The Lausanne forensic pathology approach to post-mortem imaging for natural and non-natural deaths

Post-mortem imaging by computed tomography (PMCT) and post-mortem CT angiography (PMCTA) are used routinely in forensic practice as components to the autopsy. PMCT is efficient for gas detection, foreign body visualization and skeleton analysis. Various parameters can lead to the indication for contrast agent injection. Contrast injection into the vascular system can overcome the disadvantages of non-contrast PMCT by visualization of solid organ parenchyma and vessels. This can also assist the conventional autopsy, allowing one to investigate the vascular system. It is the method of choice for the analysis of the blood vessels by showing vascular pathology, congenital or postsurgical anatomical variations and an exact source of bleeding. By knowing the artefacts linked to the angiographic technique, we limit the risk of misinterpretation. The use of post-mortem MRI (PMMR) for diagnostic purposes is still limited to rare indications. These include review of the neck in cases of death by mechanical asphyxia, total-body PMMR in neonatal and pediatric death and cardiac PMMR in case of suspected myocardial infraction. Currently, in our daily practice, the vast majority or PMMR is only performed for research purposes.     

A rapid solid-phase extraction and HPLC/DAD procedure for the simultaneous determination and quantification of different benzodiazepines in serum,blood and post-mortem blood

Summary A rapid and quantitative method for the determination of benzodiazepines using high-performance liquid chromatography (HPLC) with diode-array detection (DAD) is reported. The drugs were extracted from serum, blood or post-mortem blood using C₁₈ extraction columns. Brotizolam was used as internal standard. Experiments with spiked serum/blood samples resulted in recoveries between 75% and 94% for all investigated benzodiazepines. Excellent linearity was obtained over the concentration range 5–1500 ng benzodiazepine/ml. The limit of detection was approximately 2 ng/ml. The detection of low therapeutic serum levels of highly potent benzodiazepines is also possible.      

Use of post-mortem human synaptosomes for studies of metabolism and transmitter amino acid release

Synaptosomes have been prepared from human brain obtained at autopsies carried out up to 24 h postmortem (p.m.). They showed generally good retention of morphology, as well as accumulation of tissue potassium and linear rates of oxygen uptake. In response to veratrine depolarization they showed increased respiration rate, decreased tissue potassium content and the specific release of transmitter amino acids. Regression analysis indicated that metabolically and functionally active preparations may be obtained up to ca. 25 h p.m. Preparations obtained from patients dying with brain injury were inactive.     

The toxicological significance of post-mortem drug concentrations in bile

Context: Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value.

Aim: To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature.

Methods: We made a systematic search of EMBASE 1980–2016 using the search terms (“bile/” OR “exp drug bile level/concentration/”) AND “drug blood level/concentration/”, PubMed 1975–2017 for (“bile[tw]” OR “biliary[tw]”) AND (“concentration[tw]” OR “concentrations[tw]” OR “level[tw]” OR “levels[tw]”) AND “post-mortem[tw]” and also MEDLINE 1990–2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs.

Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058–0.32) for dextromoramide to 520 (range 0.62–43,000) for buprenorphine. Median bile concentrations exceeded blood concentrations by one order of magnitude for several drugs, including dihydrocodeine, quetiapine and sildenafil; and by two orders of magnitude of for buprenorphine, colchicine and 3,4-methylenedioxy-methamphetamine (MDMA), among others. The minimum and maximum values for the ratio differed by a factor of three or more in three-quarters of the cases where data were available and by a factor of 10 or more for over half of the analytes.

Limitations: The data were difficult to find. Medline does not explicitly index the term “drug bile concentration”. It may well be that other reports exist, although they would not alter our major conclusion. Many of the papers that contributed data failed to specify the source of the blood samples or the post-mortem interval, so that no judgment was possible regarding post-mortem redistribution in whole blood or bile.

Conclusions: For most drugs, there are wide ranges of bile:blood concentration ratios, which means that bile and blood concentrations are generally poorly correlated. Bile concentration measurements cannot readily be used to establish post-mortem blood concentrations; nor can they be extrapolated to ante-mortem concentrations. However, because drug concentrations in bile often exceed those in blood, bile may allow qualitative identification of drugs present, even when the blood concentration is below the limit of detection.     

COVID-19 autopsies: conclusions from international studies

The rapid pace at which COVID-19 studies are being published is surpassed only by the spread of the virus and the destruction wreaked by the pandemic globally. Therefore, it is likely that, even in the few months prior to this article reaching print, the COVID-19 literature would have moved on. The authors of this article work at a centre for COVID autopsies in London, and the aim of the article is, using their first-hand experience of COVID-19 autopsies, to distil what in their judgement are the most valid and important findings of internationally published COVID-19 autopsy studies. The intention is to provide an illustrated summary of the pathology of the organ systems most often affected by COVID-19, which will be particularly useful to trainee histopathologists and to busy consultant surgical histopathologists who may not have encountered COVID-19 first hand. For the reader who wishes to probe further the question of pathogenesis, a few pertinent references are provided.     

Profuse Mediastinal Haemorrhage Due to Mediastinitis after Sternotomy: Report of Three Cases and Review of the Literature

Profuse spontaneous haemorrhage occurred in association with mediastinitis after median sternotomy for coronary bypass surgery in three men aged 54, 47 and 59 years. The bleeding sites were aorta, right ventricle and saphenous bypass graft. The aortic rupture occurred during closed lavage, the right ventricle ruptured during open saline mediastinal packing and the saphenous vein graft was eroded by a mediastinal drainage tube after discontinuation of closed lavage. This third patient survived and recovered, but the two others died. Previously published reports of 56 patients with 65 bleedings from this rare complication are reviewed. The outcome was fatal in 34% of cases.     

Does alcohol increase the risk of overdose death: the need for a translational approach

Background We argue for a translational approach to addiction science, using an important current research question as a case study. Case study What is the evidence in support of the hypothesis that alcohol increases the risk of a heroin/opiate overdose through a pharmacological interaction? Findings The positive epidemiological evidence shows that opiate overdose deaths rarely involve a single drug; that alcohol is the most common other drug involved; that there is a negative association between alcohol and morphine concentration at post mortem; and that post‐mortem levels of morphine are often below the levels expected of highly tolerant individuals. The evidence is consistent with the hypothesis that heroin users who drink may require less heroin to overdose than those who do not drink (all other factors being equal) because of a pharmacological interaction. However, the evidence is consistent with, and does not rule out, other causal (and non‐causal) pathways. Alcohol could be associated negatively with tolerance, or confounded by other factors. Experimental evidence is required which is unlikely to be obtained through further epidemiological study or through randomized clinical trials. Conclusions We believe that animal models could provide the key evidence to test the hypothesis for a ‘pharmacodynamic’ or ‘pharmacokinetic’ interaction, which could be corroborated in clinical challenge studies and epidemiological studies. Such a translational approach demands greater collaboration between addiction scientists from basic to applied science and from neuroscience to social science, and would be able to address other key research questions and hypotheses in addiction.     

Scyllo-inositol in post-mortem brain of bipolar, unipolar and schizophrenic patients

Summary. Inositol levels measured in postmortem brain of unipolar, bipolar and schizophrenic patients, suicide victims and normal controls showed no difference in scyllo-inositol levels in frontal or occipital cortex between any of the groups. We could not replicate previous reports of low myo-inositol levels in the frontal cortex of unipolar, bipolar and schizophrenic patients and suicide victims. There was no correlation between myo-inositol levels and estimated chlorpromazine equivalents in neuroleptic-treated subjects, and no effect of chronic haloperidol treatment on rat brain myo-inositol levels. Received July 23, 1999; accepted January 18, 2000     

Cu,Zn- and Mn-superoxide dismutase levels in brains of patients with schizophrenic psychosis

Summary. Impaired oxidative stress defense has been reported in blood of both drug-naïve and antipsychotic-treated patients suffering from schizophrenic psychosis, indicating the involvement of free radical metabolism in the pathogenetic processes of schizophrenia.In this study, the concentrations of two isoenzymes of superoxide dismutase (SOD), Cu, Zn- and MnSOD, were determined with ELISA in various cortical (frontal, parietal, temporal and occipital cortex) and subcortical areas (putamen, caudate nucleus, thalamus, and substantia innominata) of post-mortem brain tissue from patients diagnosed with a schizophrenia spectrum disorder and compared with those of controls. Post-mortem brain tissue from individuals without neuropsychiatric disoders served for control.Cu, Zn- and MnSOD levels were significantly increased in frontal cortex and substantia innominata of the index group, respectively. In all other areas both types of SOD remained virtually unchanged.Detection of SOD changes in the brain supports previous reports of alterations of antioxidant indices in blood cells of patients with schizophrenia and suggests a specific neuroanatomical distribution pattern of oxidative stress processes possibly related to the pathophysiology of schizophrenia.