder, liver tissue, cerebellum, cerebrum, and stomach contents, respectively.

[Aquatic fatalities--a systematic retrospective analysis]. / Ertrinkungstod--eine systematische retrospektive Untersuchung.

In a retrospective analysis of the autopsy material (n = 5,767) of the Institute of Legal Medicine of the Hanover Medical School covering the period of 1998-2007, all aquatic fatalities were evaluated, categorized and systematically compared under epidemiological and forensic criteria. The total of 156 cases of death by drowning (2.7 % of all autopsies) included 38 bathtub drownings and 28 deaths in the water for which no pathological anatomical cause of death could be reliably demonstrated. A control group (n = 221) was investigated for the presence of aqueous liquid in the sphenoid sinuses and compared with the findings of the drowning cases without signs of putrefaction. About 16 % of the control cases had fluid in the sphenoid sinuses compared with 57.6 % in the drowning group. Most of the drowning victims were men (60.9 %), whereas in the group of bathtub drownings the majority were women. More than half of the drowning cases (n = 89) could be classified as accidents. The individual groups showed a different incidence of findings associated with drowning.

[Placental findings in perinatal cases of death]. / Plazentabefunde bei perinatalen Todesfällen.

Autopsy is an indispensable tool to clarify the cause of death in perinatal cases of death. The authors report on two cases of perinatal death, in which not only a forensic autopsy including histological and microbiological examinations had been performed, but the placenta had also been pathologically assessed. Only on the basis of the placental findings was it possible to clarify the cause of death and to answer the question if the physician had committed medical malpractice. The results underline the importance of examining the placenta in perinatal deaths as a matter of routine. In forensic cases, the police should therefore not only confiscate the infant's body, but also the placenta.

[Post-mortal detection of clostridia--putrefaction or infection?]. / Postmortaler Nachweis von Clostridien--Fäulnisbakterien oder Infektionskeime?

Clostridia are often found in the heart blood and organs of corpses showing putrefactive changes, and it can sometimes be difficult to distinguish between an ante-mortem infection caused by these gram-positive, anaerobic, spore-forming bacteria and post-mortal putrefactive changes. Microbiological tests ordered by the Institute of Legal Medicine of the Hanover Medical School following autopsy between July 2006 and June 2009 were analyzed retrospectively. In all, 50 bacteriological analyses were performed. In 2006, no clostridia were detected, whereas in 2007 the bacteria were demonstrated in 3 (18.8%), in 2008 in 4 (23.5%) and in 2009 in 5 (33.3%) cases. In 50% of the cases, there had been an ante-mortal clostridia infection. The remaining 50% were due to post-mortem transmigration of clostridia species. The results of this study underline the importance of additional post-mortem bacteriological and histological investigations.

Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry.

The current paper describes a validated method for the detection and quantification of naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018), an ingredient of a herbal mixture called "Spice", by means of HPLC-ESI-MS-MS in serum. Lower limit of detection and lower limit of quantification were 0.07 and 0.21 ng/ml, respectively. In 2 subjects who consumed ca. 50 µg/kg of JWH-018 by smoking, the active ingredient was detected by means of the described method. Thereby, the serum concentrations reached values of approx. 10 ng/ml and dropped within 3 h very fast (<10% of the measured maximum concentrations).

[Aortic dissection - a not so rare disease]. / Aneurysma dissecans - keine so seltene Erkrankung.

BACKGROUND AND PURPOSE: Acute aortic dissection is a life-threatening disease with a high rate of mortality. The dissection of the artery with a distal blood flow can explain the variable and changeable symptoms. Aortic dissections require immediate diagnosis and therapy. METHODS: In the Institute of Legal Medicine of the Hannover Medical School, 34 cases of aortic dissection were found during autopsy between 2006 and 2009. The cases were analysed retrospectively. RESULTS: In the majority of cases (55.9%) an antemortem medical consultation has taken place. In only one case an aortic dissection could be diagnosed at a later time. CONCLUSION: Key in the management of acute aortic dissection is to maintain a high clinical index of suspicion for this diagnosis. Etiologically hereditary diseases (Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome) should be taken into consideration as a possible cause. In all unexpected deaths of young adults an autopsy should be performed to detect the cause of death and for genetic testing to provide information for the relatives in case an aortic aneurysm can be found.

[Clinical forensic examination findings in assault cases among adolescents]. / Untersuchungsergebnisse bei Gewaltdelikten unter Jugendlichen.

Child and youth criminality has risen markedly over the past 25 years and causes increasing concern to the general public. The clinical forensic examination cases of youth violence victims examined at the Institute of Legal Medicine of the Hanover Medical School and its Oldenburg Branch between 1999 and 2008 were retrospectively analyzed. In all, 55 adolescents (37 females, 18 males; median age 15.5 years) were examined. In most cases the suspect was a close (40.0%) or passing (23.6%) acquaintance. 16 assaults were committed by two or more adolescents jointly. Most of the juveniles were victims of sexual assaults (56.4%). In 15 victims of sexual offences (51.7%) diagnostic findings were obtained on the basis of anogenital injuries and/or the presence of sperm. In summary, the analysis shows that adolescents frequently become victims of sexual assault. In addition, youth violence is often committed in a group.

[Examination results and autopsy findings in assaults on elderly people]. / Untersuchungsergebnisse und Obduktionsbefunde bei Gewaltdelikten gegen ältere Menschen.

As the percentage of elderly people in the population grows, violence against persons of advanced age constitutes an increasing social problem. The findings of the clinical forensic examinations (CE group) and autopsies performed on elderly violence victims (> or = 60 years) between 1999 and 2008 at the Institute of Legal Medicine of the Hanover Medical School were retrospectively analysed. In all, the study material comprised 55 victims of the CE group (35 females and 20 males, median age 73.5 years) and 55 autopsies (33 females and 22 males, median age 72.7 years). In most of the autopsy cases, the suspect was a family member or partner. In contrast, the alleged perpetrator was a stranger in most cases of the CE group. Blunt force injuries were most often found in the CE group victims (63.6%). Altogether, 38.2% (CE group) and 20.0% (autopsy cases) of the violent assaults were associated with robbery. In the majority of the CE cases, the victims suffered potentially or acute life-threatening injuries. In summary, the analysis shows that elderly people frequently become victims of robbery and blunt force injury. In most homicides of old people, the perpetrator is familiar to the victim. In surviving elderly violence victims, the assault is more likely to be reported to the police if the suspect is a stranger.

[Causes of death among pilots: "acute myocardial infarction"--are the present examination methods for airworthiness sufficient?]. / Todesfälle bei Piloten: "Der akute Myokardinfarkt"--Sind die derzeitigen Flugtauglichkeitsuntersuchungen ausreichend?

The European Union plans to harmonize the aviation requirements, in particular the flight crew licensing requirements. On 23 May 2007, the German Federal Ministry of Transport, Building and Urban Affairs published the Flight Crew Licensing Requirements, which are based on the Joint Aviation Requirements, Flight Crew Licensing 3, Amendment 5. These guidelines also list the examination methods to be used for testing the medical fitness of pilots. In this Amendment some examinations which were part of the routine tests before JAR-FCL3 became effective have been deleted, e.g. the exercise ECG. This article presents two cases from the autopsy material of the Institute of Legal Medicine in Hanover and discusses the problems associated with the new examination guidelines.

[First report of lethal gamma-hydroxybutyrate (GHB) intoxication after consumption of gamma-butyrolactone (GBL) in Lower Saxony]. / Erster Todesfall durch gamma-hydroxybuttersäure (GHB) nach Aufnahme von gamma-Butyrolacton (GBL) in Niedersachsen.

A 25-year-old drug addict died from an overdose of GBL after mistaking it for water in preparing a dilution. He realized his error and wrote a call for help in the chat room of a drug forum, so that we know the time, type and approximate amount of drug consumed. The deceased had written numerous contributions in this drug forum before, which provide further information on his drug habits and the duration of the abuse of GHB, GBL and other drugs. According to the Criminal Investigation Department of Lower Saxony, this is the first death due to GHB/GBL reported in Lower Saxony.

[Fatalities after injuries by wild animals]. / Todesfälle nach Verletzungen durch Wildtiere.

The article summarises three fatalities after attacks by wild animals. The first case describes a 90-year-old woman who died as a result of pneumonia after a bear fell on her and caused multiple chest fractures. The second case deals with a 76-year-old woman who was hit in the middle face by the hoof of a camel and, thereafter, died of myocardial infarction. The third case describes a 27-year-old biologist who died from severe blunt trauma after an attack of a wild living elephant. The article gives a summary of typical injury patterns of selected wild animals and outlines potential reasons of death as a result of the injuries.

Fatal trauma to the neck: immunohistochemical study of local injuries.

As fatal trauma to the neck is often associated with short survival times, proof of vitality may often be difficult using standard histochemical techniques. Soft tissue neck injuries resulting from strangulation by ligature or manual strangulation were examined immunohistochemically using antibodies to myoglobin, fibronectin, C5b-9 and MRP14, and compared to controls consisting of accidental soft tissue neck injuries as well as undamaged neck soft tissue. Although survival times in the study and control groups were unknown and certainly some individual variation may be expected in the time course of normal wound development, both the study and control groups demonstrated similar time courses in the immunohistochemical detection of antigen. Myoglobin was always found in those samples in which only one antigen was shown to be involved in an injury-specific pattern; myoglobin and fibronectin were found in samples with dual antigen involvement. Samples involving three antigens always included C5b-9 in addition to myoglobin and fibronectin. The single positive MRP14 sample in the study and control groups was simultaneously positive for the other markers used. Myoglobin, fibronectin, C5b-9 and MRP14 are therefore suitable for immunohistochemical detection of vital reactions and estimation of temporal relationships in the early posttraumatic period after neck trauma.

[An unusual case of double death]. / Ein ungewöhnlicher Doppeltodesfall.

The report presents the case of an alleged double homicide or a homicide followed by suicide of a couple, in which the court-ordered autopsy of both victims revealed that the homicide had been committed by the husband immediately before he died himself from cardiac failure. The article gives a short summary of the pathophysiological relations between emotional tension (stress) and physical strain and the effects on the cardiovascular system. The case report describes a homicide by strangulation immediately followed by the perpetuator's death from a natural cause.

Expression of vascular adhesion protein-1 in normal and inflamed mice lungs and normal human lungs.

Recently, vascular adhesion protein-1 (VAP-1) was implicated in adhesion and transmigration of lymphocytes across endothelial cells in liver and other organs. There is very little information on VAP-1 expression in normal and inflamed lungs. Therefore, we conducted a study to localize VAP-1 in normal mice and human lungs and in two distinct murine models of lung inflammation. Normal mice and human lungs revealed VAP-1 expression in the endothelium of large and mid-sized pulmonary vessels but not in alveolar septae, airway epithelium or blood cells. Mice that lack the lpr(-/-) gene and develop extensive lymphocytic infiltration in their lungs showed VAP-1 expression similar to the normal mice lungs. Mice subjected to cecal ligation and puncture developed acute lung inflammation and showed VAP-1 not only in endothelial cells but also in inflammatory cells in perivascular areas at 72 h after the procedure. We concluded that VAP-1 expression may contribute to the functional heterogeneity of endothelial cells within the lung to create distinct sites for the recruitment of inflammatory cells. Furthermore, since VAP-1 is expressed over a longer period of time in inflamed lungs, it may even be a suitable target for drug delivery and therapeutic manipulations.