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1.
J Nippon Med Sch ; 91(3): 261-269, 2024.
Article in English | MEDLINE | ID: mdl-38972738

ABSTRACT

BACKGROUND: Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood. METHODS: We used immunohistochemical techniques to characterize staining patterns of in-house rabbit polyclonal anti-κ, anti-λ, anti-transthyretin antibodies, and commercial anti-amyloid A and anti-ß2-microglobulin antibodies in 40 autopsy cases. RESULTS: In thirty cases (75%), the subtype was determined by using the criterion that amyloid is strongly and diffusely positive for one antibody while negative for other antibodies. We then performed proteomic analysis of all 40 cases. In 39 cases, we identified only one amyloid protein and confirmed the immunohistochemically determined subtypes of the abovementioned 30 cases. In seven other cases, we could retrospectively determine subtypes with immunohistochemistry by using information from proteomic analysis, which increased the immunohistochemistry diagnosis rate to 92.5% (37/40). In one case, we identified double subtypes, both immunohistochemically and with proteomic analysis. In the remaining three cases, proteomic analysis was essential for typing diagnosis. CONCLUSIONS: The present findings suggest that combined immunohistochemistry and proteomic analysis is more useful than immunohistochemistry alone. Our findings highlight the importance of carefully interpreting immunohistochemistry for anti-TTR and light chain and offer insights that can guide amyloid typing through immunohistochemistry.


Subject(s)
Amyloidosis , Immunohistochemistry , Proteomics , Tandem Mass Spectrometry , Humans , Immunohistochemistry/methods , Tandem Mass Spectrometry/methods , Proteomics/methods , Amyloidosis/diagnosis , Amyloidosis/metabolism , Amyloidosis/pathology , Chromatography, Liquid/methods , Female , Aged, 80 and over , Male , Aged , Middle Aged , Autopsy , Amyloid/metabolism , Amyloid/analysis , Retrospective Studies , beta 2-Microglobulin/analysis , beta 2-Microglobulin/metabolism , Serum Amyloid A Protein/analysis , Adult
2.
Bull Exp Biol Med ; 177(1): 109-114, 2024 May.
Article in English | MEDLINE | ID: mdl-38960958

ABSTRACT

We studied morphometric changes in the liver acini of dead newborns depending on the duration of the postmortem period. Autopsy samples of the liver tissue from 49 dead newborns were divided into 7 groups depending on the time of death. Liver tissue samples were taken from the upper and lower areas of the liver in the supine position of newborns; paraffin sections were prepared and stained with hematoxylin and eosin. The morphometric analysis of histological preparations revealed a progressive decrease in the mean size of the liver plates (trabeculae) and, conversely, an increase in the area of sinusoids with increasing the duration of the postmortem period; these changes were due to the postmortem redistribution of the blood and autolysis processes. More significant changes were noted in acinar zone 3 of the lower part of the liver. The revealed intra-acinar features of postmortem changes should be taken into account for their differential diagnosis with pathological processes that developed during life, in particular, the signs of congestion and peliosis of the liver.


Subject(s)
Autopsy , Liver , Postmortem Changes , Humans , Liver/pathology , Infant, Newborn , Male , Female , Time Factors
3.
Ulus Travma Acil Cerrahi Derg ; 30(7): 493-499, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38967528

ABSTRACT

BACKGROUND: In Türkiye, as in other parts of the world, there is a rising trend in individual armament and firearm violence, resembling an epidemic. When fired into the air, bullets eventually lose the initial speed with which they left the barrel and begin to accelerate downwards under the influence of gravity as they fall to the ground. At this point, these projectiles are referred to as 'tired bullets,' which cause serious injuries and fatalities. This study evaluates autopsy cases of deaths due to tired bullet injuries. We aimed to raise social awareness and contribute to the literature by exploring the forensic, legal, and social dimensions of tired bullet injuries. METHODS: From 2013 to 2022, 695 forensic autopsies of gunshot wounds were reviewed at the Trabzon Forensic Medicine Group Presidency. Nine cases were identified where individuals had undergone autopsies and the cause of death was attributed to tired bullet injuries. The data for the cases included in the study was sourced from our archive records and the UYAP (National Judicial Network Project) system. The second stage involved analyzing reports of falling bullet injuries from local and national newspaper websites. In the third stage, the Supreme Court decisions regarding perpetrators of tired bullet incidents were examined. RESULTS: The study included six male and three female cases, with an average age of 32.5 years. Injuries were predominantly located in the head in seven cases, the eye in one case, and the inguinal region in another. In eight cases, the bullet trajectory was from top to bottom. The incidents predominantly occurred in residential areas. It was observed that all cases received coverage in both national and local media, and campaigns against tired bullet injuries were organized. The perpetrators of these injuries were frequently sentenced for murder with probable intent. CONCLUSION: Tired bullet injuries represent a significant public health issue that necessitates comprehensive preventative measures addressing medical, legal, and social dimensions. There should be national and international campaigns led by the media, involving all public institutions, organizations, and non-governmental organizations to promote individual disarmament, highlight the dangers of firearms, and stress the importance of these initiatives.


Subject(s)
Wounds, Gunshot , Humans , Wounds, Gunshot/mortality , Male , Female , Adult , Middle Aged , Turkey/epidemiology , Autopsy , Young Adult , Adolescent , Cause of Death , Forensic Ballistics
4.
Front Cell Infect Microbiol ; 14: 1394721, 2024.
Article in English | MEDLINE | ID: mdl-38975331

ABSTRACT

Since 2019, Coronavirus Disease 2019(COVID-19) has affected millions of people worldwide. Except for acute respiratory distress syndrome, dysgeusis is also a common symptom of COVID-19 that burdens patients for weeks or permanently. However, the mechanisms underlying taste dysfunctions remain unclear. Here, we performed complete autopsies of five patients who died of COVID-19. Integrated tongue samples, including numerous taste buds, salivary glands, vessels, and nerves were collected to map the pathology, distribution, cell tropism, and receptor distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the tongue. Our results revealed that all patients had moderate lymphocyte infiltration around the salivary glands and in the lamina propria adjacent to the mucosa, and pyknosis in the epithelia of taste buds and salivary glands. This may be because the serous acini, salivary gland ducts, and taste buds are the primary sites of SARS-CoV-2 infection. Multicolor immunofluorescence showed that SARS-CoV-2 readily infects Keratin (KRT)7+ taste receptor cells in taste buds, secretory cells in serous acini, and inner epithelial cells in the ducts. The major receptors, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), were both abundantly expressed in these cells. Viral antigens and receptor were both rarely detected in vessels and nerves. This indicates that SARS-CoV-2 infection triggers pathological injury in the tongue, and that dysgeusis may be directly related to viral infection and cellular damage.


Subject(s)
Angiotensin-Converting Enzyme 2 , Autopsy , COVID-19 , SARS-CoV-2 , Serine Endopeptidases , Tongue , Viral Tropism , Humans , COVID-19/pathology , COVID-19/virology , SARS-CoV-2/pathogenicity , Tongue/virology , Tongue/pathology , Male , Angiotensin-Converting Enzyme 2/metabolism , Female , Middle Aged , Serine Endopeptidases/metabolism , Salivary Glands/virology , Salivary Glands/pathology , Aged , Taste Buds/virology , Taste Buds/pathology , Receptors, Virus/metabolism
5.
J Clin Psychiatry ; 85(3)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39028543

ABSTRACT

Background: This study explored the characteristics of people who die by suicide, comparing those who had depression with those who did not.Methods: Clinical data were collected through a postmortem proxy-based semistructured interview (psychological autopsy). Postmortem toxicological analysis provides data on the presence of substances or drugs in the blood of suicides. Participants were adults who died by suicide in the province of Seville, Spain, during 2006-2016. The main independent variables were previous diagnosis, postmortem diagnosis, prescribed treatment, and treatment found in blood. The primary outcome was the postmortem diagnosis of depression, after which the sample was divided into 2 groups according to DSM IV criteria to the presence or absence of major depressive episode (MDE).Results: Our sample is composed of 313 people, of which 200 (63.9%) had a diagnosis of MDE according to the psychological autopsy. Predeath diagnosis of depression was more frequent in MDE suicides than in non-MDE suicides (18.6% vs 3.5%, respectively; Χ2 = 23.420; df = 9; P = .005) and had more access to mental health treatment previous to death (67.7% vs 35.6%, respectively; Χ2 = 27.572; df = 1; P < .001). Antidepressants were prescribed in 21.5% of the MDE suicides, but only 8.5% of them were taking them at the time of death according to the toxicology exam.Conclusions: The underdiagnosis of depression in people who die by suicide is striking, as is the undertreatment. Further efforts must be made to train primary care physicians in the proper identification of persons at risk of suicide, as they are one of the main gatekeepers in the fight for suicide prevention.


Subject(s)
Depressive Disorder, Major , Humans , Female , Male , Middle Aged , Spain/epidemiology , Adult , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Suicide/statistics & numerical data , Suicide/psychology , Suicide, Completed/statistics & numerical data , Aged , Antidepressive Agents/therapeutic use , Autopsy , Undertreatment
6.
BMJ Open ; 14(7): e079405, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013644

ABSTRACT

INTRODUCTION: Understanding suicide in more isolated territories is a challenge because of the entanglement of cultural identity with historical, geographical and sociocultural specificities. This knowledge is a necessary precondition for the implementation of targeted prevention strategies in regions such as the French overseas territories (FOT), where data concerning suicidal risk factors is still incomplete. We aim to untangle sociocultural and clinical suicide risk factors by integrating a novel anthropological and psycholinguistic approach into the psychological autopsy method. This article describes the protocol of the clinical study 'Contribution of Psychological Autopsy to the Understanding of Suicidal Behaviours in Overseas France' (AUTOPSOM study), designed to identify common or new specific suicide risk factors in four FOT. METHODS AND ANALYSIS: A multicentre epidemiological study will be carried out in four FOTs (French Polynesia, Martinique, La Reunion and French Guiana) and at a comparison site in mainland France (La Somme). The methodology will be based on a mixed-methods (quantitative and qualitative) approach using a psychological autopsy to collect clinical data and life events in the deceased's life. We implemented an exploratory multimethod strategy that combines a succession of epidemiological, anthropological, psycholinguistic and psychological methods with a semiautomated analysis of the discourse of relatives bereaved by suicide. ETHICS AND DISSEMINATION: The study protocol (first version) was approved by the French Ethics Committee (CPP OUEST II, approval #22.04267.000122) and the Ethics Committee of French Polynesia (JOPF of 5 April 2022; CEPF opinion n°91 of 29 March 2022). The overall results and the perspectives established at the end of the study will be communicated to the bereaved relatives according to their will and serve for local suicide prevention purposes. TRIAL REGISTRATION NUMBER: NCT05773898.


Subject(s)
Suicide , Female , Humans , Male , Autopsy , France/epidemiology , French Guiana/epidemiology , Polynesia/epidemiology , Research Design , Risk Factors , Suicide/psychology , Suicide Prevention , Multicenter Studies as Topic
7.
Viruses ; 16(6)2024 May 27.
Article in English | MEDLINE | ID: mdl-38932146

ABSTRACT

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity changes contributing to disease severity. Nevertheless, limited information is available regarding the immune response in human lung tissue, which is the primary site of infection. In this study, we conducted an extensive analysis of lung tissue to screen for differentially expressed miRNAs and mRNAs in five individuals who died due to COVID-19 and underwent a rapid autopsy, as well as seven control individuals who died of other causes unrelated to COVID-19. To analyze the host response gene expression, miRNA microarray and Nanostring's nCounter XT gene expression assay were performed. Our study identified 37 downregulated and 77 upregulated miRNAs in COVID-19 lung biopsy samples compared to the controls. A total of 653 mRNA transcripts were differentially expressed between the two sample types, with most transcripts (472) being downregulated in COVID-19-positive specimens. Hierarchical and PCA K-means clustering analysis showed distinct clustering between COVID-19 and control samples. Enrichment and network analyses revealed differentially expressed genes important for innate immunity and inflammatory response in COVID-19 lung biopsies. The interferon-signaling pathway was highly upregulated in COVID-19 specimens while genes involved in interleukin-17 signaling were downregulated. These findings shed light on the mechanisms of host cellular responses to COVID-19 infection in lung tissues and could help identify new targets for the prevention and treatment of COVID-19 infection.


Subject(s)
Autopsy , COVID-19 , Gene Regulatory Networks , Lung , MicroRNAs , SARS-CoV-2 , Humans , COVID-19/genetics , COVID-19/virology , COVID-19/immunology , Lung/virology , Lung/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Male , Female , Middle Aged , Aged , Gene Expression Profiling , RNA, Messenger/genetics , Adult
8.
Viruses ; 16(6)2024 May 31.
Article in English | MEDLINE | ID: mdl-38932183

ABSTRACT

Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After the termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using a real-time polymerase chain reaction. Histopathological examination involved hematoxylin-eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 × 103 to 1.0 × 104 copies/mL. These results highlight a quantifiable relationship between the organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , DNA, Viral , Fetus , Viral Load , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/diagnosis , Humans , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , DNA, Viral/genetics , Male , Female , Fetus/virology , Pregnancy , Adult , Autopsy , Pregnancy Complications, Infectious/virology
9.
Diagn Pathol ; 19(1): 89, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943126

ABSTRACT

BACKGROUND: Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and comprises > 95% of all LPL cases. Rituximab-based regimens have been predominant in the management of WM. Infusion-related reactions (IRRs) are a primary concern with rituximab, although it is generally better tolerated with less toxicity than conventional anticancer agents. Here, we present an autopsy case of an elderly man who died suddenly after receiving the initial infusion of rituximab for WM/LPL. CASE PRESENTATION: An 84-year-old man was found dead in his bedroom. He had undergone the initial intravenous rituximab infusion for progressive anemia related to Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) approximately 15 h before death. Although the protocol for rituximab administration and additional medication was considered appropriate, he exhibited several symptoms consistent with infusion-related reactions (IRRs) during the infusion. Autopsy revealed monotonous proliferation of small-to-medium-sized lymphocytic cells in the bone marrow, consistent with the premortem diagnosis of WM/LPL. Additionally, immunoglobulin λ-light chain-derived amyloid (ALλ) deposition was identified in all organs other than the brain. Although ALλ deposition and LPL infiltration were found in the heart, they were not severe enough to cause severe functional impairment. Severe congestion and/or edema were observed in the lungs, liver, and brain. Although significant inflammatory cell infiltration was not found in any organs, laboratory tests revealed elevated serum levels of inflammatory cytokines, including interleukin-1ß, interleukin-6, tumor necrosis factor-α and the presence of IgM-λ monoclonal protein. CONCLUSION: Acute IRRs associated with the initial rituximab infusion were the major contributing factor to his sudden unexpected death. The autopsy findings of present case suggest the necessity for thorough monitoring of older patients with WM/LPL undergoing rituximab treatment, particularly when pronounced IRRs occur during the first administration, in addition to investigating complications of WM/LPL before infusion.


Subject(s)
Autopsy , Rituximab , Waldenstrom Macroglobulinemia , Humans , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/pathology , Waldenstrom Macroglobulinemia/complications , Rituximab/adverse effects , Rituximab/administration & dosage , Male , Aged, 80 and over , Death, Sudden/etiology , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/administration & dosage , Bone Marrow/pathology , Fatal Outcome , Infusions, Intravenous
10.
Article in English | MEDLINE | ID: mdl-38878710

ABSTRACT

Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.


Subject(s)
Anti-Arrhythmia Agents , Antihypertensive Agents , Limit of Detection , Tandem Mass Spectrometry , Humans , Tandem Mass Spectrometry/methods , Reproducibility of Results , Antihypertensive Agents/blood , Chromatography, Liquid/methods , Anti-Arrhythmia Agents/blood , Linear Models , Forensic Toxicology/methods , Autopsy
11.
Emerg Infect Dis ; 30(7): 1352-1360, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38916546

ABSTRACT

Accurate and timely mortality surveillance is crucial for elucidating risk factors, particularly for emerging diseases. We compared use of COVID-19 keywords on death certificates alone to identify COVID-19 deaths in Minnesota, USA, during 2020-2022, with use of a standardized mortality definition incorporating additional clinical data. For analyses, we used likelihood ratio χ2 and median 1-way tests. Death certificates alone identified 96% of COVID-19 deaths confirmed by the standardized definition and an additional 3% of deaths that had been classified as non-COVID-19 deaths by the standardized definition. Agreement between methods was >90% for most groups except children, although agreement among adults varied by demographics and location at death. Overall median time from death to filing of death certificate was 3 days; decedent characteristics and whether autopsy was performed varied. Death certificates are an efficient and timely source of COVID-19 mortality data when paired with SARS-CoV-2 testing data.


Subject(s)
COVID-19 , Death Certificates , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/epidemiology , Minnesota/epidemiology , Male , Middle Aged , Female , Adult , Aged , Child , Adolescent , Child, Preschool , Young Adult , Infant , Aged, 80 and over , Cause of Death , Autopsy , COVID-19 Testing/methods
12.
Neuroimage ; 296: 120680, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38857819

ABSTRACT

Magnetic Resonance Imaging (MRI) can provide the location and signal characteristics of pathological regions within a postmortem tissue block, thereby improving the efficiency of histopathological studies. However, such postmortem-MRI guided histopathological studies have so far only been performed on fixed samples as imaging tissue frozen at the time of extraction, while preserving its integrity, is significantly more challenging. Here we describe the development of cold-postmortem-MRI, which can preserve tissue integrity and help target techniques such as transcriptomics. As a first step, RNA integrity number (RIN) was used to determine the rate of tissue biomolecular degradation in mouse brains placed at various temperatures between -20 °C and +20 °C for up to 24 h. Then, human tissue frozen at the time of autopsy was immersed in 2-methylbutane, sealed in a bio-safe tissue chamber, and cooled in the MRI using a recirculating chiller to determine MRI signal characteristics. The optimal imaging temperature, which did not show significant RIN deterioration for over 12 h, at the same time giving robust MRI signal and contrast between brain tissue types was deemed to be -7 °C. Finally, MRI was performed on human tissue blocks at this optimal imaging temperatures using a magnetization-prepared rapid gradient echo (MPRAGE, isotropic resolution between 0.3-0.4 mm) revealing good gray-white matter contrast and revealing subpial, subcortical, and deep white matter lesions. RINs measured before and after imaging revealed no significant changes (n = 3, p = 0.18, paired t-test). In addition to improving efficiency of downstream processes, imaging tissue at sub-zero temperatures may also improve our understanding of compartment specificity of MRI signal.


Subject(s)
Autopsy , Brain , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology , Mice , Autopsy/methods , Animals , Freezing , Male , Female , Mice, Inbred C57BL , Neuroimaging/methods
14.
Virol J ; 21(1): 131, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840200

ABSTRACT

Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.


Subject(s)
Cytomegalovirus Infections , Hemorrhage , Humans , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Infant, Newborn , Male , Fatal Outcome , Hemorrhage/etiology , Cytomegalovirus , Lung/pathology , Lung/diagnostic imaging , Lung/virology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Autopsy , Lung Diseases/virology , Lung Diseases/etiology
15.
J Anal Toxicol ; 48(6): 405-412, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38850225

ABSTRACT

While postmortem (PM) toxicology results provide valuable information towards ascertaining both the cause and manner of death in coronial cases, there are also significant difficulties associated with the interpretation of PM drug levels. Such difficulties are influenced by several pharmacokinetic and pharmacodynamic factors including PM redistribution, diffusion, site-to-site variability in drug levels, different drug properties and metabolism, bacterial activity, genetic polymorphisms, tolerance, resuscitation efforts, underlying conditions, and the toxicity profile of cases (i.e. single- or mixed-drug toxicity). A large body of research has been dedicated for better understanding and even quantifying the influence of these factors on PM drug levels. For example, several investigative matrices have been developed as potential indicators of PM redistribution, but they have limited practical value. Reference tables of clinically relevant therapeutic, toxic, and potentially fatal drug concentrations have also been compiled, but these unfortunately do not provide reliable reference values for PM toxicology. More recent research has focused on developing databases of peripheral PM drug levels for a variety of case-types to increase transferability to real-life cases and improve interpretations. Changes to drug levels after death are inevitable and unavoidable. As such, guidelines and practices will continue to evolve as we further our understanding of such phenomena.


Subject(s)
Autopsy , Forensic Toxicology , Postmortem Changes , Humans , Cause of Death , Forensic Toxicology/methods , Pharmaceutical Preparations
16.
Nat Commun ; 15(1): 5366, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926387

ABSTRACT

Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.


Subject(s)
Adenosine Deaminase , Adenosine , Autopsy , Brain , Inosine , RNA Editing , RNA-Binding Proteins , Humans , Adenosine/metabolism , Adenosine Deaminase/metabolism , Adenosine Deaminase/genetics , Brain/metabolism , Inosine/metabolism , Inosine/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Prefrontal Cortex/metabolism , Postmortem Changes , Male
18.
PLoS One ; 19(6): e0304993, 2024.
Article in English | MEDLINE | ID: mdl-38848411

ABSTRACT

This study aimed to establish the diagnostic criteria for upper gastrointestinal bleeding (UGIB) using postmortem computed tomography (PMCT). This case-control study enrolled 27 consecutive patients with autopsy-proven UGIB and 170 of the 566 patients without UGIB who died in a university hospital in Japan after treatment and underwent both noncontrast PMCT and conventional autopsy between 2009 and 2020. Patients were randomly allocated to two groups: derivation and validation sets. Imaging findings of the upper gastrointestinal contents, including CT values, were recorded and evaluated for their power to diagnose UGIB in the derivation set and validated in the validation set. In the derivation set, the mean CT value of the upper gastrointestinal contents was 48.2 Hounsfield units (HU) and 22.8 HU in cases with and without UGIB. The optimal cutoff CT value for diagnosing UGIB was ≥27.7 HU derived from the receiver operating characteristic curve analysis (sensitivity, 91.7%; specificity, 81.2%; area under the curve, 0.898). In the validation set, the sensitivity and specificity in diagnosing UGIB for the CT cutoff value of ≥27.7 HU were 84.6% and 77.6%, respectively. In addition to the CT value of ≥27.7 HU, PMCT findings of solid-natured gastrointestinal content and intra/peri-content bubbles ≥4 mm, extracted from the derivation set, increased the specificity for UGIB (96.5% and 98.8%, respectively) but decreased the sensitivity (61.5% and 38.5%, respectively) in the validation set. In diagnosing UGIB on noncontrast PMCT, the cutoff CT value of ≥27.7 HU and solid gastrointestinal content were valid and reproducible diagnostic criteria.


Subject(s)
Autopsy , Gastrointestinal Hemorrhage , Tomography, X-Ray Computed , Humans , Male , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/diagnosis , Female , Aged , Tomography, X-Ray Computed/methods , Middle Aged , Case-Control Studies , Aged, 80 and over , ROC Curve , Adult , Sensitivity and Specificity , Postmortem Imaging
19.
J UOEH ; 46(2): 221-226, 2024.
Article in English | MEDLINE | ID: mdl-38839290

ABSTRACT

A woman in her 30s who was being treated for a mental illness with several psychotropic drugs was admitted to the hospital after being found in a state of unconsciousness and respiratory arrest at home. She was pronounced dead 12 hours after she was discovered. Her autopsy revealed symmetrical hemorrhagic necrosis in the putamen on both sides of her cerebrum. Although many drugs were detected in her blood, all of those other than dextromethorphan (DXM) were within or below the therapeutic range. Her blood DXM was 1.73 µg/ml at admission and 1.61 µg/ml at autopsy, which were within the toxic range or coma-to-death range. The cause of death was diagnosed as DXM poisoning. DXM can cause hallucinations and euphoria if taken in excess, but since it is available as an over-the-counter drug at general pharmacies, an increasing number of young people are overdosing on it, mistakenly believing it to be a safe drug with few side effects. We believe that further social measures against DXM are necessary in Japan, such as disseminating correct knowledge in society and regulating over-the-counter sales.


Subject(s)
Autopsy , Dextromethorphan , Humans , Dextromethorphan/poisoning , Female , Adult , Fatal Outcome
20.
Vopr Virusol ; 69(2): 134-150, 2024 May 06.
Article in Russian | MEDLINE | ID: mdl-38843020

ABSTRACT

INTRODUCTION: SARS-CoV-2 infection causes immune disorders that create conditions for the reactivation of human herpesviruses (HHVs). However, the estimates of the HHVs effect on the course and outcome of COVID-19 are ambiguous. Аim - to study the possible relationship between the HHV reactivation and the adverse outcome of COVID-19. MATERIALS AND METHODS: Postmortem samples from the brain, liver, spleen, lymph nodes and lungs were obtained from 59 patients treated at the Moscow Infectious Diseases Hospital No.1 in 2021-2023. The group 1 comprised 39 patients with fatal COVID-19; group 2 (comparison group) included 20 patients not infected with SARS-CoV-2 who died from various somatic diseases. HHV DNA and SARS-CoV-2 RNA were determined by PCR. RESULTS: HHV DNA was found in autopsy samples from all patients. In group 1, EBV was most often detected in lymph nodes (94%), HHV-6 in liver (68%), CMV in lymph nodes (18%), HSV in brain (16%), VZV in lung and spleen (3% each). The detection rates of HHVs in both groups was similar. Important differences were found in viral load. In patients with COVID-19, the number of samples containing more than 1,000 copies of HHV DNA per 100,000 cells was 52.4%, in the comparison group - 16.6% (p < 0.002). An association has been established between the reactivation of HSV and HHV-6 and the severity of lung damage. Reactivation of EBV correlated with increased levels of liver enzymes. CONCLUSION: Reactivation of HHVs in patients with fatal COVID-19 was associated with severe lung and liver damages, which indicates a link between HHV reactivation and COVID-19 deaths.


Subject(s)
Autopsy , COVID-19 , DNA, Viral , Herpesviridae Infections , Herpesviridae , SARS-CoV-2 , Humans , COVID-19/virology , COVID-19/mortality , COVID-19/diagnosis , COVID-19/pathology , Female , Male , DNA, Viral/genetics , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Middle Aged , Aged , Herpesviridae/genetics , Herpesviridae/isolation & purification , Herpesviridae Infections/virology , Herpesviridae Infections/mortality , Adult , Lung/virology , Lung/pathology , Virus Activation , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/isolation & purification , Moscow , Viral Load , Lymph Nodes/virology , Lymph Nodes/pathology , Aged, 80 and over , Spleen/virology , Spleen/pathology
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