Effect of vaporizing cannabis rich in cannabidiol on cannabinoid levels in blood and on driving ability - a randomized clinical trial.

The aim of this prospective, placebo-controlled, double-blind, randomized, cross-over study was to determine cannabinoid levels in blood and driving-related ability after single (S1) and repetitive (S2) vaporization of cannabis rich in cannabidiol (CBD) containing < 1% Δ9-etrahydrocannabinol (THC). Healthy adult volunteers (Nsingle = 27, Nrepetitive = 20) with experience in smoking vapor-inhaled two low-THC/CBD-rich cannabis products both with < 1% THC (product 1: 38 mg CBD, 1.8 mg THC; product 2: 39 mg CBD, 0.6 mg THC) and placebo. Main outcomes were THC- and CBD-levels in whole blood and overall assessment of driving-related ability by computerized tests. Among 74 participants included, 27 (mean age ± SD, 28.9 ± 12.5 years) completed S1, and 20 (25.2 ± 4.0) completed S2. Peak concentrations and duration of detectability depended on the THC-content of the product. After single consumption THC dropped below 1.5 µg/L after 1.5 h, but was detected in some participants up to 5 h. Pairwise comparison of driving-related ability revealed no significant differences between low-THC/CBD-rich products (P1, P2) and placebo. Detection of THC after consumption of low-THC/CBD-rich cannabis might have legal consequences for drivers. Regarding overall driving-related ability, no significant differences were observed between the interventional products. This trial was registered with the German Clinical Trials Register (DRKS00018836) on 25.10.2019 and with the Coordination Office for Human Research (kofam) which is operated by the Federal Office of Public Health (FOPH) (SNCTP000003294).

Investigation of post mortem brain, rectal and forehead temperature relations.

It is well known that magnetic resonance (MR) imaging is temperature sensitive, which is highly relevant for post mortem examinations. Therefore, the determination of the exact temperature of the investigated body site, e.g. the brain, is crucial. However, direct temperature measurements are invasive and inconvenient. Thus, in view of post mortem MR imaging of the brain, this study aims at investigating the relation between the brain and the forehead temperature for modelling the brain temperature based on the non-invasive forehead temperature. In addition, the brain temperature will be compared to the rectal temperature. Brain temperature profiles measured in the longitudinal fissure between the brain hemispheres, as well as rectal and forehead temperature profiles of 16 deceased were acquired continuously. Linear mixed, linear, quadratic and cubic models were fitted to the relation between the longitudinal fissure and the forehead and between the longitudinal fissure and the rectal temperature, respectively. Highest adjusted R2 values were found between the longitudinal fissure and the forehead temperature, as well as between the longitudinal fissure and the rectal temperature using a linear mixed model including the sex, environmental temperature and humidity as fixed effects. The results indicate that the forehead, as well as the rectal temperature, can be used to model the brain temperature measured in the longitudinal fissure. Comparable fit results were observed for the longitudinal fissure-forehead temperature relation and for the longitudinal fissure-rectal temperature relation. Combined with the fact that the forehead temperature overcomes the problem of measurement invasiveness, the results suggest using the forehead temperature for modelling the brain temperature in the longitudinal fissure.

Post mortem evaluation of brain edema using quantitative MRI.

The post mortem assessment of brain edema is routinely performed during autopsy by forensic pathologists who evaluate the macroscopically visible signs. In this study, the suitability of magnetic resonance imaging (MRI) for a differentiation between edematous and nonedematous brains was examined as an objective, noninvasive and quantitative rating method. In this study, 22 deceased underwent post mortem in situ MRI prior to regular autopsy. Acquired MRI sequences allowed the computation of the quantitative MRI parameters T1, T2, T2*, fractional anisotropy (FA) and mean diffusivity for the cortex, white matter and deep gray matter separately. Beside the autopsy results, which represent the gold standard for rating brain edema, also the normalized cerebral weight (NCW) was determined by dividing the brain weight by the intracranial volume as developed by Bauer et al. [10]. For further examination of the relation of MRI parameters with the NCW, linear regression models were calculated. The results revealed highly significant correlations of the MRI parameters T2 and FA with the NCW in the cortex. These combinations additionally showed the best fitting results of the linear regression models. In conclusion, quantitative MRI is suitable for differentiating edematous from nonedematous brains by calculating T2 and FA in the cortex. A post mortem in situ MRI scan of the brain can, besides delivering morphological information, add relevant and objective information on the edema status of the brain prior to autopsy or when no autopsy is ordered.

Which tissue to take? A retrospective study of the identification success of altered human remains.

In forensic medicine, deceased are usually identified by comparing ante- and post-mortem dental or radiological features. However, in severe putrefaction, burning or absent reference data, the remaining tool for identifying human remains is DNA genotyping. But even a DNA-based identification can be challenging when confronted with a high post-mortem interval or heat impacts because it can lead to undesirable degradation of the DNA that varies among tissue types. This retrospective study investigated the identification success in 402 altered human corpses over seven years by comparing the examined tissue types from decomposed, skeletonised and burnt corpses as well as bodies found in water. For each tissue, the STR genotyping results and the number of additional or parallel genetic analyses were evaluated. By comparing the amplification success in samples from altered and unaltered remains, condition-based and tissue-specific differences were observed. With a mean number of 1.6 additional amplifications in cases with well-preserved corpses and 4.5 in altered corpses, the results showed significantly more DNA analyses for altered remains. In 83% of the cases, extra amplifications were performed to identify the corpse. The tissue-specific differences revealed an uncertainty in choosing suitable material from altered corpses for a successful DNA profile. Especially for bone and muscle samples, the genotyping success was the most unpredictable. Furthermore, comparing the retrospective outcome with other research findings, a remarkable variety of recommendations for the "best tissue choice" exists in the forensic community. Thus, our survey highlights the advantages of a broader and systematic approach on hard and soft tissues for successful DNA-based identification of altered human remains at first attempt.

Analysis of different post mortem assessment methods for cerebral edema.

While cerebral edema is a live-threatening condition in living persons, also an edema-like fluid redistribution can occur post mortem. In deceased, usually macroscopic signs are evaluated during autopsy in order to determine the presence or absence of cerebral edema. As a quantitative and objective classification is beneficial, an already existing method (Radojevic et al., 2017), which is based on a mathematical formula using the intracranial dimensions and the cerebral weight, was compared to the evaluation of macroscopic signs in 31 cases. The results showed an excellent agreement for the comparison between the raters as well as the measurement methods (at opened skull or in CT images). However, both measurement methods only poorly agree with the macroscopic edema evaluation. In order to find a more concordant method, the normalized cerebral weight, which puts the cerebral weight in relation to the intracranial volume, was calculated for 115 cases. This method resulted in an excellent agreement with the macroscopic rating and showed a clear numerical difference between the edematous and nonedematous group. While the influence of the post mortem time and the cooling time was found to be negligible, the age at death might confound the edema classification due to pre-existing cerebral atrophy leading to lower cerebral weights. In summary, the present study compared different assessment methods to classify cerebral edema and developed a rater independent, objective and quantitative classification method, which was as reliable as the rating of the forensic pathologists.

A suicide involving intraperitoneal injection of pentobarbital.

We present an unusual case of suicide by intraperitoneal injection of pentobarbital, an overdose of zolpidem and the intake of diazepam, ethanol and other psychoactive substances. The autopsy and specimen collection were conducted in a 10 to 18 h postmortem interval. The toxicological analysis revealed a significantly higher pentobarbital concentration in femoral blood compared to cardiac blood (36 vs. 15 mg/L). On the contrary, zolpidem and diazepam concentrations in cardiac blood (2700 and 590 µg/L) were found to be significantly higher than in femoral blood (1500 and 230 µg/L). These findings point to a postmortem redistribution with a distinct gradient from areas of high drug concentrations in the gastrointestinal tract (zolpidem and diazepam) and the injection site (pentobarbital) to peripheral tissue. Ethanol concentration was 0.95 ‰ which amplified the CNS depression. The choice of this unusual suicide method was associated with the deceased's former job as a veterinarian's assistant. In veterinary medicine, the intraperitoneal injection of a lethal dose of pentobarbital is quite commonly performed to euthanise small animals. Intraperitoneal injection is rare as route of administration in humans.

Endothelin receptor-antagonists suppress lipopolysaccharide-induced cytokine release from alveolar macrophages of non-smokers, smokers and COPD subjects.

Smoking-induced COPD is characterized by chronic airway inflammation, which becomes enhanced by bacterial infections resulting in accelerated disease progression called exacerbation. Alveolar macrophages (AM) release endothelin-1 (ET-1), IL-6, CCL-2 and MMP-9, all of which are linked to COPD pathogenesis and exacerbation. ET-1 signals via ETA- and ETB-receptors (ETAR, ETBR). This is blocked by endothelin receptor antagonists (ERAs), like bosentan, which targets both receptors, ETAR-selective ambrisentan and ETBR-specific BQ788. Therefore, ERAs could have anti-inflammatory potential, which might be useful in COPD and other inflammatory lung diseases. We hypothesized that ERAs suppress cytokine release from AM of smokers and COPD subjects induced by lipopolysaccharide (LPS), the most important immunogen of gram-negative bacteria. AM were isolated from the broncho-alveolar lavage (BAL) of n=29 subjects (11 non-smokers, 10 current smokers without COPD, 8 smokers with COPD), cultivated and stimulated with LPS in the presence or absence of ERAs. Cytokines were measured by ELISA. Endothelin receptor expression was investigated by RT-PCR and western blot. AM expressed ETAR and ETBR mRNA, but only ETBR protein was detected. LPS and ET-1 both induced IL-6, CCL-2 and MMP-9. LPS-induced IL-6 release was increased in COPD versus non-smokers and smokers. Bosentan, ambrisentan and BQ788 all partially reduced all cytokines without differences between cohorts. Specific ETBR inhibition was most effective. LPS induced ET-1, which was exclusively blocked by BQ788. In conclusion, LPS induces ET-1 release in AM, which in turn leads to CCL-2, IL-6 and MMP-9 expression rendering AM sensitive for ERAs. ERAs could have anti-inflammatory potential in smoking-induced COPD.

[Unusual findings in carbon monoxide-related deaths]. / Ungewöhnliche Aspekte im Zusammenhang mit tödlich verlaufenen Kohlenmonoxidintoxikationen.

The authors present three cases of carbon monoxide poisoning (two suicides and one accident) from the autopsy material of the Institute of Legal Medicine at Basel, which are unusual with regard to the circumstances at the scene of death, the method of suicide and the post-mortem findings: Suicide of a 27-year-old male by burning charcoal in the bathroom, documentation of the suicide and previous attempted suicides on a tablet PC. Suicide of a 27-year-old male by carbon monoxide chemically, produced by dehydration of formic acid with sulphuric acid and inhalation of the gas through a breathing mask. Accidental carbon monoxide poisoning of a 34-year-old male by car exhaust fumes in an open garage. Difficult establishment of the diagnosis in the post-mortem examination due to unspecific colour of livores and varnished fingernails.

[Physical and sexual child abuse]. / Kindliche Opfer sexueller und körperlicher Gewalt.

Child abuse may result in dramatic short and longtime damage of children's physical and emotional well being. This underscores the clinician's special responsibility to contribute a sound professional and scientific approach to the multiprofessional diagnosis and intervention in suspected child abuse cases. The approach is to correlate the probability of a given finding with the history and comparing it to biomechanical principles. Of concern are especially all serious injuries with an alleged trivial or inadequate for age mechanism, missing, vague or changing patterns of explanation, injuries of different age, delay of medical care and allegations by independent observers or even the child. Exact documentation of all medical examinations is the basis of any forensic expertise if child abuse is to be considered. This paper ist dealing with morhological findings following various kinds of violence which can often be observed in connection with child abuse, as well as the interpretation of characteristic patterns of findings. Furthermore, practicable procedures after diagnosing child abuse ar being discussed on the basis of legal terms.