Isolating Viral and Host RNA Sequences from Archival Material and Production of cDNA Libraries for High-Throughput DNA Sequencing

PubMed Central

Xiao, Yongli; Sheng, Zong-Mei; Taubenberger, Jeffery K.

2015-01-01

The vast majority of surgical biopsy and post-mortem tissue samples are formalin-fixed and paraffin-embedded (FFPE), but this process leads to RNA degradation that limits gene expression analysis. As an example, the viral RNA genome of the 1918 pandemic influenza A virus was previously determined in a 9-year effort by overlapping RT-PCR from post-mortem samples. Using the protocols described here, the full genome of the 1918 virus at high coverage was determined in one high-throughput sequencing run of a cDNA library derived from total RNA of a 1918 FFPE sample after duplex-specific nuclease treatments. This basic methodological approach should assist in the analysis of FFPE tissue samples isolated over the past century from a variety of infectious diseases. PMID:26344216

Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia.

PubMed

Yamamori, Hidenaga; Hashimoto, Ryota; Verrall, Louise; Yasuda, Yuka; Ohi, Kazutaka; Fukumoto, Motoyuki; Umeda-Yano, Satomi; Ito, Akira; Takeda, Masatoshi

2011-07-01

The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia. Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects with schizophrenia. In addition to the difficulty of sampling, the use of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes in schizophrenia have been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R and GNAO1) in immortalized lymphocytes from 45 patients with schizophrenia and 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1, NPY1R or GNAO1 gene. Our findings suggest that the gene expression profile of immortalized lymphocyte from schizophrenic patients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes.

Comparison of premortem and postmortem estimates of plutonium deposited in the skeleton and liver of six individuals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sula, M.J.; Bihl, D.E.; Carbaugh, E.H.

1988-04-01

Assessment of organ burdens after internal exposures to radionuclides is often necessary to evaluate the health and regulatory implications of the exposure. The assessment of plutonium activity in skeleton and liver is usually estimated from measurements of plutonium excreted via urine. As part of the overall evaluation of internal dose assessment techniques, it is useful to compare the results of organ burden estimates made from evaluation of urinary excretion data with those made at death from tissue samples collected posthumously from the individual. Estimates of plutonium in the skeleton and liver, based on postmortem analysis of tissue samples for sixmore » individuals, were obtained from the US Transuranium Registry (USTR). Bioassay data and other radiation exposure information obtained from the individuals' files were used to estimate their skeleton and liver burdens at the times of their deaths, and these estimates were compared to those obtained through tissue analysis. 6 refs., 2 tabs.« less

Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death

PubMed Central

Poklis, Justin L.; Devers, Kelly G.; Arbefeville, Elise F.; Pearson, Julia M.; Houston, Eric; Poklis, Alphonse

2014-01-01

We present a traumatic fatality of a 19-year-old man who had ingested blotter paper containing 25INBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine]. Postmortem specimens were analyzed by high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). Toxicology findings for fluids based upon blood or urine calibrators were as follows: peripheral blood, 405 pg/mL; heart blood, 410 pg/mL; urine, 2.86 ng/mL; and vitreous humor, 99 pg/mL. While findings based upon the method of standard additions were: gastric contents, 7.1 μg total; bile, 10.9 ng/g; brain, 2.54 ng/g and liver, 7.2 ng/g. To our knowledge the presented case is the first postmortem case of 25I-NBOMe intoxication documented by toxicological analysis of tissues and body fluids. PMID:24215811

Effect of postmortem time interval on in vitro culture potential of goat skin tissues stored at room temperature.

PubMed

Singh, Mahipal; Ma, Xiaoling; Sharma, Anil

2012-09-01

Animal cloning using somatic cell nuclear transfer technology has renewed the interest in postmortem tissue storage, since these tissues can be used to reintroduce the lost genes back into the breeding pool in animal agriculture, preserve the genetic diversity, and revive the endangered species. However, for successful cloning of animals, integrity of nuclear DNA is essential. Cell viability and their potential to in vitro culture ensure nuclear integrity. The aim of this study was to determine the limits of postmortem time interval within which live cells can be recovered from goat skin tissues. To test the postmortem tissue storage limits, we cultured 2-3 mm(2) skin pieces (n = 70) from the ears of three breeds of goats (n = 7) after 0, 2, 4, and 6 days of postmortem storage at 24°C. After 10 days of culture, outgrowth of fibroblast-like cells (>50 cells) around the explants was scored. All the explants irrespective of breed displayed outgrowth of cells on the dish containing fresh tissues (i.e., day 0 of storage). However, the number of explants exhibiting outgrowth reduced with increasing time interval. Only 53.85 % explants displayed outgrowth after 2 days of tissue storage. The number of explants displaying outgrowth was much smaller after 4 (16.67 %) and 6 days (13.3 %) of storage. In general, the number of outgrowing cells per explant, on a given day, also decreased with increasing postmortem storage time interval. To test the differences between cell cultures, we established secondary cultures from one of the goats exhibiting outgrowth of cells after 6 days of tissue storage and compared them to similar cells from fresh tissues. Comparison of both the cell lines revealed similar cell morphology and growth curves and had doubling times of 23.04 and 22.56 h, respectively. These results suggest that live cells can be recovered from goat (and perhaps other animal) tissues stored at room temperature even after 6 days of their death with comparable growth profiles and, thus, can be used for tissue banking for preservation of superior genetics, genetic diversity, and cloning of animals.

Postmortem brain MRI with selective tissue biopsy as an adjunct to autopsy following neonatal encephalopathy.

PubMed

Nicholl, R M; Balasubramaniam, V P; Urquhart, D S; Sellathurai, N; Rutherford, M A

2007-05-01

Following the death of a neonate it is essential that parents are given full and accurate information about the probable cause of death. Perinatal autopsy often adds new information or may even change the presumed diagnosis [Cartlidge PH, Dawson AT, Stewart JH, Vujanic GM. Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths. Br Med J 1995;310(6973):155-8; Khong TY. Falling neonatal autopsy rates. Br Med J 2002;324(7340):749-50] informing decisions regarding the management of any future pregnancy. Autopsy can be considered the "gold standard" for the identification of antecedent events leading to a neonatal death. However, recent events in the UK have added to an already declining rate in neonatal autopsies [Brodlie M, Laing IA. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. Br Med J 2002;324(7340):761-3]. To try and redress this balance the Chief Medical Officer has recommended that research should be commissioned into the use of non-invasive imaging to provide a similar standard of information [The Chief Medical Officer. The removal, retention and use of human organs and tissues from post mortem examination. London, England: The Stationary Office, Department of Health; 2001]. Previous publications on postmortem MRI have focused largely on investigation of the foetus and of still birth [Griffiths PD, Variend D, Evans M, Jones A, Wilkinson ID, Paley MNJ, et al. Postmortem MR imaging of the fetal and stillborn central nervous system. Am J Neuroradiol 2003;24(1):22-7; Whitby EH, Paley MN, Cohen M, GriffithsPD. Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy? Semin Fetal Neonatal Med 2005;10(5):475-83]. We report our experience on the use of postmortem brain MRI combined with selective tissue biopsy, in six neonatal deaths in the setting of a large district general hospital.

Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector

PubMed Central

Chun, Hao-Jung; Poklis, Justin L.; Poklis, Alphonse; Wolf, Carl E.

2016-01-01

Ethanol is the most widely used and abused drug. While blood is the preferred specimen for analysis, tissue specimens such as brain serve as alternative specimens for alcohol analysis in post-mortem cases where blood is unavailable or contaminated. A method was developed using headspace gas chromatography with flame ionization detection (HS-GC-FID) for the detection and quantification of ethanol, acetone, isopropanol, methanol and n-propanol in brain tissue specimens. Unfixed volatile-free brain tissue specimens were obtained from the Department of Pathology at Virginia Commonwealth University. Calibrators and controls were prepared from 4-fold diluted homogenates of these brain tissue specimens, and were analyzed using t-butanol as the internal standard. The chromatographic separation was performed with a Restek BAC2 column. A linear calibration was generated for all analytes (mean r2 > 0.9992) with the limits of detection and quantification of 100–110 mg/kg. Matrix effect from the brain tissue was determined by comparing the slopes of matrix prepared calibration curves with those of aqueous calibration curves; no significant differences were observed for ethanol, acetone, isopropanol, methanol and n-propanol. The bias and the CVs for all volatile controls were ≤10%. The method was also evaluated for carryover, selectivity, interferences, bench-top stability and freeze-thaw stability. The HS-GC-FID method was determined to be reliable and robust for the analysis of ethanol, acetone, isopropanol, methanol and n-propanol concentrations in brain tissue, effectively expanding the specimen options for post-mortem alcohol analysis. PMID:27488829

Influence of postmortem time on the outcome of blood cultures among cadaveric tissue donors.

PubMed

Saegeman, V; Verhaegen, J; Lismont, D; Verduyckt, B; De Rijdt, T; Ectors, N

2009-02-01

Tissue banks provide tissues of human cadaver donors for transplantation. The maximal time limit for tissue retrieval has been set at 24 h postmortem. This study aimed at evaluating the evidence for this limit from a microbiological point of view. The delay of growth in postmortem blood cultures, the identification of the species isolated and clinical/environmental factors were investigated among 100 potential tissue donors. No significant difference was found in the rate of donors with grown blood cultures within (25/65=38%) compared with after (24/65=37%) 24 h of death. Coagulase-negative staphylococci and gastro-intestinal microorganisms were isolated within and after 24 h of death. Two factors--antimicrobial therapy and "delay before body cooling"--were significantly inversely related with donors' blood culture results. From a microbiological point of view, there is no evidence for avoiding tissue retrieval among donors after 24 h of death.

Biochemical Fractionation and Stable Isotope Dilution Liquid Chromatography-mass Spectrometry for Targeted and Microdomain-specific Protein Quantification in Human Postmortem Brain Tissue*

PubMed Central

MacDonald, Matthew L.; Ciccimaro, Eugene; Prakash, Amol; Banerjee, Anamika; Seeholzer, Steven H.; Blair, Ian A.; Hahn, Chang-Gyu

2012-01-01

Synaptic architecture and its adaptive changes require numerous molecular events that are both highly ordered and complex. A majority of neuropsychiatric illnesses are complex trait disorders, in which multiple etiologic factors converge at the synapse via many signaling pathways. Investigating the protein composition of synaptic microdomains from human patient brain tissues will yield valuable insights into the interactions of risk genes in many disorders. These types of studies in postmortem tissues have been limited by the lack of proper study paradigms. Thus, it is necessary not only to develop strategies to quantify protein and post-translational modifications at the synapse, but also to rigorously validate them for use in postmortem human brain tissues. In this study we describe the development of a liquid chromatography-selected reaction monitoring method, using a stable isotope-labeled neuronal proteome standard prepared from the brain tissue of a stable isotope-labeled mouse, for the multiplexed quantification of target synaptic proteins in mammalian samples. Additionally, we report the use of this method to validate a biochemical approach for the preparation of synaptic microdomain enrichments from human postmortem prefrontal cortex. Our data demonstrate that a targeted mass spectrometry approach with a true neuronal proteome standard facilitates accurate and precise quantification of over 100 synaptic proteins in mammalian samples, with the potential to quantify over 1000 proteins. Using this method, we found that protein enrichments in subcellular fractions prepared from human postmortem brain tissue were strikingly similar to those prepared from fresh mouse brain tissue. These findings demonstrate that biochemical fractionation methods paired with targeted proteomic strategies can be used in human brain tissues, with important implications for the study of neuropsychiatric disease. PMID:22942359

Reliability of postmortem fentanyl concentrations in determining the cause of death.

PubMed

Gill, James R; Lin, Peter T; Nelson, Lewis

2013-03-01

Transdermal fentanyl, an opioid used for management of marked pain, also is abused and may cause death. We reviewed medical examiner reports of 92 decedents who had one or more fentanyl transdermal patches on their body and had fentanyl detected in their postmortem toxicology analysis. The manners of death included 40 accidents, 36 natural, 8 suicides, 5 therapeutic complications, and 3 undetermined deaths. Among the accidental fentanyl intoxication deaths, 32 of 37 involved substance abuse. The majority (95 %) of the 37 accidental deaths involving fentanyl were multi-drug intoxications. The substance abuse deaths had a mean fentanyl blood concentration (26.4 ng/ml or μg/L) that was over twice that of the natural group (11.8 ng/ml). Our analysis suggests a relationship between total patch dosage and mean postmortem fentanyl concentration up to the 100-μg/h dose. The very wide and overlapping ranges of postmortem fentanyl concentrations effectively nullify the utility of correlating the dose and expected postmortem concentration for any particular death. Based on the variable relationship between dose and blood concentration, the antemortem dose cannot be reliably predicted based on the postmortem concentration. This does not, however, render the medical examiner/coroner unable to determine the cause and manner of death because the toxicology results are only one datum point among several that are considered. Although there was a weakly positive relationship between body mass index and fentanyl concentration, further research is needed to determine whether adipose tissue represents a significant depot for postmortem release of fentanyl.

Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death.

PubMed

Poklis, Justin L; Devers, Kelly G; Arbefeville, Elise F; Pearson, Julia M; Houston, Eric; Poklis, Alphonse

2014-01-01

We present a traumatic fatality of a 19-year-old man who had ingested blotter paper containing 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine]. Postmortem specimens were analyzed by high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). Toxicology findings for fluids based upon blood or urine calibrators were as follows: peripheral blood, 405 pg/mL; heart blood, 410 pg/mL; urine, 2.86 ng/mL; and vitreous humor, 99 pg/mL. While findings based upon the method of standard additions were: gastric contents, 7.1 μg total; bile, 10.9 ng/g; brain, 2.54 ng/g and liver, 7.2 ng/g. To our knowledge the presented case is the first postmortem case of 25I-NBOMe intoxication documented by toxicological analysis of tissues and body fluids. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dead in the water--are we killing the hospital autopsy with poor consent practices?

PubMed

Henry, Jaimie; Nicholas, Nick

2012-07-01

It is now a recognized fact that the practice of conducting a consent (or hospital) post-mortem examination is in decline. There have been many reasons put forth to explain this demise, but the quality of the consenting process is frequently cited as having a high impact. This article focuses on consent practices for post-mortem examinations in England and Wales, and considers if our consent techniques are adversely affecting post-mortem examination uptake. We examine the regulatory compliance of trusts with their statutory obligations by analyzing the Human Tissue Authority's compliance and inspection reports. We further analyze 21 publicly available NHS Trust policies on post-mortem examination consent procedures, and consider whether these are fit for the purpose of meeting the dual needs of clinicians and the bereaved. Despite more Human Tissue Authority inspections, there is a disproportionate rise in enforcement actions, with up to 48% of sampled Trusts exhibiting shortcomings in their legal duties. Additionally, only 52.4% of sampled trusts follow the Human Tissue Authority best-practice model, with 23.8% having no documented procedures. Despite the well founded evidence base for best-practice models, consent practices for post-mortem examinations remains poor and is likely to have a gross adverse effect on the rate of post-mortem examinations. We recommend that NHS Trusts rigorously review their protocols and introduce a team-approach between clinicians and trained bereavement staff in core-consent teams, as the Human Tissue Authority suggests, whilst at the same time placing a strong emphasis on education for junior and senior colleagues alike.

Translational Research in Pediatrics IV: Solid Tissue Collection and Processing.

PubMed

Gillio-Meina, Carolina; Zielke, H Ronald; Fraser, Douglas D

2016-01-01

Solid tissues are critical for child-health research. Specimens are commonly obtained at the time of biopsy/surgery or postmortem. Research tissues can also be obtained at the time of organ retrieval for donation or from tissue that would otherwise have been discarded. Navigating the ethics of solid tissue collection from children is challenging, and optimal handling practices are imperative to maximize tissue quality. Fresh biopsy/surgical specimens can be affected by a variety of factors, including age, gender, BMI, relative humidity, freeze/thaw steps, and tissue fixation solutions. Postmortem tissues are also vulnerable to agonal factors, body storage temperature, and postmortem intervals. Nonoptimal tissue handling practices result in nucleotide degradation, decreased protein stability, artificial posttranslational protein modifications, and altered lipid concentrations. Tissue pH and tryptophan levels are 2 methods to judge the quality of solid tissue collected for research purposes; however, the RNA integrity number, together with analyses of housekeeping genes, is the new standard. A comprehensive clinical data set accompanying all tissue samples is imperative. In this review, we examined: the ethical standards relating to solid tissue procurement from children; potential sources of solid tissues; optimal practices for solid tissue processing, handling, and storage; and reliable markers of solid tissue quality. Copyright © 2016 by the American Academy of Pediatrics.

Ex vivo measurement of postmortem tissue changes in the crystalline lens by Brillouin spectroscopy and confocal reflectance microscopy.

PubMed

Reiss, Stephan; Sperlich, K; Hovakimyan, M; Martius, P; Guthoff, R F; Stolz, H; Stachs, O

2012-08-01

Use of Brillouin spectroscopy in ophthalmology enables noninvasive, spatially resolved determination of the rheological properties of crystalline lens tissue. Furthermore, the Brillouin shift correlates with the protein concentration inside the lens. In vitro measurements on extracted porcine lenses demonstrate that results obtained with Brillouin spectroscopy depend strongly on time after death. The intensity of the Brillouin signal decreases significantly as early as 5 h postmortem. Moreover, the fluctuation of the Brillouin frequency shift inside the lens increases with postmortem time. Images of lens tissue taken with a confocal reflectance microscope between measurements reveal a degenerative aging process. These tissue changes correlate with our results from Brillouin spectroscopy. It is concluded that only in vivo measurements appropriately reflect the rheological properties of the eye lens and its protein concentration.

DNA and RNA profiling of excavated human remains with varying postmortem intervals.

PubMed

van den Berge, M; Wiskerke, D; Gerretsen, R R R; Tabak, J; Sijen, T

2016-11-01

When postmortem intervals (PMIs) increase such as with longer burial times, human remains suffer increasingly from the taphonomic effects of decomposition processes such as autolysis and putrefaction. In this study, various DNA analysis techniques and a messenger RNA (mRNA) profiling method were applied to examine for trends in nucleic acid degradation and the postmortem interval. The DNA analysis techniques include highly sensitive DNA quantitation (with and without degradation index), standard and low template STR profiling, insertion and null alleles (INNUL) of retrotransposable elements typing and mitochondrial DNA profiling. The used mRNA profiling system targets genes with tissue specific expression for seven human organs as reported by Lindenbergh et al. (Int J Legal Med 127:891-900, 27) and has been applied to forensic evidentiary traces but not to excavated tissues. The techniques were applied to a total of 81 brain, lung, liver, skeletal muscle, heart, kidney and skin samples obtained from 19 excavated graves with burial times ranging from 4 to 42 years. Results show that brain and heart are the organs in which both DNA and RNA remain remarkably stable, notwithstanding long PMIs. The other organ tissues either show poor overall profiling results or vary for DNA and RNA profiling success, with sometimes DNA and other times RNA profiling being more successful. No straightforward relations were observed between nucleic acid profiling results and the PMI. This study shows that not only DNA but also RNA molecules can be remarkably stable and used for profiling of long-buried human remains, which corroborate forensic applications. The insight that the brain and heart tissues tend to provide the best profiling results may change sampling policies in identification cases of degrading cadavers.

Analysis of citalopram and desmethylcitalopram in postmortem fluids and tissues using liquid chromatography-mass spectrometry.

DOT National Transportation Integrated Search

2011-10-01

"Citalopram is a selective serotonin reuptake inhibitor that is a commonly prescribed drug for the treatment of : depression, obsessive-compulsive disorder, panic disorder, anxiety disorder, and post-traumatic stress disorder. : While the use of cita...

Differential Nuclear and Mitochondrial DNA Preservation in Post-Mortem Teeth with Implications for Forensic and Ancient DNA Studies

PubMed Central

Higgins, Denice; Rohrlach, Adam B.; Kaidonis, John; Townsend, Grant; Austin, Jeremy J.

2015-01-01

Major advances in genetic analysis of skeletal remains have been made over the last decade, primarily due to improvements in post-DNA-extraction techniques. Despite this, a key challenge for DNA analysis of skeletal remains is the limited yield of DNA recovered from these poorly preserved samples. Enhanced DNA recovery by improved sampling and extraction techniques would allow further advancements. However, little is known about the post-mortem kinetics of DNA degradation and whether the rate of degradation varies between nuclear and mitochondrial DNA or across different skeletal tissues. This knowledge, along with information regarding ante-mortem DNA distribution within skeletal elements, would inform sampling protocols facilitating development of improved extraction processes. Here we present a combined genetic and histological examination of DNA content and rates of DNA degradation in the different tooth tissues of 150 human molars over short-medium post-mortem intervals. DNA was extracted from coronal dentine, root dentine, cementum and pulp of 114 teeth via a silica column method and the remaining 36 teeth were examined histologically. Real time quantification assays based on two nuclear DNA fragments (67 bp and 156 bp) and one mitochondrial DNA fragment (77 bp) showed nuclear and mitochondrial DNA degraded exponentially, but at different rates, depending on post-mortem interval and soil temperature. In contrast to previous studies, we identified differential survival of nuclear and mtDNA in different tooth tissues. Futhermore histological examination showed pulp and dentine were rapidly affected by loss of structural integrity, and pulp was completely destroyed in a relatively short time period. Conversely, cementum showed little structural change over the same time period. Finally, we confirm that targeted sampling of cementum from teeth buried for up to 16 months can provide a reliable source of nuclear DNA for STR-based genotyping using standard extraction methods, without the need for specialised equipment or large-volume demineralisation steps. PMID:25992635

Screening of post-mortem tissue donors for Coxiella burnetii infection after large outbreaks of Q fever in The Netherlands

PubMed Central

2014-01-01

Background After the largest outbreaks of Q fever ever recorded in history occurred in the Netherlands, concern arose that Coxiella may be transmitted via donated tissues of latent or chronically infected donors. The Dutch Health Council recently advised to screen tissue donors, donating high risk tissues, for Coxiella infection. Methods After validation of an enzyme immunoassay (EIA) test for IgG antibodies against phase 2 of C. burnetii for use on post-mortem samples, serum samples of 1033 consecutive Dutch post-mortem tissue donors were tested for IgG antibodies against phase 2 of C. burnetii. Confirmation of reactive results was done by immunofluorescence assay (IFA). All available tissues (corneas, heart valves, skin and bone marrow) from donors with IgG reactivity were tested for presence of Coxiella DNA by PCR. Risk factors for IgG reactivity were investigated. Results After validation of the tests for use on post-mortem samples, 50/1033 donors (4.8%) screened positive for phase 2 anti-Coxiella IgG by EIA, and 31 were confirmed by IFA (3.0%). One donor showed a serological profile compatible with chronic infection. All tested tissues (25 corneas, 6 heart valves, 4 skin and 3 bone marrow) from donors with IgG reactivity tested negative for the presence of Coxiella DNA. Except for living in a postal code area with a high number of Q fever notifications, no risk factors for IgG reactivity were found. Conclusions The strong correlation between notifications and seroprevalence confirms that the used assays are sufficiently specific for use on post-mortem samples, although one has to be aware of differences between batches. Thus, this study provides a validated method for screening tissue donors for infection with Coxiella burnetii that can be used in future outbreaks. PMID:24393298

Skeletal muscle proteins: a new approach to delimitate the time since death.

PubMed

Foditsch, Elena Esra; Saenger, Alexandra Maria; Monticelli, Fabio Carlo

2016-03-01

Skeletal muscle tissue is proposed as a forensic model tissue with strong potential, as it is easily accessible and its true-to-life state structure and function is well known. Despite this strong potential, skeletal muscle degradation studies are rare. The aim of this study was to test if a skeletal muscle-based protein analysis is applicable to delimitate the time since death. Under standard conditions, two pigs were stored either at 22 °C for 5 days or 4 °C for 21 days. Their Mm. biceps femori were sampled periodically for analyses of ten skeletal muscle proteins postmortem. All analyzed proteins can serve as markers for a delimitation of the time since death. Desmin, nebulin, titin, and SERCA 1 displayed distinct protein patterns at certain points of time. The other five proteins, α-actinin, calsequestrin-1, laminin, troponin T-C, and SERCA 2, showed no degradation patterns within the analyzed postmortem time frame. Referring to specific skeletal muscle proteins, results showed short-term stabilities for just a minority of analyzed proteins, while the majority of investigated proteins displayed characteristics as long-term markers. Due to specific patterns and the possibility to determine definite constraints of the presence, absence, or pattern alterations of single proteins, the feasibility of porcine skeletal muscle as forensic model tissue is outlined and the potential of skeletal muscle as forensic model tissue is underlined, especially with respect to later postmortem phases, which so far lack feasible methods to delimitate the time since death.

Analysis of zolpidem in postmortem fluids and tissues using ultra-performance liquid chromatography-mass spectrometry.

DOT National Transportation Integrated Search

2014-02-01

Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. Its : use is common and wide-spread. While quite effective in producing sedation, zolpidem has potentially : hazardous side effects when put in the ...

Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons

PubMed Central

Krishnaswami, Suguna Rani; Grindberg, Rashel V; Novotny, Mark; Venepally, Pratap; Lacar, Benjamin; Bhutani, Kunal; Linker, Sara B; Pham, Son; Erwin, Jennifer A; Miller, Jeremy A; Hodge, Rebecca; McCarthy, James K; Kelder, Martin; McCorrison, Jamison; Aevermann, Brian D; Fuertes, Francisco Diez; Scheuermann, Richard H; Lee, Jun; Lein, Ed S; Schork, Nicholas; McConnell, Michael J; Gage, Fred H; Lasken, Roger S

2016-01-01

A protocol is described for sequencing the transcriptome of a cell nucleus. Nuclei are isolated from specimens and sorted by FACS, cDNA libraries are constructed and RNA-seq is performed, followed by data analysis. Some steps follow published methods (Smart-seq2 for cDNA synthesis and Nextera XT barcoded library preparation) and are not described in detail here. Previous single-cell approaches for RNA-seq from tissues include cell dissociation using protease treatment at 30 °C, which is known to alter the transcriptome. We isolate nuclei at 4 °C from tissue homogenates, which cause minimal damage. Nuclear transcriptomes can be obtained from postmortem human brain tissue stored at −80 °C, making brain archives accessible for RNA-seq from individual neurons. The method also allows investigation of biological features unique to nuclei, such as enrichment of certain transcripts and precursors of some noncoding RNAs. By following this procedure, it takes about 4 d to construct cDNA libraries that are ready for sequencing. PMID:26890679

Low μ-Opioid Receptor Status in Alcohol Dependence Identified by Combined Positron Emission Tomography and Post-Mortem Brain Analysis

PubMed Central

Hermann, Derik; Hirth, Natalie; Reimold, Matthias; Batra, Anil; Smolka, Michael N; Hoffmann, Sabine; Kiefer, Falk; Noori, Hamid R; Sommer, Wolfgang H; Reischl, Gerald; la Fougère, Christian; Mann, Karl; Spanagel, Rainer; Hansson, Anita C

2017-01-01

Blockade of the μ-opioid receptor (MOR) by naltrexone reduces relapse risk in a subpopulation of alcohol-dependent patients. Previous positron-emission-tomography (PET) studies using the MOR ligand [11C]carfentanil have found increased MOR availability in abstinent alcoholics, which may reflect either increased MOR expression or lower endogenous ligand concentration. To differentiate between both effects, we investigated two cohorts of alcoholic subjects using either post-mortem or clinical PET analysis. Post-mortem brain tissue of alcohol-dependent subjects and controls (N=43/group) was quantitatively analyzed for MOR ([3H]DAMGO)-binding sites and OPRM1 mRNA in striatal regions. [11C]carfentanil PET was performed in detoxified, medication free alcohol-dependent patients (N=38), followed by a randomized controlled study of naltrexone versus placebo and follow-up for 1 year (clinical trial number: NCT00317031). Because the functional OPRM1 variant rs1799971:A>G affects the ligand binding, allele carrier status was considered in the analyses. MOR-binding sites were reduced by 23–51% in post-mortem striatal tissue of alcoholics. In the PET study, a significant interaction of OPRM1 genotype, binding potential (BPND) for [11C]carfentanil in the ventral striatum, and relapse risk was found. Particularly in G-allele carriers, lower striatal BPND was associated with a higher relapse risk. Interestingly, this effect was more pronounced in the naltrexone treatment group. Reduced MOR is interpreted as a neuroadaptation to an alcohol-induced release of endogenous ligands in patients with severe alcoholism. Low MOR availability may explain the ineffectiveness of naltrexone treatment in this subpopulation. Finally, low MOR-binding sites are proposed as a molecular marker for a negative disease course. PMID:27510425

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

PubMed Central

Sue, Lucia I.; Walker, Douglas G.; Roher, Alex E.; Lue, LihFen; Vedders, Linda; Connor, Donald J.; Sabbagh, Marwan N.; Rogers, Joseph

2008-01-01

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability. PMID:18347928

[Postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pigs].

PubMed

Liu, Wei; Da, Qing; Shen, Min

2012-06-01

To investigate the postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pig, and to provide method and evidence for forensic identification and clinical diagnosis and treatment. Guinea pigs were intragastric administrated with 100, 50, 15 microg/kg tetrodotoxin, respectively. The poisoning symptoms were observed. The samples of heart, liver, spleen, lung, kidney, brain, stomach, intestines, bile, heart blood and urine were collected. The concentrations of tetrodotoxin in tissues and body fluids were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). After administrated with tetrodotoxin, all guinea pigs came out poisoning signs including tachypnea, weary and dead finally. Tetrodotoxin concentrations in lung, stomach, intestines and urine were higher, followed by blood, heart and brain. The concentration in bile was the lowest. Postmortem distribution of tetrodotoxin in guinea pig is uneven. The concentration in the lung, stomach, intestines, urine and heart blood are higher, those tissues could be used for diagnosis of tetrodotoxin poisoning.

Experimental forensic and bioanthropological aspects of soft tissue taphonomy: 1. Factors influencing postmortem tissue desiccation rate.

PubMed

Aturaliya, S; Lukasewycz, A

1999-09-01

Euthanized rats' carcasses were exposed in an environmental chamber to multiple variables including: (1) position, (2) enveloping clothing, and (3) soil interment in an effort to determine the individual variables' effect on postmortem rate of body and visceral organ water loss. Results indicated that body water loss was enhanced by a horizontal position versus vertical, probably because of wider spread of bacteria- and enzyme-laden abdominal fluid secondary to diaphragm digestion with consequent greater tissue digestion and liquefaction. Clothing also accelerated the desiccation rate. Desiccation was about equally as effective by soil interment as by air exposure, though simulating windy conditions by tripling the air flow rate resulted in much more rapid desiccation in the air-exposed specimen. These studies suggest that the single most important factor influencing postmortem body water loss rate is the environment at the skin surface that acts to enhance or impair water removal from the skin surface and thus influences the water concentration gradient between the skin and underlying deeper tissues.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptormore » density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.« less

Duragesic transdermal patch: postmortem tissue distribution of fentanyl in 25 cases.

PubMed

Anderson, D T; Muto, J J

2000-10-01

Fentanyl is a potent, short-acting narcotic analgesic widely used as a surgical anesthetic and for the control of pain when administered in the form of a transdermal patch. The success of the patch can be attributed to fentanyl's low molecular weight and its highly lipophilic nature, which enables it to be readily absorbed through the skin and subsequently distributed throughout the body. Over the past three years, the Los Angeles County Coroner's Toxicology Laboratory has encountered 25 cases involving Duragesic patches (fentanyl), and their postmortem tissue distributions are presented here. The analysis of fentanyl from postmortem specimens (3-mL or g sample size) consisted of an n-butyl chloride basic extraction followed by identification and quantitation on a gas chromatograph-mass spectrometer using the selected ion monitoring (SIM) mode. The fentanyl ions monitored were m/z 245, 146, and 189 and the internal standard, fentanyl-d5 ions, were m/z 250, 151, and 194 (quantitation ion underlined). The linear range of the assay was 1.67 microg/L to 500 microg/L with the limit of quantitation and detection of 1.67 microg/L. The postmortem tissue distribution ranges of fentanyl in the 25 fatalities were as follows: heart blood, 1.8-139 microg/L (23 cases); femoral blood, 3.1-43 microg/L (13 cases); vitreous, +<2.0-20 microg/L (4 cases); liver, 5.8-613 microg/kg (22 cases); bile, 3.5-262 microg/L (15 cases); urine, 2.9-895 microg/L (19 cases); gastric, 0-1200 microg total (17 cases); spleen, 7.8-79 microg/kg (3 cases); kidney, 11 microg/kg (1 case); and lung, 31 microg/kg (1 case). The age of the decedents in this study ranged from 19 to 84, with an average age of 46. The modes of death included 15 accidental, 5 natural, 3 suicidal, and 2 undetermined. The main objectives of this paper are to show the prevalence of fentanyl patches in our community and to aid the forensic toxicologist with the interpretation of postmortem fentanyl levels in casework.

An audit of parents'/guardians' wishes recorded after coronial autopsies in cases of sudden unexpected death in infancy: issues raised and future directions.

PubMed

Cohen, M C; Blakey, S; Donn, T; McGovern, S; Parry, L

2009-07-01

In the U.K., cases of sudden unexpected death in infancy are under the jurisdiction of the Coroner and consent for a post-mortem is not required. Prior to the Human Tissue Act 2006 (HTA) there was also no requirement to request retention of tissue (blocks and slides). The HTA stipulates that parental/ guardian consent is mandatory to retain or dispose of all tissues after the Coroners' purposes have been fulfilled. In 2007, in order to avoid confusion with the consent needed for hospital post-mortems, a new form was introduced by Sheffield Children's Hospital NHS Foundation Trust (SCH) called Record of parents'/guardians'wishes regarding samples taken at a Coroner's post mortem. This version specifically asks if blocks and slides may be retained as part of the medical record, or are to be disposed of, and for parental agreement (or not) for the frozen tissue, blocks and slides to be used for education, audit, quality control and medical research. One hundred and nineteen Coroners' postmortems covering the years 2006-2007 were reviewed. All parents/guardians (P/G) were contacted and the outcomes of P/G wishes recorded by SCH staff, Coroners' Officers (CO) and Police Family Liaison Officers (PFLO) were analysed and compared (44% from CO were outstanding at the time of audit). Any delay in recording P/G wishes by these three groups was also compared. In 2006, parental agreement to the use of blocks and slides for education, audit, quality control and medical research was 94%, 77% and 75% for SCH, CO and PFLO, respectively. In 2007 it was 84%, 37% and 100% for the same groups. Permission for the retention of frozen tissue given to SCH, CO and PFLO was 90%, 62% and 100% in 2006 and 90%, 44% and 100% in 2007, respectively. Cases where parents did not wish for the retention or use of tissue (including blocks and slides) were 3%, 15% and 0% in 2006 for SCH, CO and PFLO respectively, and 0% for all groups in 2007. Training of staff in all aspects of post-mortem and bereavement care is essential for ascertaining parental wishes. Families should be provided with the knowledge that allows them to make informed choices. The analysis of the results of the audit supports this view.

Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature.

PubMed

Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe; Linnet, Kristian

2016-09-01

To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association With Schizophrenia Endophenotypes

PubMed Central

Wonodi, Ikwunga; Stine, O. Colin; Sathyasaikumar, Korrapati V.; Roberts, Rosalinda C.; Mitchell, Braxton D.; Hong, L. Elliot; Kajii, Yasushi; Thaker, Gunvant K.; Schwarcz, Robert

2013-01-01

Context Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations are elevated in the brain and cerebrospinal fluid of schizophrenia patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the branching point of the kynurenine pathway. Objectives To examine KMO messenger RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared with healthy control individuals and to explore the relationship between KMO single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes. Design Case-control postmortem and clinical study. Setting Maryland Brain Collection, outpatient clinics. Participants Postmortem specimens from schizophrenia patients (n=32) and control donors (n=32) and a clinical sample of schizophrenia patients (n=248) and healthy controls (n=228). Main Outcome Measures Comparison of quantitative KMO messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of KMO single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response). Results In postmortem tissue, we found a significant and correlated reduction in KMO gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes. Conclusion Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits. PMID:21727251

Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes.

PubMed

Wonodi, Ikwunga; Stine, O Colin; Sathyasaikumar, Korrapati V; Roberts, Rosalinda C; Mitchell, Braxton D; Hong, L Elliot; Kajii, Yasushi; Thaker, Gunvant K; Schwarcz, Robert

2011-07-01

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, is an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors and modulates glutamate, dopamine, and acetylcholine signaling. Cortical kynurenic acid concentrations are elevated in the brain and cerebrospinal fluid of schizophrenia patients. The proximal cause may be an impairment of kynurenine 3-monooxygenase (KMO), a rate-limiting enzyme at the branching point of the kynurenine pathway. To examine KMO messenger RNA expression and KMO enzyme activity in postmortem tissue from the frontal eye field (FEF; Brodmann area 6) obtained from schizophrenia individuals compared with healthy control individuals and to explore the relationship between KMO single-nucleotide polymorphisms and schizophrenia oculomotor endophenotypes. Case-control postmortem and clinical study. Maryland Brain Collection, outpatient clinics. Postmortem specimens from schizophrenia patients (n = 32) and control donors (n = 32) and a clinical sample of schizophrenia patients (n = 248) and healthy controls (n = 228). Comparison of quantitative KMO messenger RNA expression and KMO enzyme activity in postmortem FEF tissue between schizophrenia patients and controls and association of KMO single-nucleotide polymorphisms with messenger RNA expression in postmortem FEF and schizophrenia and oculomotor endophenotypes (ie, smooth pursuit eye movements and oculomotor delayed response). In postmortem tissue, we found a significant and correlated reduction in KMO gene expression and KMO enzyme activity in the FEF in schizophrenia patients. In the clinical sample, KMO rs2275163 was not associated with a diagnosis of schizophrenia but showed modest effects on predictive pursuit and visuospatial working memory endophenotypes. Our results provide converging lines of evidence implicating reduced KMO activity in the etiopathophysiology of schizophrenia and related neurocognitive deficits.

Oxidative Damage in Parkinson’s Disease

DTIC Science & Technology

2005-01-01

inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy . J Neurol Sci 2004; 218:39-45. Martinat C, Shendelman S...inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy . J Neurol Sci 2004; 218:39-45. Martinat C...excess can have serious neurologi- effects at the higher dosages needed to overcome the In Viva Iron Chelation Prevents MPTP Toxicity 905 A 0 20 in

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saito, Kayoko; Ikeya, Kiyoko; Kondo, Eri

Mosaicism is a mixed state, with two cell populations of different genetic origins caused by a cell mutation occurring after fertilization. In the present case, DNA analysis of lymphocytes led to a DMD diagnosis before death. Postmortem immunocytochemical and DNA analysis showed somatic mosaicism. At age 18 years, blood lymphocyte DNA analysis showed a DMD gene deletion, upstream from exon 7 to the 5{prime} end containing both muscle and brain promoters. As the patient`s mother and elder sister had no deletions, he was considered to have a new mutation. Immunocytochemical studies of postmortem tissues showed that dystrophin was absent frommore » the tongue, deltoid, intercostal, psoas and rectus femoris muscles, but there was a mix of dystrophin-positive and negative fibers in the rectus abdominis, cardiac, temporalis and sternocleidomastoid muscles. All diaphragm cells were dystrophin positive. Polymerase chain reaction (PCR) amplification from all tissues except the temporalis and sternocleidomastoid muscles, diaphragm and kidney, in which no deletion was found, showed the deletion from at least exon 6 to the 5{prime} end containing both muscle and brain promoters. In this case, a genomic deletion of the DMD gene contributed to the formation of tissues derived from both ectoderm and endoderm, and cells of mesodermal origin showed genotypic and phenotypic heterogeneity. Our results indicate a mutation of the present case may have occurred just before the period of germ layer formation. 34 refs., 7 figs.« less

Forensic molecular pathology of violent deaths.

PubMed

Maeda, Hitoshi; Zhu, Bao-li; Ishikawa, Takaki; Michiue, Tomomi

2010-12-15

In forensic pathology, while classical morphology remains a core procedure to investigate deaths, a spectrum of ancillary procedures has been developed and incorporated to detail the pathology. Among them, postmortem biochemistry is important to investigate the systemic pathophysiological changes involved in the dying process that cannot be detected by morphology. In addition, recent advances in molecular biology have provided a procedure to investigate genetic bases of diseases that might present with sudden death, which is called 'molecular autopsy'. Meanwhile, the practical application of RNA analyses to postmortem investigation has not been accepted due to rapid decay after death; however, recent experimental and practical studies using real-time reverse transcription-PCR have suggested that the relative quantification of mRNA transcripts can be applied in molecular pathology for postmortem investigation of deaths, which may be called 'advanced molecular autopsy'. In a broad sense, forensic molecular pathology implies applied medical sciences to investigate the genetic basis of diseases, and the pathophysiology of diseases and traumas leading to death at a biological molecular level in the context of forensic pathology. The possible applications include analyses of local pathology, including tissue injury, ischemia/hypoxia and inflammation at the site of insult or specific tissue damage from intoxication, systemic responses to violence or environmental hazards, disorders due to intoxication, and systemic pathophysiology of fatal process involving major life-support organs. A review of previous studies suggests that systematic postmortem quantitative analysis of mRNA transcripts can be established from multi-faceted aspects of molecular biology and incorporated into death investigations in forensic pathology, to support and reinforce morphological evidence. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

SU-F-207-02: Use of Postmortem Subjects for Subjective Image Quality Assessment in Abdominal CT Protocols with Iterative Reconstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mench, A; Lipnharski, I; Carranza, C

Purpose: New radiation dose reduction technologies are emerging constantly in the medical imaging field. The latest of these technologies, iterative reconstruction (IR) in CT, presents the ability to reduce dose significantly and hence provides great opportunity for CT protocol optimization. However, without effective analysis of image quality, the reduction in radiation exposure becomes irrelevant. This work explores the use of postmortem subjects as an image quality assessment medium for protocol optimizations in abdominal CT. Methods: Three female postmortem subjects were scanned using the Abdomen-Pelvis (AP) protocol at reduced minimum tube current and target noise index (SD) settings of 12.5, 17.5,more » 20.0, and 25.0. Images were reconstructed using two strengths of iterative reconstruction. Radiologists and radiology residents from several subspecialties were asked to evaluate 8 AP image sets including the current facility default scan protocol and 7 scans with the parameters varied as listed above. Images were viewed in the soft tissue window and scored on a 3-point scale as acceptable, borderline acceptable, and unacceptable for diagnosis. The facility default AP scan was identified to the reviewer while the 7 remaining AP scans were randomized and de-identified of acquisition and reconstruction details. The observers were also asked to comment on the subjective image quality criteria they used for scoring images. This included visibility of specific anatomical structures and tissue textures. Results: Radiologists scored images as acceptable or borderline acceptable for target noise index settings of up to 20. Due to the postmortem subjects’ close representation of living human anatomy, readers were able to evaluate images as they would those of actual patients. Conclusion: Postmortem subjects have already been proven useful for direct CT organ dose measurements. This work illustrates the validity of their use for the crucial evaluation of image quality during CT protocol optimization, especially when investigating the effects of new technologies.« less

Supraorbital Postmortem Brain Sampling for Definitive Quantitative Confirmation of Cerebral Sequestration of Plasmodium falciparum Parasites

PubMed Central

Milner, Danny A.; Valim, Clarissa; Luo, Robert; Playforth, Krupa B.; Kamiza, Steve; Molyneux, Malcolm E.; Seydel, Karl B.; Taylor, Terrie E.

2012-01-01

Background The conventional clinical case definition of cerebral malaria (CM) is imprecise but specificity is improved by a definitive clinical feature such as retinopathy or confirming sequestration of parasites in a post-mortem examination of the brain. A full autopsy is often not possible, since it is costly and may encounter resistance of the deceased's family. Methods We have assessed the use of a cytological smear of brain tissue, obtained post-mortem by supraorbital sampling, for the purpose of quantifying cerebral sequestration in children with fatal malaria in Blantyre, Malawi. We have compared this method to histological quantification of parasites at autopsy. Results The number of parasites present on cytological smears correlated with the proportion of vessels parasitized as assessed by histology of fixed and stained brain tissue. Use of cytological results in addition to the standard clinical case definition increases the specificity of the clinical case definition alone from 48.3% to 100% with a minimal change in sensitivity. Conclusions Post-mortem supraorbital sampling of brain tissue improves the specificity of the diagnosis of fatal cerebral malaria and provides accurate quantitative estimates of cerebral sequestration. This tool can be of great value in clinical, pathogenetic, and epidemiological research studies on cerebral malaria. PMID:22291197

Characterization of human brown adipose tissue by chemical-shift water-fat MRI.

PubMed

Hu, Houchun H; Perkins, Thomas G; Chia, Jonathan M; Gilsanz, Vicente

2013-01-01

The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.

Identification of Pulmonary Edema in Forensic Autopsy Cases of Sudden Cardiac Death Using Fourier Transform Infrared Microspectroscopy: A Pilot Study.

PubMed

Lin, Hancheng; Luo, Yiwen; Sun, Qiran; Zhang, Ji; Tuo, Ya; Zhang, Zhong; Wang, Lei; Deng, Kaifei; Chen, Yijiu; Huang, Ping; Wang, Zhenyuan

2018-02-20

Many studies have proven the usefulness of biofluid-based infrared spectroscopy in the clinical domain for diagnosis and monitoring the progression of diseases. Here we present a state-of-the-art study in the forensic field that employed Fourier transform infrared microspectroscopy for postmortem diagnosis of sudden cardiac death (SCD) by in situ biochemical investigation of alveolar edema fluid in lung tissue sections. The results of amide-related spectral absorbance analysis demonstrated that the pulmonary edema fluid of the SCD group was richer in protein components than that of the neurologic catastrophe (NC) and lethal multiple injuries (LMI) groups. The complementary results of unsupervised principle component analysis (PCA) and genetic algorithm-guided partial least-squares discriminant analysis (GA-PLS-DA) further indicated different global spectral band patterns of pulmonary edema fluids between these three groups. Ultimately, a random forest (RF) classification model for postmortem diagnosis of SCD was built and achieved good sensitivity and specificity scores of 97.3% and 95.5%, respectively. Classification predictions of unknown pulmonary edema fluid collected from 16 cases were also performed by the model, resulting in 100% correct discrimination. This pilot study demonstrates that FTIR microspectroscopy in combination with chemometrics has the potential to be an effective aid for postmortem diagnosis of SCD.

Breast tissue decomposition with spectral distortion correction: A postmortem study

PubMed Central

Ding, Huanjun; Zhao, Bo; Baturin, Pavlo; Behroozi, Farnaz; Molloi, Sabee

2014-01-01

Purpose: To investigate the feasibility of an accurate measurement of water, lipid, and protein composition of breast tissue using a photon-counting spectral computed tomography (CT) with spectral distortion corrections. Methods: Thirty-eight postmortem breasts were imaged with a cadmium-zinc-telluride-based photon-counting spectral CT system at 100 kV. The energy-resolving capability of the photon-counting detector was used to separate photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose for each breast ranged from 1.8 to 2.2 mGy. Two spectral distortion correction techniques were implemented, respectively, on the raw images to correct the nonlinear detector response due to pulse pileup and charge-sharing artifacts. Dual energy decomposition was then used to characterize each breast in terms of water, lipid, and protein content. In the meantime, the breasts were chemically decomposed into their respective water, lipid, and protein components to provide a gold standard for comparison with dual energy decomposition results. Results: The accuracy of the tissue compositional measurement with spectral CT was determined by comparing to the reference standard from chemical analysis. The averaged root-mean-square error in percentage composition was reduced from 15.5% to 2.8% after spectral distortion corrections. Conclusions: The results indicate that spectral CT can be used to quantify the water, lipid, and protein content in breast tissue. The accuracy of the compositional analysis depends on the applied spectral distortion correction technique. PMID:25281953

Post-mortem cytogenomic investigations in patients with congenital malformations.

PubMed

Dias, Alexandre Torchio; Zanardo, Évelin Aline; Dutra, Roberta Lelis; Piazzon, Flavia Balbo; Novo-Filho, Gil Monteiro; Montenegro, Marilia Moreira; Nascimento, Amom Mendes; Rocha, Mariana; Madia, Fabricia Andreia Rosa; Costa, Thais Virgínia Moura Machado; Milani, Cintia; Schultz, Regina; Gonçalves, Fernanda Toledo; Fridman, Cintia; Yamamoto, Guilherme Lopes; Bertola, Débora Romeo; Kim, Chong Ae; Kulikowski, Leslie Domenici

2016-08-01

Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations. Copyright © 2016 Elsevier Inc. All rights reserved.

Pleural tissue hyaluronan produced by postmortem ventilation in rabbits.

PubMed

Wang, P M; Lai-Fook, S J

2000-01-01

We developed a method that used Alcian blue bound to hyaluronan to measure pleural hyaluronan in rabbits postmortem. Rabbits were killed, then ventilated with 21% O2--5% CO2--74% N2 for 3 h. The pleural liquid was removed by suction and 5 ml Alcian blue stock solution (0.33 mg/ml, 3.3 pH) was injected into each chest cavity. After 10 min, the Alcian blue solution was removed and the unbound Alcian blue solution (supernatant) separated by centrifugation and filtration. The supernatant transmissibility (T) was measured spectrophotometrically at 613 nm. Supernatant Alcian blue concentration (Cab) was obtained from a calibration curve of T versus dilutions of stock solution Cab. Alcian blue bound to pleural tissue hyaluronan was obtained by subtracting supernatant Cab from stock solution Cab. Pleural tissue hyaluronan was obtained from a calibration curve of hyaluronan versus Alcian blue bound to hyaluronan. Compared with control rabbits, pleural tissue hyaluronan (0.21 +/- 0.04 mg/kg) increased twofold, whereas pleural liquid volume decreased by 30% after 3 h of ventilation. Pleural effusions present 3 h postmortem without ventilation did not change pleural tissue hyaluronan from control values. Thus ventilation-induced pleural liquid shear stress, not increased filtration, was the stimulus for the increased hyaluronan produced from pleural mesothelial cells.

Nitrobenzodiazepines: Postmortem brain and blood reference concentrations.

PubMed

Skov, Louise; Holm, Karen Marie Dollerup; Linnet, Kristian

2016-11-01

Reference concentrations are needed to evaluate postmortem toxicology results and usually femoral blood is the specimen of choice. However, brain tissue has been suggested as a viable alternative specimen, since postmortem blood concentrations can be difficult to interpret due to postmortem redistribution, among other factors. Here we present reference concentrations of postmortem brain and femoral blood of the nitrobenzodiazepines clonazepam, flunitrazepam, and nitrazepam that are of particular interest since they commonly are converted to their corresponding 7-aminometabolites in the postmortem situation. The drugs and metabolites were quantified in both matrices using LC-MS-MS in 69 cases. In 63 cases the compounds were judged not to have been of significance for the death (C cases), whereas they were considered to have been a contributing factor in 6 cases (B cases). No cases were observed with a nitrobenzodiazepine being the sole cause of death (A cases). The brain-blood ratios for clonazepam and nitrazepam were 5.5 and 4.7, respectively, while the brain-blood ratios for the 7-aminometabolites ranged from 0.4 to 0.5. Flunitrazepam only occurred as the 7-aminometabolite. A positive correlation between brain and blood concentrations was found with Spearman's rank correlation coefficients (r s ) ranging from 0.77 to 0.96. The measured femoral blood concentrations agree with literature values, but only few brain concentrations were available for comparison. The drug-metabolite ratios for clonazepam and nitrazepam were 10-12 times higher in brain than in blood. The pre-analytical variation in brain of 5.9% was fairly low, suggesting that brain tissue is a useful alternative to blood. The reported brain and femoral blood concentrations serve as reference values in postmortem investigations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Necromechanics: Death-induced changes in the mechanical properties of human tissues.

PubMed

Martins, Pedro A L S; Ferreira, Francisca; Natal Jorge, Renato; Parente, Marco; Santos, Agostinho

2015-05-01

After the death phenomenon, the rigor mortis development, characterized by body stiffening, is one of the most evident changes that occur in the body. In this work, the development of rigor mortis was assessed using a skinfold caliper in human cadavers and in live people to measure the deformation in the biceps brachii muscle in response to the force applied by the device. Additionally, to simulate the measurements with the finite element method, a two-dimensional model of an arm section was used. As a result of the experimental procedure, a decrease in deformation with increasing postmortem time was observed, which corresponds to an increase in rigidity. As expected, the deformations for the live subjects were higher. The finite element method analysis showed a correlation between the c1 parameter of the neo-Hookean model in the 4- to 8-h postmortem interval. This was accomplished by adjusting the c1 material parameter in order to simulate the measured experimental displacement. Despite being a preliminary study, the obtained results show that combining the proposed experimental procedure with a numerical technique can be very useful in the study of the postmortem mechanical modifications of human tissues. Moreover, the use of data from living subjects allows us to estimate the time of death paving the way to establish this process as an alternative to the existing techniques. This solution constitutes a portable, non-invasive method of estimating the postmortem interval with direct quantitative measurements using a skinfold caliper. The tools and methods described can be used to investigate the subject and to gain epidemiologic knowledge on rigor mortis phenomenon. © IMechE 2015.

Postmortem CT Angiography Compared with Autopsy: A Forensic Multicenter Study.

PubMed

Grabherr, Silke; Heinemann, Axel; Vogel, Hermann; Rutty, Guy; Morgan, Bruno; Woźniak, Krzysztof; Dedouit, Fabrice; Fischer, Florian; Lochner, Stefanie; Wittig, Holger; Guglielmi, Giuseppe; Eplinius, Franziska; Michaud, Katarzyna; Palmiere, Cristian; Chevallier, Christine; Mangin, Patrice; Grimm, Jochen M

2018-05-01

Purpose To determine if postmortem computed tomography (CT) and postmortem CT angiography help to detect more lesions than autopsy in postmortem examinations, to evaluate the strengths and weaknesses of each method, and to define their indications. Materials and Methods Postmortem CT angiography was performed on 500 human corpses and followed by conventional autopsy. Nine centers were involved. All CT images were read by an experienced team including one forensic pathologist and one radiologist, blinded to the autopsy results. All findings were recorded for each method and categorized by anatomic structure (bone, organ parenchyma, soft tissue, and vascular) and relative importance in the forensic case (essential, useful, and unimportant). Results Among 18 654 findings, autopsies helped to identify 61.3% (11 433 of 18 654), postmortem CT helped to identify 76.0% (14 179 of 18 654), and postmortem CT angiography helped to identify 89.9% (16 780 of 18 654; P < .001). Postmortem CT angiography was superior to autopsy, especially at helping to identify essential skeletal lesions (96.1% [625 of 650] vs 65.4% [425 of 650], respectively; P < .001) and vascular lesions (93.5% [938 of 1003] vs 65.3% [655 of 1003], respectively; P < .001). Among the forensically essential findings, 23.4% (1029 of 4393) were not detected at autopsy, while only 9.7% (428 of 4393) were missed at postmortem CT angiography (P < .001). The best results were obtained when postmortem CT angiography was combined with autopsy. Conclusion Postmortem CT and postmortem CT angiography and autopsy each detect important lesions not detected by the other method. More lesions were identified by combining postmortem CT angiography and autopsy, which may increase the quality of postmortem diagnosis. Online supplemental material is available for this article.

Methamphetamine and amphetamine concentrations in postmortem rabbit tissues.

PubMed

Nagata, T; Kimura, K; Hara, K; Kudo, K

1990-11-01

The feasibility of detecting methamphetamine and its major metabolite, amphetamine, in postmortem tissues over a 2-year period was examined. It is important to determine if the abuse and toxic effects of drugs can be proved from evidence found in decayed, submerged, or stained tissue materials. The blood, urine, liver, skeletal muscle, skin and extremity bones from rabbits given methamphetamine intravenously were kept at room temperature, under 4 different conditions: sealed in a test tube, dried in the open air, submerged in tap water and stained on gauze. Methamphetamine was present in all the samples, with slight change in concentration in case of sealed and air dried tissues. Changes varied in bones kept in water. There were considerable decreases in methamphetamine in blood and urine stains. Despite long term storage, drug abuse and/or toxicity could be determined, in all tissues examined.

Distribution of ∆(9)-Tetrahydrocannabinol and 11-Nor-9-Carboxy-∆(9)-Tetrahydrocannabinol Acid in Postmortem Biological Fluids and Tissues From Pilots Fatally Injured in Aviation Accidents.

PubMed

Kemp, Philip M; Cardona, Patrick S; Chaturvedi, Arvind K; Soper, John W

2015-07-01

Little is known of the postmortem distribution of ∆(9)-tetrahydrocannabinol (THC) and its major metabolite, 11-nor-9-carboxy-∆(9)-tetrahydrocannabinol (THCCOOH). Data from 55 pilots involved in fatal aviation accidents are presented in this study. Gas chromatography/mass spectrometry analysis obtained mean THC concentrations in blood from multiple sites, liver, lung, and kidney of 15.6 ng/mL, 92.4 ng/g, 766.0 ng/g, 44.1 ng/g and mean THCCOOH concentrations of 35.9 ng/mL, 322.4 ng/g, 42.6 ng/g, 138.5 ng/g, respectively. Heart THC concentrations (two cases) were 184.4 and 759.3 ng/g, and corresponding THCCOOH measured 11.0 and 95.9 ng/g, respectively. Muscle concentrations for THC (two cases) were 16.6 and 2.5 ng/g; corresponding THCCOOH, "confirmed positive" and 1.4 ng/g. The only brain tested in this study showed no THC detected and 2.9 ng/g THCCOOH, low concentrations that correlated with low values in other specimens from this case. This research emphasizes the need for postmortem cannabinoid testing and demonstrates the usefulness of a number of tissues, most notably lung, for these analyses. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Distribution of Delta 9-Tetrahydrocannabinol and 11-Nor-9-Carboxy-Delta 9-Tetrahydrocannabinol Acid in Postmortem Biological Fluids and Tissues From Pilots Fatally Injured in Aviation Accidents

DTIC Science & Technology

2013-12-01

classified as current marijuana ( Cannabis sativa) users in the United States and 5.4 million people aged 12 and older used marijuana on a daily or almost...report from the European Union, cannabis use is common in many parts of the world.3 As a result of such widespread marijuana use and its well...knowledge regarding the postmortem distribution of cannabi - noids in humans primarily because cannabinoid testing is not routine in many postmortem

Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population.

PubMed

Micera, Alessandra; Quaranta, Luciano; Esposito, Graziana; Floriani, Irene; Pocobelli, Augusto; Saccà, Sergio Claudio; Riva, Ivano; Manni, Gianluca; Oddone, Francesco

2016-02-01

Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by impaired aqueous outflow and extensive remodeling in the trabecular meshwork (TM). The aim of this study was to characterize and compare the expression patterns of selected proteins belonging to the tissue remodeling, inflammation and growth factor pathways in ex vivo glaucomatous and post-mortem TMs using protein-array analysis. TM specimens were collected from 63 white subjects, including 40 patients with glaucoma and 23 controls. Forty POAG TMs were collected at the time of surgery and 23 post-mortem specimens were from non-glaucomatous donor sclerocorneal tissues. Protein profiles were evaluated using a chip-based array consisting of 60 literature-selected antibodies. A different expression of some factors was observed in POAG TMs with respect to post-mortem specimens, either in abundance (interleukin [IL]10, IL6, IL5, IL7, IL12, IL3, macrophage inflammatory protein [MIP]1δ/α, vascular endothelial growth factor [VEGF], transforming growth factor beta 1 [TGFβ1], soluble tumor necrosis factor receptor I [sTNFRI]) or in scarcity (IL16, IL18, intercellular adhesion molecule 3 [ICAM3], matrix metalloproteinase-7 [MMP7], tissue inhibitor of metalloproteinase 1 [TIMP1]). MMP2, MMP7, TGFβ1, and VEGF expressions were confirmed by Western blot, zymography, and polymerase chain reaction. No difference in protein profile expression was detected between glaucomatous subtypes. The analysis of this small TM population highlighted some proteins linked to POAG, some previously reported and others of new detection (IL7, MIPs, sTNFαRI). A larger POAG population is required to select promising disease-associated biomarker candidates. This study was partially supported by the Fondazione Roma, the Italian Ministry of Health and the "National 5xMille 2010 tax donation to IRCCS-G.B. Bietti Foundation".

Is flow cytometric evaluation of DNA degradation a reliable method to investigate the early postmortem period?

PubMed

Di Nunno, N R; Costantinides, F; Bernasconi, P; Bottin, C; Melato, M

1998-03-01

The time of death can be established by determining the length of the postmortem interval. Many methods have been proposed to achieve this goal. Flow cytometric evaluation of DNA degradation seems to be reliable for the first 72 hours after death. Our study evaluated the correspondence of the corruption process between in vitro and corpse tissues. We chose spleen tissue to perform our investigation because it is rich in nucleated cells. Results showed a precise correspondence between the two kinds of samples in the time period between 24 and 36 hours. The period from 36 to 72 hours is characterized by a much looser correspondence than that found in the first period. After the first 72 hours, DNA denaturation is massive and does not allow useful cytofluorimetric readings. The spleen does not seem to be the most suitable organ for this type of investigation because it tends to colliquate very rapidly. We therefore are evaluating other organs to identify a more suitable tissue source for the investigation of longer postmortem period using flow cytometry.

Viability and infectivity of Ichthyophonus sp. in post-mortem Pacific herring, Clupea pallasii

USGS Publications Warehouse

Kocan, Richard M.; Hart, Lucas M.; Lewandowski, Naomi; Hershberger, Paul

2014-01-01

Ichthyophonus-infected Pacific herring, Clupea pallasii, were allowed to decompose in ambient seawater then serially sampled for 29 days to evaluate parasite viability and infectivity for Pacific staghorn sculpin, Leptocottus armatus. Ichthyophonus sp. was viable in decomposing herring tissues for at least 29 days post-mortem and could be transmitted via ingestion to sculpin for up to 5 days. The parasite underwent morphologic changes during the first 48 hr following death of the host that were similar to those previously reported, but as host tissue decomposition progressed, several previously un-described forms of the parasite were observed. The significance of long-term survival and continued morphologic transformation in the post-mortem host is unknown, but it could represent a saprozoic phase of the parasite life cycle that has survival value for Ichthyophonus sp.

Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosal associated lymphoid tissues from elk by real time quaking-induced conversion

USGS Publications Warehouse

Haley, Nicholas J.; Siepker, Chris; Hoon-Hanks , Laura L.; Mitchell, Gordon; Walter, W. David; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen a.; Fenwick, B.W.

2016-01-01

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

The Distribution of Fluoxetine and Norfluoxetine in Postmortem Fluids and Tissues

DTIC Science & Technology

2007-06-01

of fluoxetine and nor- fluoxetine in dogs following oral administration of fluoxetine hydrochloride ( Prozac ). J Forensic Sci, 42(5):812-6, 1997. 6...flight crews are submitted to the Federal Aviation Administration’s Civil Aerospace Medical Institute for toxicological analysis. Fluoxetine ( Prozac ...heart muscle, and brain. Specimens were extracted using solid-phase extraction and analyzed by GC/MS. Deuterated fluoxetine and norfluoxetine were

EQUIFAT: A novel scoring system for the semi-quantitative evaluation of regional adipose tissues in Equidae.

PubMed

Morrison, Philippa K; Harris, Patricia A; Maltin, Charlotte A; Grove-White, Dai; Argo, Caroline McG

2017-01-01

Anatomically distinct adipose tissues represent variable risks to metabolic health in man and some other mammals. Quantitative-imaging of internal adipose depots is problematic in large animals and associations between regional adiposity and health are poorly understood. This study aimed to develop and test a semi-quantitative system (EQUIFAT) which could be applied to regional adipose tissues. Anatomically-defined, photographic images of adipose depots (omental, mesenteric, epicardial, rump) were collected from 38 animals immediately post-mortem. Images were ranked and depot-specific descriptors were developed (1 = no fat visible; 5 = excessive fat present). Nuchal-crest and ventro-abdominal-retroperitoneal adipose depot depths (cm) were transformed to categorical 5 point scores. The repeatability and reliability of EQUIFAT was independently tested by 24 observers. When half scores were permitted, inter-observer agreement was substantial (average κw: mesenteric, 0.79; omental, 0.79; rump 0.61) or moderate (average κw; epicardial, 0.60). Intra-observer repeatability was tested by 8 observers on 2 occasions. Kappa analysis indicated perfect (omental and mesenteric) and substantial agreement (epicardial and rump) between attempts. A further 207 animals were evaluated ante-mortem (age, height, breed-type, gender, body condition score [BCS]) and again immediately post-mortem (EQUIFAT scores, carcass weight). Multivariable, random effect linear regression models were fitted (breed as random effect; BCS as outcome variable). Only height, carcass weight, omental and retroperitoneal EQUIFAT scores remained as explanatory variables in the final model. The EQUIFAT scores developed here demonstrate clear functional differences between regional adipose depots and future studies could be directed towards describing associations between adiposity and disease risk in surgical and post-mortem situations.

EQUIFAT: A novel scoring system for the semi-quantitative evaluation of regional adipose tissues in Equidae

PubMed Central

Morrison, Philippa K.; Harris, Patricia A.; Maltin, Charlotte A.; Grove-White, Dai; Argo, Caroline McG.

2017-01-01

Anatomically distinct adipose tissues represent variable risks to metabolic health in man and some other mammals. Quantitative-imaging of internal adipose depots is problematic in large animals and associations between regional adiposity and health are poorly understood. This study aimed to develop and test a semi-quantitative system (EQUIFAT) which could be applied to regional adipose tissues. Anatomically-defined, photographic images of adipose depots (omental, mesenteric, epicardial, rump) were collected from 38 animals immediately post-mortem. Images were ranked and depot-specific descriptors were developed (1 = no fat visible; 5 = excessive fat present). Nuchal-crest and ventro-abdominal-retroperitoneal adipose depot depths (cm) were transformed to categorical 5 point scores. The repeatability and reliability of EQUIFAT was independently tested by 24 observers. When half scores were permitted, inter-observer agreement was substantial (average κw: mesenteric, 0.79; omental, 0.79; rump 0.61) or moderate (average κw; epicardial, 0.60). Intra-observer repeatability was tested by 8 observers on 2 occasions. Kappa analysis indicated perfect (omental and mesenteric) and substantial agreement (epicardial and rump) between attempts. A further 207 animals were evaluated ante-mortem (age, height, breed-type, gender, body condition score [BCS]) and again immediately post-mortem (EQUIFAT scores, carcass weight). Multivariable, random effect linear regression models were fitted (breed as random effect; BCS as outcome variable). Only height, carcass weight, omental and retroperitoneal EQUIFAT scores remained as explanatory variables in the final model. The EQUIFAT scores developed here demonstrate clear functional differences between regional adipose depots and future studies could be directed towards describing associations between adiposity and disease risk in surgical and post-mortem situations. PMID:28296956

USE OF THE GEOGRAPHIC INFORMATION SYSTEM TO INVESTIGATE MERCURY LEVELS IN CORRELATION WITH POSTMORTEM FINDINGS OF ASPERGILLUS INDUCED LESIONS IN THE COMMON LOON (GAVIA IMMER) IN THE NORTHEASTERN USA

EPA Science Inventory

This study employed the Geographic Information System (GIS) to correlate total mercury levels in liver tissue with post-mortem findings of aspergillosis in common loons (Gavia immer) in the northeast United States of America (USA). Aspergillosis is an opportunistic fungal infecti...

Postmortem Findings in Patient with Guillain-Barré Syndrome and Zika Virus Infection

PubMed Central

Torres, José V.; Martines, Roosecelis Brasil; Reagan-Steiner, Sarah; Pérez, George Venero; Rivera, Aidsa; Major, Chelsea; Matos, Desiree; Muñoz-Jordan, Jorge; Shieh, Wun-Ju; Zaki, Sherif R.; Sharp, Tyler M.

2018-01-01

Postmortem examination results of a patient with Guillain-Barré syndrome and confirmed Zika virus infection revealed demyelination of the sciatic and cranial IV nerves, providing evidence of the acute demyelinating inflammatory polyneuropathy Guillain-Barré syndrome variant. Lack of evidence of Zika virus in nervous tissue suggests that pathophysiology was antibody mediated without neurotropism. PMID:29261094

Considerations for optimal use of postmortem human brains for molecular psychiatry: lessons from schizophrenia.

PubMed

Weickert, Cynthia Shannon; Rothmond, Debora A; Purves-Tyson, Tertia D

2018-01-01

Schizophrenia is a disabling disease impacting millions of people around the world, for which there is no known cure. Current antipsychotic treatments for schizophrenia mainly target psychotic symptoms, do little to ameliorate social or cognitive deficits, have side-effects that cause weight gain, and diabetes and 30% of people do not respond. Thus, better therapeutics for schizophrenia aimed at the route biologic changes are needed and discovering the underlying neurobiology is key to this quest. Postmortem brain studies provide the most direct and detailed way to determine the pathophysiology of schizophrenia. This chapter outlines steps that can be taken to ensure the best-quality molecular data from postmortem brain tissue are obtained. In this chapter, we also discuss targeted and high-throughput methods for examining gene and protein expression and some of the strengths and limitations of each method. We briefly consider why gene and protein expression changes may not always concur within brain tissue. We conclude that postmortem brain research that investigates gene and protein expression in well-characterized and matched brain cohorts provides an important foundation to be considered when interpreting data obtained from studies of living schizophrenia patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem

PubMed Central

Freeman, Sara M.; Smith, Aaron L.; Goodman, Mark M.; Bales, Karen L.

2017-01-01

Intranasal oxytocin affects a suite of human social behaviors, including trust, eye contact, and emotion recognition. However, it is unclear where oxytocin receptors (OXTR) and the structurally related vasopressin 1a receptors (AVPR1a) are expressed in the human brain. We have previously described a reliable, pharmacologically informed receptor autoradiography protocol for visualizing these receptors in postmortem primate brain tissue. We used this technique in human brainstem tissue to identify the neural targets of oxytocin and vasopressin. To determine binding selectivity of the OXTR radioligand and AVPR1a radioligand, sections were incubated in four conditions: radioligand alone, radioligand with the selective AVPR1a competitor SR49059, and radioligand with a low or high concentration of the selective OXTR competitor ALS-II-69. We found selective OXTR binding in the spinal trigeminal nucleus, a conserved region of OXTR expression in all primate species investigated to date. We found selective AVPR1a binding in the nucleus prepositus, an area implicated in eye gaze stabilization. The tissue's postmortem interval was not correlated with either the specific or nonspecific binding of either radioligand, indicating that it will not likely be a factor in similar postmortem studies. This study provides critical data for future studies of OXTR and AVPR1a in human brain tissue. PMID:26911439

Virtopsy: postmortem imaging of laryngeal foreign bodies.

PubMed

Oesterhelweg, Lars; Bolliger, Stephan A; Thali, Michael J; Ross, Steffen

2009-05-01

Death from corpora aliena in the larynx is a well-known entity in forensic pathology. The correct diagnosis of this cause of death is difficult without an autopsy, and misdiagnoses by external examination alone are common. To determine the postmortem usefulness of modern imaging techniques in the diagnosis of foreign bodies in the larynx, multislice computed tomography, magnetic resonance imaging, and postmortem full-body computed tomography-angiography were performed. Three decedents with a suspected foreign body in the larynx underwent the 3 different imaging techniques before medicolegal autopsy. Multislice computed tomography has a high diagnostic value in the noninvasive localization of a foreign body and abnormalities in the larynx. The differentiation between neoplasm or soft foreign bodies (eg, food) is possible, but difficult, by unenhanced multislice computed tomography. By magnetic resonance imaging, the discrimination of the soft tissue structures and soft foreign bodies is much easier. In addition to the postmortem multislice computed tomography, the combination with postmortem angiography will increase the diagnostic value. Postmortem, cross-sectional imaging methods are highly valuable procedures for the noninvasive detection of corpora aliena in the larynx.

Postmortem Cholesterol Levels in Peripheral Nerve Tissue: Preliminar Considerations on Interindividual and Intraindividual Variation.

PubMed

Vacchiano, Giuseppe; Luna Maldonado, Aurelio; Matas Ros, Maria; Fiorenza, Elisa; Silvestre, Angela; Simonetti, Biagio; Pieri, Maria

2018-06-01

The study reports the evolution of the demyelinization process based on cholesterol ([CHOL]) levels quantified in median nerve samples and collected at different times-from death from both right and left wrists. The statistical data show that the phenomenon evolves differently in the right and left nerves. Such a difference can reasonably be attributed to a different multicenter evolution of the demyelinization. For data analysis, the enrolled subjects were grouped by similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48 hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected within 48 hours of death allowed for a PMI estimation according to the following equations: PMI = 0.000 + 0.7623 [CHOL]right (R = 0.581) for the right wrist and PMI = 0.000 + 0.8911 [CHOL]left (R = 0.794) for the left wrist.At present, this correlation cannot be considered to be definitive because of the limitation of the small size of the samples analyzed, because the differences in the sampling time and the interindividual and intraindividual variation may influence the demyelinization process.

Automating cell detection and classification in human brain fluorescent microscopy images using dictionary learning and sparse coding.

PubMed

Alegro, Maryana; Theofilas, Panagiotis; Nguy, Austin; Castruita, Patricia A; Seeley, William; Heinsen, Helmut; Ushizima, Daniela M; Grinberg, Lea T

2017-04-15

Immunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility. Dictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set. Our method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings. We compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples. The proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

[Biodistribution and Postmortem Redistribution of Emamectin Benzoate in Intoxicated Mice].

PubMed

Tang, Wei-wei; Lin, Yu-cai; Lu, Yan-xu

2016-02-01

To investigate the lethal blood level, the target organs and tissues, the toxicant storage depots and the postmortem redistribution in mice died of emamectin benzoate poisoning. The mice model of emamectin benzoate poisoning was established via intragastric injection. The main poisoning symptoms and the clinical death times of mice were observed and recorded dynamically in the acute poisoning group as well as the sub-acute poisoning death group. The pathological and histomorphological changes of organs and tissues were observed after poisoning death. The biodistribution and postmortem redistribution of emamectin benzoate in the organs and tissues of mice were assayed by the enzyme-linked immunosorbent assay (ELISA) at 0h, 24h, 48h and 72h after death. The lethal blood concentrations and the concentrations of emamectin benzoate were detected by high performance liquid chromatography (HPLC) at different time points after death. The symptoms of nervous and respiratory system were observed within 15-30 min after intragastric injection. The average time of death was (45.8 ± 7.9) min in the acute poisoning group and (8.0 ± 1.4) d in the sub-acute poisoning group, respectively. The range of acute lethal blood level was 447.164 0-524.463 5 mg/L. The pathological changes of the organs and tissues were observed via light microscope and immunofluorescence microscope. The changes of emamectin benzoate content in the blood, heart, liver, spleen, lung, kidney and brain of poisoning mice showed regularity within 72 h after death (P < 0.05). The target organs of emamectin benzoate poisoning include heart, liver, kidney, lung, brain and contact position (stomach). The toxicant storage depots are kidney and liver. There is emamectin benzoate postmortem redistribution in mice.

Single cell gene expression profiling in Alzheimer's disease.

PubMed

Ginsberg, Stephen D; Che, Shaoli; Counts, Scott E; Mufson, Elliott J

2006-07-01

Development and implementation of microarray techniques to quantify expression levels of dozens to hundreds to thousands of transcripts simultaneously within select tissue samples from normal control subjects and neurodegenerative diseased brains has enabled scientists to create molecular fingerprints of vulnerable neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is to sample gene expression from homogeneous cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and nonneuronal cells. The precise resolution afforded by single cell and population cell RNA analysis in combination with microarrays and real-time quantitative polymerase chain reaction (qPCR)-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease progression. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models of neurodegeneration as well as postmortem human brain tissues. Gene expression analysis in postmortem AD brain regions including the hippocampal formation and neocortex reveals selectively vulnerable cell types share putative pathogenetic alterations in common classes of transcripts, for example, markers of glutamatergic neurotransmission, synaptic-related markers, protein phosphatases and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of vulnerable regions and neurons may reveal important clues toward the understanding of the molecular pathogenesis of various neurological diseases and aid in identifying rational targets toward pharmacotherapeutic interventions for progressive, late-onset neurodegenerative disorders such as mild cognitive impairment (MCI) and AD.

Absence of significant dissent should be sufficient for deceased donor organ procurement in New Zealand.

PubMed

Douglas, Thomas M; Douglas, Nicholas M

2009-10-01

New Zealand's organ donation rates are among the lowest in the OECD. In a bid to increase organ availability, the New Zealand Human Tissue Act 2008 introduces new consent arrangements for deceased donor organ procurement. This article assesses these new arrangements and presents the case for further reform. Our assessment and arguments are based on philosophical analysis informed by empirical data on the effectiveness of alternative consent systems. We: 1) Identify widely held ethical judgments about policies and practices relevant to organ donation (e.g. those relating to coronial post-mortems), 2) Assess the implications of these judgments for the Human Tissue Act and the assumptions that underpin it, and 3) Derive policy recommendations that are consistent with the judgments. The Human Tissue Act 2008 retains a strong consent requirement for organ procurement: organs may not be transplanted unless either the deceased or the family consents. We argue that organ availability could and should be increased by shifting from a model that requires consent to one that requires the absence of significant dissent. We recommend that New Zealand adopt either 1) an organ donation system similar to the existing system for ordering coronial post-mortems, or 2) a variant of the 'opt-out' system already in place in several other countries.

Forensic implication of muscle level of nicotine in an adipocere body found in the sea.

PubMed

Nishimura, Hiroyuki; Furumiya, Junichi; Nakanishi, Akinori; Hashimoto, Yoshiaki

2009-04-01

We reported previously that blood levels of nicotine in suicidal smokers tend to be significantly higher than those in non-suicidal smokers, and blood level of nicotine seems to be a useful criterion for discriminating suicide from other types of death. In this paper, we report nicotine and cotinine levels in various tissues of an adipocere body found in the sea. The cause of death was drowning, and the postmortem time interval was approximately 5 months at autopsy. His driver's license was concealed in his sock, which seemed to suggest that he committed to suicide. In toxicological analysis by gas chromatography, nicotine and cotinine in the femoral muscle were detected at concentrations of 213 and 488 ng/g, respectively, and these substances were also detected in the brain, liver and kidney. For evaluating the tissue levels of nicotine and cotinine in the adipocere body, we analyzed these levels in blood and various tissues of 13 autopsy cases of smokers. Nicotine and cotinine levels in blood were the most similar to those in skeletal muscle. Although the postmortem time interval, the formation process of adipocere and the environmental condition in water may affect nicotine and cotinine levels in the femoral muscle, the high muscle level of nicotine in the present case seem to implicate suicidal death.

Isolation of Cardiomyocyte Nuclei from Post-mortem Tissue

PubMed Central

Bergmann, Olaf; Jovinge, Stefan

2012-01-01

Identification of cardiomyocyte nuclei has been challenging in tissue sections as most strategies rely only on cytoplasmic marker proteins1. Rare events in cardiac myocytes such as proliferation and apoptosis require an accurate identification of cardiac myocyte nuclei to analyze cellular renewal in homeostasis and in pathological conditions2. Here, we provide a method to isolate cardiomyocyte nuclei from post mortem tissue by density sedimentation and immunolabeling with antibodies against pericentriolar material 1 (PCM-1) and subsequent flow cytometry sorting. This strategy allows a high throughput analysis and isolation with the advantage of working equally well on fresh tissue and frozen archival material. This makes it possible to study material already collected in biobanks. This technique is applicable and tested in a wide range of species and suitable for multiple downstream applications such as carbon-14 dating3, cell-cycle analysis4, visualization of thymidine analogues (e.g. BrdU and IdU)4, transcriptome and epigenetic analysis. PMID:22805241

Implications of human tissue studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.

1986-10-01

Through radiochemical analysis of voluntary tissue donations, the United States Transuranium and Uranium Registries are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole body contributions to the Transuranium Registry revealed an inverse proportionality between actinide concentration and bone ash fraction. The analysis of a whole body with a documented /sup 241/Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies of the Registries are designed to evaluate in vivo estimates of actinide depositionmore » with those derived from postmortem tissue analysis, compare results of animal experiments with human data, and reviw histopathologic slides for tissue toxicity that might be attributable to exposure to uranium and the transuranic elements. The implications of these recent findings and other work of the Registries are discussed from the standpoint of their potential impact on biokinetic modeling, internal dose assessment, safety standards, and operational health physics practices.« less

Autism BrainNet: A network of postmortem brain banks established to facilitate autism research.

PubMed

Amaral, David G; Anderson, Matthew P; Ansorge, Olaf; Chance, Steven; Hare, Carolyn; Hof, Patrick R; Miller, Melissa; Nagakura, Ikue; Pickett, Jane; Schumann, Cynthia; Tamminga, Carol

2018-01-01

Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators. Copyright © 2018 Elsevier B.V. All rights reserved.

The art of matching brain tissue from patients and controls for postmortem research.

PubMed

Bao, Ai-Min; Swaab, Dick F

2018-01-01

The quality of postmortem research depends strongly on a thorough clinical investigation and documentation of the patient's disorder and therapies. In addition, a systematic and professional neuropathologic investigation of both cases and controls is absolutely crucial. In the experience of the Netherlands Brain Bank (NBB), about 20% of clinical neurologic diagnoses, despite being made in first-rate clinics, have to be revised or require an extra diagnosis after a complete and thorough review by the NBB. The neuropathology examination may reveal for instance that the "controls" already have preclinical neurodegenerative alterations. In postmortem studies the patient and control groups must be matched for as many of the known confounding factors as possible. This is necessary to make the groups as similar as possible, except for the topic being investigated. Confounding factors are present before, during, and after death. They are respectively: (1) genetic background, systemic diseases, duration and gravity of illness, medicines and addictive compounds used, age, sex, gender identity, sexual orientation, circadian and seasonal fluctuations, lateralization; (2) agonal state, stress of dying; and (3) postmortem delay, freezing procedures, fixation and storage time. Consequently, a brain bank should have a large number of controls at its disposal for appropriate matching. If matching fails for some confounders, then their influence may be determined by statistical methods such as analysis of variance or regression models. Copyright © 2018 Elsevier B.V. All rights reserved.

Sex-related differences in the thanatomicrobiome in postmortem heart samples using bacterial gene regions V1-2 and V4.

PubMed

Bell, Courtnee R; Wilkinson, Jeremy E; Robertson, Boakai K; Javan, Gulnaz T

2018-05-10

Recent studies have revealed distinct thanatomicrobiome (microbiome of death) signatures in human body sites after death. Thanatomicrobiome studies suggest that microbial succession after death may have the potential to reveal important postmortem biomarkers for the identification of time of death. We surveyed the postmortem microbiomes of cardiac tissues from ten corpses with varying times of death (6-58 h) using amplicon-based sequencing of the 16S rRNA gene' V1-2 and V4 hypervariable regions. The results demonstrated that amplicons had statistically significant (p <0.05) sex-dependent changes. Clostridium sp., Pseudomonas sp., Pantoea sp., and Streptococcus sp. had the highest enrichment for both V1-2 and V4 regions. Interestingly, the results also show that V4 amplicons had higher abundance of Clostridium sp. and Pseudomonas sp. in female hearts compared to males. Additionally, Streptococcus sp. was solely found in male heart samples. The distinction between sexes was further supported by Principle Coordinate Analysis, which revealed microbes in female hearts formed a distinctive cluster separate from male cadavers for both hypervariable regions. This study provides data that demonstrates that two hypervariable regions show discriminatory power for sex differences in postmortem heart samples. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of Intraosseous Fluid as an Alternative Biological Specimen in Postmortem Toxicology.

PubMed

Rodda, Luke N; Volk, Justin A; Moffat, Ellen; Williams, Chinyere M; Lynch, Kara L; Wu, Alan H B

2018-04-01

The postmortem redistribution phenomenon is an important factor in the interpretation of blood drug concentrations as a cause or factor in death. Intraosseous fluid (IOF) may serve as an alternative matrix for drug testing. Intraosseous fluid was collected from the left and right tibias and humerus of 29 decedents using the Arrow EZ-IO Intraosseous Vascular Access System. Standard autopsy specimens including blood were also collected at the same time during autopsy. Blood and IOF specimens were screened by immunoassay for opioids, fentanyl analogs, oxycodone, methadone, cocaine, methamphetamine, amphetamines, phencyclidine, tricyclic antidepressants, benzodiazepines and cannabinoids, using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Correlation between cardiac/central blood ELISA and IOF ELISA results was mostly 100% for drug targets. Further blood confirmation analysis was performed by gas chromatography mass spectrometry also showed comparable correlation to IOF screen results. There was no significant difference between the IOF sites or sides of the body. This novel study supports the use of IOF as an alternative postmortem specimen for toxicological investigations as a potentially less-compromised tissue in decomposed or traumatized bodies. Preliminary data is provided for the screening of common drugs of abuse in IOF that may show to be subject to alternative rates of postmortem redistribution than to that of other biological specimens in future studies that quantitate IOF drug concentrations.

Fatal fentanyl patch misuse in a hospitalized patient with a postmortem increase in fentanyl blood concentration.

PubMed

Moore, Philip W; Palmer, Robert B; Donovan, Joseph Ward

2015-01-01

Opioid-related mortality happens, even in healthcare settings. We describe serial postmortem fentanyl blood concentrations in a hospital inpatient who fatally abused transdermal fentanyl. This is a single-patient case report. A 42-year-old man with lymphoma was started on transdermal fentanyl therapy while hospitalized for chronic abdominal pain. The patient was last seen awake 1.3 h prior to being found apneic and cyanotic. During the resuscitation attempt, a small square-shaped film was removed from the patient's oropharynx. Femoral blood was collected 0.5 and 2 h postmortem, and the measured fentanyl concentration increased from 1.6 to 14 ng/mL. Study limitations include potential laboratory or collection errors and missing data. (i) Providers must be vigilant for signs of fentanyl patch abuse. (ii) Postmortem blood concentrations are not static postmortem, likely secondary to decreasing pH, increased aqueous solubility, and tissue redistribution, and are therefore unlikely to accurately represent antemortem blood concentrations. © 2014 American Academy of Forensic Sciences.

Minimizing Postsampling Degradation of Peptides by a Thermal Benchtop Tissue Stabilization Method

PubMed Central

Segerström, Lova; Gustavsson, Jenny

2016-01-01

Enzymatic degradation is a major concern in peptide analysis. Postmortem metabolism in biological samples entails considerable risk for measurements misrepresentative of true in vivo concentrations. It is therefore vital to find reliable, reproducible, and easy-to-use procedures to inhibit enzymatic activity in fresh tissues before subjecting them to qualitative and quantitative analyses. The aim of this study was to test a benchtop thermal stabilization method to optimize measurement of endogenous opioids in brain tissue. Endogenous opioid peptides are generated from precursor proteins through multiple enzymatic steps that include conversion of one bioactive peptide to another, often with a different function. Ex vivo metabolism may, therefore, lead to erroneous functional interpretations. The efficacy of heat stabilization was systematically evaluated in a number of postmortem handling procedures. Dynorphin B (DYNB), Leu-enkephalin-Arg6 (LARG), and Met-enkephalin-Arg6-Phe7 (MEAP) were measured by radioimmunoassay in rat hypothalamus, striatum (STR), and cingulate cortex (CCX). Also, simplified extraction protocols for stabilized tissue were tested. Stabilization affected all peptide levels to varying degrees compared to those prepared by standard dissection and tissue handling procedures. Stabilization increased DYNB in hypothalamus, but not STR or CCX, whereas LARG generally decreased. MEAP increased in hypothalamus after all stabilization procedures, whereas for STR and CCX, the effect was dependent on the time point for stabilization. The efficacy of stabilization allowed samples to be left for 2 hours in room temperature (20°C) without changes in peptide levels. This study shows that conductive heat transfer is an easy-to-use and efficient procedure for the preservation of the molecular composition in biological samples. Region- and peptide-specific critical steps were identified and stabilization enabled the optimization of tissue handling and opioid peptide analysis. The result is improved diagnostic and research value of the samples with great benefits for basic research and clinical work. PMID:27007059

Post-mortem detection of gasoline residues in lung tissue and heart blood of fire victims.

PubMed

Pahor, Kevin; Olson, Greg; Forbes, Shari L

2013-09-01

The purpose of this study was to determine whether gasoline residues could be detected post-mortem in lung tissue and heart blood of fire victims. The lungs and heart blood were investigated to determine whether they were suitable samples for collection and could be collected without contamination during an autopsy. Three sets of test subjects (pig carcasses) were investigated under two different fire scenarios. Test subjects 1 were anaesthetized following animal ethics approval, inhaled gasoline vapours for a short period and then euthanized. The carcasses were clothed and placed in a house where additional gasoline was poured onto the carcass post-mortem in one fire, but not in the other. Test subjects 2 did not inhale gasoline, were clothed and placed in the house and had gasoline poured onto them in both fires. Test subjects 3 were clothed but had no exposure to gasoline either ante- or post-mortem. Following controlled burns and suppression with water, the carcasses were collected, and their lungs and heart blood were excised at a necropsy. The headspace from the samples was analysed using thermal desorption-gas chromatography-mass spectroscopy. Gasoline was identified in the lungs and heart blood from the subjects that were exposed to gasoline vapours prior to death (test subjects 1). All other samples were negative for gasoline residues. These results suggest that it is useful to analyse for volatile ignitable liquids in lung tissue and blood as it may help to determine whether a victim was alive and inhaling gases at the time of a fire.

Breast density quantification with cone-beam CT: A post-mortem study

PubMed Central

Johnson, Travis; Ding, Huanjun; Le, Huy Q.; Ducote, Justin L.; Molloi, Sabee

2014-01-01

Forty post-mortem breasts were imaged with a flat-panel based cone-beam x-ray CT system at 50 kVp. The feasibility of breast density quantification has been investigated using standard histogram thresholding and an automatic segmentation method based on the fuzzy c-means algorithm (FCM). The breasts were chemically decomposed into water, lipid, and protein immediately after image acquisition was completed. The percent fibroglandular volume (%FGV) from chemical analysis was used as the gold standard for breast density comparison. Both image-based segmentation techniques showed good precision in breast density quantification with high linear coefficients between the right and left breast of each pair. When comparing with the gold standard using %FGV from chemical analysis, Pearson’s r-values were estimated to be 0.983 and 0.968 for the FCM clustering and the histogram thresholding techniques, respectively. The standard error of the estimate (SEE) was also reduced from 3.92% to 2.45% by applying the automatic clustering technique. The results of the postmortem study suggested that breast tissue can be characterized in terms of water, lipid and protein contents with high accuracy by using chemical analysis, which offers a gold standard for breast density studies comparing different techniques. In the investigated image segmentation techniques, the FCM algorithm had high precision and accuracy in breast density quantification. In comparison to conventional histogram thresholding, it was more efficient and reduced inter-observer variation. PMID:24254317

Automating Cell Detection and Classification in Human Brain Fluorescent Microscopy Images Using Dictionary Learning and Sparse Coding

PubMed Central

Alegro, Maryana; Theofilas, Panagiotis; Nguy, Austin; Castruita, Patricia A.; Seeley, William; Heinsen, Helmut; Ushizima, Daniela M.

2017-01-01

Background Immunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility. New method Dictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set. Results Our method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings. Comparison with existing methods We compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples. Conclusion The proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks. PMID:28267565

Human exposure to natural uranium: A case history and analytical results from some postmortem tissues

PubMed Central

Donoghue, J. K.; Dyson, E. D.; Hislop, J. S.; Leach, A. M.; Spoor, N. L.

1972-01-01

Donoghue, J. K., Dyson, E. D., Hislop, J. S., Leach, A. M., and Spoor, N. L. (1972).Brit. J. industr. Med.,29, 81-89. Human exposure to natural uranium: a case history and analytical results from some postmortem tissues. After the collapse and sudden death of an employee who had worked for 10 years in a natural uranium workshop, in which the airborne uranium was largely U3O8 with an Activity Median Aerodynamic Diameter in the range 3·5-6·0 μm and average concentration of 300 μg/m3, his internal organs were analysed for uranium. The tissues examined included lungs (1041 g), pulmonary lymph nodes (12 g), sternum (114 g), and kidneys (217 g). Uranium was estimated by neutron activation analysis, using irradiated tissue ash, and counting the delayed neutrons from uranium-235. The concentrations of uranium (μg U/g wet tissue) in the lungs, lymph nodes, sternum, and kidneys were 1·2, 1·8, 0·09, and 0·14 respectively. The weights deposited in the lungs and lymph nodes are less than 1% of the amounts calculated from the environmental data using the parameters currently applied in radiological protection. The figures are compatible with those reported by Quigley, heartherton, and Ziegler in 1958 and by Meichen in 1962. The relation between these results, the environmental exposure data, and biological monitoring data is discussed in the context of current views on the metabolism of inhaled insoluble uranium. PMID:5060250

Breast density quantification using magnetic resonance imaging (MRI) with bias field correction: A postmortem study

PubMed Central

Ding, Huanjun; Johnson, Travis; Lin, Muqing; Le, Huy Q.; Ducote, Justin L.; Su, Min-Ying; Molloi, Sabee

2013-01-01

Purpose: Quantification of breast density based on three-dimensional breast MRI may provide useful information for the early detection of breast cancer. However, the field inhomogeneity can severely challenge the computerized image segmentation process. In this work, the effect of the bias field in breast density quantification has been investigated with a postmortem study. Methods: T1-weighted images of 20 pairs of postmortem breasts were acquired on a 1.5 T breast MRI scanner. Two computer-assisted algorithms were used to quantify the volumetric breast density. First, standard fuzzy c-means (FCM) clustering was used on raw images with the bias field present. Then, the coherent local intensity clustering (CLIC) method estimated and corrected the bias field during the iterative tissue segmentation process. Finally, FCM clustering was performed on the bias-field-corrected images produced by CLIC method. The left–right correlation for breasts in the same pair was studied for both segmentation algorithms to evaluate the precision of the tissue classification. Finally, the breast densities measured with the three methods were compared to the gold standard tissue compositions obtained from chemical analysis. The linear correlation coefficient, Pearson's r, was used to evaluate the two image segmentation algorithms and the effect of bias field. Results: The CLIC method successfully corrected the intensity inhomogeneity induced by the bias field. In left–right comparisons, the CLIC method significantly improved the slope and the correlation coefficient of the linear fitting for the glandular volume estimation. The left–right breast density correlation was also increased from 0.93 to 0.98. When compared with the percent fibroglandular volume (%FGV) from chemical analysis, results after bias field correction from both the CLIC the FCM algorithms showed improved linear correlation. As a result, the Pearson's r increased from 0.86 to 0.92 with the bias field correction. Conclusions: The investigated CLIC method significantly increased the precision and accuracy of breast density quantification using breast MRI images by effectively correcting the bias field. It is expected that a fully automated computerized algorithm for breast density quantification may have great potential in clinical MRI applications. PMID:24320536

Breast density quantification using magnetic resonance imaging (MRI) with bias field correction: a postmortem study.

PubMed

Ding, Huanjun; Johnson, Travis; Lin, Muqing; Le, Huy Q; Ducote, Justin L; Su, Min-Ying; Molloi, Sabee

2013-12-01

Quantification of breast density based on three-dimensional breast MRI may provide useful information for the early detection of breast cancer. However, the field inhomogeneity can severely challenge the computerized image segmentation process. In this work, the effect of the bias field in breast density quantification has been investigated with a postmortem study. T1-weighted images of 20 pairs of postmortem breasts were acquired on a 1.5 T breast MRI scanner. Two computer-assisted algorithms were used to quantify the volumetric breast density. First, standard fuzzy c-means (FCM) clustering was used on raw images with the bias field present. Then, the coherent local intensity clustering (CLIC) method estimated and corrected the bias field during the iterative tissue segmentation process. Finally, FCM clustering was performed on the bias-field-corrected images produced by CLIC method. The left-right correlation for breasts in the same pair was studied for both segmentation algorithms to evaluate the precision of the tissue classification. Finally, the breast densities measured with the three methods were compared to the gold standard tissue compositions obtained from chemical analysis. The linear correlation coefficient, Pearson's r, was used to evaluate the two image segmentation algorithms and the effect of bias field. The CLIC method successfully corrected the intensity inhomogeneity induced by the bias field. In left-right comparisons, the CLIC method significantly improved the slope and the correlation coefficient of the linear fitting for the glandular volume estimation. The left-right breast density correlation was also increased from 0.93 to 0.98. When compared with the percent fibroglandular volume (%FGV) from chemical analysis, results after bias field correction from both the CLIC the FCM algorithms showed improved linear correlation. As a result, the Pearson's r increased from 0.86 to 0.92 with the bias field correction. The investigated CLIC method significantly increased the precision and accuracy of breast density quantification using breast MRI images by effectively correcting the bias field. It is expected that a fully automated computerized algorithm for breast density quantification may have great potential in clinical MRI applications.

Basolateral amygdala volume and cell numbers in major depressive disorder: a postmortem stereological study.

PubMed

Rubinow, Marisa J; Mahajan, Gouri; May, Warren; Overholser, James C; Jurjus, George J; Dieter, Lesa; Herbst, Nicole; Steffens, David C; Miguel-Hidalgo, Jose J; Rajkowska, Grazyna; Stockmeier, Craig A

2016-01-01

Functional imaging studies consistently report abnormal amygdala activity in major depressive disorder (MDD). Neuroanatomical correlates are less clear: imaging studies have produced mixed results on amygdala volume, and postmortem neuroanatomic studies have only examined cell densities in portions of the amygdala or its subregions in MDD. Here, we present a stereological analysis of the volume of, and the total number of, neurons, glia, and neurovascular (pericyte and endothelial) cells in the basolateral amygdala in MDD. Postmortem tissues from 13 subjects with MDD and 10 controls were examined. Sections (~15/subject) taken throughout the rostral-caudal extent of the basolateral amygdala (BLA) were stained for Nissl substance and utilized for stereological estimation of volume and cell numbers. Results indicate that depressed subjects had a larger lateral nucleus than controls and a greater number of total BLA neurovascular cells than controls. There were no differences in the number or density of neurons or glia between depressed and control subjects. These findings present a more detailed picture of BLA cellular anatomy in depression than has previously been available. Further studies are needed to determine whether the greater number of neurovascular cells in depressed subjects may be related to increased amygdala activity in depression.

Antemortem detection of chronic wasting disease prions in nasal brush collections and rectal biopsies from white-tailed deer by real time quaking-induced conversion

USGS Publications Warehouse

Haley, Nicholas J.; Siepker, Chris; Walter, W. David; Thomsen, Bruce V.; Greenlee, Justin J.; Lehmkuhl, Aaron D.; Richt, Jürgen a.

2016-01-01

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since spread to cervids in 23 states, two Canadian provinces, and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction of farmed or free-ranging deer and elk or surveillance studies of private or protected herds, where depopulation is contraindicated. This study sought to evaluate the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay by using recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brush samples collected antemortem from farmed white-tailed deer (n = 409). Antemortem findings were then compared to results from ante- and postmortem samples (RAMALT, brainstem, and medial retropharyngeal lymph nodes) evaluated by using the current gold standard in vitro assay, immunohistochemistry (IHC) analysis. We hypothesized that the sensitivity of RT-QuIC would be comparable to IHC analysis in antemortem tissues and would correlate with both the genotype and the stage of clinical disease. Our results showed that RAMALT testing by RT-QuIC assay had the highest sensitivity (69.8%) compared to that of postmortem testing, with a specificity of >93.9%. These data suggest that RT-QuIC, like IHC analysis, is an effective assay for detection of PrPCWD in rectal biopsy specimens and other antemortem samples and, with further research to identify more sensitive tissues, bodily fluids, or experimental conditions, has potential for large-scale and rapid automated testing for CWD diagnosis.

DNA analysis of dental pulp to link incinerated remains of homicide victim to crime scene.

PubMed

Sweet, D J; Sweet, C H

1995-03-01

Teeth endure postmortem degradation and extreme changes in ambient temperature and pressure better than most human tissues. This ability to resist deterioration allows the teeth to be studied as a method of establishing the identity of a decedent. Additionally, dental hard tissues, and in some instances soft tissues, may provide investigators with other sources of forensic data. In this case, a female homicide victim was transported to a location where her remains were burned. The high temperatures of a gasoline fire effectively incinerated the body precluding deoxyribonucleic acid (DNA) analysis from conventional sites. However, most of the teeth survived the conflagration. They were used to identify the victim. Additionally, the dental pulps were found to be an excellent source of high molecular weight genomic DNA. This proved to be an effective method to link the victim's body to biological evidence recovered from the site of the murder.

Altered transition metal homeostasis in Niemann-Pick disease, Type C1

PubMed Central

Hung, Ya Hui; Faux, Noel G.; Killilea, David W.; Yanjanin, Nicole; Firnkes, Sally; Volitakis, Irene; Ganio, George; Walterfang, Mark; Hastings, Caroline; Porter, Forbes D.; Ory, Daniel S.; Bush, Ashley I.

2014-01-01

The loss of NPC1 protein function is the predominant cause of Niemann-Pick type C1 disease (NP-C1), a systemic and neurodegenerative disorder characterized by late-endosomal/lysosomal accumulation of cholesterol and other lipids. Limited evidence from post-mortem human tissues, an Npc1−/− mouse model, and cell culture studies also suggest failure of metal homeostasis in NP-C1. To investigate these findings, we performed a comprehensive transition metal analysis of cerebrospinal fluid (CSF), plasma and tissue samples from human NP-C1 patients and an Npc1−/− mouse model. NPC1 deficiency in the Npc1−/− mouse model resulted in a perturbation of transition metal homeostasis in the plasma and key organs (brain, liver, spleen, heart, lungs, and kidneys). Analysis of human patient CSF, plasma and post-mortem brain tissues also indicated disrupted metal homeostasis. There was a disparity in the direction of metal changes between the human and the Npc1−/− mouse samples, which may reflect species-specific metal metabolism. Nevertheless, common to both species is brain zinc accumulation. Furthermore, treatment with the glucosylceramide synthase inhibitor miglustat, the only drug shown in a controlled clinical trial to have some efficacy for NP-C1, did not correct the alterations in CSF and plasma transition metal and ceruloplasmin (CP) metabolism in NP-C1 patients. These findings highlight the importance of NPC1 function in metal homeostasis, and indicate that metal-targeting therapy may be of value as a treatment for NP-C. PMID:24343124

Tissue-Specific Reduction in Splicing Efficiency of IKBKAP Due to the Major Mutation Associated with Familial Dysautonomia

PubMed Central

Cuajungco, Math P.; Leyne, Maire; Mull, James; Gill, Sandra P.; Lu, Weining; Zagzag, David; Axelrod, Felicia B.; Maayan, Channa; Gusella, James F.; Slaugenhaupt, Susan A.

2003-01-01

We recently identified a mutation in the I-κB kinase associated protein (IKBKAP) gene as the major cause of familial dysautonomia (FD), a recessive sensory and autonomic neuropathy. This alteration, located at base pair 6 of the intron 20 donor splice site, is present on >99.5% of FD chromosomes and results in tissue-specific skipping of exon 20. A second FD mutation, a missense change in exon 19 (R696P), was seen in only four patients heterozygous for the major mutation. Here, we have further characterized the consequences of the major mutation by examining the ratio of wild-type to mutant (WT:MU) IKBKAP transcript in EBV-transformed lymphoblast lines, primary fibroblasts, freshly collected blood samples, and postmortem tissues from patients with FD. We consistently found that WT IKBKAP transcripts were present, albeit to varying extents, in all cell lines, blood, and postmortem FD tissues. Further, a corresponding decrease in the level of WT protein is seen in FD cell lines and tissues. The WT:MU ratio in cultured lymphoblasts varied with growth phase but not with serum concentration or inclusion of antibiotics. Using both densitometry and real-time quantitative polymerase chain reaction, we found that relative WT:MU IKBKAP RNA levels were highest in cultured patient lymphoblasts and lowest in postmortem central and peripheral nervous tissues. These observations suggest that the relative inefficiency of WT IKBKAP mRNA production from the mutant alleles in the nervous system underlies the selective degeneration of sensory and autonomic neurons in FD.Therefore, exploration of methods to increase the WT:MU IKBKAP transcript ratio in the nervous system offers a promising approach for developing an effective therapy for patients with FD. PMID:12577200

The detection of African horse sickness virus antigens and antibodies in young Equidae.

PubMed Central

Hamblin, C.; Anderson, E. C.; Mellor, P. S.; Graham, S. D.; Mertens, P. P.; Burroughs, J. N.

1992-01-01

Four ponies were each inoculated with a different serotype of African horse sickness virus (AHSV) which had been passaged through cell culture in order to achieve attenuation. Three of the ponies died suddenly after showing mild clinical signs, the fourth pony remained clinically normal and was killed at day 38. Infectious AHSV was isolated from blood samples collected at intervals from all four ponies. Positive antigen ELISA reactions were only observed with blood samples from two of the ponies on the two days preceding death. Specific AHSV antibodies were detected by ELISA in serum samples from the other two ponies although one eventually died. African horse sickness viral antigens were detected by ELISA in post-mortem tissue samples collected from all four ponies. No infectious virus could be detected in tissue samples taken post-mortem from the pony which survived African horse sickness (AHS) infection. In the event of a suspected outbreak of AHS it is recommended that sera and heparinized blood should be tested for specific antibodies and AHSV antigen respectively. When available, post-mortem tissues, including spleen, heart, lung and liver, should also be tested for AHSV antigen. Although the ELISA used for the detection of AHSV antigen is highly sensitive and specific, negative ELISA results should be confirmed by virus isolation attempts. PMID:1547837

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation.

PubMed

Rubio-González, A; Potes, Y; Illán-Rodríguez, D; Vega-Naredo, I; Sierra, V; Caballero, B; Fàbrega, E; Velarde, A; Dalmau, A; Oliván, M; Coto-Montes, A

2015-07-01

The objective of this work was to study the postmortem evolution of potential biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and oxidative stress (total antioxidant activity, TAA; superoxide dismutase activity, SOD and catalase activity, CAT) in the Longissimus dorsi muscle of entire male ((Large White×Landrace)×Duroc) pigs subjected to different management treatments that may promote stress, such as mixing unfamiliar animals at the farm and/or during transport and lairage before slaughter. During the rearing period at the farm, five animals were never mixed after the initial formation of the experimental groups (unmixed group at the farm, UF), whereas 10 animals were subjected to a common routine of being mixed with unfamiliar animals (mixed group at the farm, MF). Furthermore, two different treatments were used during the transport and lairage before slaughter: 10 pigs were not mixed (unmixed group during transport and lairage, UTL), whereas five pigs were mixed with unfamiliar animals on the lorry and during lairage (mixed group during transport and lairage, MTL). These mixing treatments were then combined into three pre-slaughter treatments - namely, UF-UTL, MF-UTL and MF-MTL. The results show that MF-UTL and MF-MTL increased significantly the muscle antioxidant defense (TAA, SOD and CAT) at short postmortem times (4 and 8 h; P<0.001), followed by an earlier depletion of the antioxidant activity at 24 h postmortem (P<0.05). We also found that mixing unfamiliar animals, both at the farm and during transport and lairage, triggers postmortem muscle autophagy, which showed an earlier activation (higher expression of Beclin 1 and LC3-II/LC3-I ratio at 4 h postmortem followed by a decreasing pattern of this ratio along first 24 h postmortem) in the muscle tissues of animals from the MF-UTL and MF-MTL groups, as an adaptive strategy of the muscle cells for counteracting induced stress. From these results, we propose that monitoring the evolution of the main biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and muscle antioxidant defense (TAA, SOD, CAT) in the muscle tissue within the first 24 h postmortem may help the detection of animal stress and its potential effect on the postmortem muscle metabolism.

Post-mortem redistribution of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in the rabbit. Part I: experimental approach after in vivo intravenous infusion.

PubMed

De Letter, Els A; Clauwaert, Karine M; Belpaire, Frans M; Lambert, Willy E; Van Bocxlaer, Jan F; Piette, Michel H A

2002-08-01

Post-mortem redistribution is known to influence blood and tissue levels of various drugs. An animal model was used in an attempt to elucidate this problem for the amphetamine analogue, 3,4-methylenedioxymethamphetamine (MDMA). Rabbits received 1 mg/kg MDMA intravenously (iv) and were killed 2 h later in order to simulate the state of complete distribution in the body. MDMA and 3,4-methylenedioxyamphetamine (MDA) concentrations were determined in blood, urine, bile, vitreous humour, and various tissues (eye globe walls, brain, cardiac muscle, lungs, liver, kidneys, iliopsoas muscle and adipose tissue) using a high pressure liquid chromatographic (HPLC) procedure with fluorescence detection. In the first group (control group, sampling immediately post mortem) considerable MDMA concentrations were found in the brain and both lungs. In addition, our data indicate the elimination of MDMA by hepatic biotransformation and excretion via the bile. When the animals were preserved either 24 or 72 h post mortem (second group), an increase of MDMA and MDA levels in the liver and the eye globe walls was noticed. In the lungs, on the other hand, they tended to decline as a function of increasing post-mortem interval. MDMA levels in cardiac and iliopsoas muscle were fairly comparable and remained stable up to 72 h after death. In the third group, ligation of the large vessels around the heart took place immediately post mortem, but significant differences in blood and tissue MDMA concentrations between rabbits of group 2 and 3 could not be demonstrated. We therefore conclude that post-mortem redistribution of MDMA at the cellular level (viz. by pure diffusion gradient from higher to lower concentrations) is more important than its redistribution via the vascular pathway. Finally, MDA levels were relatively low in all samples, thus indicating that this is not a major metabolite in the rabbit, at least within the first 2 h after administration.

Autism Post-Mortem Neuroinformatic Resource: The Autism Tissue Program (ATP) Informatics Portal

ERIC Educational Resources Information Center

Brimacombe, Michael B.; Pickett, Richard; Pickett, Jane

2007-01-01

The Autism Tissue Program (ATP) was established to oversee and manage brain donations related to neurological research in autism. The ATP Informatics Portal (www.atpportal.org) is an integrated data access system based on Oracle technology, developed to provide access for researchers to information on this rare tissue resource. It also permits…

Gene expression associated with suicide attempts in US veterans (Open Access)

DTIC Science & Technology

2017-09-05

schizophrenia who had died from suicide. This gene codes for a cytokine that is part of the tumor necrosis factor family. In addition, the PIK3C3...expression level of eIF2 (and mTOR and WNT) was downregulated in one published report examining post- mortem tissue in people who had a schizophrenia ...HK. Suicide candidate genes associated with bipolar disorder and schizophrenia : an exploratory gene expression profiling analysis of post-mortem

Distribution of kerosene components in rats following dermal exposure.

PubMed

Tsujino, Y; Hieda, Y; Kimura, K; Eto, H; Yakabe, T; Takayama, K; Dekio, S

2002-08-01

The systemic distribution of kerosene components in blood and tissues was analysed in rats following dermal exposure. Four types of trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) with carbon numbers 9-16 (C(9)-C(16)) were analysed as major kerosene components by capillary gas chromatography/mass spectrometry (GC/MS). The kerosene components were detected in blood and all tissues after a small piece of cotton soaked with kerosene was applied to the abdominal skin. The amounts of TMBs detected were higher than those of AHCs. Greater increases in TMB levels were found in adipose tissue in an exposure duration-dependent manner. The amounts of TMBs detected were only at trace levels following post-mortem dermal exposure to kerosene. These findings suggest that kerosene components were absorbed percutaneously and distributed to various organs via the blood circulation. Post-mortem or ante-mortem exposure to kerosene could be distinguished when the exposure duration was relatively long. Adipose tissue would seem to be the most useful for estimating the degree of kerosene exposure.

[Postmortem CT examination in a case of alleged drowning--a case report].

PubMed

Woźniak, Krzysztof; Urbanik, Andrzej; Rzepecka-Woźniak, Ewa; Moskała, Artur; Kłys, Małgorzata

2009-01-01

The authors present an analysis of postmortem CT examination in a case of drowning in fresh water of a young male. Both the results of conventional forensic autopsy and radiologic examination have been compared. The analysis is illustrated by two-dimensional and three-dimensional reconstructions based on the DICOM files obtained during postmortem CT examination.

Blood creatinine level in postmortem cases.

PubMed

Nishida, Atsushi; Funaki, Hironao; Kobayashi, Masaki; Tanaka, Yuka; Akasaka, Yoshihisa; Kubo, Toshikazu; Ikegaya, Hiroshi

2015-05-01

Blood chemical analysis for the diagnosis of diseases in forensic cases should be conducted in the same way as for clinical cases. However, it is sometimes difficult to obtain serum samples in forensic cases because of postmortem changes such as hemolysis and putrefaction. This study aimed to evaluate renal function in postmortem cases by blood creatinine analysis. The blood creatinine level was measured by high performance liquid chromatography (HPLC) using whole blood samples taken from 77 postmortem cases, and the relationships between blood creatinine level, postmortem interval, and cause of death were examined. The median blood creatinine level was found to be 1.15 mg/dL, with no significant differences between blood samples taken from different parts of the body. The blood creatinine level was stable for 3 days after death and gradually increased after that period, in line with a previous study using enzymatic analysis that found the serum creatinine level was stable in the early postmortem period. The blood creatinine level was high in the cases of blunt injury, intoxication, and in deaths caused by fire. This was considered to reflect acute renal dysfunction. However, the postmortem blood creatinine level remained higher than the clinical normal value despite omitting cases with renal dysfunction from the analysis. Therefore, we next investigated the change in postmortem creatinine levels in mice and found that the blood creatinine level increased with the emergence of rigor mortis. Our findings indicate that HPLC is useful in the postmortem evaluation of renal function even in the cases where serum cannot be obtained. However, the presence of rigor mortis should be considered in the evaluation of blood creatinine values. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

Dental x-ray image segmentation

NASA Astrophysics Data System (ADS)

Said, Eyad; Fahmy, Gamal F.; Nassar, Diaa; Ammar, Hany

2004-08-01

Law enforcement agencies have been exploiting biometric identifiers for decades as key tools in forensic identification. With the evolution in information technology and the huge volume of cases that need to be investigated by forensic specialists, it has become important to automate forensic identification systems. While, ante mortem (AM) identification, that is identification prior to death, is usually possible through comparison of many biometric identifiers, postmortem (PM) identification, that is identification after death, is impossible using behavioral biometrics (e.g. speech, gait). Moreover, under severe circumstances, such as those encountered in mass disasters (e.g. airplane crashers) or if identification is being attempted more than a couple of weeks postmortem, under such circumstances, most physiological biometrics may not be employed for identification, because of the decay of soft tissues of the body to unidentifiable states. Therefore, a postmortem biometric identifier has to resist the early decay that affects body tissues. Because of their survivability and diversity, the best candidates for postmortem biometric identification are the dental features. In this paper we present an over view about an automated dental identification system for Missing and Unidentified Persons. This dental identification system can be used by both law enforcement and security agencies in both forensic and biometric identification. We will also present techniques for dental segmentation of X-ray images. These techniques address the problem of identifying each individual tooth and how the contours of each tooth are extracted.

Factors impacting the success of post-mortem sperm rescue in the rhinoceros.

PubMed

Roth, T L; Stoops, M A; Robeck, T R; O'Brien, J K

2016-04-01

The goal of this study was to identify factors that influenced the ability to successfully rescue sperm post-mortem from rhinoceroses maintained in North American zoos. Factors considered included procedural technicalities, individual rhinoceros characteristics and timing. Gross testicular pathology was noted in 17.4% of males (4/23) but did not impact sperm recovery except in one case of azoospermia (4.3%). Of the males in which sperm recovery was attempted (n=21), 62% yielded quality samples considered adequate for cryopreservation (≥ 30% motility with ≥ 2.0 forward progressive status). A high percentage of males (70.6%; 12/17) from which reproductive tissue was removed an d cooled ≤ 4 h after death yielded quality sperm samples, whereas only 25% (1/4) of males from which tissue was removed>4h after death yielded quality samples. Quality samples were recovered 1-51 h post-mortem from rhinoceroses 8 to 36 years old. Neither type of illness (prolonged or acute), or method of death (euthanasia or natural) affected the ability to harvest quality samples (P > 0.05). The Indian rhinoceros yielded significantly more sperm on average (40 × 10(9)) than the African black rhinoceros (3.6 × 10(9); P < 0.01) and the African white rhinoceros (3.2 × 10(9); P < 0.05). Across all species and samples assessed (n = 11), mean post-thaw sperm motility (41%), was only 15% less than pre-freeze motility (56%) and only decreased to 22% during the 6h post-thaw assessment period. Rhinoceros sperm rescue post-mortem is relatively successful across a wide range of variables, especially when tissues are removed and cooled promptly after death, and should be considered standard practice among zoos. Copyright © 2016 Elsevier B.V. All rights reserved.

Postmortem ventilation in cases of penetrating gunshot and stab wounds to the chest.

PubMed

Germerott, Tanja; Preiss, Ulrich S; Ross, Steffen G; Thali, Michael J; Flach, Patricia M

2013-11-01

We sought to determine the effect of postmortem ventilation in combination with a suction pump in cases showing penetrating trauma to the chest with haemo- and/or pneumothorax, for better evaluation of the lungs in postmortem computed tomography (PMCT). The study included 6 subjects (1 female, 5 male; age 32-67years) with a penetrating gunshot or stab wound to the chest and consecutive pneumo- and/or haemothorax. The pneumo- and haemothorax were evacuated by a suction pump, and postmortem ventilation was applied using a home care ventilator. PMCT images with and without postmortem ventilation were compared, as well as the autopsy results. In three cases haemo- and pneumothorax was clearly reduced. Postmortem ventilation led to distinct re-expansion of the lungs in two cases, and to re-expansion of single lung lobes in two cases with shotgun injuries. No visible effect was seen in the remaining two cases, because of extensive destruction of lung tissue and blood aspiration. In two cases the injuries sustained in the individual lung lobes were successfully located during postmortem ventilation. The bullet channel was apparent in one case; in another case, injury of the pericardium became visible by generating pneumopericardium. The present method is capable of improving evaluation of the postmortem lung in the presence of single stab or gunshot wounds and if there is no severe destruction of the respiratory system and aspiration. Forensic autopsy should still be considered as the gold standard, although in some cases the present method might be helpful, especially where no autopsy is required. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Development and application of specific cytokine assays in tissue samples from a bottlenose dolphin with hyperinsulinemia

USDA-ARS?s Scientific Manuscript database

Chronic inflammation has been associated with insulin resistance and type 2 diabetes in humans. Postmortem hepatic and splenic tissue from a 46-year old geriatric male bottlenose dolphin (Tursiops truncatus) with insulin resistance (chronic hyperinsulinemia with hyperglycemia) , chronic = inflamma...

Effect of antemortem and postmortem factors on ( sup 3 H)MK-801 binding in the human brain: Transient elevation during early childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kornhuber, J.; Mack-Burkhardt, F.; Konradi, C.

1989-01-01

The effect of a number of antemortem and postmortem factors on ({sup 3}H)MK-801 binding was investigated under equilibrium conditions in the frontal cortex of human brains of 38 controls. Binding values transiently increased during the early postnatal period reaching a maximum at the age of about 2 years. After age 10 years ({sup 3}H)MK-801 binding sites disappeared at 5.7% per decade. The storage time of brain tissue had a reducing effect on these binding sites. There was no effect of gender, brain weight or postmortem time interval and the binding sites were bilaterally symmetrically distributed in the frontal cortex.

High-contrast differentiation resolution 3D imaging of rodent brain by X-ray computed microtomography

NASA Astrophysics Data System (ADS)

Zikmund, T.; Novotná, M.; Kavková, M.; Tesařová, M.; Kaucká, M.; Szarowská, B.; Adameyko, I.; Hrubá, E.; Buchtová, M.; Dražanová, E.; Starčuk, Z.; Kaiser, J.

2018-02-01

The biomedically focused brain research is largely performed on laboratory mice considering a high homology between the human and mouse genomes. A brain has an intricate and highly complex geometrical structure that is hard to display and analyse using only 2D methods. Applying some fast and efficient methods of brain visualization in 3D will be crucial for the neurobiology in the future. A post-mortem analysis of experimental animals' brains usually involves techniques such as magnetic resonance and computed tomography. These techniques are employed to visualize abnormalities in the brains' morphology or reparation processes. The X-ray computed microtomography (micro CT) plays an important role in the 3D imaging of internal structures of a large variety of soft and hard tissues. This non-destructive technique is applied in biological studies because the lab-based CT devices enable to obtain a several-micrometer resolution. However, this technique is always used along with some visualization methods, which are based on the tissue staining and thus differentiate soft tissues in biological samples. Here, a modified chemical contrasting protocol of tissues for a micro CT usage is introduced as the best tool for ex vivo 3D imaging of a post-mortem mouse brain. This way, the micro CT provides a high spatial resolution of the brain microscopic anatomy together with a high tissue differentiation contrast enabling to identify more anatomical details in the brain. As the micro CT allows a consequent reconstruction of the brain structures into a coherent 3D model, some small morphological changes can be given into context of their mutual spatial relationships.

Analysis of Zolpidem in Postmortem Fluids and Tissues Using Ultra-Performance Liquid Chromatography-Mass Spectrometry

DTIC Science & Technology

2014-02-01

16. Abstract Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. Its use is common and wide-spread...Classif. (of this page) 21. No. of Pages 22. Price Unclassified Unclassified 15 Form DOT F 1700.7 (8-72) Reproduction of completed page authorized iii...INTRODUCTION Zolpidem is a nonbenzodiazepine sedative hypnotic drug used to treat insomnia by slowing the activity in the brain. It is prescribed as a short

Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

2006-02-01

Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

Optimized magnetic resonance diffusion protocol for ex-vivo whole human brain imaging with a clinical scanner

NASA Astrophysics Data System (ADS)

Scherrer, Benoit; Afacan, Onur; Stamm, Aymeric; Singh, Jolene; Warfield, Simon K.

2015-03-01

Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a novel insight into the brain to facilitate our understanding of the brain connectivity and microstructure. While in-vivo DW-MRI enables imaging of living patients and longitudinal studies of brain changes, post-mortem ex-vivo DW-MRI has numerous advantages. Ex-vivo imaging benefits from greater resolution and sensitivity due to the lack of imaging time constraints; the use of tighter fitting coils; and the lack of movement artifacts. This allows characterization of normal and abnormal tissues with unprecedented resolution and sensitivity, facilitating our ability to investigate anatomical structures that are inaccessible in-vivo. This also offers the opportunity to develop today novel imaging biomarkers that will, with tomorrow's MR technology, enable improved in-vivo assessment of the risk of disease in an individual. Post-mortem studies, however, generally rely on the fixation of specimen to inhibit tissue decay which starts as soon as tissue is deprived from its blood supply. Unfortunately, fixation of tissues substantially alters tissue diffusivity profiles. In addition, ex-vivo DW-MRI requires particular care when packaging the specimen because the presence of microscopic air bubbles gives rise to geometric and intensity image distortion. In this work, we considered the specific requirements of post-mortem imaging and designed an optimized protocol for ex-vivo whole brain DW-MRI using a human clinical 3T scanner. Human clinical 3T scanners are available to a large number of researchers and, unlike most animal scanners, have a bore diameter large enough to image a whole human brain. Our optimized protocol will facilitate widespread ex-vivo investigations of large specimen.

Involved in the Business of Death: The Social Work Role in Postmortem Care.

PubMed

Sefansky, Susan

2017-02-01

One way that hospitals address concerns about postmortem care is through an office of decedent affairs (ODA). Many hospitals use this office to collect death paperwork, release bodies to funeral homes, perform autopsies, or increase rates of autopsies and organ and tissue donations. It is not common for an ODA to report to the Department of Social Work rather than the Department of Pathology. Few offices put the emphasis on postmortem care for families or staff members. A comprehensive postmortem program needs many different components, including support to families (for example, viewing the dead, advising on next steps after a death, and providing bereavement support), consulting with and supporting multidisciplinary staffers, and coordinating with multiple medical center departments. This article examines a hospital's use of social work principles and clinical training to provide leadership to an ODA and describes the key elements and advantages of a successful program. © 2016 National Association of Social Workers.

A Postmortem Study of Frontal and Temporal Gyri Thickness and Cell Number in Human Obesity.

PubMed

Gómez-Apo, Erick; García-Sierra, Adrián; Silva-Pereyra, Juan; Soto-Abraham, Virgilia; Mondragón-Maya, Alejandra; Velasco-Vales, Verónica; Pescatello, Linda S

2018-01-01

This study aimed to compare cortex thickness and neuronal cell density in postmortem brain tissue from people with overweight or obesity and normal weight. The cortex thickness and neuron density of eight donors with overweight or obesity (mean = 31.6 kg/m 2 ; SD = 4.35; n = 8; 6 male) and eight donors with normal weight (mean = 21.8 kg/m 2 ; SD = 1.5; n = 8; 5 male) were compared. All participants were Mexican and lived in Mexico City. Randomly selected thickness measures of different cortex areas from the frontal and temporal lobes were analyzed based on high-resolution real-size photographs. A histological analysis of systematic-random fields was used to quantify the number of neurons in postmortem left and right of the first, second, and third gyri of frontal and temporal lobe brain samples. No statistical difference was found in cortical thickness between donors with overweight or obesity and individuals with normal weight. A smaller number of neurons was found among the donors with overweight or obesity than the donors with normal weight at different frontal and temporal areas. A lower density of neurons is associated with overweight or obesity. The morphological basis for structural brain changes in obesity requires further investigation. © 2017 The Obesity Society.

The importance of post-mortem computed tomography (PMCT) in confrontation with conventional forensic autopsy of victims of motorcycle accidents.

PubMed

Moskała, Artur; Woźniak, Krzysztof; Kluza, Piotr; Romaszko, Karol; Lopatin, Oleksij

2016-01-01

Since traffic accidents are an important problem in forensic medicine, there is a constant search for new solutions to help with an investigation process in such cases. In recent years there was a rapid development of post-mortem imaging techniques, especially post-mortem computed tomography (PMCT). In our work we concentrated on a potential advantage of PMCT in cases of motorcycle accident fatalities. The results of forensic autopsy were compared with combined results of the autopsy and PMCT to check in which areas use of these two techniques gives statistically important increase in number of findings. The hypothesis was confirmed in case of pneumothorax and fractures of skull, spine, clavicle, scapula, lower leg bones. As for majority of other bone fractures locations and brain injures there were single cases with pathologies visible only in PMCT, but too few to reach expected level of p-value. In case of injuries of solid organs and soft tissues statistical analysis did not confirmed any advantage of unenhanced PMCT use. On the whole it has been shown that PMCT used as an adjunct to forensic autopsy can cause an increase in information about vitally important regions in case of motorcycle accident fatalities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles.

PubMed

Pearson, Brandon L; Corley, Michael J; Vasconcellos, Amy; Blanchard, D Caroline; Blanchard, Robert J

2013-04-15

Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n=4) and age-matched typically developing (TD) individuals (n=4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

Trace elements distribution and post-mortem intake in human bones from Middle Age by total reflection X-ray fluorescence*1

NASA Astrophysics Data System (ADS)

Carvalho, M. L.; Marques, A. F.; Lima, M. T.; Reus, U.

2004-08-01

The purpose of the present work is to investigate the suitability of TXRF technique to study the distribution of trace elements along human bones of the 13th century, to conclude about environmental conditions and dietary habits of old populations and to study the uptake of some elements from the surrounding soil. In this work, we used TXRF to quantify and to make profiles of the elements through long bones. Two femur bones, one from a man and another from a woman, buried in the same grave were cross-sectioned in four different points at a distance of 1 cm. Microsamples of each section were taken at a distance of 1 mm from each other. Quantitative analysis was performed for Ca, Mn, Fe, Cu, Zn, Sr, Ba and Pb. Very high concentrations of Mn and Fe were obtained in the whole analysed samples, reaching values higher than 2% in some samples of trabecular tissue, very much alike to the concentrations in the burial soil. A sharp decrease for both elements was observed in cortical tissue. Zn and Sr present steady concentration levels in both kinds of bone tissues. Pb and Cu show very low concentrations in the inner tissue of cortical bone. However, these concentrations increase in the regions in contact to trabecular tissue and external surface in contact with the soil, where high levels of both elements were found. We suggest that contamination from the surrounding soil exists for Mn and Fe in the whole bone tissue. Pb can be both from post-mortem and ante-mortem origin. Inner compact tissue might represent in vivo accumulation and trabecular one corresponds to uptake during burial. The steady levels of Sr and Zn together with soil concentration lower levels for these elements may allow us to conclude that they are originated from in vivo incorporation in the hydroxyapatite bone matrix.

Two fatal intoxication cases with imidacloprid: LC/MS analysis.

PubMed

Proença, Paula; Teixeira, Helena; Castanheira, Fernando; Pinheiro, João; Monsanto, Paula V; Marques, Estela P; Vieira, Duarte Nuno

2005-10-04

Imidacloprid [1-(6-chloro-3pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine] is a new and potent nitromethylene insecticide with high insecticidal activity at very low application rates. It is the first highly effective insecticide that, like nicotine, acts on the nervous system, causing blockage of postsynaptic nicotinergic acetylcholine receptors. Two fatal cases with this insecticide in two male individuals, of 33 and 66 years old, are presented. An LC/MS with electrospray method for measuring imidacloprid and its metabolites in post-mortem samples is described. In the chromatographic separation, a reverse-phase column XTerra MS C18 (2.1mm i.d.x 150 mm, 5 microm) was used and the mobile phase composed with acetonitrile and 0.1% formic acid (15:85), at a 0.25 mL/min flow rate. Samples were prepared with a liquid-liquid extraction procedure with dichloromethane. Calibration curves for imidacloprid in blood and urine samples were linear from 0.2 to 15 microg/mL. The mean recovery was 86% with a coefficient of variation of +/-5.9%. The detection limit was 0.002 microg/mL. Quantitative results were obtained for all post-mortem matrices available of the two fatal cases: blood, urine, stomach contents, lung, liver and kidney. The imidacloprid blood concentrations found in two-cases were 12.5 and 2.05 microg/mL. The authors validated a method to detect and quantify imidacloprid in post-mortem samples, and to our knowledge for the first time a post-mortem tissue distribution was performed on various samples for this insecticide.

Relevance of postmortem radiology to the diagnosis of fatal cerebral gas embolism from compressed air diving.

PubMed

Cole, A J; Griffiths, D; Lavender, S; Summers, P; Rich, K

2006-05-01

To test the hypothesis that artefact caused by postmortem off-gassing is at least partly responsible for the presence of gas within the vascular system and tissues of the cadaver following death associated with compressed air diving. Controlled experiment sacrificing sheep after a period of simulated diving in a hyperbaric chamber and carrying out sequential postmortem computed tomography (CT) on the cadavers. All the subject sheep developed significant quantities of gas in the vascular system within 24 hours, as demonstrated by CT and necropsy, while the control animals did not. The presence of gas in the vascular system of human cadavers following diving associated fatalities is to be expected, and is not necessarily connected with gas embolism following pulmonary barotrauma, as has previously been claimed.

Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

NASA Astrophysics Data System (ADS)

Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

2014-01-01

We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

PubMed

Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

2008-08-01

Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

28 CFR 549.80 - Authority to conduct autopsies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... this section, the Warden may order an autopsy or post-mortem operation, including removal of tissue for... person (e.g., coroner, or next-of-kin, or the decedent's consent in the case of tissue removed for...-of-kin that they may telegraph the institution collect with their response. Where permission is not...

28 CFR 549.80 - Authority to conduct autopsies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... this section, the Warden may order an autopsy or post-mortem operation, including removal of tissue for... person (e.g., coroner, or next-of-kin, or the decedent's consent in the case of tissue removed for...-of-kin that they may telegraph the institution collect with their response. Where permission is not...

Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry.

PubMed

Schäfer, Karl-Christian; Balog, Júlia; Szaniszló, Tamás; Szalay, Dániel; Mezey, Géza; Dénes, Júlia; Bognár, László; Oertel, Matthias; Takáts, Zoltán

2011-10-15

Direct combination of cavitron ultrasonic surgical aspirator (CUSA) and sonic spray ionization mass spectrometry is presented. A commercially available ultrasonic surgical device was coupled to a Venturi easy ambient sonic-spray ionization (V-EASI) source by directly introducing liquified tissue debris into the Venturi air jet pump. The Venturi air jet pump was found to efficiently nebulize the suspended tissue material for gas phase ion production. The ionization mechanism involving solely pneumatic spraying was associated with that of sonic spray ionization. Positive and negative ionization spectra were obtained from brain and liver samples reflecting the primary application areas of the surgical device. Mass spectra were found to feature predominantly complex lipid-type constituents of tissues in both ion polarity modes. Multiply charged peptide anions were also detected. The influence of instrumental settings was characterized in detail. Venturi pump geometry and flow parameters were found to be critically important in ionization efficiency. Standard solutions of phospholipids and peptides were analyzed in order to test the dynamic range, sensitivity, and suppression effects. The spectra of the intact tissue specimens were found to be highly specific to the histological tissue type. The principal component analysis (PCA) and linear discriminant analysis (LDA) based data analysis method was developed for real-time tissue identification in a surgical environment. The method has been successfully tested on post-mortem and ex vivo human samples including astrocytomas, meningeomas, metastatic brain tumors, and healthy brain tissue. © 2011 American Chemical Society

Immunohistochemical Analysis of Human Vallate Taste Buds

PubMed Central

Tizzano, Marco; Grigereit, Laura; Shultz, Nicole; Clary, Matthew S.

2015-01-01

The morphology of the vallate papillae from postmortem human samples was investigated with immunohistochemistry. Microscopically, taste buds were present along the inner wall of the papilla, and in some cases in the outer wall as well. The typical taste cell markers PLCβ2, GNAT3 (gustducin) and the T1R3 receptor stain elongated cells in human taste buds consistent with the Type II cells in rodents. In the human tissue, taste bud cells that stain with Type II cell markers, PLCβ2 and GNAT3, also stain with villin antibody. Two typical immunochemical markers for Type III taste cells in rodents, PGP9.5 and SNAP25, fail to stain any taste bud cells in the human postmortem tissue, although these antibodies do stain numerous nerve fibers throughout the specimen. Car4, another Type III cell marker, reacted with only a few taste cells in our samples. Finally, human vallate papillae have a general network of innervation similar to rodents and antibodies directed against SNAP25, PGP9.5, acetylated tubulin and P2X3 all stain free perigemmal nerve endings as well as intragemmal taste fibers. We conclude that with the exception of certain molecular features of Type III cells, human vallate papillae share the structural, morphological, and molecular features observed in rodents. PMID:26400924

Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy.

PubMed

Holleran, Laurena; Kim, Joong Hee; Gangolli, Mihika; Stein, Thor; Alvarez, Victor; McKee, Ann; Brody, David L

2017-03-01

Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm 3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.

A Method for Whole Brain Ex Vivo Magnetic Resonance Imaging with Minimal Susceptibility Artifacts

PubMed Central

Shatil, Anwar S.; Matsuda, Kant M.; Figley, Chase R.

2016-01-01

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains. PMID:27965620

Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

PubMed

Fais, Paolo; Viero, Alessia; Viel, Guido; Giordano, Renzo; Raniero, Dario; Kusstatscher, Stefano; Giraudo, Chiara; Cecchetto, Giovanni; Montisci, Massimo

2018-04-07

Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

Postmortem Biochemistry of Meat and Fish.

ERIC Educational Resources Information Center

Hultin, Herbert O.

1984-01-01

Discusses structural and chemical features of muscle tissue. Emphasizes chemical and physical changes which occur during processing and storage and how these changes affect the eating quality of meat and fish. (JN)

A spectroscopic approach to monitor the cut processing in pulsed laser osteotomy.

PubMed

Henn, Konrad; Gubaidullin, Gail G; Bongartz, Jens; Wahrburg, Jürgen; Roth, Hubert; Kunkel, Martin

2013-01-01

During laser osteotomy surgery, plasma arises at the place of ablation. It was the aim of this study to explore whether a spectroscopic analysis of this plasma would allow identification of the type of tissue that was affected by the laser. In an experimental setup (Rofin SCx10, CO(2) Slab Laser, wavelength 10.6 μm, pulse duration 80 μs, pulse repetition rate 200 Hz, max. output in cw-mode 100 W), the plasma spectra evoked by a pulsed laser, cutting 1-day postmortem pig and cow bones, were recorded. Spectra were compared to the reference spectrum of bone via correlation analysis. Our measurements show a clear differentiation between the plasma spectra when cutting either a bone or a soft tissue. The spectral changes could be detected from one to the next spectrum within 200 ms. Continuous surveillance of plasma spectra allows us to differentiate whether bone or soft tissue is hit by the last laser pulse. With this information, it may be possible to stop the laser when cutting undesired soft tissue and to design an automatic control of the ablation process.

Determining composition of micron-scale protein deposits in neurodegenerative disease by spatially targeted optical microproteomics.

PubMed

Hadley, Kevin C; Rakhit, Rishi; Guo, Hongbo; Sun, Yulong; Jonkman, James E N; McLaurin, Joanne; Hazrati, Lili-Naz; Emili, Andrew; Chakrabartty, Avijit

2015-09-29

Spatially targeted optical microproteomics (STOMP) is a novel proteomics technique for interrogating micron-scale regions of interest (ROIs) in mammalian tissue, with no requirement for genetic manipulation. Methanol or formalin-fixed specimens are stained with fluorescent dyes or antibodies to visualize ROIs, then soaked in solutions containing the photo-tag: 4-benzoylbenzyl-glycyl-hexahistidine. Confocal imaging along with two photon excitation are used to covalently couple photo-tags to all proteins within each ROI, to a resolution of 0.67 µm in the xy-plane and 1.48 µm axially. After tissue solubilization, photo-tagged proteins are isolated and identified by mass spectrometry. As a test case, we examined amyloid plaques in an Alzheimer's disease (AD) mouse model and a post-mortem AD case, confirming known plaque constituents and discovering new ones. STOMP can be applied to various biological samples including cell lines, primary cell cultures, ex vivo specimens, biopsy samples, and fixed post-mortem tissue.

Implications of human tissue studies for radiation protection.

PubMed

Kathren, R L

1988-08-01

Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238Pu and 241Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices.

Implications of human tissue studies for radiation protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.

1988-08-01

Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant /sup 241/Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for /sup 238/Pu and /sup 241/Am andmore » the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices.« less

Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

PubMed

Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

2012-10-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson's disease, including greater susceptibility of females. Copyright © 2012 Elsevier Inc. All rights reserved.

Association between polychlorinated biphenyls and Parkinson’s disease neuropathology

PubMed Central

Hatcher-Martin, Jaime M.; Gearing, Marla; Steenland, Kyle; Levey, Allan I.; Miller, Gary W.; Pennell, Kurt D.

2012-01-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females. PMID:22906799

Relevance of postmortem radiology to the diagnosis of fatal cerebral gas embolism from compressed air diving

PubMed Central

Cole, A J; Griffiths, D; Lavender, S; Summers, P; Rich, K

2006-01-01

Aims To test the hypothesis that artefact caused by postmortem off‐gassing is at least partly responsible for the presence of gas within the vascular system and tissues of the cadaver following death associated with compressed air diving. Methods Controlled experiment sacrificing sheep after a period of simulated diving in a hyperbaric chamber and carrying out sequential postmortem computed tomography (CT) on the cadavers. Results All the subject sheep developed significant quantities of gas in the vascular system within 24 hours, as demonstrated by CT and necropsy, while the control animals did not. Conclusions The presence of gas in the vascular system of human cadavers following diving associated fatalities is to be expected, and is not necessarily connected with gas embolism following pulmonary barotrauma, as has previously been claimed. PMID:16489175

Novel application and serial evaluation of tissue-engineered portal vein grafts in a murine model.

PubMed

Maxfield, Mark W; Stacy, Mitchel R; Kurobe, Hirotsugu; Tara, Shuhei; Yi, Tai; Cleary, Muriel A; Zhuang, Zhen W; Rodriguez-Davalos, Manuel I; Emre, Sukru H; Iwakiri, Yasuko; Shinoka, Toshiharu; Breuer, Christopher K

2017-12-01

Surgical management of pediatric extrahepatic portal vein obstruction requires meso-Rex bypass using autologous or synthetic grafts. Tissue-engineered vascular grafts (TEVGs) provide an alternative, but no validated animal models using portal TEVGs exist. Herein, we preclinically assess TEVGs as portal vein bypass grafts. TEVGs were implanted as portal vein interposition conduits in SCID-beige mice, monitored by ultrasound and micro-computed tomography, and histologically assessed postmortem at 12 months. TEVGs remained patent for 12 months. Histologic analysis demonstrated formation of neovessels that resembled native portal veins, with similar content of smooth muscle cells, collagen type III and elastin. TEVGs are feasible portal vein conduits in a murine model. Further preclinical evaluation of TEVGs may facilitate pediatric clinical translation.

Determination of Etomidate in Human Postmortem Fluids and Tissues

DTIC Science & Technology

2009-02-01

8-72) Reproduction of completed page authorized CONTENTs IntroductIon...on.Agent ..Pharma- cotherapy,.3:.251-8.(1983) . 2 .. Doencke,.A ..Etomidate, a New Hypnotic Agent for Intravenous Application.,. 1. ed .. (Sprnger

Metabolomics and neuroanatomical evaluation of post-mortem changes in the hippocampus.

PubMed

Gonzalez-Riano, Carolina; Tapia-González, Silvia; García, Antonia; Muñoz, Alberto; DeFelipe, Javier; Barbas, Coral

2017-08-01

Understanding the human brain is the ultimate goal in neuroscience, but this is extremely challenging in part due to the fact that brain tissue obtained from autopsy is practically the only source of normal brain tissue and also since changes at different levels of biological organization (genetic, molecular, biochemical, anatomical) occur after death due to multiple mechanisms. Here we used metabolomic and anatomical techniques to study the possible relationship between post-mortem time (PT)-induced changes that may occur at both the metabolomics and anatomical levels in the same brains. Our experiments have mainly focused on the hippocampus of the mouse. We found significant metabolomic changes at 2 h PT, whereas the integrity of neurons and glia, at the anatomical/ neurochemical level, was not significantly altered during the first 5 h PT for the majority of histological markers.

Ethical considerations in forensic genetics research on tissue samples collected post-mortem in Cape Town, South Africa.

PubMed

Heathfield, Laura J; Maistry, Sairita; Martin, Lorna J; Ramesar, Raj; de Vries, Jantina

2017-11-29

The use of tissue collected at a forensic post-mortem for forensic genetics research purposes remains of ethical concern as the process involves obtaining informed consent from grieving family members. Two forensic genetics research studies using tissue collected from a forensic post-mortem were recently initiated at our institution and were the first of their kind to be conducted in Cape Town, South Africa. This article discusses some of the ethical challenges that were encountered in these research projects. Among these challenges was the adaptation of research workflows to fit in with an exceptionally busy service delivery that is operating with limited resources. Whilst seeking guidance from the literature regarding research on deceased populations, it was noted that next of kin of decedents are not formally recognised as a vulnerable group in the existing ethical and legal frameworks in South Africa. The authors recommend that research in the forensic mortuary setting is approached using guidance for vulnerable groups, and the benefit to risk standard needs to be strongly justified. Lastly, when planning forensic genetics research, consideration must be given to the potential of uncovering incidental findings, funding to validate these findings and the feedback of results to family members; the latter of which is recommended to occur through a genetic counsellor. It is hoped that these experiences will contribute towards a formal framework for conducting forensic genetic research in medico-legal mortuaries in South Africa.

Bilateral lenticular Encephalitozoon cuniculi infection in a snow leopard (Panthera uncia).

PubMed

Scurrell, Emma Jane; Holding, Ellen; Hopper, Jane; Denk, Daniela; Fuchs-Baumgartinger, Andrea; Silbermayr, Katja; Nell, Barbara

2015-01-01

Bilateral phacoclastic uveitis caused by lenticular infection with Encephalitozoon cuniculi is described in a snow leopard. The diagnosis was made on histopathological and immunohistological examination of both eyes submitted after postmortem examination. There was a positive antibody titer for E. cuniculi (1:320). Polymerase chain reaction (PCR) and sequence analysis of formalin-fixed, paraffin-embedded ocular tissue detected the DNA of E. cuniculi, strain III. No other systemic lesions attributable to the E. cuniculi infection were identified. © 2014 American College of Veterinary Ophthalmologists.

Postmortem eyefluid analysis in dogs, cats and cattle as an estimate of antemortem serum chemistry profiles.

PubMed Central

Hanna, P E; Bellamy, J E; Donald, A

1990-01-01

This study was carried out to determine the diagnostic usefulness of postmortem eyefluid analysis in estimating antemortem concentrations of serochemical constituents. A total of 31 cattle, 18 dogs and 22 cats were selected from routine elective euthanasia submissions to a diagnostic laboratory. For all cases, a biochemical profile, including determinations for electrolytes, glucose, urea, creatinine, enzymes, cholesterol, bilirubin, protein and osmolality was performed on antemortem serum, and postmortem aqueous and vitreous humors at 0 and 24 h incubation periods. The association between serum and postmortem eyefluid chemistry values was examined using simple linear regression. A strong correlation between serum and postmortem eyefluid urea and creatinine concentrations was demonstrated in the three species examined over a 24 h postmortem interval. We concluded that an accurate estimate of antemortem serum urea or creatinine can be made from the analysis of aqueous or vitreous fluid at necropsy. An estimation of antemortem serum electrolytes (including calcium in cattle) cannot be made with a high degree of accuracy due to the amount of variability in the relationship between serum and eyefluid electrolyte values. For large molecules such as proteins, enzymes, cholesterol and bilirubin there was very poor correlation between serum and eyefluid values. PMID:2249181

Interpretation of analytical toxicology results in life and at postmortem.

PubMed

Flanagan, Robert J; Connally, Geraldine

2005-01-01

Interpretation of analytical toxicology results from live patients is sometimes difficult. Possible factors may be related to: (i) the nature of the poison(s) present; (ii) sample collection, transport and storage; (iii) the analytical methodology used; (iv) the circumstances of exposure; (v) mechanical factors such as trauma or inhalation of stomach contents; and (vi) pharmacological factors such as tolerance or synergy. In some circumstances, detection of a drug or other poison may suffice to prove exposure. At the other extreme, the interpretation of individual measurements may be simplified by regulation. Examples here include whole blood alcohol (ethanol) in regard to driving a motor vehicle and blood lead assays performed to assess occupational exposure. With pharmaceuticals, the plasma or serum concentrations of drugs and metabolites attained during treatment often provide a basis for the interpretation of quantitative measurements. With illicit drugs, comparative information from casework may be all that is available. Postmortem toxicology is an especially complex area since changes in the composition of fluids such as blood depending on the site of collection from the body and the time elapsed since death, amongst other factors, may influence the result obtained. This review presents information to assist in the interpretation of analytical results, especially regarding postmortem toxicology. Collection and analysis of not only peripheral blood, but also other fluids/tissues is usually important in postmortem work. Alcohol, for example, can be either lost from, or produced in, blood especially if there has been significant trauma, hence measurements in urine or vitreous humour are needed to confirm the reliability of a blood result. Measurement of metabolites may also be valuable in individual cases.

Pathological changes in Alzheimer"s brain evaluated with fluorescence emission analysis (FEA)

NASA Astrophysics Data System (ADS)

Christov, Alexander; Ottman, Todd; Grammas, Paula

2004-07-01

Development of AD is associated with cerebrovascular deposition of amyloid beta (Aβ) as well as a progressive increase in vasular collagen content. Both AΒ and collagen are naturally fluorescent compounds when exposed to UV light. We analyzed autofluorescence emitted from brain tissue samples and isolated brain resistance vessels harvested postmortem from patients with Alzheimer's disease (AD) and age-matched controls. Fluorescence emission, excited at 355 nm with an Nd:YAG laser, was measured using a fiber-optic based fluorescence spectroscopic system for tissue analysis. Significantly higher values of fluorescence emission intensity (P<0.001) in the spectral region from 465 to 490 nm were detected in brain resistance vessel samples from AD patients compared to the normal individuals. Results from western blot analysis showed elevated levels of type I and type III collagen, and reduced levels of type IV collagen in resistance vessels from AD patients, compared to control samples. In addition, using direct scanning of the cortical suface for fluoresxcence emission by the laser-induced fluorescence spectroscopy system we detected a significantly (P<0.05) higher level of apoptosis in AD brain tissue compared to age-matched controls. Fluorescence emission analysis (FEA) appears to be a sensitive technique for detecting structural changes in AD brain tissue.

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens

DOT National Transportation Integrated Search

2017-01-01

This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approa...

[Comparison of two different real-time PCR systems in postmortem diagnosis of tuberculosis in paraffin-embedded tissues].

PubMed

Yağmur, Gülhan; Albayrak, Nurhan; Daş, Taner; Yıldırım, Muzaffer; Ozgün, Ayşe; Büyük, Yalçın

2014-10-01

Tuberculosis (TB) is one of those infections with high morbidity and mortality in all around the world. Hundreds of people died from this disease without diagnosed or due to resistant strains in Turkey. Therefore, it is important to identify postmortem cases who have died from tuberculosis. Molecular methods have been widely used as well as conventional methods in the diagnosis of tuberculosis. The aim of this study was to compare the two different real-time polymerase chain reaction (Rt-PCR) system in the postmortem diagnosis of Mycobacterium tuberculosis infections in paraffin-embedded tissues. A total of 40 paraffin-embedded tissue samples [lung (n= 35), brain (n= 2), heart (n= 2), lymph node (n= 1)] in which histopathologic findings consistent with TB (necrotizing granulomatous inflammation, gelatinous caseous pneumonia, necrotic fibrous nodul) obtained from 37 autopsy cases (31 male, 6 female; age range: 25-85 yrs) were included in the study. Paraffin-embedded tissues were deparafinized with xylene and ethyl alcohol and then DNA isolation was done with QIAsymphony DSP Virus/Pathogen Midi kit in the QIAsymphony device. DNA amplification process was performed by Rt-PCR using the kit Artus® M. tuberculosis RG-PCR in the Rotor-Gene® Q device (Qiagen, Germany). Likewise, after deparafinization process, samples placed in the cartridge and isolation and Rt-PCR was performed by Xpert® MTB/RIF (Cepheid, USA) system, simultaneosly. Seventeen and 20 out of the 40 paraffin-embedded tissues yielded positive results with Qiagen and Xpert system, respectively. M.tuberculosis DNA was found positive in 13 (32.5%) and negative in 16 (40%) of the samples by both of the systems, exhibiting 72.5% (29/40) of concordance. On the other hand, seven (17.5%) samples that were positive with Xpert system yielded negative result with the Qiagen, while four (10%) samples that were positive with Qiagen yielded negative result with the Xpert system. Of the 20 positive cases detected with Xpert MTB/RIF system, 15 were found rifampicin-susceptible, and three were rifampicin-resistant. In two samples in which M. tuberculosis DNA was low positive, rifampicin resistance could not be detected. The identification of M.tuberculosis infections in postmortem cases will contribute epidemiological data in Turkey. In these cases, effective sampling and diagnosing of M.tuberculosis infections by acid-fast stain and culture methods are crucial. However, in cases without microbiological sampling the detection of M.tuberculosis DNA in paraffin-embedded tissues with PCR, although there are differences between PCR systems has diagnostic value. In conclusion, our data indicated that Xpert MTB/RIF system is more favourable to detect M.tuberculosis DNA in paraffin-embedded tissues, with the advantages of determination of rifampicin resistance, and detection of more positive results within a shorter time.

Combining Patient-Reprogrammed Neural Cells and Proteomics as a Model to Study Psychiatric Disorders.

PubMed

Zuccoli, Giuliana S; Martins-de-Souza, Daniel; Guest, Paul C; Rehen, Stevens K; Nascimento, Juliana Minardi

2017-01-01

The mechanisms underlying the pathophysiology of psychiatric disorders are still poorly known. Most of the studies about these disorders have been conducted on postmortem tissue or in limited preclinical models. The development of human induced pluripotent stem cells (iPSCs) has helped to increase the translational capacity of molecular profiling studies of psychiatric disorders through provision of human neuronal-like tissue. This approach consists of generation of pluripotent cells by genetically reprogramming somatic cells to produce the multiple neural cell types as observed within the nervous tissue. The finding that iPSCs can recapitulate the phenotype of the donor also affords the possibility of using this approach to study both the disease and control states in a given medical area. Here, we present a protocol for differentiation of human pluripotent stem cells to neural progenitor cells followed by subcellular fractionation which allows the study of specific cellular organelles and proteomic analysis.

Tight-frame based iterative image reconstruction for spectral breast CT

PubMed Central

Zhao, Bo; Gao, Hao; Ding, Huanjun; Molloi, Sabee

2013-01-01

Purpose: To investigate tight-frame based iterative reconstruction (TFIR) technique for spectral breast computed tomography (CT) using fewer projections while achieving greater image quality. Methods: The experimental data were acquired with a fan-beam breast CT system based on a cadmium zinc telluride photon-counting detector. The images were reconstructed with a varying number of projections using the TFIR and filtered backprojection (FBP) techniques. The image quality between these two techniques was evaluated. The image's spatial resolution was evaluated using a high-resolution phantom, and the contrast to noise ratio (CNR) was evaluated using a postmortem breast sample. The postmortem breast samples were decomposed into water, lipid, and protein contents based on images reconstructed from TFIR with 204 projections and FBP with 614 projections. The volumetric fractions of water, lipid, and protein from the image-based measurements in both TFIR and FBP were compared to the chemical analysis. Results: The spatial resolution and CNR were comparable for the images reconstructed by TFIR with 204 projections and FBP with 614 projections. Both reconstruction techniques provided accurate quantification of water, lipid, and protein composition of the breast tissue when compared with data from the reference standard chemical analysis. Conclusions: Accurate breast tissue decomposition can be done with three fold fewer projection images by the TFIR technique without any reduction in image spatial resolution and CNR. This can result in a two-third reduction of the patient dose in a multislit and multislice spiral CT system in addition to the reduced scanning time in this system. PMID:23464320

Immunohistochemical Analysis of Human Vallate Taste Buds.

PubMed

Tizzano, Marco; Grigereit, Laura; Shultz, Nicole; Clary, Matthew S; Finger, Thomas E

2015-11-01

The morphology of the vallate papillae from postmortem human samples was investigated with immunohistochemistry. Microscopically, taste buds were present along the inner wall of the papilla, and in some cases in the outer wall as well. The typical taste cell markers PLCβ2, GNAT3 (gustducin) and the T1R3 receptor stain elongated cells in human taste buds consistent with the Type II cells in rodents. In the human tissue, taste bud cells that stain with Type II cell markers, PLCβ2 and GNAT3, also stain with villin antibody. Two typical immunochemical markers for Type III taste cells in rodents, PGP9.5 and SNAP25, fail to stain any taste bud cells in the human postmortem tissue, although these antibodies do stain numerous nerve fibers throughout the specimen. Car4, another Type III cell marker, reacted with only a few taste cells in our samples. Finally, human vallate papillae have a general network of innervation similar to rodents and antibodies directed against SNAP25, PGP9.5, acetylated tubulin and P2X3 all stain free perigemmal nerve endings as well as intragemmal taste fibers. We conclude that with the exception of certain molecular features of Type III cells, human vallate papillae share the structural, morphological, and molecular features observed in rodents. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fatty acid composition of the postmortem corpus callosum of patients with schizophrenia, bipolar disorder, or major depressive disorder.

PubMed

Hamazaki, K; Maekawa, M; Toyota, T; Dean, B; Hamazaki, T; Yoshikawa, T

2017-01-01

Studies investigating the relationship between n-3 polyunsaturated fatty acid (PUFA) levels and psychiatric disorders have thus far focused mainly on analyzing gray matter, rather than white matter, in the postmortem brain. In this study, we investigated whether PUFA levels showed abnormalities in the corpus callosum, the largest area of white matter, in the postmortem brain tissue of patients with schizophrenia, bipolar disorder, or major depressive disorder. Fatty acids in the phospholipids of the postmortem corpus callosum were evaluated by thin-layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to some previous studies, no significant differences were found in the levels of PUFAs or other fatty acids in the corpus callosum between patients and controls. A subanalysis by sex gave the same results. No significant differences were found in any PUFAs between suicide completers and non-suicide cases regardless of psychiatric disorder diagnosis. Patients with psychiatric disorders did not exhibit n-3 PUFAs deficits in the postmortem corpus callosum relative to the unaffected controls, and the corpus callosum might not be involved in abnormalities of PUFA metabolism. This area of research is still at an early stage and requires further investigation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[The foreign experience with the application of the modern radiodiagnostic methods for the estimation of prescription of death coming and time of infliction of injury].

PubMed

Fetisov, V A; Kuprina, T A; Sinitsyn, V E; Dubrova, S E; Filimonov, B A

2016-01-01

We undertook the analysis of the foreign publications concerning the application of the modern radiodiagnostic methods (including MSCT- and MRI-visualization) with reference to the solution of the traditional problems facing forensic medical expertise, such as the estimation of prescription of death coming and time of infliction of injury in the dead bodies. Both advantages and disadvantages of postmortem visualization of the corpses of adult subjects are discussed taking into consideration the period of time that elapsed between the death and the onset of the study as well as the character of the injuries. It was shown that the examination of the corpses using the up-to-date methods of radiodiagnostics prior to autopsy makes it possible for morphologists, jointly with radiologists, to identify, to see in the new light, and to evaluate the number of charges in the dead body, such as the alteration of the blood cell sedimentation rate, the formation of postmortem hypostases in the internal organs, the hardening of the walls of aorta and major blood vessels, right heart dilatation, gradual smoothing of the borderline between grey and white matter of the brain. Virtual autopsy can be useful , even for the study of such long-term processes in the corpses as putrefaction, saponification, mummification, and peat tanning. Moreover, this technique may be instrumental in the elucidation of the specific features of topographic-anatomical relationships between individual 'tissues and organs, detection of the concealed lesions, and a variety of pathological changes. Postmortem visualization allows for the quantitative evaluation of the severity of these transformations and the preliminary estimation of prescription of death coming. Also, radiodiagnostic methods can be employed to reliably visualize and measure various hemorrhagic events (from the density of such ones as liquid and clotted blood) in the tissues surrounding the fractures, in body cavities, and internal organs as well as to establish the facts of inter-vital aspiration of blood, alimentary masses, liquid and solid foreign bodies penetrating into the upper sections of the respiratory and gastrointestinal tracts as the consequence f an injury. It is concluded that the postmortem visualization techniques employed to estimate prescription of death coming and time of infliction of injury as well as other complicated problems facing forensic medical expertize need the further scientifically based development.

The role of histopathology in forensic practice: an overview.

PubMed

Dettmeyer, R B

2014-09-01

The role of forensic histopathology in routine practice is to establish the cause of death in particular cases. This is achieved on the basis of microscopic analysis of representative cell and tissue samples taken from the major internal organs and from abnormal findings made at autopsy. A prerequisite of this is adherence to the quality standards set out for conventional histological/cytological staining and enzyme histochemical and immunohistochemical methods. The interpretation of histological findings is performed by taking into account macroscopic autopsy findings and information on previous history. Histological analysis may prompt postmortem biochemical and chemical-toxicological investigations. The results of histological analysis need to be classified by experts in the context of the available information and the need to withstand the scrutiny of other experts.

Metabolic half-life of somatostatin and peptidase activities are altered in Alzheimer's disease.

PubMed

Weber, S J; Louis, R B; Trombley, L; Bissette, G; Davies, P; Davis, T P

1992-01-01

Several reports have described decreased immunoreactive somatostatin levels in specific regions of post-mortem brain tissue from patients diagnosed with senile dementia of the Alzheimer type (SDAT). In an attempt to determine if the metabolism of somatostatin is also altered as a result of SDAT, we examined the regional metabolic half-life of somatostatin-28 (SS-28) and somatostatin-14 (SS-14). The activity of the following peptidases was also determined: neutral endopeptidase E.C. 3.4.24.11; metalloendopeptidase E.C. 3.4.24.15; carboxypeptidase E (E.C. 3.4.17.10); and trypsin-like serine protease. The metabolic half-life of SS-28 was significantly reduced in post-mortem Brodmann Area 22 of SDAT tissue. This decrease in SS-28 metabolic half-life was correlated with a significant increase in trypsin-like serine protease activity in the same SDAT brain region. The formation rate of SS-14 from SS-28 incubated with Brodmann Area 22 homogenates was also increased in SDAT tissues as compared to controls. A regional variation in neutral endopeptidase E.C. 3.4.24.11 was also noted in both controls and SDAT samples. Although postmortem intervals of samples varied significantly, no effect was seen on any biochemical parameter measured. Results from this study provide evidence that a correlation can be made between changes in metabolic half-life somatostatin and alterations in neuropeptidase activities due to SDAT. As these data show alterations in both proteolytic metabolism and peptidase activities, many other biologically active peptide substrates could also be affected in SDAT.

Dynamics of Necrophagous Insect and Tissue Bacteria for Postmortem Interval Estimation During the Warm Season in Romania.

PubMed

Iancu, Lavinia; Sahlean, Tiberiu; Purcarea, Cristina

2016-01-01

The estimation of postmortem interval (PMI) is affected by several factors including the cause of death, the place where the body lay after death, and the weather conditions during decomposition. Given the climatic differences among biogeographic locations, the understanding of necrophagous insect species biology and ecology is required when estimating PMI. The current experimental model was developed in Romania during the warm season in an outdoor location. The aim of the study was to identify the necrophagous insect species diversity and dynamics, and to detect the bacterial species present during decomposition in order to determine if their presence or incidence timing could be useful to estimate PMI. The decomposition process of domestic swine carcasses was monitored throughout a 14-wk period (10 July-10 October 2013), along with a daily record of meteorological parameters. The chronological succession of necrophagous entomofauna comprised nine Diptera species, with the dominant presence of Chrysomya albiceps (Wiedemann 1819) (Calliphoridae), while only two Coleoptera species were identified, Dermestes undulatus (L. 1758) and Creophilus maxillosus Brahm 1970. The bacterial diversity and dynamics from the mouth and rectum tissues, and third-instar dipteran larvae were identified using denaturing gradient gel electrophoresis analysis and sequencing of bacterial 16S rRNA gene fragments. Throughout the decomposition process, two main bacterial chronological groups were differentiated, represented by Firmicutes and Gammaproteobacteria. Twenty-six taxa from the rectal cavity and 22 from the mouth cavity were identified, with the dominant phylum in both these cavities corresponding to Firmicutes. The present data strengthen the postmortem entomological and microbial information for the warm season in this temperate-continental area, as well as the role of microbes in carcass decomposition. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

STREPTOCOCCUS PHOCAE IN MARINE MAMMALS OF NORTHEASTERN PACIFIC AND ARCTIC CANADA: A RETROSPECTIVE ANALYSIS OF 85 POSTMORTEM INVESTIGATIONS.

PubMed

Taurisano, Nicole D; Butler, Brian P; Stone, Diana; Hariharan, Harry; Fields, Paul J; Ferguson, Hugh W; Haulena, Martin; Cotrell, Paul; Nielsen, Ole; Raverty, Stephen

2018-01-01

:  Streptococcus phocae is a pathogen of marine mammals, although its pathogenicity remains poorly understood. Recovery of this bacterium from asymptomatic carriers suggests that it is an opportunistic pathogen. We investigated the role of S. phocae in naturally occurring disease and its significance as a pathogen based on postmortem investigations. Between 2007 and 2012, 1,696 whole carcasses, tissue samples, or both were submitted from the northeastern Pacific and Arctic Canada for diagnostic testing. Streptococcus phocae was cultured from phocids ( n=66), otariids ( n=12), harbor porpoises ( Phocoena phocoena; n=5), and sea otters ( Enhydra lutris; n=2). Pathologic manifestations of S. phocae-associated disease included localized, as well as systemic, inflammatory lesions with common findings of suppurative bronchopneumonia ( n=17) and bacteremia ( n=27). Lung lesions were frequently culture-positive for S. phocae, suggesting commensal colonization of the oropharynx with subsequent opportunistic infection of the respiratory tract during tissue injury, coinfection, immunosuppression, or other debilitating conditions. The presence of a positive spleen culture, and interpretations at necropsy and histopathology, were used to determine the presence of S. phocae bacteremia. Less frequent lesions that were culture positive for S. phocae included abscesses ( n=9), meningitis ( n=7), and cellulitis ( n=1). The majority of cases with S. phocae lesions featured pre-existing conditions that presumably contributed to some degree of debilitation or immunosuppression, including emaciation ( n=29), liver mercury accumulation ( n=29), trauma ( n=22), severe pulmonary or cardiovascular nematodiasis ( n=9), concurrent bacterial or viral infections ( n=8), or sarcocystosis ( n=6). These findings suggest that S. phocae could be characterized as an opportunistic pathogen, associated with debilitating conditions in stranded and rehabilitating marine mammals. Wildlife investigators can use these results to draw more definitive conclusions regarding positive S. phocae cultures during postmortem studies in marine mammals.

Genetic analysis of sudden cardiac death victims: a survey of current forensic autopsy practices.

PubMed

Michaud, Katarzyna; Mangin, Patrice; Elger, Bernice S

2011-05-01

Autopsy-negative sudden cardiac deaths (SCD) seen in forensic practice are most often thought to be the result of sudden arrhythmic death syndrome. Postmortem genetic analysis is recommended in such cases, but is currently performed in only a few academic centers. In order to determine actual current practice, an on-line questionnaire was sent by e-mail to members of various forensic medical associations. The questions addressed routine procedures employed in cases of sudden cardiac death (autopsy ordering, macroscopic and microscopic cardiac examination, conduction tissue examination, immunohistochemistry and electron microscopy, biochemical markers, sampling and storage of material for genetic analyses, toxicological analyses, and molecular autopsy). Some questions concerned the legal and ethical aspects of genetic analyses in postmortem examinations, as well as any existing multidisciplinary collaborations in SCD cases. There were 97 respondents, mostly from European countries. Genetic testing in cases of sudden cardiac death is rarely practiced in routine forensic investigation. Approximately 60% of respondents reported not having the means to perform genetic postmortem testing and 40% do not collect adequate material to perform these investigations at a later date, despite working at university hospitals. The survey demonstrated that many of the problems involved in the adequate investigation of SCD cases are often financial in origin, due to the fact that activities in forensic medicine are often paid by and dependent on the judicial authorities. Problems also exist concerning the contact with family members and/or the family doctor, as well as the often-nonexistent collaboration with others clinicians with special expertise beneficial in the investigation of SCD cases, such as cardiologists and geneticists. This study highlights the importance in establishing guidelines for molecular autopsies in forensic medicine.

Fatal overdose of 2,4-dichlorophenoxyacetic acid (2,4-D).

PubMed

Keller, T; Skopp, G; Wu, M; Aderjan, R

1994-03-01

An ingestion of an unknown quantity of U 46 D-Fluid (500 g dichlorophenoxyacetic acid/l) in a suicide is described. Although 2,4-dichlorophenoxyacetic acid (2,4 D) is widely used as a herbicide, intoxications are relatively rare. Quantitation of 2,4-D was performed by diethyl ether extraction from acidified samples (viscera) or by deproteinization (blood, plasma) with methanol before HPLC analysis. Postmortem concentrations of 2,4-D in body fluids and tissues are given. The proposed method resulted in a rapid procedure most useful in cases of deliberate poisoning with phenoxyacetic herbicides.

Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora's box.

PubMed

Atkinson, Mark A

2014-04-01

Over a century ago, inquisitive physicians made remarkable discoveries regarding pancreatic pathology in individuals with diabetes, including those who were likely afflicted with the type 1 (autoimmune) form of the disease. Those studies of post-mortem tissues noted unique anatomical changes in islet architecture as well as the presence of unusual cellular infiltrates. In the time since, investigations of pancreatic pathology have, with near uniformity, been restricted to analysis of organs obtained post-mortem. While clearly beneficial for addressing questions of the disorder's pathogenesis, concern exists regarding potential artefacts that might occur through analysis of tissues that have been recovered hours, often many hours, following death. Beyond this, studies of tissues obtained long after the diagnosis of type 1 diabetes may not disclose important physiological events occurring at onset or even earlier in the natural history of disease, before symptomatic hyperglycaemia. To this end, Krogvold and colleagues (in this issue of Diabetologia, doi: 10.1007/s00125-013-3155-y) undertook a potentially high-reward strategy involving pancreatic biopsy in living adults with recent-onset type 1 diabetes. Procedures were performed under informed consent, undertaken based on recent improvements in laparoscopic techniques, and carried out by individuals with considerable surgical experience. These efforts were terminated for ethical reasons following the occurrence of serious complications (including post-operative bleeding and pancreatic leakage). The experience lends itself to analogy with the Greek myth of Pandora's box where curiosity, in terms of a desire to see what resided inside a closed container, unleashed a series of ills on humans once the container was opened. In considering the moral of that myth, one must question whether the secrets of the pancreas in those living with type 1 diabetes should, for now, remain a mystery as the process of manipulating that organ for the purpose of curiosity does not occur without harm.

Laser balloon angioplasty: effect of tissue temperature on weld strength of human postmortem intima-media separations.

PubMed

Jenkins, R D; Sinclair, I N; Anand, R; Kalil, A G; Schoen, F J; Spears, J R

1988-01-01

Dehiscence of portions of atheromatous plaques fractured during percutaneous transluminal coronary angioplasty may contribute to both abrupt reclosure and gradual restenosis. Laser balloon angioplasty has been shown to be effective in welding human plaque-arterial wall separations in vitro by heating tissues with a Nd:YAG laser during balloon inflation. To define the potentially useful therapeutic range of tissue temperature required to achieve thermal welds, 220 1-cm diameter discs of human postmortem atheromatous aortic tissue, the intimal plaque of which had been separated from the media, were exposed to 3-25 watts of Nd:YAG laser radiation delivered over a 12-mm2 nominal spot size for 20 seconds via a 400-micron core optical fiber. As measured with a thermistor, adventitial temperature reflected the temperature at the plaque-media junction to within 10 degrees C. The degree of tissue temperature elevation was related to delivered energy, while effective tissue penetration increased to maximum depth of 3 mm at the highest power density. Strength of tissue welds was defined as the force required to shear opposing layers of welded segments. Adventitial tissue temperatures below 80 degrees C were not associated with appreciable welds, while equilibrium temperatures between 95 degrees C and 140 degrees C were consistently associated with effective mean weld strengths, which increased linearly from 25 to 110 g, respectively. Temperatures greater than 150 degrees C were associated with rapid tissue dehydration and charring. These data suggest that the therapeutic range of tissue temperature that provides effective thermal fusion of intima-media separations is broad and that the depth and degree of thermal coagulation can be controlled by manipulation of laser energy delivery.

[Post-mortem microbiology analysis].

PubMed

Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

2013-12-01

Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. Crown Copyright © 2012. Published by Elsevier Espana. All rights reserved.

Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping.

PubMed

Nishiyama, Yuichi; Kanayama, Hidekazu; Mori, Hiroshi; Tada, Keiji; Yamamoto, Yasushi; Katsube, Takashi; Takeshita, Haruo; Kawakami, Kazunori; Kitagaki, Hajime

2017-06-01

This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. • The original brain CT template achieved successful normalization of brain morphology. • Postmortem changes in the brain were independent of sex. • Cortical GM density decreased rapidly after death. • WM and deep GM densities increased following cortical GM density change. • SPM could be useful for assessment of whole brain postmortem changes.

Postmortem memantine concentration in a non-intoxication case, and the possibility of postmortem redistribution: A case report.

PubMed

Nagasawa, Sayaka; Yajima, Daisuke; Torimitsu, Suguru; Chiba, Fumiko; Iwase, Hirotaro

2015-12-01

In this case study, we measured the concentration of memantine in the heart blood, peripheral blood, urine, liver, thigh muscle, and subcutaneous fat of a 64-year-old woman who was prescribed memantine for early-onset Alzheimer's disease. She died in hospital after an altercation with her husband. Cause of death was clearly not drug intoxication or overdose, so we investigated the postmortem redistribution (PMR) of memantine in the various tissues and blood ratios of the postmortem samples. Memantine concentrations detected were 1.31 μg/mL in the peripheral blood, 3.95 μg/mL in central blood, 2.09 μg/mL in the urine, 25.54 μg/g in the liver, 1.16 μg/g in the thigh muscle and 2.13 μg/g in the subcutaneous fat. In all samples, the concentrations were higher than the accepted therapeutic range (which is approximately 0.09-0.15 μg/mL). The central blood to peripheral blood (C/P) memantine ratio was 3.01 while the liver to peripheral blood (L/P) ratio was 19.5. It is documented that a C/P ratio exceeding 2 and L/P ratio exceeding 20 highlight a propensity for significant PMR. Although this is a single case study, our data suggest that memantine exhibits PMR. Additionally, a lowered pH was found in peripheral blood (pH 6.2) and central blood (pH 6.1). This postmortem reduction in blood pH may also promote the PMR of memantine. Because there is very little available postmortem toxicological data on memantine, our case study will serve as a foundation to assist in future forensic investigations. Copyright © 2015. Published by Elsevier Ireland Ltd.

The neuropathological study of myelin oligodendrocyte glycoprotein in the temporal lobe of schizophrenia patients.

PubMed

Marui, Tomoyasu; Torii, Youta; Iritani, Shuji; Sekiguchi, Hirotaka; Habuchi, Chikako; Fujishiro, Hiroshige; Oshima, Kenichi; Niizato, Kazuhiro; Hayashida, Shotaro; Masaki, Katsuhisa; Kira, Junichi; Ozaki, Norio

2018-03-22

Recent studies based on the neuroimaging analysis, genomic analysis and transcriptome analysis of the postmortem brain suggest that the pathogenesis of schizophrenia is related to myelin-oligodendrocyte abnormalities. However, no serious neuropathological investigation of this protein in the schizophrenic brain has yet been performed. In this study, to confirm the change in neuropathological findings due to the pathogenesis of this disease, we observed the expression of myelin-oligodendrocyte directly in the brain tissue of schizophrenia patients. Myelin oligodendrocyte glycoprotein (MOG) was evaluated in the cortex of the superior temporal gyrus (STG) and the hippocampus in 10 schizophrenic and nine age- and sex-matched normal control postmortem brains. The expression of MOG was significantly lower in the middle layer of the neocortex of the STG and stratum lucidum of CA3 in the hippocampus in the long-term schizophrenic brains (patients with ≥30 years of illness duration) than in the age-matched controls. Furthermore, the thickness of MOG-positive fibre-like structures was significantly lower in both regions of the long-term schizophrenic brains than in the age-matched controls. These findings suggest that a long duration of illness has a marked effect on the expression of MOG in these regions, and that myelin-oligodendrocyte abnormalities in these regions may be related to the progressive pathophysiology of schizophrenia.

Transplacental toxoplasmosis in a wild southern sea otter (Enhydra lutris nereis).

PubMed

Miller, Melissa; Conrad, Patricia; James, E R; Packham, Andrea; Toy-Choutka, Sharon; Murray, Michael J; Jessup, David; Grigg, Michael

2008-05-06

In September 2004, a neonatal sea otter pup was found alive on the beach in northern Monterey Bay, CA. Efforts to locate the mother were unsuccessful. Due to a poor prognosis for successful rehabilitation, the pup was euthanized. Postmortem examination revealed emaciation, systemic lymphadenopathy and a malformation of the left cerebral temporal lobe. On histopathology, free tachyzoites and tissue cysts compatible with Toxoplasma gondii were observed in the brain, heart, thymus, liver, lymph nodes and peri-umbilical adipose. The presence of T. gondii within host tissues was associated with lymphoplasmacytic inflammation and tissue necrosis. Immunofluorescent antibody tests using postmortem serum were positive for anti-T. gondii IgM and IgG (at 1:320 and 1:1280 serum dilution, respectively), but were negative for IgG directed against Sarcocystis neurona and Neospora caninum (<1:40 each). Brain immunohistochemistry revealed positive staining for tachyzoites and tissue cysts using antiserum raised to T. gondii, but not S. neurona or N. caninum. T. gondii parasite DNA was obtained from extracts of brain and muscle by PCR amplification using the diagnostic B1 locus. Restriction enzyme digestion followed by gel electrophoresis and DNA sequencing confirmed the presence of Type X T. gondii, the strain identified in the majority of southern sea otter infections.

Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders.

PubMed

Edlow, Brian L; Takahashi, Emi; Wu, Ona; Benner, Thomas; Dai, Guangping; Bu, Lihong; Grant, Patricia Ellen; Greer, David M; Greenberg, Steven M; Kinney, Hannah C; Folkerth, Rebecca D

2012-06-01

The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions of the ARAS cause coma, the most severe disorder of consciousness. Because of current methodological limitations, including of postmortem tissue analysis, the neuroanatomic connectivity of the human ARAS is poorly understood. We applied the advanced imaging technique of high angular resolution diffusion imaging (HARDI) to elucidate the structural connectivity of the ARAS in 3 adult human brains, 2 of which were imaged postmortem. High angular resolution diffusion imaging tractography identified the ARAS connectivity previously described in animals and also revealed novel human pathways connecting the brainstem to the thalamus, the hypothalamus, and the basal forebrain. Each pathway contained different distributions of fiber tracts from known neurotransmitter-specific ARAS nuclei in the brainstem. The histologically guided tractography findings reported here provide initial evidence for human-specific pathways of the ARAS. The unique composition of neurotransmitter-specific fiber tracts within each ARAS pathway suggests structural specializations that subserve the different functional characteristics of human arousal. This ARAS connectivity analysis provides proof of principle that HARDI tractography may affect the study of human consciousness and its disorders, including in neuropathologic studies of patients dying in coma and the persistent vegetative state.

The medico-legal investigation of the El Aqsah Intifada.

PubMed

Hiss, Jehuda; Freund, Maya; Motro, Uzi; Kahana, Tzipi

2002-07-01

The majority (n = 445) of the Israeli and Palestinian fatal victims of the El Aqsah Intifada was examined at the National Center of Forensic Medicine in Tel Aviv. Analysis of the trauma sustained and the anthropologic profile of both the victims and the perpetrators elucidates the trends and contrasts them with the phenomenon in the past. The purpose of the forensic investigation of mass casualty incidents is manifold: establishing the minimal number of individuals involved, identifying the victims and perpetrators, collecting material evidence, and determining the modus operandi. The postmortem examination includes external description of the bodies and their injuries, photo-documentation, and sampling of tissues. Radiography, dental examination, and a ten-print card of each cadaver are also recorded. The modus operandi of the current Intifada is somewhat different from that of the previous wave of terrorism and includes more road shootings and vehicular terrorism. In addition, three suicide bombers who detonated explosive devices within crowded areas were young women, and the age of the perpetrators has increased from up to 35 years to individuals as old as 47, thus greatly enlarging the potential number of suicide terrorists. Virologic and biologic tests have been introduced to examine the tissues of the suicide bombers since they are possible sources of contagion to the wounded victims. The results of the medico-legal investigation of victims and perpetrators of terrorism enable us to establish the modus operandi and the profile of potential perpetrators, which can help in the prevention of similar attacks. Documentation of the different types of injuries in fatal victims of explosion and shooting contributes to improving the awareness of the medical staff treating the wounded of similar attacks. Further investigation into the reliability of virologic and biologic tests conducted on postmortem tissue is recommended.

Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

PubMed

Tylutki, Zofia; Polak, Sebastian

2015-03-12

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Improvements in Alzheimer's disease diagnosis using principle components analysis (PCA) in combination with Raman spectroscopy

NASA Astrophysics Data System (ADS)

Archer, John K. J.; Sudworth, Caroline D.; Williams, Rachel; How, Thien; Stone, Nicholas; Mann, David; Black, Richard A.

2007-07-01

The significant achievements of medical science over the last century are evident in the increasing age of the global population, however this now brings new problems, the most prominent being the growth in the number of people suffering from dementia. Over half the people with dementia in the UK are sufferers of Alzheimer's disease, a condition in which intraneuronal neurofibrillary tangles and extraneuronal senile tangles take over neurons prompting their death. A definitive diagnosis is still only currently available post-mortem, whilst current symptom based processes of elimination are far from perfect, especially when the only treatments available are symptom inhibiting drugs. Principal component analysis (PCA) of the Raman spectra taken from brain tissue has proved to be a potential tool in the diagnosis. However, this work now has to be refined in order to progress to tissue less associated with the symptoms of Alzheimer's disease. The first step of this has already been taken in progressing from frontal tissue to occipital tissue point spectra taken at random positions from bulk tissue. Now we present initial work into acquiring Raman spectral maps from across a tissue area, in pursuit of identifying unique plaque and tangle spectra. These spectra are presented alongside synthetic β-Amyloid spectra, in a study of the role that the peptide plays in the biomarker spectra, and how this information can aid the PCA of bulk tissue, and point towards a Raman spectroscopic test on less sensitive tissue, such as blood.

Attitudes Concerning Postmortem Organ Donation: A Multicenter Survey in Various German Cohorts.

PubMed

Uhlig, Constantin E; Böhringer, Daniel; Hirschfeld, Gerrit; Seitz, Berthold; Schmidt, Hartmut

2015-10-13

The aim of this study was to characterize postmortem organ donation attitudes in various German cohorts. Employees of 2 German cities and 2 German university hospitals, employees of a German automobile enterprise, and members of a German Medical Society were administered a questionnaire about postmortem organ and tissue donation attitudes. Demographic data and general attitudes were questioned and focused on: I) willingness to donate organs, II) holding a donor card, and III) having discussed the topic with the family. Of 5291 participants, 65.2% reported favoring postmortem organ donation. Missing negative experiences, the idea that donation is helpful, a non-medical professional environment, excellent general health, gender, agreement with the brain-death paradigm, and age significantly influenced the participants' attitudes. Participants were more likely to possess donor cards and had discussed more often with family members if they agreed with the brain-death paradigm and considered donation to be helpful. Males and older participants were the most likely to neglect donor cards, and Catholics, Protestants, and participants with poor health were the least likely to donate organs. Interest in receiving more information was expressed by 38.1% and 50.6% of participants refusing donation of all or of specific organs, respectively, and suggested the internet (60.0%) and family doctors (35.0%) as preferred sources of information. Public campaigns in Germany should focus on males and older people as regards donor cards, and females, younger, and religiously affiliated persons as regards the general willingness to donate organs postmortem.

Post-mortem clinical pharmacology

PubMed Central

Ferner, R E

2008-01-01

Clinical pharmacology assumes that deductions can be made about the concentrations of drugs from a knowledge of the pharmacokinetic parameters in an individual; and that the effects are related to the measured concentration. Post-mortem changes render the assumptions of clinical pharmacology largely invalid, and make the interpretation of concentrations measured in post-mortem samples difficult or impossible. Qualitative tests can show the presence of substances that were not present in life, and can fail to detect substances that led to death. Quantitative analysis is subject to error in itself, and because post-mortem concentrations vary in largely unpredictable ways with the site and time of sampling, as a result of the phenomenon of post-mortem redistribution. Consequently, compilations of ‘lethal concentrations’ are misleading. There is a lack of adequate studies of the true relationship between fatal events and the concentrations that can be measured subsequently, but without such studies, clinical pharmacologists and others should be wary of interpreting post-mortem measurements. PMID:18637886

The Importance of Brain Banks for Molecular Neuropathological Research: The New South Wales Tissue Resource Centre Experience

PubMed Central

Dedova, Irina; Harding, Antony; Sheedy, Donna; Garrick, Therese; Sundqvist, Nina; Hunt, Clare; Gillies, Juliette; Harper, Clive G.

2009-01-01

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders. PMID:19333451

[Value of specific 16S rDNA fragment of algae in diagnosis of drowning: an experiment with rabbits].

PubMed

Li, Peng; Xu, Qu-Yi; Chen, Ling; Liu, Chao; Zhao, Jian; Wang, Yu-Zhong; Yu, Zheng-Liang; Hu, Sun-Lin; Wang, Hui-Jun

2015-08-01

To establish a method for amplifying specific 16S rDNA fragment of algae related with drowning and test its value in drowning diagnosis. Thirty-five rabbits were randomly divided into 3 the drowning group (n=15), postmortem water immersion group (n=15, subjected to air embolism before seawater immersion), and control group(n=5, with air embolism only). Twenty samples of the liver tissues from human corpses found in water were also used, including 14 diatom-positive and 6 diatom-negative samples identified by microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM). Seven known species of algae served as the control algae (Melosira sp, Nitzschia sp, Synedra sp, Navicula sp, Microcystis sp, Cyclotella meneghiniana, and Chlorella sp). The total DNA was extracted from the tissues and algae to amplify the specific fragment of algae followed by 8% polyacrylamide gelelectrophoresis and sliver-staining. In the drowning group, algae was detected in the lungs (100%), liver (86%), and kidney (86%); algae was detected in the lungs in 2 rabbits in the postmortem group (13%) and none in the control group. The positivity rates of algae were significantly higher in the drowning group than in the postmortem group (P<0.05). Of the 20 tissue samples from human corps found in water, 15 were found positive for algae, including sample that had been identified as diatom-negative by MD-VF-Auto SEM. All the 7 control algae samples yielded positive results in PCR. The PCR-based method has a high sensitivity in algae detection for drowning diagnosis and allows simultaneous detection of multiple algae species related with drowning.

Examination of forensic entomology evidence using computed tomography scanning: case studies and refinement of techniques for estimating maggot mass volumes in bodies.

PubMed

Johnson, Aidan; Archer, Melanie; Leigh-Shaw, Lyndie; Pais, Mike; O'Donnell, Chris; Wallman, James

2012-09-01

A new technique has recently been developed for estimating the volume of maggot masses on deceased persons using post-mortem CT scans. This allows volume to be measured non-invasively and factored into maggot mass temperature calculations for both casework and research. Examination of admission scans also allows exploration of entomological evidence in anatomical areas not usually exposed by autopsy (e.g. nasal cavities and facial sinuses), and before autopsy disrupts the maggot distribution on a body. This paper expands on work already completed by providing the x-ray attenuation coefficient by way of Hounsfield unit (HU) values for various maggot species, maggot masses and human tissue adjacent to masses. Specifically, this study looked at the HU values for four forensically important blowfly larvae: Lucilia cuprina, L. sericata, Calliphora stygia and C. vicina. The Calliphora species had significantly lower HU values than the Lucilia species. This might be explained by histological analysis, which revealed a non-significant trend, suggesting that Calliphora maggots have a higher fat content than the Lucilia maggots. It is apparent that the variation in the x-ray attenuation coefficient usually precludes its use as a tool for delineating the maggot mass from human tissue and that morphology is the dominant method for delineating a mass. This paper also includes three case studies, which reveal different applications for interpreting entomological evidence using post-mortem CT scans.

Sudden aortic death-proposal for a comprehensive diagnostic approach in forensic and in clinical pathology practice.

PubMed

de Boer, Hans H; Dedouit, Fabrice; Chappex, Nina; van der Wal, Allard C; Michaud, Katarzyna

2017-11-01

Aortic rupture or dissection as immediate cause of sudden death is encountered in forensic and clinical autopsy practice. Despite a common denominator of 'sudden aortic death' (SAD), we expect that in both settings the diagnostic workup, being either primarily legal or primarily disease related, differs substantially, which may affect the eventual diagnoses. We retrospectively reviewed case records of deceased persons who fitted a diagnosis of SAD in the continuous autopsy cohorts in a forensic (Suisse) and a clinical setting (The Netherlands). Clinical characteristics, data from post-mortem imaging, tissue blocks for histological analysis and results of ancillary studies were reviewed for its presence and outcome. SAD was found in 7.7% in the forensic versus 2.2% in the clinical autopsies. In the forensic setting, autopsy was always combined with post-mortem imaging, showing variable outcome on detection of aortic disruption and/or pericardial bleeding. Histology of aorta was performed in 12/35 cases, mostly in the natural deaths. In the clinical setting, histology of the aorta was available in all cases, but post-mortem imaging in none. In both settings, underlying aortic disease was mostly cystic medial degeneration, atherosclerosis or a combination of both, with occasional rare unexpected diagnosis. Also in both, a genetic cause of aortic dissection was revealed in a minority (three cases). Sudden aortic death (SAD) is more commonly encountered in a forensic than in a clinical setting. Major differences in the approach of SAD between these settings coincide with similarities in causes of death and underlying diseases. To ensure a correct diagnosis, we recommend that the investigation of SAD includes a study of the medical history, a full autopsy with histology of major organs including aorta, and storage of material for toxicological and genetic testing. Post-mortem radiological examination, useful for documentation and screening purposes, is feasible as non-invasive alternative when autopsy is not possible, but cannot substitute a full autopsy.

A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

PubMed Central

Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

2012-01-01

Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies. PMID:23065787

A pilot to examine the logistical and feasibility issues in testing deceased tissue donors for vCJD using tonsil as the analyte.

PubMed

Warwick, Ruth M; Armitage, W John; Chandrasekar, Akila; Mallinson, Gary; Poniatowski, Stefan; Clarkson, Anthony

2012-03-01

Transplanted tissues have transmitted transmissible spongiform encephalopathies and in the UK there have been more cases of variant Creutzfeldt-Jakob disease (vCJD) than elsewhere in the world. A pilot study was undertaken to look at the feasibility of testing for vCJD in deceased donors using tonsillar tissue. This pilot showed that obtaining consent for removal and testing tonsil tissue was feasible. Donor eligibility for inclusion in the pilot was limited to tissue donors from the National Health Service Blood and Transplant, Tissue Services and to donors shared with the Corneal Transplant Service Eye Banks. Obtaining tonsillar tissue in the immediate post-mortem period was limited by the presence of rigor mortis. Tonsillar tissue was suitable for routine analysis for the presence of prion associated with vCJD in deceased tissue donors. Production and processing of tissue was straightforward and a low assay background was obtained from most samples. Since palatine and lingual tonsil tissue can be obtained in pairs it was possible, in the majority of cases, to set aside an intact sample for confirmatory testing if required. In one instance a sample was reactive by Western blot. However, the pattern of reactivity was not typical for that obtained from vCJD patients. Unfortunately the sample was not of sufficient quality for the confirmatory test to provide a conclusive result.

Perinatal Mortality Associated with Positive Postmortem Cultures for Common Oral Flora.

PubMed

He, Mai; Migliori, Alison R; Lauro, Patricia; Sung, C James; Pinar, Halit

2017-01-01

Introduction . To investigate whether maternal oral flora might be involved in intrauterine infection and subsequent stillbirth or neonatal death and could therefore be detected in fetal and neonatal postmortem bacterial cultures. Methods . This retrospective study of postmortem examinations from 1/1/2000 to 12/31/2010 was searched for bacterial cultures positive for common oral flora from heart blood or lung tissue. Maternal age, gestational age, age at neonatal death, and placental and fetal/neonatal histopathological findings were collected. Results . During the study period 1197 postmortem examinations (861 stillbirths and 336 neonatal deaths) were performed in our hospital with gestational ages ranging from 13 to 40+ weeks. Cultures positive for oral flora were identified in 24 autopsies including 20 pure and 8 mixed growths (26/227, 11.5%), found in 16 stillbirths and 8 neonates. Microscopic examinations of these 16 stillbirths revealed 8 with features of infection and inflammation in fetus and placenta. The 7 neonatal deaths within 72 hours after birth grew 6 pure isolates and 1 mixed, and 6 correlated with fetal and placental inflammation. Conclusions . Pure isolates of oral flora with histological evidence of inflammation/infection in the placenta and fetus or infant suggest a strong association between maternal periodontal conditions and perinatal death.

Feasibility, diagnostic validity and limits of postmortem evaluation of a newborn infant following an extremely prolonged freezing interval: a thanatological case study.

PubMed

Krajčovič, Jozef; Janík, Martin; Novomeský, František; Straka, Lubomír; Hejna, Petr

2014-11-01

In forensic assessment, denial and concealment of pregnancy has wide-ranging implications including criminal abortions, extramural deliveries, concealment of birth, newborn infant abandonment or even neonaticide. Clarification of whether a newborn was born alive is the most important factor when evaluating an abandoned neonate or concealment of birth. Other points that need to be addressed are determination of viability and maturity of the newborn infant, and the identity of the mother. A prolonged postmortem interval following illegal disposal of a dead body often leads to advanced decomposition, making postmortem elucidation difficult. We report an exceptionally uncommon autopsy case of a well-preserved female newborn, which was accidentally found after eight years in a home freezer. Despite the prolonged postmortem interval, tissue preservation was sufficient for a meaningful autopsy including a comprehensive histopathological study. The purpose of the present investigations was to expand our understanding of thanatological processes, as well as detectability of particular histological findings on the remains of a newborn after extremely prolonged storage in an artificially frozen environment. In addition, this article discusses forensically important issues regarding concealment of newborn infant under specific conditions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Statistical and fractal analysis of autofluorescent myocardium images in posthumous diagnostics of acute coronary insufficiency

NASA Astrophysics Data System (ADS)

Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Garazdiuk, M.; Motrich, A. V.

2014-08-01

This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

Pork Quality Traits According to Postmortem pH and Temperature in Berkshire

PubMed Central

Kim, Tae Wan; Kim, Chul Wook; Yang, Mi Ra; No, Gun Ryoung; Kim, Il-Suk

2016-01-01

This study was performed to investigate the role of pH and temperature postmortem, and to demonstrate the importance of these factors in determining meat quality. Postmortem pH45min (pH at 45 min postmortem or initial pH) via analysis of Pearson’s correlation showed high positive correlation with pH change pHc24 (pH change from pH45min to pH24h postmortem). However, postmortem pH after 24 h (pH24h or ultimate pH) had a high negative correlation with pH change, pHc24, CIE L*, and protein content. Initial temperature postmortem (T1h ) was positively associated with a change in temperature from 45 min to 24 h postmortem (Tc24) and cooking loss, but negatively correlated with water holding capacity. Temperature at 24 h postmortem (T24h) was negatively associated with Tc24. Collectively, these results indicate that higher initial pH was associated with higher pHc24, T1h, and Tc24. However, higher initial pH was associated with a reduction in carcass weight, backfat thickness, CIE a* and b*, water holding capacity, collagen and fat content, drip loss, and cooking loss as well as decreased shear force. In contrast, CIE a* and b*, drip loss, cooking loss, and shear force in higher ultimate pH was showed by a similar pattern to higher initial pH, whereas pHc24, carcass weight, backfat thickness, water holding capacity, fat content, moisture content, protein content, T1h, T24h, and Tc24 were exhibited by completely differential patterns (p<0.05). Therefore, we suggest that initial pH, ultimate pH, and temperatures postmortem are important factors in determining the meat quality of pork. PMID:27499661

Modeling ancient Egyptian mummification on fresh human tissue: macroscopic and histological aspects.

PubMed

Papageorgopoulou, Christina; Shved, Natallia; Wanek, Johann; Rühli, Frank J

2015-06-01

Many studies have been concerned with the ancient Egyptian mummification method; nevertheless, little effort has been made to explore it experimentally. The goal of this study is to apply evidence-based diagnostic criteria and state-of-the art methodology in order to improve knowledge on soft tissues preservation and postmortem alterations. Two human lower limbs (LL) from a female donor were (1) "naturally" mummified by dry heat and (2) artificially in natron. At specific time intervals a macroscopic and radiological examination of the LL was performed and skin and muscle samples were taken for histological and biomolecular analysis. Temperature, humidity, pH, and weight of the LL were systematically measured. The mummification by dry heat was stopped after 7 days due to unexpected lack of mummification progress. The mummification in natron was completed successfully after 208 days. The humidity, the external temperature, and the pH were proven with Pearson correlation and principal component analysis as important factors for the mummification process. The steady removal of water from the tissues through the natron has prevented the putrefaction. This is also evident in the absence of bacteria or fungi through the microbiological analysis. The histological analysis revealed very good preservation of the skin and the muscle tissues. In the muscular sample certain degree of structural disintegration can be seen, particularly affecting the epimysium whilst in the skin samples the epidermis, especially the stratum corneum, is mostly affected. The samples show better preservation compared with ancient Egyptian sections and other mummified tissues from historic or forensic context. © 2015 Wiley Periodicals, Inc.

Anatomical Distribution of Lipids in Human Brain Cortex by Imaging Mass Spectrometry

NASA Astrophysics Data System (ADS)

Veloso, Antonio; Astigarraga, Egoitz; Barreda-Gómez, Gabriel; Manuel, Iván; Ferrer, Isidro; Teresa Giralt, María; Ochoa, Begoña; Fresnedo, Olatz; Rodríguez-Puertas, Rafael; Fernández, José A.

2011-02-01

Molecular mass images of tissues will be biased if differences in the physicochemical properties of the microenvironment affect the intensity of the spectra. To address this issue, we have performed—by means of MALDI-TOF mass spectrometry—imaging on slices and lipidomic analysis in extracts of frontal cortex, both from the same postmortem tissue samples of human brain. An external calibration was used to achieve a mass accuracy of 10 ppm (1 σ) in the spectra of the extracts, although the final assignment was based on a comparison with previously reported species. The spectra recorded directly from tissue slices (imaging) show excellent s/n ratios, almost comparable to those obtained from the extracts. In addition, they retain the information about the anatomical distribution of the molecular species present in autopsied frozen tissue. Further comparison between the spectra from lipid extracts devoid of proteins and those recorded directly from the tissue unambiguously show that the differences in lipid composition between gray and white matter observed in the mass images are not an artifact due to microenvironmental influences of each anatomical area on the signal intensity, but real variations in the lipid composition.

Amyloid associated with elastin-staining laminar aggregates in the lungs of patients diagnosed with acute respiratory distress syndrome

PubMed Central

Fan, Kang; Nagle, William A

2002-01-01

Background The heterogeneity of conditions underlying respiratory distress, whether classified clinically as acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS), has hampered efforts to identify and more successfully treat these patients. Examination of postmortem lungs among cases clinically diagnosed as ARDS identified a cohort that showed a consistent morphology at the light and electron microscope levels, and featured pathognomonic structures which we termed elastin-staining laminar structures (ELS). Methods Postmortem tissues were stained using the Verhoeff-Van Gieson procedure for elastic fibers, and with Congo red for examination under a polarizing microscope. Similar samples were examined by transmission EM. Results The pathognomonic ELS presented as ordered molecular aggregates when stained using the Verhoeff-van Gieson technique for elastic fibers. In several postmortem lungs, the ELS also displayed apple-green birefringence after staining with Congo red, suggesting the presence of amyloid. Remarkably, most of the postmortem lungs with ELS exhibited no significant acute inflammatory cellular response such as neutrophilic reaction, and little evidence of widespread edema except for focal intra-alveolar hemorrhage. Conclusions Postmortem lungs that exhibit the ELS constitute a morphologically-identifiable subgroup of ARDS cases. The ordered nature of the ELS, as indicated by both elastin and amyloid stains, together with little morphological evidence of inflammation or edema, suggests that this cohort of ARDS may represent another form of conformational disease. If this hypothesis is confirmed, it will require a new approach in the diagnosis and treatment of patients who exhibit this form of acute lung injury. PMID:12377106

Relationship between water-holding capacity and protein denaturation in broiler breast meat.

PubMed

Bowker, B; Zhuang, H

2015-07-01

The objective of this study was to determine the relationship between water-holding capacity (WHC) attributes and protein denaturation in broiler breast meat. Boneless skinless breast fillets (n = 72) were collected from a commercial processing plant at 2 h postmortem and segregated into low-WHC and high-WHC groups based on muscle pH and color (L*a*b*). At 6 and 24 h postmortem, brine uptake (%), cooking loss (%), and protein solubility (sarcoplasmic and myofibrillar) were measured and protein fractions were analyzed using SDS-PAGE. Drip loss accumulation (%) was measured after storage for 2 and 7 days postmortem. High-WHC fillets exhibited lower L*-lightness values and greater pH values at 2 and 24 h postmortem than low-WHC fillets. High-WHC fillets had greater brine uptake and less cooking loss at both 6 and 24 h postmortem compared to low-WHC fillets. Aging from 6 to 24 h postmortem increased brine uptake in high-WHC fillets, but did not affect cooking loss in either low-WHC or high-WHC fillets. Drip loss accumulation was greater in low-WHC fillets at both 2 and 7 days postmortem. Myofibrillar protein solubility decreased with postmortem time but was not different between low-WHC and high-WHC fillets. Sarcoplasmic protein solubility increased with postmortem time and was greater in high-WHC fillets. SDS-PAGE analysis indicated that low-WHC fillets exhibited more glycogen phosphorylase denaturation than high-WHC fillets as evidenced by a more extensive shift of the protein from the sarcoplasmic to the myofibrillar protein fraction. Correlation analysis revealed that overall protein solubility measurements were not related to WHC attributes but that the degree of glycogen phosphorylase denaturation was significantly correlated (|r| = 0.52 to 0.80) to measures of WHC. Data indicated that WHC differences in broiler breast fillets were not due to differences in myofibrillar protein denaturation and suggested that the denaturation of sarcoplasmic proteins onto myofibrils may influence WHC in breast meat. © 2015 Poultry Science Association Inc.

[Gunshot wounds caused by non-lethal ammunition on the porcine model post-mortem].

PubMed

Jabrocký, Peter; Pivko, Juraj; Vondráková, Mária; Tažký, Boris

2013-10-01

In this article we focus on the effects of so called non-lethal ammunition. We studied possible mechanism of firearm injury formation as a consequence of using firearm on the body, to present a more comprehensive material in wound ballistics. We pointed out possible actions of a projectile causes on human, respectively other animal organisms, as well as to a manner in which an injury is caused by rifles or shotguns using non-lethal ammunition with rubber projectiles. In the experiment, we have focused on macroscopic analysis of the tissue penetrated by a rubber projectile fired from a long firearm and pump-action shotgun while focusing on the anatomical-morphological analysis of entry wounds to determine the effectiveness respectively, the wounding potential of the projectile. The results of the experiment based on the macroscopic analysis of entry wounds, cavities and exit wounds, show that when a rubber projectile penetrates the body it causes loss of the tissue (i.e. the minus effect) and mechanical disruption of the tissue similar to lethal projectile. Based on the measures and ballistic computations we concluded that in specific cases, like for example in a close range hit, a penetration of vital organs can cause serious or even lethal injuries.

In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder.

PubMed

Andrews, Derek Sayre; Avino, Thomas A; Gudbrandsen, Maria; Daly, Eileen; Marquand, Andre; Murphy, Clodagh M; Lai, Meng-Chuan; Lombardo, Michael V; Ruigrok, Amber N V; Williams, Steven C; Bullmore, Edward T; The Mrc Aims Consortium; Suckling, John; Baron-Cohen, Simon; Craig, Michael C; Murphy, Declan G M; Ecker, Christine

2017-02-01

Atypical cortical organization and reduced integrity of the gray-white matter boundary have been reported by postmortem studies in individuals with autism spectrum disorder (ASD). However, there are no in vivo studies that examine these particular features of cortical organization in ASD. Hence, we used structural magnetic resonance imaging to examine differences in tissue contrast between gray and white matter in 98 adults with ASD and 98 typically developing controls, to test the hypothesis that individuals with ASD have significantly reduced tissue contrast. More specifically, we examined contrast as a percentage between gray and white matter tissue signal intensities (GWPC) sampled at the gray-white matter boundary, and across different cortical layers. We found that individuals with ASD had significantly reduced GWPC in several clusters throughout the cortex (cluster, P < 0.05). As expected, these reductions were greatest when tissue intensities were sampled close to gray-white matter interface, which indicates a less distinct gray-white matter boundary in ASD. Our in vivo findings of reduced GWPC in ASD are therefore consistent with prior postmortem findings of a less well-defined gray-white matter boundary in ASD. Taken together, these results indicate that GWPC might be utilized as an in vivo proxy measure of atypical cortical microstructural organization in future studies. © The Author 2017. Published by Oxford University Press.

Histology-derived volumetric annotation of the human hippocampal subfields in postmortem MRI.

PubMed

Adler, Daniel H; Pluta, John; Kadivar, Salmon; Craige, Caryne; Gee, James C; Avants, Brian B; Yushkevich, Paul A

2014-01-01

Recently, there has been a growing effort to analyze the morphometry of hippocampal subfields using both in vivo and postmortem magnetic resonance imaging (MRI). However, given that boundaries between subregions of the hippocampal formation (HF) are conventionally defined on the basis of microscopic features that often lack discernible signature in MRI, subfield delineation in MRI literature has largely relied on heuristic geometric rules, the validity of which with respect to the underlying anatomy is largely unknown. The development and evaluation of such rules are challenged by the limited availability of data linking MRI appearance to microscopic hippocampal anatomy, particularly in three dimensions (3D). The present paper, for the first time, demonstrates the feasibility of labeling hippocampal subfields in a high resolution volumetric MRI dataset based directly on microscopic features extracted from histology. It uses a combination of computational techniques and manual post-processing to map subfield boundaries from a stack of histology images (obtained with 200μm spacing and 5μm slice thickness; stained using the Kluver-Barrera method) onto a postmortem 9.4Tesla MRI scan of the intact, whole hippocampal formation acquired with 160μm isotropic resolution. The histology reconstruction procedure consists of sequential application of a graph-theoretic slice stacking algorithm that mitigates the effects of distorted slices, followed by iterative affine and diffeomorphic co-registration to postmortem MRI scans of approximately 1cm-thick tissue sub-blocks acquired with 200μm isotropic resolution. These 1cm blocks are subsequently co-registered to the MRI of the whole HF. Reconstruction accuracy is evaluated as the average displacement error between boundaries manually delineated in both the histology and MRI following the sequential stages of reconstruction. The methods presented and evaluated in this single-subject study can potentially be applied to multiple hippocampal tissue samples in order to construct a histologically informed MRI atlas of the hippocampal formation. © 2013 Elsevier Inc. All rights reserved.

Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology

PubMed Central

Catarino, Claudia B.; Liu, Joan Y.W.; Liagkouras, Ioannis; Gibbons, Vaneesha S.; Labrum, Robyn W.; Ellis, Rachael; Woodward, Cathy; Davis, Mary B.; Smith, Shelagh J.; Cross, J. Helen; Appleton, Richard E.; Yendle, Simone C.; McMahon, Jacinta M.; Bellows, Susannah T.; Jacques, Thomas S.; Zuberi, Sameer M.; Koepp, Matthias J.; Martinian, Lillian; Scheffer, Ingrid E.; Thom, Maria

2011-01-01

Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20–66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy. PMID:21719429

Rocky Mountain spotted fever, Panama.

PubMed

Estripeaut, Dora; Aramburú, María Gabriela; Sáez-Llorens, Xavier; Thompson, Herbert A; Dasch, Gregory A; Paddock, Christopher D; Zaki, Sherif; Eremeeva, Marina E

2007-11-01

We describe a fatal pediatric case of Rocky Mountain spotted fever in Panama, the first, to our knowledge, since the 1950s. Diagnosis was established by immunohistochemistry, PCR, and isolation of Rickettsia rickettsii from postmortem tissues. Molecular typing demonstrated strong relatedness of the isolate to strains of R. rickettsii from Central and South America.

9 CFR 71.21 - Tissue and blood testing at slaughter.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., taking into account whether APHIS will be conducting complete tests at the facility, or only collecting..., until after the post-mortem examination is completed; (4) Includes tables, benches, and other equipment on which sample collection and processing are to be performed, of such design, material, and...

The impact of antemortem computed tomographic scanning on postmortem examination rate and frequency of missed diagnosis: A retrospective analysis of postmortem examination data.

PubMed

Liisanantti, Janne Henrik; Ala-Kokko, Tero Ilmari

2015-12-01

The present study was conducted to explore the impact of computed tomographic (CT) scanning on the diagnostic discrepancy rate. This single-center, retrospective study reviewed postmortem examination results, clinical diagnoses, and radiologic imaging data for patients admitted to the intensive care unit (ICU) in 2008 to 2013. The Goldman criteria were used to classify diagnostic discrepancies. The data of 577 patients who died during their ICU stay were retrieved. The postmortem examination rate was 42.9% (n=248). Significant diagnostic discrepancies (Goldman I and II) were recorded in 24 cases (9.7%). The postmortem examination rate decreased significantly from the first half (n=143; 51.1%) to the second half (n=105; 35.4%) of the study period (P<.0001). Among those with postmortem examinations, the use of antemortem body CT scans increased significantly from the first half (n=59; 41.3%) to the second half (n=64; 51.0%; P=.002) of the study period. The significant diagnostic discrepancy rate did not change with time (8.4% vs 11.4%, respectively; P=.424). The postmortem examination rate has decreased, whereas antemortem CT scans has increased. Copyright © 2015 Elsevier Inc. All rights reserved.

16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer’s Post-Mortem Brain

PubMed Central

Emery, David C.; Shoemark, Deborah K.; Batstone, Tom E.; Waterfall, Christy M.; Coghill, Jane A.; Cerajewska, Tanya L.; Davies, Maria; West, Nicola X.; Allen, Shelley J.

2017-01-01

The neurological deterioration associated with Alzheimer’s disease (AD), involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is associated with evident neuroinflammation. This is now seen to be a significant contributor to pathology. Recently the tenet of the privileged status of the brain, regarding microbial compromise, has been questioned, particularly in terms of neurodegenerative diseases. It is now being considered that microbiological incursion into the central nervous system could be either an initiator or significant contributor to these. This is a novel study using 16S ribosomal gene-specific Next generation sequencing (NGS) of extracted brain tissue. A comparison was made of the bacterial species content of both frozen and formaldehyde fixed sections of a small cohort of Alzheimer-affected cases with those of cognitively unimpaired (normal). Our findings suggest an increase in bacterial populations in Alzheimer brain tissue compared with normal. PMID:28676754

Effect of supplemental vitamin D3 concentration on concentrations of calcium, phosphorus, and magnesium relative to protein in subcellular components of the longissimus and the distribution of calcium within longissimus muscle of beef steers.

PubMed

Montgomery, J L; Blanton, J R; Horst, R L; Galyean, M L; Morrow, K J; Allen, V G; Wester, D B; Miller, M F

2004-09-01

The effect of supplementing diets with various levels of vitamin D3 to provide 0, 0.5, 1, and 5 million IU/(steer x d) for 8 d before slaughter on the mineral content and localization of Ca in LM and muscle fragments was studied during the postmortem aging process. Twelve feedlot steers of three biological types were given access to the four levels of vitamin D for 8 d before slaughter. Differential centrifugation techniques were used to determine the concentrations of minerals relative to protein in different muscle fragments on d 3 and 21 postmortem. Electron microscopy visualization of bound Ca indicated that vitamin D3 mobilized Ca from the sarcoplasmic reticulum and transverse tubule system into the myofibrils. Bound Ca was concentrated near the Z-line at the A-band/I-band juncture within the sarcomere. Supplementing steers with 1 and 5 million IU/(steer x d) of vitamin D3 increased (P < 0.05) Ca, P, and Mg concentrations per unit of protein in the cytosol. Soluble cytosolic Ca concentrations were greater (P < 0.05) on d 21 than on d 3 postmortem only when steers were supplemented with 5 million IU/d. Concentrations of Ca, P, and Mg in isolated tissues were increased (P < 0.05) in nuclei and myofibrilar proteins by supplementing steers with 1 and 5 million IU/ (steer x d) of vitamin D3. All supplemental vitamin D3 treatments also increased (P < 0.001) Mg concentrations in the cytosol, regardless of aging treatment, and increased Mg concentrations (P < 0.04) within the mitochondria at d 3 postmortem. Thus, supplementation of feedlot steers with vitamin D3 at levels of 0.5 to 5 million IU/(steer x d) increased Ca concentrations within respiring muscle, resulting in increased bound tissue Ca concentrations. When the respiring muscle was converted to meat, the increased bound tissue Ca resulting from vitamin D3 treatment released Ca concentrations into the cytosol during aging (P < 0.05). Results of this study indicate that vitamin D3 supplementation increased total cytosolic Ca, P, and Mg concentrations in meat.

Estimation of postmortem interval based on colony development time for Anoplolepsis longipes (Hymenoptera: Formicidae).

PubMed

Goff, M L; Win, B H

1997-11-01

The postmortem interval for a set of human remains discovered inside a metal tool box was estimated using the development time required for a stratiomyid fly (Diptera: Stratiomyidae), Hermetia illucens, in combination with the time required to establish a colony of the ant Anoplolepsis longipes (Hymenoptera: Formicidae) capable of producing alate (winged) reproductives. This analysis resulted in a postmortem interval estimate of 14 + months, with a period of 14-18 months being the most probable time interval. The victim had been missing for approximately 18 months.

Cerebrospinal fluid PCR analysis and biochemistry in bodies with severe decomposition.

PubMed

Palmiere, Cristian; Vanhaebost, Jessica; Ventura, Francesco; Bonsignore, Alessandro; Bonetti, Luca Reggiani

2015-02-01

The aim of this study was to assess whether Neisseria meningitidis, Listeria monocytogenes, Streptococcus pneumoniae and Haemophilus influenzae can be identified using the polymerase chain reaction technique in the cerebrospinal fluid of severely decomposed bodies with known, noninfectious causes of death or whether postmortem changes can lead to false positive results and thus erroneous diagnostic information. Biochemical investigations, postmortem bacteriology and real-time polymerase chain reaction analysis in cerebrospinal fluid were performed in a series of medico-legal autopsies that included noninfectious causes of death with decomposition, bacterial meningitis without decomposition, bacterial meningitis with decomposition, low respiratory tract infections with decomposition and abdominal infections with decomposition. In noninfectious causes of death with decomposition, postmortem investigations failed to reveal results consistent with generalized inflammation or bacterial infections at the time of death. Real-time polymerase chain reaction analysis in cerebrospinal fluid did not identify the studied bacteria in any of these cases. The results of this study highlight the usefulness of molecular approaches in bacteriology as well as the use of alternative biological samples in postmortem biochemistry in order to obtain suitable information even in corpses with severe decompositional changes. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Small vessel disease, neurovascular regulation and cognitive impairment: post-mortem studies reveal a complex relationship, still poorly understood.

PubMed

Love, Seth; Miners, J Scott

2017-07-15

The contribution of vascular disease to cognitive impairment is under-recognized and the pathogenesis is poorly understood. This information gap has multiple causes, including a lack of post-mortem validation of clinical diagnoses of vascular cognitive impairment (VCI) or vascular dementia (VaD), the exclusion of cases with concomitant neurodegenerative disease when diagnosing VCI/VaD, and a lack of standardization of neuropathological assessment protocols for vascular disease. Other contributors include a focus on end-stage destructive lesions to the exclusion of more subtle types of diffuse brain injury, on structural abnormalities of arteries and arterioles to the exclusion of non-structural abnormalities and capillary damage, and the use of post-mortem sampling strategies that are biased towards the identification of neurodegenerative pathologies. Recent studies have demonstrated the value of detailed neuropathology in characterizing vascular contributions to cognitive impairment (e.g. in diabetes), and highlight the importance of diffuse white matter changes, capillary damage and vasoregulatory abnormalities in VCI/VaD. The use of standardized, evidence-based post-mortem assessment protocols and the inclusion of biochemical as well as morphological methods in neuropathological studies should improve the accuracy of determination of the contribution of vascular disease to cognitive impairment and clarify the relative contribution of different pathogenic processes to the tissue damage. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Gene expression in the twilight of death: The increase of thousands of transcripts has implications to transplantation, cancer, and forensic research.

PubMed

Pozhitkov, Alexander E; Noble, Peter A

2017-09-01

After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while its body no longer works as a whole. We define this state as the "twilight of death" - the transition from a living body to a decomposed corpse. We claim that the study of the twilight of death is important to ethical, legal and medical science. We examined gene expression at the twilight of death in the zebrafish and mouse reaching the conclusion that apparently thousands of transcripts significantly increase in abundance from life to several hours/days postmortem relative to live controls. Transcript dynamics of different genes provided "proof-of-principle" that models accurately predict an individual's elapsed-time-of-death (i.e. postmortem interval). While many transcripts were associated with survival and stress compensation, others were associated with epigenetic factors, developmental control, and cancer. Future studies are needed to determine whether the high incidence of cancer in transplant recipients is due to the postmortem processes in donor organs. © 2017 WILEY Periodicals, Inc.

Alterations in the sarcoplasmic protein fraction of beef muscle with postmortem aging and hydrodynamic pressure processing

USDA-ARS?s Scientific Manuscript database

Capillary electrophoresis (CE) and reversed-phase high performance liquid chromatography (RP-HPLC) analysis were utilized to detect differences in the sarcoplasmic protein profiles of beef strip loins subjected to aging and hydrodynamic pressure processing (HDP) treatments. At 48 h postmortem, stri...

Measurement of Postmortem Pupil Size: A New Method with Excellent Reliability and Its Application to Pupil Changes in the Early Postmortem Period.

PubMed

Fleischer, Luise; Sehner, Susanne; Gehl, Axel; Riemer, Martin; Raupach, Tobias; Anders, Sven

2017-05-01

Measurement of postmortem pupil width is a potential component of death time estimation. However, no standardized measurement method has been described. We analyzed a total of 71 digital images for pupil-iris ratio using the software ImageJ. Images were analyzed three times by four different examiners. In addition, serial images from 10 cases were taken between 2 and 50 h postmortem to detect spontaneous pupil changes. Intra- and inter-rater reliability of the method was excellent (ICC > 0.95). The method is observer independent and yields consistent results, and images can be digitally stored and re-evaluated. The method seems highly eligible for forensic and scientific purposes. While statistical analysis of spontaneous pupil changes revealed a significant polynomial of quartic degree for postmortem time (p = 0.001), an obvious pattern was not detected. These results do not indicate suitability of spontaneous pupil changes for forensic death time estimation, as formerly suggested. © 2016 American Academy of Forensic Sciences.

Pulsatile Lavage of Musculoskeletal Wounds Causes Muscle Necrosis and Dystrophic Calcification in a Rat Model.

PubMed

Chiaramonti, Alexander M; Robertson, Astor D; Nguyen, Thao P; Jaffe, David E; Hanna, E Lex; Holmes, Robert; Barfield, William R; Fourney, William L; Stains, Joseph P; Pellegrini, Vincent D

2017-11-01

Adequate irrigation of open musculoskeletal injuries is considered the standard of care to decrease bacterial load and other contaminants. While the benefit of debris removal compared with the risk of further seeding by high-pressure lavage has been studied, the effects of irrigation on muscle have been infrequently reported. Our aim in the present study was to assess relative damage to muscle by pulsatile lavage compared with bulb-syringe irrigation. In an animal model of heterotopic ossification, 24 Sprague-Dawley rats underwent hindlimb blast amputation via detonation of a submerged explosive, with subsequent through-the-knee surgical amputation proximal to the zone of injury. All wounds were irrigated and underwent primary closure. In 12 of the animals, pulsatile lavage (20 psi [138 kPa]) was used as the irrigation method, and in the other 12 animals, bulb-syringe irrigation was performed. A third group of 6 rats did not undergo the blast procedure but instead underwent surgical incision into the left thigh muscle followed by pulsatile lavage. Serial radiographs of the animals were made to monitor the formation of soft-tissue radiopaque lesions until euthanasia at 6 months. Image-guided muscle biopsies were performed at 8 weeks and 6 months (at euthanasia) on representative animals from each group. Histological analysis was performed with hematoxylin and eosin, alizarin red, and von Kossa staining on interval biopsy and postmortem specimens. All animals managed with pulsatile lavage, with or without blast injury, developed soft-tissue radiopaque lesions, whereas no animal that had bulb-syringe irrigation developed these lesions (p = 0.001). Five of the 12 animals that underwent blast amputation with pulsatile lavage experienced wound complications, whereas no animal in the other 2 groups experienced wound complications (p = 0.014). Radiopaque lesions appeared approximately 10 days postoperatively, increased in density until approximately 16 weeks, then demonstrated signs of variable regression. Histological analysis of interval biopsy and postmortem specimens demonstrated tissue damage with inflammatory cells, cell death, and dystrophic calcification. Pulsatile lavage of musculoskeletal wounds can cause irreversible insult to tissue, resulting in myonecrosis and dystrophic calcification. The benefits and offsetting harm of pulsatile lavage (20 psi) should be considered before its routine use in the management of musculoskeletal wounds.

Usefulness and limitations of postmortem computed tomography in forensic analysis of gunshot injuries: Three case reports.

PubMed

Usui, Akihito; Kawasumi, Yusuke; Hosokai, Yoshiyuki; Kozakai, Masataka; Saito, Haruo; Funayama, Masato

2016-01-01

Gunshot injury has always been an important field of investigation in postmortem forensic radiology. The localization and retrieval of the bullet and of potentially important fragments are vital to these cases. Using postmortem multidetector-row computed tomography (MDCT) prior to forensic autopsy, we sought to illustrate the importance of this modality in the noninvasive characterization of gunshot wounds. We obtained and analyzed MDCT images in three cases of gunshot wounds (accidental close-range shotgun shooting, suicidal contact gunshot to the head and accidental long-range buckshot shooting). We discuss the value of postmortem MDCT findings in gunshot wound cases by comparing with forensic autopsy findings in Japan, a developing country with miserably low autopsy rate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rocky Mountain Spotted Fever, Panama

PubMed Central

Estripeaut, Dora; Aramburú, María Gabriela; Sáez-Llorens, Xavier; Thompson, Herbert A.; Dasch, Gregory A.; Paddock, Christopher D.; Zaki, Sherif

2007-01-01

We describe a fatal pediatric case of Rocky Mountain spotted fever in Panama, the first, to our knowledge, since the 1950s. Diagnosis was established by immunohistochemistry, PCR, and isolation of Rickettsia rickettsii from postmortem tissues. Molecular typing demonstrated strong relatedness of the isolate to strains of R. rickettsii from Central and South America. PMID:18217566

Metastatic anal sac adenocarcinoma in a dog presenting for acute paralysis

PubMed Central

2004-01-01

Abstract A 4-year old, female spayed terrier was referred for hind end paresis that rapidly progressed to paralysis. Spinal radiographs revealed vertebral collapse and bony lysis. Myelography confirmed spinal cord compression and surgical exploration found an extradural soft tissue mass. Metastatic anal sac adenocarcinoma was diagnosed at postmortem examination. PMID:15368742

Metastatic anal sac adenocarcinoma in a dog presenting for acute paralysis.

PubMed

Brisson, Brigitte A; Whiteside, Douglas P; Holmberg, David L

2004-08-01

A 4-year old, female spayed terrier was referred for hind end paresis that rapidly progressed to paralysis. Spinal radiographs revealed vertebral collapse and bony lysis. Myelography confirmed spinal cord compression and surgical exploration found an extradural soft tissue mass. Metastatic anal sac adenocarcinoma was diagnosed at postmortem examination.

Suspected systemic calcinosis and calciphylaxis in 5 horses

PubMed Central

Tan, Jean-Yin; Valberg, Stephanie J.; Sebastian, Manu M.; Davis, Gordon D.; Kelly, Jenny R.; Goehring, Lutz S.; Harland, Malte M.; Kuebelbeck, K. Leann; Waldridge, Bryan M.; Newton, Joseph C.; Reimer, Johanna M.

2010-01-01

Five horses were presented with signs of myopathy along with systemic malaise, hyperfibrinogenemia, hyperphosphatemia, and an elevated calcium phosphorus product (Ca*P). Postmortem findings were consistent with systemic calcinosis, a syndrome of calcium deposition in the tissue of organs including lungs, kidneys, muscle, and heart that has not been previously described in horses. PMID:21119866

9 CFR 310.6 - Carcasses and parts passed for cooking; marking.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Carcasses and parts passed for cooking... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.6 Carcasses and parts passed for cooking; marking. Carcasses and parts passed for cooking shall be marked conspicuously on the surface tissues thereof by a...

Pulmonary thromboembolism on unenhanced postmortem computed tomography: Feasibility and findings.

PubMed

Ampanozi, Garyfalia; Held, Ulrike; Ruder, Thomas D; Ross, Steffen G; Schweitzer, Wolf; Fornaro, Juergen; Franckenberg, Sabine; Thali, Michael J; Flach, Patricia M

2016-05-01

The purpose of this study was to evaluate the feasibility of diagnosing fatal pulmonary thromboembolism (PTE) with unenhanced postmortem computed tomography (PMCT). Twelve cases with autopsy confirmed PTE and matched controls (n=19) were retrospectively examined for PTE signs on PMCT. The following variables were evaluated: edema of the lower extremities (areal and Hounsfield Unit measurements) and observer dependent patterns of the morphology of the sedimentation in the pulmonary arteries and trunk. The median absolute difference between the areal measurements of the right and left lower leg and thigh and the attenuation of the popliteal adipose tissue did not differ significantly between the groups. In contrast, the categorical assessment of soft tissue edema in the lower extremities was significantly different. A statistically significant difference could also be found in the shape of the vascular content within the pulmonary trunk and arteries. PTE may be assessed on unenhanced PMCT using diagnostic clues such as a distinct pattern of the pulmonary artery content and the presence of perivascular edema in the lower extremities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transcriptome-Wide Mega-Analyses Reveal Joint Dysregulation of Immunologic Genes and Transcription Regulators in Brain and Blood in Schizophrenia

PubMed Central

Hess, Jonathan L.; Tylee, Daniel S.; Barve, Rahul; de Jong, Simone; Ophoff, Roel A.; Kumarasinghe, Nishantha; Tooney, Paul; Schall, Ulrich; Gardiner, Erin; Beveridge, Natalie Jane; Scott, Rodney J.; Yasawardene, Surangi; Perera, Antionette; Mendis, Jayan; Carr, Vaughan; Kelly, Brian; Cairns, Murray; Tsuang, Ming T.; Glatt, Stephen J.

2016-01-01

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia. PMID:27450777

Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia.

PubMed

Hess, Jonathan L; Tylee, Daniel S; Barve, Rahul; de Jong, Simone; Ophoff, Roel A; Kumarasinghe, Nishantha; Tooney, Paul; Schall, Ulrich; Gardiner, Erin; Beveridge, Natalie Jane; Scott, Rodney J; Yasawardene, Surangi; Perera, Antionette; Mendis, Jayan; Carr, Vaughan; Kelly, Brian; Cairns, Murray; Tsuang, Ming T; Glatt, Stephen J

2016-10-01

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n=315) and from ex-vivo blood tissues (n=578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia. Published by Elsevier B.V.

A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer's disease mice.

PubMed

Maiti, Panchanan; Hall, Tia C; Paladugu, Leela; Kolli, Nivya; Learman, Cameron; Rossignol, Julien; Dunbar, Gary L

2016-11-01

Deposition of amyloid beta protein (Aβ) is a key component in the pathogenesis of Alzheimer's disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Aβ, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Aβ plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Aβ plaques in brain tissues from the 5×-familial AD (5×FAD) mice than the classical Aβ-binding dyes, such as Congo red and Thioflavin-S. These comparisons were made in postmortem brain tissues from the 5×FAD mice. We observed that Cur and NC labeled Aβ plaques to the same degree as Aβ-specific antibody and to a greater extent than those of the classical amyloid-binding dyes. Cur and NC also labeled Aβ plaques in 5×FAD brain tissues when injected intraperitoneally. Nanomolar concentrations of Cur or NC are sufficient for labeling and imaging of Aβ plaques in 5×FAD brain tissue. Cur and NC also labeled different types of Aβ plaques, including core, neuritic, diffuse, and burned-out, to a greater degree than other amyloid-binding dyes. Therefore, Cur and or NC can be used as an alternative to Aβ-specific antibody for labeling and imaging of Aβ plaques ex vivo and in vivo. It can provide an easy and inexpensive means of detecting Aβ-plaque load in postmortem brain tissue of animal models of AD after anti-amyloid therapy.

United States Transuranium and Uranium Registries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.; Filipy, R.E.; Dietert, S.E.

1991-06-01

This report summarizes the primary scientific activities of the United States Transuranium and Uranium Registries for the period October 1, 1989 through September 30, 1990. The Registries are parallel human tissue research programs devoted to the study of the actinide elements in humans. To date there have been 261 autopsy or surgical specimen donations, which include 11 whole bodies. The emphasis of the Registry was directed towards quality improvement and the development of a fully computerized data base that would incorporate not only the results of postmortem radiochemical analysis, but also medical and monitoring information obtained during life. Human subjectsmore » reviews were also completed. A three compartment biokinetic model for plutonium distribution is proposed. 2 tabs.« less

In vivo biocompatibility of three potential intraperitoneal implants.

PubMed

Defrère, Sylvie; Mestagdt, Mélanie; Riva, Raphaël; Krier, Fabrice; Van Langendonckt, Anne; Drion, Pierre; Jérôme, Christine; Evrard, Brigitte; Dehoux, Jean-Paul; Foidart, Jean-Michel; Donnez, Jacques

2011-10-10

The intraperitoneal biocompatibility of PDMS, polyHEMA and pEVA was investigated in rats, rabbits and rhesus monkeys. No inflammation was evidenced by hematological analyses and measurement of inflammatory markers throughout the experiment and by post-mortem examination of the pelvic cavity. After 3 or 6 months, histological analysis revealed fibrous tissue encapsulating PDMS and PEVA implants in all species and polyHEMA implants in rabbits and monkeys. Calcium deposits were observed inside polyHEMA implants. The intraperitoneal biocompatibility of all 3 polymers makes them suitable for the design of drug delivery systems, which may be of great interest for pathologies confined to the pelvic cavity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel method for the determination of Sildenafil (Viagra) and its metabolite (UK-103,320) in postmortem specimens using LC/MS/MS and LC/MS/MS/MS.

DOT National Transportation Integrated Search

2000-05-01

During the investigation of aviation accidents, postmortem samples from victims are submitted to the FAAs : Civil Aeromedical Institute for drug analysis. Because new drugs are continually being released to the market, it : is our laboratorys r...

Magnetic Analysis of Post-mortem Hippocampal Tissue from Alzheimer's Patients: Changes with Progression of the Disease.

NASA Astrophysics Data System (ADS)

Fuller, M.; Zinin, P.; Favia, J.; Tatsumi, L.; Kletetschka, G.; Adachi, T.

2007-12-01

Increases of iron in the human brain with age have been observed and may be accompanied by the development of neurodegenerative diseases, such as Alzheimer's. We have measured the magnetic characteristics of several sets of slides of hippocampal tissue from deceased Alzheimer patients. The slides were made available by the Harvard Brain Bank. The pathology of the tissue was classified in the Braak stages I to VI used to describe the progression of the disease. In general, the slides from patients with higher Braak stages and development of fibrillary tangles and plaques had greater magnetic moments than did those with Braak stage II. However, the peak values were at stage IV and V. To mitigate errors due to the inevitable differences in masses of the tissue on individual slides and their precise location in the hippocampus, ratios of magnetic properties were also observed. Ratios of Anhysteretic Remanent Magnetizaton (ARM) to Isothermal Remanent Magnetization (IRM) were obtained and showed a decrease from Stage II to the more advanced stages, with the minimum values at stages IV and V. The acquisition and demagnetization of IRM are consistent with the presence of magnetite, but also indicate a magnetically harder phase.

Suprapubic track pressure and force--deformation measurements in a (live) human subject and in animal models post-mortem.

PubMed

Coveney, V A; Gepi-Attee, S; Gröver, D; Painter, D

2001-01-01

Tests have been performed on animal models shortly post-mortem and on a healthy human subject in order to obtain estimates of the forces which act on suprapubic urinary catheters and similar devices and to develop an abdominal wall simulator. Such data and test methods are required for the systematic design of suprapubic devices because of the dual need to maintain the functionality of devices and to avoid excessive pressure on soft body tissue which could lead to ischaemia and in turn necrosis. In the post-mortem animal models, electrical excitation was applied to the abdominal wall in order to stimulate muscle activity. Two types of transducers were used: a soft membrane transducer (SMT) for pressure measurement and novel instrumented 'tongs' to determine indentation stiffness characteristics in the suprapubic track or artificial pathway created for a device. The SMT has been extensively used in the urethras and bladders of human subjects while the tongs were built specifically for these tests. Only the well-established SMT was used with the human subject; a peak pressure of 22 kPa was obtained. In the animal models the pressure profile given by the SMT had a peak whose position corresponded well with the estimated location of the rectus muscle measured on the fixed tissue section. The peak value was 5.5 kPa, comparable with values likely to cause necrosis if maintained for more than 1 day. Remarkably consistent indentation stiffness values were obtained with the instrumented tongs; all values were close to 0.45 N/mm (33 kPa/mm).

Prevalence of systemic air-embolism after prolonged cardiopulmonary resuscitation in newborns: A pilot study.

PubMed

Halbertsma, Feico J J; Mohns, Thilo; Bok, Levinus A; Niemarkt, Hendrik J; Kramer, Boris W

2015-08-01

Chest compressions (CC) during cardiopulmonary resuscitation (CPR) are the cornerstone of adult CPR protocols and are meant to restore circulation and improve outcome. Although adverse effects such as air-embolisms have been reported, these are rare and considered to be outweighed by beneficial effect. In newborns, however, the lung tissue is more fragile. Thus, the high intra-thoracic pressures resulting from CC may make the newborns more vulnerable for air-embolisms. We studied the postmortem prevalence of air-embolism in neonates that have received CPR. Prospective cohort analysis of newborns receiving CC during CPR. CPR was performed by trained staff according to ILCOR guidelines, in a tertiary hospital. Air-embolisms were sought after using CT/MRI and autopsy. During a 61/2 year period (2007-2014), n = 56 newborns received CC. Newborns were resuscitated following severe perinatal hypoxia, or due to complications during NICU treatment. In n = 14 (25.0%) circulation could not be restored (mean CPR duration: 32.7 ± 15.2 min). Post-mortem CT/MRI was performed in n = 9, of whom n = 8 (88.9%) had air-embolisms. Autopsy was performed in n = 9. The air-embolisms could not be retraced on autopsy except for n = 1 patient. In patients with CPR resulting in restored circulation (n = 42), no CT or MRI was performed for comparison due to radiation and/or hemodynamic instability. Cerebral ultrasound could not identify or exclude air-embolisms in this subgroup. Post-mortem CT after prolonged resuscitation showed a high prevalence of intravascular air-embolism. Autopsy was not suited to detect air-embolism. The clinical importance of air-embolisms on the lethal outcome needs further research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

PubMed

Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Methodology of determination of the time of death and outlooks for the further development].

PubMed

Novikov, P I; Vlasov, A Iu; Shved, E F; Natsentov, E O; Korshunov, N V; Belykh, S A

2004-01-01

A methodological analysis of diagnosing the prescription of death coming (PDC) is described in the paper. Key philosophic fundamentals for further novel and more effective methods of PDC determination are elucidated. Main requirement applicable to postmortem diagnosis are defined. Different methods of modeling the postmortem process are demonstrated by the example of cadaver cooling, i.e. in real time, by analogue computer systems and by mathematic modeling. The traditional empiric and the adaptive approaches are comparatively analyzed in modeling the postmortem processes for the PDC diagnosis. A variety of promising trends for further related research is outlined.

Selection of novel reference genes for use in the human central nervous system: a BrainNet Europe Study.

PubMed

Durrenberger, Pascal F; Fernando, Francisca S; Magliozzi, Roberta; Kashefi, Samira N; Bonnert, Timothy P; Ferrer, Isidro; Seilhean, Danielle; Nait-Oumesmar, Brahim; Schmitt, Andrea; Gebicke-Haerter, Peter J; Falkai, Peter; Grünblatt, Edna; Palkovits, Miklos; Parchi, Piero; Capellari, Sabina; Arzberger, Thomas; Kretzschmar, Hans; Roncaroli, Federico; Dexter, David T; Reynolds, Richard

2012-12-01

The use of an appropriate reference gene to ensure accurate normalisation is crucial for the correct quantification of gene expression using qPCR assays and RNA arrays. The main criterion for a gene to qualify as a reference gene is a stable expression across various cell types and experimental settings. Several reference genes are commonly in use but more and more evidence reveals variations in their expression due to the presence of on-going neuropathological disease processes, raising doubts concerning their use. We conducted an analysis of genome-wide changes of gene expression in the human central nervous system (CNS) covering several neurological disorders and regions, including the spinal cord, and were able to identify a number of novel stable reference genes. We tested the stability of expression of eight novel (ATP5E, AARS, GAPVD1, CSNK2B, XPNPEP1, OSBP, NAT5 and DCTN2) and four more commonly used (BECN1, GAPDH, QARS and TUBB) reference genes in a smaller cohort using RT-qPCR. The most stable genes out of the 12 reference genes were tested as normaliser to validate increased levels of a target gene in CNS disease. We found that in human post-mortem tissue the novel reference genes, XPNPEP1 and AARS, were efficient in replicating microarray target gene expression levels and that XPNPEP1 was more efficient as a normaliser than BECN1, which has been shown to change in expression as a consequence of neuronal cell loss. We provide herein one more suitable novel reference gene, XPNPEP1, with no current neuroinflammatory or neurodegenerative associations that can be used for gene quantitative gene expression studies with human CNS post-mortem tissue and also suggest a list of potential other candidates. These data also emphasise the importance of organ/tissue-specific stably expressed genes as reference genes for RNA studies.

Post-mortem biochemistry of NSE and S100B: A supplemental tool for detecting a lethal traumatic brain injury?

PubMed

Sieber, Monique; Dreßler, Jan; Franke, Heike; Pohlers, Dirk; Ondruschka, Benjamin

2018-04-01

Traumatic brain injury (TBI) is a very common entity that leads to numerous fatalities all over the world. Therefore, forensic pathologists are in desperate need of supplemental methodological tools for the diagnosis of TBI in everyday practice besides the standard autopsy. The present study determined post-mortem neuron specific enolase (NSE) and S100 calcium-binding protein B (S100B) levels as biological markers of an underlying TBI in autopsy cases. Paired serum and CSF samples of 92 fatalities were collected throughout routine autopsies. Afterwards, the marker levels were assessed using commercially available immunoassays (ECLIA, Roche Diagnostics). For statistical analysis, we compared the TBI cases to three control groups (sudden natural death by acute myocardial infarction, traumatic death without impact on the head, cerebral hypoxia). Moreover, the TBI cases were subdivided according to their survival time of the trauma. Brain specimens have been collected and stained immunohistochemically against the aforementioned proteins to illustrate their typical cellular staining patterns with an underlying TBI compared to non-TBI fatalities. CSF NSE and S100B levels were elevated after TBI compared to all control groups (p < 0.001). Although this finding can already be investigated among the TBI cases dying immediately subsequent to the trauma, the marker levels in CSF increase with longer survival times until a peak level within the first three days after trauma. There is a strong correlation between both marker levels in CSF (r = 0.67). The presence or absence of cerebral tissue contusion following the initial trauma does not seem to affect the CSF levels of both proteins (p > 0.05). Post-mortem serum levels of both proteins were not elevated in TBI cases compared to controls (p > 0.05). Former elaborated cut-off values in CSF were confirmed and were only exceeded when a TBI survival time of at least 30 min was reached. The present results report that post-mortem NSE and S100B CSF levels are significantly elevated subsequent to a fatal TBI. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Relationship between sudden natural death and abdominal fat evaluated on postmortem CT scans.

PubMed

Kaichi, Y; Sakane, H; Higashibori, H; Honda, Y; Tatsugami, F; Baba, Y; Iida, M; Awai, K

2017-06-01

This study examined the association between sudden natural death and abdominal fat using postmortem computed tomography (CT) scans. Postmortem CT images at the umbilical level of 241 subjects were used to measure abdominal areas of subcutaneous- and visceral fat, the rate of visceral fat and the waist circumference. Of the study subjects, 174 died of sudden natural death (130 men and 44 women), and 67 died of different causes (46 men and 21 women). All were between 40 and 75 years of age. Logistic regression analysis was performed to identify independent abdominal parameters associated with sudden natural death. By univariate analysis, the areas of subcutaneous and visceral fat were significantly larger in sudden natural death than who died of different causes (subcutaneous fat, odds ratio [OR] = 1.004, 95% confidence interval [CI] = 1.000-1.007, p  = 0.03; visceral fat, OR = 1.008, 95% CI = 1.003-1.013, p  < 0.01). Multivariate analysis showed that the area of visceral fat was an independent factor associated with the risk of sudden natural death (OR = 1.008, 95% CI = 1.002-1.015, p  = 0.02). Postmortem CT revealed that sudden natural death was related to abdominal fat deposits.

Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains.

PubMed

Zeppenfeld, Douglas M; Simon, Matthew; Haswell, J Douglas; D'Abreo, Daryl; Murchison, Charles; Quinn, Joseph F; Grafe, Marjorie R; Woltjer, Randall L; Kaye, Jeffrey; Iliff, Jeffrey J

2017-01-01

Cognitive impairment and dementia, including Alzheimer disease (AD), are common within the aging population, yet the factors that render the aging brain vulnerable to these processes are unknown. Perivascular localization of aquaporin-4 (AQP4) facilitates the clearance of interstitial solutes, including amyloid-β, through the brainwide network of perivascular pathways termed the glymphatic system, which may be compromised in the aging brain. To determine whether alterations in AQP4 expression or loss of perivascular AQP4 localization are features of the aging human brain and to define their association with AD pathology. Expression of AQP4 was analyzed in postmortem frontal cortex of cognitively healthy and histopathologically confirmed individuals with AD by Western blot or immunofluorescence for AQP4, amyloid-β 1-42, and glial fibrillary acidic protein. Postmortem tissue and clinical data were provided by the Oregon Health and Science University Layton Aging and Alzheimer Disease Center and Oregon Brain Bank. Postmortem tissue from 79 individuals was evaluated, including cognitively intact "young" individuals aged younger than 60 years (range, 33-57 years), cognitively intact "aged" individuals aged older than 60 years (range, 61-96 years) with no known neurological disease, and individuals older than 60 years (range, 61-105 years) of age with a clinical history of AD confirmed by histopathological evaluation. Forty-eight patient samples (10 young, 20 aged, and 18 with AD) underwent histological analysis. Sixty patient samples underwent Western blot analysis (15 young, 24 aged, and 21 with AD). Expression of AQP4 protein, AQP4 immunoreactivity, and perivascular AQP4 localization in the frontal cortex were evaluated. Expression of AQP4 was associated with advancing age among all individuals (R2 = 0.17; P = .003). Perivascular AQP4 localization was significantly associated with AD status independent of age (OR, 11.7 per 10% increase in localization; z = -2.89; P = .004) and was preserved among eldest individuals older than 85 years of age who remained cognitively intact. When controlling for age, loss of perivascular AQP4 localization was associated with increased amyloid-β burden (R2 = 0.15; P = .003) and increasing Braak stage (R2 = 0.14; P = .006). In this study, altered AQP4 expression was associated with aging brains. Loss of perivascular AQP4 localization may be a factor that renders the aging brain vulnerable to the misaggregation of proteins, such as amyloid-β, in neurodegenerative conditions such as AD.

Mortality During U.S. Armed Forces Basic Training: A 25-Year Review (1977-2001)

DTIC Science & Technology

2002-08-01

post-mortem lung tissue cultures Pneumonia 6 23/W/M 1987 Army GABHS Blood culture Necrotizing fasciitis 7 20/W/M 1991 Air Force GABHS Unknown...Force 30 Infection Necrotizing Fasciitis 8 Infection 3 19/B/M Army 57 Toxic Shock Syndrome 20 59 4 19/B/M Army Infection Meningococcemia 9

Distinct Lineage of Vesiculovirus from Big Brown Bats, United States

PubMed Central

Driscoll, Cindy; Carlos, Maria Paz; Prioleau, Algernon; Schmieder, Robert; Dwivedi, Bhakti; Wong, Jakk; Cha, Yunhee; Head, Steven; Breitbart, Mya; Delwart, Eric

2013-01-01

We identified a novel rhabdovirus, American bat vesiculovirus, from postmortem tissue samples from 120 rabies-negative big brown bats with a history of human contact. Five percent of the tested bats were infected with this virus. The extent of zoonotic exposure and possible health effects in humans from this virus are unknown. PMID:24274823

Poppy Seed Consumption or Opiate Use: The Determination of Thebaine and Opiates of Abuse in Postmortem Fluids and Tissues

DTIC Science & Technology

2005-06-01

codeine, following the consumption of poppy seeds .4-8 Scientific literature has clearly demonstrated the distinct possibil- ity of a morphine and/or...poppy seeds and is only present following heroin use.5 Therefore, 6-MAM is considered a heroin- specific catabolite and is legally defensible

A novel method for the determination of sildenafil (Viagra(R)) and its metabolite (UK-103,320) in postmortem specimens using LC/MS/MS and LC/MS/MS/MS : final report.

DOT National Transportation Integrated Search

2000-05-01

During the investigation of aviation accidents, postmortem samples from victims are submitted to the FAAs Civil Aeromedical Institute for drug analysis. Because new drugs are continually being released to the market, it is our laboratorys respo...

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens.

PubMed

Canfield, Dennis V; Dubowski, Kurt M; Whinnery, James M; Forster, Estrella M

2018-01-01

This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approach: Compare the drug found by toxicology analysis with the drug reported by the pilot. This study uniquely examined first the pilot-reported medication and then compared it to that detected by toxicology analysis. This study will serve two purposes: (i) to determine the capability of a toxicology laboratory to detect reported medications, and (ii) to identify pilots with medications below detectable limits. All information required for this study was extracted from the Toxicology Data Base system and was searched using ToxFlo or SQL Server Management Studio. The following information was collected and analyzed: pilot-reported trade and/or generic drug, date specimens received, time of accident, type of aviation operations (CFR), state, pilot level, age, class of medical, specimen type, specimen concentration, dose reported, frequency reported associated with the accident, quantity reported, National Transportation Safety Board (NTSB) accident event number, and all NTSB reports. There were 319 pilots that either reported taking a beta-blocker or were found to be taking a beta-blocker by postmortem toxicology analysis. Time of death, therapeutic concentration and specimen type were found to be factors in the ability of the laboratory to detect beta-blockers. Beta-blockers taken by pilots will, in most cases, be found by a competent postmortem forensic toxicology laboratory at therapeutic concentrations. The dose taken by the pilot was not found to be a factor in the ability of the laboratory to identify beta-blockers. Time of dose, route of administration, specimen tested and therapeutic concentration of the drug were found to be factors in the ability of the laboratory to identify beta-blockers in postmortem specimens. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Are animal models predictive for human postmortem muscle protein degradation?

PubMed

Ehrenfellner, Bianca; Zissler, Angela; Steinbacher, Peter; Monticelli, Fabio C; Pittner, Stefan

2017-11-01

A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.

Differences in sampling techniques on total post-mortem tryptase.

PubMed

Tse, R; Garland, J; Kesha, K; Elstub, H; Cala, A D; Ahn, Y; Stables, S; Palmiere, C

2018-05-01

The measurement of mast cell tryptase is commonly used to support the diagnosis of anaphylaxis. In the post-mortem setting, the literature recommends sampling from peripheral blood sources (femoral blood) but does not specify the exact sampling technique. Sampling techniques vary between pathologists, and it is unclear whether different sampling techniques have any impact on post-mortem tryptase levels. The aim of this study is to compare the difference in femoral total post-mortem tryptase levels between two sampling techniques. A 6-month retrospective study comparing femoral total post-mortem tryptase levels between (1) aspirating femoral vessels with a needle and syringe prior to evisceration and (2) femoral vein cut down during evisceration. Twenty cases were identified, with three cases excluded from analysis. There was a statistically significant difference (paired t test, p < 0.05) between mean post-mortem tryptase by aspiration (10.87 ug/L) and by cut down (14.15 ug/L). The mean difference between the two methods was 3.28 ug/L (median, 1.4 ug/L; min, - 6.1 ug/L; max, 16.5 ug/L; 95% CI, 0.001-6.564 ug/L). Femoral total post-mortem tryptase is significantly different, albeit by a small amount, between the two sampling methods. The clinical significance of this finding and what factors may contribute to it are unclear. When requesting post-mortem tryptase, the pathologist should consider documenting the exact blood collection site and method used for collection. In addition, blood samples acquired by different techniques should not be mixed together and should be analyzed separately if possible.

Can homemade alcohol (Raksi) be useful for preserving dead bodies? An experiment on wistar albino rats.

PubMed

Dhungel, S; Maskey, D; Jha, C B; Bhattacharya, S; Paudel, B H; Shrestha, R N

2007-01-01

Embalming is the through disinfection and art of preserving bodies after death using chemical substances. It keeps a body life like in appearance during the time it lies in a state prior to funeral. This study was undertaken to investigate the effectiveness of Raksi in sacrificed rats in arresting postmortem changes and establishing scientific fact whether Raksi can be an alternative to standard embalming constituent if it is not available. 50 albino rats were systematically randomized into control and experiment groups. Raksi and distilled water were injected for embalming purpose intraventricularly in experiment and control groups of rats respectively and kept for 48 to 96 hours for observation for postmortem changes. Observations made at 48 and 72 hours of embalming revealed that Raksi can arrest postmortem changes in the rats up to 72 hours (3rd day) successfully in the experimental group whereas moderate to severe postmortem changes were seen in the control group. The experimental group showed mild degree of putrefactive changes, liberation of gases and liquefaction of tissues only at 96 hours (4th day) of embalming. The Raksi used in this experiment contained 34% of alcohol, which was determined by an alcohol hydrometer. Experiment clearly demonstrated from its result that raksi can be utilised temporarily for embalming since it contains alcohol and has preservative, bactericidal and disinfectant properties. It is concluded from the study that this knowledge if applied to dead human subjects, may preserve dead bodies temporarily allowing delayed funeral.

Sarcomere length influences postmortem proteolysis of excised bovine semitendinosus muscle.

PubMed

Weaver, A D; Bowker, B C; Gerrard, D E

2008-08-01

The interaction between sarcomere length and postmortem proteolysis as related to meat tenderness is not clear. The extent of thick and thin filament overlap alters actomyosin binding and may alter substrate availability during aging-induced tenderization. The objective of this study was to determine the influence of sarcomere length on proteolytic degradation in beef. Strips from bovine semitendinosus were either stretched 40% and restrained or allowed to shorten unrestrained in an ice bath. After rigor completion, 0.6-cm cross sections were fabricated and were randomly assigned to 2, 4, 7, or 10 d of aging treatments. Myofibrils were isolated for sarcomere length determination. Samples were collected and frozen for shear force analysis, and muscle proteins were extracted for SDS-PAGE and Western blotting analyses to determine troponin T (TnT) proteolysis. Sarcomere length was greater (P < 0.01) in stretched muscle samples compared with shortened samples (2.57 vs. 1.43 microm, respectively). Correspondingly, shear force values were greater (P < 0.05) in shortened samples than stretched samples. Western blots revealed the presence of 3 major intact TnT bands that diminished with time postmortem and 4 bands (TnT degradation products) that accumulated during postmortem storage. Quantification of intact TnT showed increased (P < 0.05) proteolysis at 4 and 7 d postmortem in samples with long sarcomeres. By 10 d, only traces of the greatest molecular weight intact TnT band were evident in both shortened and stretched samples, suggesting this TnT band may be more susceptible to proteolysis than other intact TnT bands. Degradation products of TnT appeared earlier postmortem in samples with long sarcomeres. The 30-kDa TnT fragment appeared after 7 d of postmortem storage in samples with long sarcomeres but not until 10 d in muscle containing short sarcomeres. Collectively, these data show that postmortem TnT proteolysis is sarcomere length-dependent and suggest that thick and thin filament overlap may influence the postmortem aging process in beef.

Neuropathology of SUDEP: Role of inflammation, blood-brain barrier impairment, and hypoxia.

PubMed

Michalak, Zuzanna; Obari, Dima; Ellis, Matthew; Thom, Maria; Sisodiya, Sanjay M

2017-02-07

To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP. Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls. A semiquantitative measure of immunoreactivity was scored for all markers used, and quantitative image analysis was carried out for selected markers. Immunoreactivity was observed for all markers used within all studied brain regions and groups. Immunoreactivity for inflammatory reaction, BBB leakage, and HIF-1α in SUDEP cases was not different from that seen in control groups. This study represents a starting point to explore by immunohistochemistry the mechanisms underlying SUDEP in human brain tissue. Our approach highlights the potential and importance of considering immunohistochemical analysis to help identify biomarkers of SUDEP. Our results suggest that with the markers used, there is no clear immunohistochemical signature of SUDEP in human brain. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Enhanced Characterization of the Smell of Death by Comprehensive Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry (GCxGC-TOFMS)

PubMed Central

Dekeirsschieter, Jessica; Stefanuto, Pierre-Hugues; Brasseur, Catherine; Haubruge, Eric; Focant, Jean-François

2012-01-01

Soon after death, the decay process of mammalian soft tissues begins and leads to the release of cadaveric volatile compounds in the surrounding environment. The study of postmortem decomposition products is an emerging field of study in forensic science. However, a better knowledge of the smell of death and its volatile constituents may have many applications in forensic sciences. Domestic pigs are the most widely used human body analogues in forensic experiments, mainly due to ethical restrictions. Indeed, decomposition trials on human corpses are restricted in many countries worldwide. This article reports on the use of comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) for thanatochemistry applications. A total of 832 VOCs released by a decaying pig carcass in terrestrial ecosystem, i.e. a forest biotope, were identified by GCxGC-TOFMS. These postmortem compounds belong to many kinds of chemical class, mainly oxygen compounds (alcohols, acids, ketones, aldehydes, esters), sulfur and nitrogen compounds, aromatic compounds such as phenolic molecules and hydrocarbons. The use of GCxGC-TOFMS in study of postmortem volatile compounds instead of conventional GC-MS was successful. PMID:22723918

Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

PubMed Central

Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

2015-01-01

IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological presentation reminiscent of LRRK2-associated PD neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS should be considered for genetic testing, and those with a known 22q11.2 deletion should be monitored for the development of parkinsonian symptoms. Molecular studies of the implicated genes, including DGCR8, may help shed light on the underlying pathophysiology of PD in 22q11.2DS and idiopathic PD. PMID:24018986

The use of histology in 638 coronial post-mortem examinations of adults: an audit.

PubMed

Langlois, Neil E I

2006-10-01

An audit was performed to determine the effectiveness of histological sampling of forensic post-mortem cases based on a review of three years' data, which comprised 638 adult autopsy cases. During the study period organs and tissues that appeared macroscopically normal and abnormal were extensively sampled. Histology was regarded as in some way contributory (providing, altering or confirming a cause of death) 53% of the time. The use of histology provided the cause of death in 49 (24%) of the 203 cases not given a cause of death after the completion of the macroscopic examination. When an interim cause of death had been supplied following the completion of the gross examination it was changed in 4.8% of cases, but there were no changes of the manner of death. The majority of the histological diagnoses or discrepancies involved the lungs and the heart. All diagnoses relevant to determining the cause of death would have been made if samples had been taken only from the left ventricle, right ventricle, coronary arteries, lungs, kidneys and brain with any tissue or organ that appeared abnormal macroscopically. A macroscopically identified abnormality that appeared to have been responsible for death was not sampled in 20 cases; consequently, more attention will be paid to sampling macroscopically abnormal tissues. As a result of this audit histology sampling practice has been revised and will be re-audited in the future.

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

PubMed Central

2014-01-01

Introduction Regenerative medicine challenges researchers to find noncontroversial, safe and abundant stem cell sources. In this context, harvesting from asystolic donors could represent an innovative and unlimited reservoir of different stem cells. In this study, cadaveric vascular tissues were established as an alternative source of human cadaver mesenchymal stromal/stem cells (hC-MSCs). We reported the successful cell isolation from postmortem arterial segments stored in a tissue-banking facility for at least 5 years. Methods After thawing, hC-MSCs were isolated with a high efficiency (12 × 106) and characterized with flow cytometry, immunofluorescence, molecular and ultrastructural approaches. Results In early passages, hC-MSCs were clonogenic, highly proliferative and expressed mesenchymal (CD44, CD73, CD90, CD105, HLA-G), stemness (Stro-1, Oct-4, Notch-1), pericyte (CD146, PDGFR-β, NG2) and neuronal (Nestin) markers; hematopoietic and vascular markers were negative. These cells had colony and spheroid-forming abilities, multipotency for their potential to differentiate in multiple mesengenic lineages and immunosuppressive activity to counteract proliferation of phytohemagglutinin-stimulated blood mononuclear cells. Conclusions The efficient procurement of stem cells from cadaveric sources, as postmortem vascular tissues, demonstrates that such cells can survive to prolonged ischemic insult, anoxia, freezing and dehydration injuries, thus paving the way for a scientific revolution where cadaver stromal/stem cells could effectively treat patients demanding cell therapies. PMID:24429026

Common Postmortem Computed Tomography Findings Following Atraumatic Death: Differentiation between Normal Postmortem Changes and Pathologic Lesions

PubMed Central

Gonoi, Wataru; Okuma, Hidemi; Shirota, Go; Shintani, Yukako; Abe, Hiroyuki; Takazawa, Yutaka; Fukayama, Masashi; Ohtomo, Kuni

2015-01-01

Computed tomography (CT) is widely used in postmortem investigations as an adjunct to the traditional autopsy in forensic medicine. To date, several studies have described postmortem CT findings as being caused by normal postmortem changes. However, on interpretation, postmortem CT findings that are seemingly due to normal postmortem changes initially, may not have been mere postmortem artifacts. In this pictorial essay, we describe the common postmortem CT findings in cases of atraumatic in-hospital death and describe the diagnostic pitfalls of normal postmortem changes that can mimic real pathologic lesions. PMID:26175579

Postmortem computed tomography as an adjunct to autopsy for analyzing fatal motor vehicle crash injuries: results of a pilot study.

PubMed

Sochor, Mark R; Trowbridge, Matthew J; Boscak, Alexis; Maino, John C; Maio, Ronald F

2008-09-01

Detailed fatal injury data after fatal motor vehicle crashes (MVC) are necessary to improve occupant safety and promote injury prevention. Autopsy remains the principle source of detailed fatal injury data. However, procedure rates are declining because of a range of technical, ethical, and religious concerns. Postmortem computed tomography (PMCT) is a potential alternative or adjunct to autopsy which is increasingly used by forensic researchers. However, there are only limited data regarding the utility of PMCT for analysis of fatal MVC injuries. We performed whole body PMCT and autopsy on six subjects fatally injured in MVC in a single county in Michigan. All injuries detected by either method were coded using the Abbreviated Injury Scale (AIS). Severe injuries, defined as AIS 3 or higher (AIS 3+), were tallied for each forensic procedure to allow a comparison of relative diagnostic performance. A total of 46 AIS 3+ injuries were identified by autopsy and PMCT for these cases. The addition of PMCT to autopsy increased overall detection of AIS 3+ injuries (all types) by 28%. PMCT detected 27% more AIS 3+ skeletal injuries than autopsy but 25% less soft tissue injuries. Use of PMCT improves the detection of AIS 3+ injuries after fatal MVC compared with isolated use of autopsy and also produces a highly detailed permanent objective record. PMCT appears to improve detection of skeletal injury compared with autopsy but is less sensitive than autopsy for the detection of AIS 3+ soft tissue injuries. Neither autopsy nor PMCT identified all AIS 3+ injuries revealed by the combination of the two methodologies. This suggests that PMCT should be used as an adjunct to autopsy rather than a replacement whenever feasible.

The Stone Cold Truth: The Effect of Concrete Encasement on the Rate and Pattern of Soft Tissue Decomposition.

PubMed

Martin, D C; Dabbs, Gretchen R; Roberts, Lindsey G; Cleary, Megan K

2016-03-01

This study provides a descriptive analysis of taphonomic changes observed in the soft tissue of ten pigs (Sus scrofa) after being encased in Quickrete (®) concrete and excavated at monthly or bimonthly intervals over the course of 2 years. The best method of subject excavation was investigated. Rate and pattern of decomposition were compared to a nonencased control subject. Results demonstrate subjects interred in concrete decomposed significantly slower than the control subject (p < 0.01), the difference being observable after 1 month. After 1 year, the encased subject was in the early stage of decomposition with purging fluids and intact organs present, versus complete skeletonization of the control subject. Concrete subjects also display a unique decomposition pattern, exhibiting a chemically burned outer layer of skin and a common separation of the dermal and epidermal layers. Results suggest using traditional methods to estimate postmortem interval on concrete subjects may result in underestimation. © 2015 American Academy of Forensic Sciences.

Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder.

PubMed

Cobb, J A; O'Neill, K; Milner, J; Mahajan, G J; Lawrence, T J; May, W L; Miguel-Hidalgo, J; Rajkowska, G; Stockmeier, C A

2016-03-01

Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness. Pathology in astrocytes may contribute significantly to this reduced volume and to the involvement of the hippocampus in MDD. Postmortem hippocampal tissues were collected from 17 subjects with MDD and 17 psychiatrically-normal control subjects. Sections from the body of the hippocampus were immunostained for glial fibrillary acidic protein (GFAP), a marker of intermediate filament protein expressed in astrocytes. The density of GFAP-immunoreactive astrocytes was measured in the hippocampus using 3-dimensional cell counting. Hippocampal subfields were also assessed for GFAP-immunoreactive area fraction. In CA1, there was a significant positive correlation between age and either density or area fraction in MDD. The density of astrocytes in the hilus, but not CA1 or CA2/3, was significantly decreased only in depressed subjects not taking an antidepressant drug, but not for depressed subjects taking an antidepressant drug. The area fraction of GFAP-immunoreactivity was significantly decreased in the dentate gyrus in women but not men with depression. In CA2/3, the area fraction of GFAP-immunoreactivity was inversely correlated with the duration of depression in suicide victims. Astrocyte contributions to neuronal function in the hilus may be compromised in depressed subjects not taking antidepressant medication. Due to the cross-sectional nature of the present study of postmortem brain tissue, it remains to be determined whether antidepressant drug treatment prevented a decrease in GFAP-immunoreactive astrocyte density or restored cell density to normal levels. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Forensic proteomics for the evaluation of the post-mortem decay in bones.

PubMed

Procopio, Noemi; Williams, Anna; Chamberlain, Andrew T; Buckley, Michael

2018-04-15

Current methods for evaluation the of post-mortem interval (PMI) of skeletal remains suffer from poor accuracy due to the great number of variables that affect the diagenetic process and to the lack of specific guidelines to address this issue. During decomposition, proteins can undergo cumulative decay over the time, resulting in a decrease in the range and abundance of proteins present (i.e., the proteome) in different tissues as well as in an increase of post-translational modifications occurring in these proteins. In this study, we investigate the applicability of bone proteomic analyses to simulated forensic contexts, looking for specific biomarkers that may help the estimation of PMI, as well as evaluate a previously discovered marker for the estimation of biological age. We noticed a reduction of particular plasma and muscle proteins with increasing PMIs, as well as an increased deamidation of biglycan, a protein with a role in modulating bone growth and mineralization. We also corroborated our previous results regarding the use of fetuin-A as a potential biomarker for the estimation of age-at-death, demonstrating the applicability and the great potential that proteomics may have towards forensic sciences. The estimation of the post-mortem interval has a key role in forensic investigations, however nowadays it still suffers from poor reliability, especially when body tissues are heavily decomposed. Here we propose for the first time the application of bone proteomics to the estimation of the time elapsed since death and found several new potential biomarkers to address this, demonstrating the applicability of proteomic analyses to forensic sciences. Copyright © 2018. Published by Elsevier B.V.

Postmortem endogenous ethanol production and diffusion from the lung due to aspiration of wood chip dust in the work place.

PubMed

Furumiya, Junichi; Nishimura, Hiroyuki; Nakanishi, Akinori; Hashimoto, Yoshiaki

2011-07-01

We report an autopsy case of postmortem ethanol diffusion into the cardiac blood after aspiration of wood chips, although antemortem ethanol consumption was not evident. A man in his twenties, who was loading a truck with small wood chips in a hot, humid storehouse, was accidentally buried in a heap of chips. At the time the body was discovered, 20 h after the accident, rectal temperature was 36°C. Autopsy showed the cause of death to be asphyxia due to obstruction of the airway by aspiration of wood chips. The ethanol and n-propanol levels were significantly higher in the lungs (left, 0.603 and 0.009 mg/g; right, 0.571 and 0.006 mg/g) than in other tissues. A significant difference in ethanol concentration was observed between the left cardiac blood (0.243 mg/g) and the right femoral blood (0.042 mg/g). Low levels of ethanol and n-propanol were detected in the stomach contents (0.105 and 0.001 mg/g, respectively). In order to determine whether aspiration of wood chips affects postmortem ethanol production in the lung, we measured the ethanol and n-propanol levels of homogenized rabbit lung tissue incubated with autoclaved or non-autoclaved wood chips. Levels of ethanol and n-propanol were significantly higher in the homogenates incubated with non-autoclaved chips for 24h. The results of this animal experiment suggested that the ethanol detected in the lung was produced by putrefactive bacteria within the wood chips. After death, the ethanol produced endogenously in the lung appears to have diffused and affected the ethanol concentration of the left cardiac blood. 2011 Elsevier Ireland Ltd. All rights reserved.

Virtopsy -- noninvasive detection of occult bone lesions in postmortem MRI: additional information for traffic accident reconstruction.

PubMed

Buck, Ursula; Christe, Andreas; Naether, Silvio; Ross, Steffen; Thali, Michael J

2009-05-01

In traffic accidents with pedestrians, cyclists or motorcyclists, patterned impact injuries as well as marks on clothes can be matched to the injury-causing vehicle structure in order to reconstruct the accident and identify the vehicle which has hit the person. Therefore, the differentiation of the primary impact injuries from other injuries is of great importance. Impact injuries can be identified on the external injuries of the skin, the injured subcutaneous and fat tissue, as well as the fractured bones. Another sign of impact is a bone bruise. The bone bruise, or occult bone lesion, means a bleeding in the subcortical bone marrow, which is presumed to be the result of micro-fractures of the medullar trabeculae. The aim of this study was to prove that bleeding in the subcortical bone marrow of the deceased can be detected using the postmortem noninvasive magnetic resonance imaging. This is demonstrated in five accident cases, four involving pedestrians and one a cyclist, where bone bruises were detected in different bones as a sign of impact occurring in the same location as the external and soft tissue impact injuries.

Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation with Brain Iron in Normal Aging

PubMed Central

Poynton, Clare; Jenkinson, Mark; Adalsteinsson, Elfar; Sullivan, Edith V.; Pfefferbaum, Adolf; Wells, William

2015-01-01

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or ‘QSIP’. The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase (FDRI), and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in-vivo FDRI: statistically significant Spearman correlations ranging from Rho = 0.905 to Rho = 1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions. PMID:25248179

The Impact of Oxidative Stress Factors on the Viability, Senescence, and Methylation Status of Olfactory Bulb-Derived Glial Cells Isolated from Human Cadaver Donors.

PubMed

Marycz, Krzysztof; Kornicka, Katarzyna; Grzesiak, Jakub; Tomaszewski, Krzysztof A; Szarek, Dariusz; Kopacz, Paweł

2017-01-01

The olfactory bulb (OB) is a unique structure in the central nervous system that retains the ability to create new neuronal connections. Glial cells isolated from the OB have been recently considered as a novel and promising tool to establish an effective therapy for central nervous system injuries. Due to the hindered access to autologous tissue for cell isolation, an allogeneic source of tissues obtained postmortem has been proposed. In this study, we focused on the morphological and molecular characteristics of human OB-derived glial cells isolated postmortem, at different time points after a donor's death. We evaluated the proliferative activity of the isolated cells, and investigated the ultrastructure of the mitochondria, the accumulation of intracellular reactive oxygen species, and the activity of superoxide dismutase. The data obtained clearly indicate that the duration of ischemia is crucial for the viability/senescence rate of OB-derived glial cells. The OB can be isolated during autopsy and still stand as a source of viable glial cells, but ischemia duration is a major factor limiting its potential usefulness in therapies. © 2017 S. Karger AG, Basel.

Neuronal Type-Specific Gene Expression Profiling and Laser-Capture Microdissection

PubMed Central

Pietersen, Charmaine Y.; Lim, Maribel P.; Macey, Laurel; Woo, Tsung-Ung W.; Sonntag, Kai C.

2014-01-01

The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling. To identify neurons in human postmortem brain tissue, one can use the inherent properties of the neuron, such as pigmentation and morphology or its structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neuronal cells and high-quality RNA from human postmortem brain material using a combination of rapid IHC, Nissl staining, or simple morphology with Laser-Capture Microdissection (LCM) or Laser Microdissection (LMD). PMID:21761317

Neuronal type-specific gene expression profiling and laser-capture microdissection.

PubMed

Pietersen, Charmaine Y; Lim, Maribel P; Macey, Laurel; Woo, Tsung-Ung W; Sonntag, Kai C

2011-01-01

The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling. To identify neurons in human postmortem brain tissue, one can use the inherent properties of the neuron, such as pigmentation and morphology or its structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neuronal cells and high-quality RNA from human postmortem brain material using a combination of rapid IHC, Nissl staining, or simple morphology with Laser-Capture Microdissection (LCM) or Laser Microdissection (LMD).

Application of a novel sorting system for equine mesenchymal stem cells (MSCs)

PubMed Central

Radtke, Catherine L.; Nino-Fong, Rodolfo; Esparza Gonzalez, Blanca P.; McDuffee, Laurie A.

2014-01-01

The objective of this study was to validate non-equilibrium gravitational field-flow fractionation (GrFFF), an immunotag-less method of sorting mesenchymal stem cells (MSCs) into subpopulations, for use with MSCs derived from equine muscle tissue, periosteal tissue, bone marrow, and adipose tissue. Cells were collected from 6 young, adult horses, postmortem. Cells were isolated from left semitendinosus muscle tissue, periosteal tissue from the distomedial aspect of the right tibia, bone marrow aspirates from the fourth and fifth sternebrae, and left supragluteal subcutaneous adipose tissue. Aliquots of 800 × 103 MSCs from each tissue source were separated and injected into a ribbon-like capillary device by continuous flow (GrFFF proprietary system). Cells were sorted into 6 fractions and absorbencies [optical density (OD)] were read. Six fractions from each of the 6 aliquots were then combined to provide pooled fractions that had adequate cell numbers to seed at equal concentrations into assays. Equine muscle tissue-derived, periosteal tissue-derived, bone marrow-derived, and adipose tissue-derived mesenchymal stem cells were consistently sorted into 6 fractions that remained viable for use in further assays. Fraction 1 had more cuboidal morphology in culture when compared to the other fractions. Statistical analysis of the fraction absorbencies (OD) revealed a P-value of < 0.05 when fractions 2 and 3 were compared to fractions 1, 4, 5, and 6. It was concluded that non-equilibrium GrFFF is a valid method for sorting equine muscle tissue-derived, periosteal tissue-derived, bone marrow-derived, and adipose tissue-derived mesenchymal stem cells into subpopulations that remain viable, thus securing its potential for use in equine stem cell applications and veterinary medicine. PMID:25355998

Immunohistochemical distribution of chromogranin A in medicolegal autopsy materials.

PubMed

Yoshida, Chiemi; Ishikawa, Takaki; Michiue, Tomomi; Zhao, Dong; Komatsu, Ayumi; Quan, Li; Maeda, Hitoshi

2009-04-01

Chromogranin A (CgA) was recently reported as a marker of various stress responses. The aim of this study was to investigate the immunohistochemical distribution of CgA in human tissues in medicolegal autopsy cases as a basis for postmortem investigation of stress responses. The autopsy cases (n=30, within 48 h postmortem) comprised cases of mechanical asphyxia (n=15: strangulation, n=8; hanging, n=7) and acute myocardial infarction/ischemia (AMI, n=15). Routinely formalin-fixed paraffin-embedded tissue sections, including those of the hypothalamus, pituitary gland, cardiac muscle, lungs, liver, kidneys, spleen, skeletal muscle, skin, thyroid gland, submandibular gland, pancreas, and adrenal gland, were stained with polyclonal anti-human CgA antibodies and CgA positivity was quantitatively examined. Localization of CgA immunopositivity was clearly demonstrated in specific cell components in all tissue sections. CgA was mainly observed in the anterior lobe of the pituitary, adrenal medulla, neurons and some gliocytes in the hypothalamus, submandibular gland, follicular epithelial cells and connective tissue in the thyroid gland and pancreatic islet cells. CgA immunopositivity showed no significant difference between mechanical asphyxia and AMI cases. Positivity was slightly higher in adenohypophysis, adrenal medullar, and pancreatic islet cells (approximately 50-80%) than in the thyroid and submandibular glands (approximately 30-60%); however, a large case difference was observed in hypothalamic CgA immunopositivity (0-100%). These findings suggest that hypothalamic CgA immunopositivity can be used as a marker for investigating individual differences in stress responses during the death process. Further investigation of other causes of death is needed.

Midbrain dopamine function in schizophrenia and depression: a post-mortem and positron emission tomographic imaging study.

PubMed

Howes, Oliver D; Williams, Matthew; Ibrahim, Kemal; Leung, Garret; Egerton, Alice; McGuire, Philip K; Turkheimer, Federico

2013-11-01

Elevated in vivo markers of presynaptic striatal dopamine activity have been a consistent finding in schizophrenia, and include a large effect size elevation in dopamine synthesis capacity. However, it is not known if the dopaminergic dysfunction is limited to the striatal terminals of dopamine neurons, or is also evident in the dopamine neuron cell bodies, which mostly originate in the substantia nigra. The aim of our studies was therefore to determine whether dopamine synthesis capacity is altered in the substantia nigra of people with schizophrenia, and how this relates to symptoms. In a post-mortem study, a semi-quantitative analysis of tyrosine hydroxylase staining was conducted in nigral dopaminergic cells from post-mortem tissue from patients with schizophrenia (n = 12), major depressive disorder (n = 13) and matched control subjects (n = 13). In an in vivo imaging study, nigral and striatal dopaminergic function was measured in patients with schizophrenia (n = 29) and matched healthy control subjects (n = 29) using (18)F-dihydroxyphenyl-L-alanine ((18)F-DOPA) positron emission tomography. In the post-mortem study we found that tyrosine hydroxylase staining was significantly increased in nigral dopaminergic neurons in schizophrenia compared with both control subjects (P < 0.001) and major depressive disorder (P < 0.001). There was no significant difference in tyrosine hydroxylase staining between control subjects and patients with major depressive disorder, indicating that the elevation in schizophrenia is not a non-specific indicator of psychiatric illness. In the in vivo imaging study we found that (18)F-dihydroxyphenyl-L-alanine uptake was elevated in both the substantia nigra and in the striatum of patients with schizophrenia (effect sizes = 0.85, P = 0.003 and 1.14, P < 0.0001, respectively) and, in the voxel-based analysis, was elevated in the right nigra (P < 0.05 corrected for family wise-error). Furthermore, nigral (18)F-dihydroxyphenyl-L-alanine uptake was positively related with the severity of symptoms (r = 0.39, P = 0.035) in patients. However, whereas nigral and striatal (18)F-dihydroxyphenyl-L-alanine uptake were positively related in control subjects (r = 0.63, P < 0.001), this was not the case in patients (r = 0.30, P = 0.11). These findings indicate that elevated dopamine synthesis capacity is seen in the nigral origin of dopamine neurons as well as their striatal terminals in schizophrenia, and is linked to symptom severity in patients.

Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples.

PubMed

Ugarte, Ana; Corbacho, David; Aymerich, María S; García-Osta, Ana; Cuadrado-Tejedor, Mar; Oyarzabal, Julen

2018-04-19

Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD). In addition, drugs binding to brain tissues from AD and PD animal models do not always recapitulate their binding to the corresponding human injured brain tissues. These results reveal potentially relevant implications for CNS drug discovery.

Post-sampling release of free fatty acids - effects of heat stabilization and methods of euthanasia.

PubMed

Jernerén, Fredrik; Söderquist, Marcus; Karlsson, Oskar

2015-01-01

The field of lipid research has made progress and it is now possible to study the lipidome of cells and organelles. A basic requirement of a successful lipid study is adequate pre-analytical sample handling, as some lipids can be unstable and postmortem changes can cause substantial accumulation of free fatty acids (FFAs). The aim of the present study was to investigate the effects of conductive heat stabilization and euthanasia methods on FFA levels in the rat brain and liver using liquid chromatography tandem mass spectrometry. The analysis of brain homogenates clearly demonstrated phospholipase activity and time-dependent post-sampling changes in the lipid pool of snap frozen non-stabilized tissue. There was a significant increase in FFAs already at 2min, which continued over time. Heat stabilization was shown to be an efficient method to reduce phospholipase activity and ex vivo lipolysis. Post-sampling effects due to tissue thawing and sample preparation induced a massive release of FFAs (up to 3700%) from non-stabilized liver and brain tissues compared to heat stabilized tissue. Furthermore, the choice of euthanasia method significantly influenced the levels of FFAs in the brain. The FFAs were decreased by 15-44% in the group of animals euthanized by pentobarbital injection compared with CO2 inhalation or decapitation. Our results highlight the importance of considering euthanasia methods and pre-analytical treatment in lipid analysis, factors which may otherwise interfere with the outcome of the experiments. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of Vitality in the Experimental Hanging Model of Rats by Using Immunohistochemical IL-1β Antibody Staining.

PubMed

Balandiz, Hüseyin; Pehlivan, Sultan; Çiçek, Ali Fuat; Tuğcu, Harun

2015-12-01

Hanging is the most common suicide method in the world, and the discrimination of antemortem-postmortem hanging must be done at autopsy. The aim of this experimental study was to examine the immunohistochemical expression of IL-1β antibody at the hanging mark skin samples of rats to discriminate antemortem and postmortem hangings. A total of 20 Wistar albino rats were used for this study. The groups were as follows: A-1, antemortem control group; A-2, antemortem second-hour hanging mark skin samples; A-3, antemortem 24th-hour hanging mark skin samples; A-4, antemortem 72nd-hour hanging mark skin samples; B-1, postmortem control group; and B-2, postmortem second-hour hanging mark skin samples. Interleukin-1β immunostaining was performed to all tissue samples. For epidermal cells, group A-1 samples did not show IL-1β immunostaining, group A-2 samples were severely immunostained, and groups A-3 and A-4 samples' staining were slightly decreased. There was no IL-1β antibody staining in groups B-1 and B-2 samples. For adnexal cells, groups A-1 and B-1 samples did not show IL-1β immunostaining, staining of group A-2 samples was mild to severe, and groups A-3 and A-4 samples' staining were slightly decreased. Half of the group B-2 samples did not show IL-1β immunostaining. For subepidermal cells, most of the samples of groups A-1 and B-1 showed slight immunostaining, groups A-2 and B-2 samples' staining were mild to severe, and there were slight immunostaining in groups A-3 and A-4 samples. The majority of vascular structure cells did not show IL-1β immunostaining. Interleukin-1β immunostaining of epidermal cells can discriminate antemortem-postmortem hangings, but vascular structure cells and subepidermal cells cannot discriminate vital hangings.

Alteration of fatty acid profile and nucleotide-related substances in post-mortem breast meat of α-lipoic acid-fed broiler chickens.

PubMed

Hamano, Y

2016-08-01

The present study was conducted to determine the effects of α-lipoic acid supplementation on post-mortem changes in the fatty acid profile and concentrations of nucleotide-related substances, especially those of a taste-active compound, inosine 5'-monophosphate, in chicken meat. Mixed-sex broiler chicks aged 14 d were divided into three groups of 16 birds each and were fed on diets supplemented with α-lipoic acid at levels of 0, 100 or 200 mg/kg for 4 weeks. Blood and breast muscle samples were taken at 42 d of age under the fed condition and then after fasting for 18 h. The breast muscle obtained from fasted chickens was subsequently refrigerated at 2°C for one and 3 d. α-Lipoic acid supplementation did not affect any plasma metabolite concentration independently of feeding condition, while a slight increase in plasma glucose concentration was shown with both administration levels of α-lipoic acid. In early post-mortem breast muscle under the fed condition, α-lipoic acid had no effect on concentrations of fatty acids or nucleotides of ATP, ADP, and AMP. In post-mortem breast tissues obtained from fasted chickens, total fatty acid concentrations were markedly increased by α-lipoic acid feeding at 200 mg/kg irrespective of length of refrigeration. This effect was dependent on stearic acid, oleic acid, linoleic acid and linolenic acid. However, among fatty acids, the only predominantly increased unsaturated fatty acid was oleic acid. Dietary supplementation with α-lipoic acid at 200 mg/kg increased the inosine 5'-monophosphate concentration in breast meat and, in contrast, reduced the subsequent catabolites, inosine and xanthine, regardless of the length of refrigeration. Therefore, the present study suggests that α-lipoic acid administration altered the fatty acid profile and improved meat quality by increasing taste-active substances in the post-mortem meat obtained from fasted chickens.

Preventing disease transmission by deceased tissue donors by testing blood for viral nucleic acid.

PubMed

Strong, D Michael; Nelson, Karen; Pierce, Marge; Stramer, Susan L

2005-01-01

Nucleic acid testing (NAT) has reduced the risk of transmitting infectious disease through blood transfusion. Currently NAT for HIV-1 and HCV are FDA licensed and performed by nearly all blood collection facilities, but HBV NAT is performed under an investigational study protocol. Residual risk estimates indicate that NAT could potentially reduce disease transmission through transplanted tissue. However, tissue donor samples obtained post-mortem have the potential to produce an invalid NAT result due to inhibition of amplification reactions by hemolysis and other factors. The studies reported here summarize the development of protocols to allow NAT of deceased donor samples with reduced rates of invalid results. Using these protocols, inventories from two tissue centers were tested with greater than 99% of samples producing a valid test result.

Enzooty of non-Hodgkin's malignant lymphoma of Papio hamadryas in Sukhumi monkey colony. Clinical and morphological signs of pre-lymphoma.

PubMed

Yakovleva, Lelita A; Lapin, Boris A; Agumava, Aslan A

2018-04-01

Inoculation of hamadryas baboons with blood of leukemia ill people-induced malignant non-Hodgkin's lymphoma in experimental animals for a very considerable latency period. At close contact of inoculated baboons with healthy non-inoculated animals, the lymphoma spread between them. The epidemiological analysis, postmortem examination, histological analysis, tissue culturing, and PCR were used for the diagnostics of lymphoma and pre-lymphoma, purification, identification of STLV-1, and HVP viruses. Characteristic clinical and morphological signs designated by us as pre-lymphoma often precede the lymphoma development. In some cases, pre-lymphoma does not develop in lymphoma because animals die from various diseases and do not reach the point of the lymphoma development. The horizontal transmission of lymphoma arising with the participation of T-lymphotropic retrovirus STLV-1 is shown. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Induction of hypoxia-inducible factor-1alpha in two kinds of rats asphyxiation death models].

PubMed

Zhang, Bei-lei; Yang, Zhi-hui; Ran, Peng; Liang, Wei-bo; Zhou, Bin; Zhang, Geng-qian; Lu, Mei-li; Zhang, Lin

2007-02-15

To investigate the expression of hypoxia-inducible factor 1-alpha (HIF1-alpha) in the heart, lung, liver and kidney in rats died of two typical models of asphyxia. Two asphyxia models were made and tissue samples of the dead rats were collected from different groups at various postmortem duration. The expression and the changes of HIF1-alpha in various tissues were examined by immunohistochemistry and image analysis techniques. Results Significant expression of HIF1-alpha was observed in the myocardial fibers, kidney cells, liver cells and lung cells in both asphyxia models, but not in the control group. The expression of HIF1-alpha in various tissues in the rat died of nitrogen gas breathing was found in the nuclei at 0 hour and the expression level decreased gradually thereafter. The HIF1-alpha expression level and duration in various tissues of the rat died of hanging were higher and longer than that of the former group, with a peak of the expression level observed 6 hours after death, and then started to decline in all tissues except the heart where the expression still showed an increase 24 hours after death. The control groups showed a steady expression in the cytoplasm but not in the nuclei. HIF1-alpha appears to be a valuable biomarker in the diagnosis of asphyxia within 24 hours after death.

Molecular preservation in Late Cretaceous sauropod dinosaur eggshells.

PubMed

Schweitzer, M H; Chiappe, L; Garrido, A C; Lowenstein, J M; Pincus, S H

2005-04-22

Exceptionally preserved sauropod eggshells discovered in Upper Cretaceous (Campanian) deposits in Patagonia, Argentina, contain skeletal remains and soft tissues of embryonic Titanosaurid dinosaurs. To preserve these labile embryonic remains, the rate of mineral precipitation must have superseded post-mortem degradative processes, resulting in virtually instantaneous mineralization of soft tissues. If so, mineralization may also have been rapid enough to retain fragments of original biomolecules in these specimens. To investigate preservation of biomolecular compounds in these well-preserved sauropod dinosaur eggshells, we applied multiple analytical techniques. Results demonstrate organic compounds and antigenic structures similar to those found in extant eggshells.

Molecular preservation in Late Cretaceous sauropod dinosaur eggshells

PubMed Central

Schweitzer, M.H; Chiappe, L; Garrido, A.C; Lowenstein, J.M; Pincus, S.H

2005-01-01

Exceptionally preserved sauropod eggshells discovered in Upper Cretaceous (Campanian) deposits in Patagonia, Argentina, contain skeletal remains and soft tissues of embryonic Titanosaurid dinosaurs. To preserve these labile embryonic remains, the rate of mineral precipitation must have superseded post-mortem degradative processes, resulting in virtually instantaneous mineralization of soft tissues. If so, mineralization may also have been rapid enough to retain fragments of original biomolecules in these specimens. To investigate preservation of biomolecular compounds in these well-preserved sauropod dinosaur eggshells, we applied multiple analytical techniques. Results demonstrate organic compounds and antigenic structures similar to those found in extant eggshells. PMID:15888409

Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy.

PubMed

van Veluw, Susanne J; Biessels, Geert Jan; Klijn, Catharina J M; Rozemuller, Annemieke J M

2016-03-01

To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology. Five decedents (mean age at death 79.6 ± 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury. On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury. This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease. © 2016 American Academy of Neurology.

Nodding syndrome since 2012: recent progress, challenges and recommendations for future research.

PubMed

Colebunders, R; Post, R; O'Neill, S; Haesaert, G; Opar, B; Lakwo, T; Laudisoit, A; Hendy, A

2015-02-01

We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics. © 2014 John Wiley & Sons Ltd.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Ocfentanil overdose fatality in the recreational drug scene.

PubMed

Coopman, Vera; Cordonnier, Jan; De Leeuw, Marc; Cirimele, Vincent

2016-09-01

This paper describes the first reported death involving ocfentanil, a potent synthetic opioid and structure analogue of fentanyl abused as a new psychoactive substance in the recreational drug scene. A 17-year-old man with a history of illegal substance abuse was found dead in his home after snorting a brown powder purchased over the internet with bitcoins. Acetaminophen, caffeine and ocfentanil were identified in the powder by gas chromatography mass spectrometry and reversed-phase liquid chromatography with diode array detector. Quantitation of ocfentanil in biological samples was performed using a target analysis based on liquid-liquid extraction and ultra performance liquid chromatography tandem mass spectrometry. In the femoral blood taken at the external body examination, the following concentrations were measured: ocfentanil 15.3μg/L, acetaminophen 45mg/L and caffeine 0.23mg/L. Tissues sampled at autopsy were analyzed to study the distribution of ocfentanil. The comprehensive systematic toxicological analysis on the post-mortem blood and tissue samples was negative for other compounds. Based on circumstantial evidence, autopsy findings and the results of the toxicological analysis, the medical examiner concluded that the cause of death was an acute intoxication with ocfentanil. The manner of death was assumed to be accidental after snorting the powder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Detection of butane gas inhalation at 16days after hypoxic encephalopathy: A case report.

PubMed

Sato, Takako; Nishioka, Hiroshi; Tsuboi, Kento; Katagi, Munehiro; Miki, Akihiro; Saito, Takashi; Abe, Shuntaro; Nomura, Masakatsu; Kitagawa, Misa; Tsuchihashi, Hitoshi; Suzuki, Koichi

2017-11-01

In Japan, there are increasing reports of death by poisoning following butane abuse. To determine the specific cause of death in such cases, it is important to confirm the presence of fuel gas components in the body, although careful analysis is required because of their volatile properties. In most reported cases, the subject died suddenly during or immediately after butane aspiration. Thus, the butane concentration in the samples from the deceased should be relatively high. Herein, we present a case of an 18-year-old man found with cardiopulmonary arrest, who then exhibited hypoxic encephalopathy for 16days in a hospital. At autopsy, we detected hypoxic encephalopathy, pneumonia, and ischemia-reperfusion injury of the myocardium, while the cause of cardiac arrest remained unclear. Toxicological analysis was then performed for fuel gas components in several specimens collected at autopsy. Results showed that n-butane and isobutane were detected in the adipose tissue at 16days after inhalation, indicating a role of butane gas inhalation as the cause of death. These data suggest that adipose tissue may be the most appropriate analysis sample to be collected at postmortem in cases where involvement of volatile and fat-soluble gas inhalation is suspected. Copyright © 2017 Elsevier B.V. All rights reserved.

White Matter Glial Pathology in Autism

DTIC Science & Technology

2014-09-01

Autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0302 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Gregory A. Ordway...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Methods used to directly study the autism brain include brain imaging in living patients and...pathology studies using postmortem brain tissues from deceased autism spectrum disorder (ASD) donors. These methods typically focus on brain regions

Case study: fatal poisoning by malathion.

PubMed

Thompson, T S; Treble, R G; Magliocco, A; Roettger, J R; Eichhorst, J C

1998-07-20

A case involving a fatal poisoning (suicide) by the insecticide malathion is described. The intact insecticide was found in the post-mortem blood and gastric contents at concentrations of 1.8 and 978 micrograms/ml, respectively. None of the insecticide was found in the autopsied liver tissue. Gas chromatography-mass spectrometry (GC-MS) techniques were used for the identification and quantification of malathion in the body fluids.

VeroNectin-4 is a highly sensitive cell line that can be used for the isolation and titration of Peste des Petits Ruminants virus.

PubMed

Fakri, F; Elarkam, A; Daouam, S; Tadlaoui, K; Fassi-Fihri, O; Richardson, C D; Elharrak, M

2016-02-01

Peste des Petits Ruminants virus (PPRV) is a member of the Morbillivirus subgroup of the family Paramyxoviridae, and is one of the most contagious diseases of small ruminants throughout Africa and the rest of the world. Different cell lines have previously been used to isolate PPRV but with limited success. Thus, to improve the isolation of Morbilliviruses, human, canine, and goat homologues of the lymphocyte receptor signaling lymphocyte activation molecule (SLAM) have been introduced into cells that can support virus replication. However, the amino acid sequence of SLAM varies between species, and often requires adaptation of a particular virus to different versions of the receptor. The protein sequence of Nectin-4 is highly conserved between different mammals, which eliminate the need for receptor adaptation by the virus. Cell lines expressing Nectin-4 have previously been used to propagate measles and canine distemper viruses. In this study, we compared infections in Vero cells expressing canine SLAM (VeroDogSLAM) to those in Vero cells expressing Nectin-4 (VeroNectin-4), following inoculations with wild-type strains of PPRV. Virus isolation using VeroNectin-4 cells was successful with 23% of swabbed samples obtained from live infected animals, and was 89% effective using post-mortem tissues of infected sheep. By contrast, only 4.5% efficiency was observed from swab samples and 67% efficiency was obtained in virus isolation from post-mortem tissues using VeroDogSLAM cells. The average incubation period for virus recovery from post-mortem tissues was 3.4 days using VeroNectin-4 cells, compared with 5.5 days when using VeroDogSLAM cells. The virus titers of PPRV obtained from VeroNectin-4 cells were also higher than those derived from VeroDogSLAM cells. A comparison of the growth kinetics for PPRV in the two cell lines confirmed the superiority of VeroNectin-4 cells for PPR diagnostic purposes and vaccine virus titration. Copyright © 2015 Elsevier B.V. All rights reserved.

Postmortem bone marrow analysis in forensic science: study of 73 cases and review of the literature.

PubMed

Tattoli, Lucia; Tsokos, Michael; Sautter, Julia; Anagnostopoulos, Joannis; Maselli, Eloisa; Ingravallo, Giuseppe; Delia, Mario; Solarino, Biagio

2014-01-01

In forensic sciences, bone marrow (BM) is an alternative matrix in postmortem toxicology because of its good resistance to autolysis and contaminations. Nevertheless, few studies have been focused on postmortem BM morphological changes after pathological stimuli. We examined 73 BM samples from forensic autopsies; causes of death were both natural and traumatic. BM samples were collected from the sternum by needle aspiration and biopsy; in selected cases, immunohistochemistry was performed. Few autolytic changes were found; BM cellularity decreased with increasing age and postmortem interval. Notable cell changes were detected in 45 cases (61.64%): neoplastic (n=4), and non-neoplastic BM findings (n=41), including multiorgan failure/sepsis (n=26), myelodisplastic-like conditions (n=11), and anaphylactic reactions (n=4). The results showed that BM cellularity supported circumstantial and autopsy findings, suggesting that BM samples could be a useful tool in forensic science applications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cardiac Implantable Electronic Device Interrogation at Forensic Autopsy: An Underestimated Resource?

PubMed

Lacour, Philipp; Buschmann, Claas; Storm, Christian; Nee, Jens; Parwani, Abdul Shokor; Huemer, Martin; Attanasio, Philipp; Boldt, Leif-Hendrik; Rauch, Geraldine; Kucher, Andreas; Pieske, Burkert; Haverkamp, Wilhelm; Blaschke, Florian

2018-06-19

Postmortem interrogations of cardiac implantable electronic devices (CIEDs), recommended at autopsy in suspected cases of sudden cardiac death, are rarely performed, and data on systematic postmortem CIED analysis in the forensic pathology are missing. The aim of the study was to determine whether nonselective postmortem CIED interrogations and data analysis are useful to the forensic pathologist to determine the cause, mechanism, and time of death and to detect potential CIED-related safety issues. From February 2012 to April 2017, all autopsy subjects in the department of forensic medicine at the University Hospital Charité who had a CIED underwent device removal and interrogation. Over the study period, 5368 autopsies were performed. One hundred fifty subjects had in total 151 CIEDs, including 109 pacemakers, 35 defibrillators, and 7 implantable loop recorders. In 40 cases (26.7%) time of death and in 51 cases (34.0%) cause of death could not be determined by forensic autopsy. Of these, CIED interrogation facilitated the determination of time of death in 70.0% of the cases and clarified the cause of death in 60.8%. Device concerns were identified in 9 cases (6.0%), including 3 hardware, 4 programming, and 2 algorithm issues. One CIED was submitted to the manufacturer for a detailed technical analysis. Our data demonstrate the necessity of systematic postmortem CIED interrogation in forensic medicine to determine the cause and timing of death more accurately. In addition, CIED analysis is an important tool to detect potential CIED-related safety issues. © 2018 American Heart Association, Inc.

Postmortem in vitro ethanol production-It could be more common than we think!

PubMed

Quintas, Maria José; Costa, Pedro; Melo, Paula; Castro, André; Franco, João Miguel; Teixeira, Helena M

2017-05-01

The blood alcohol concentration (BAC) is the most frequent determination in a Forensic Toxicology Laboratory. Despite its apparent simplicity, the results interpretation can be complex and always have relevant social and legal implications, particularly in postmortem analysis. In the present report we describe the case of a 55-year-old male with an apparent natural death by myocardial infarction, whose initial BAC was 0.18g/L but, in repeated determinations prompted by discrepancies observed in the first two, it rapidly increased to 0.85g/L three days later, leading to the suspicion of in vitro ethanol production. A microbiological examination of the sample revealed the presence of the bacteria Escherichia coli and Enterococcus faecalis, and yeast Candida parapsilosis, known for their involvement in ethanol production. Although this is a case report and it is not meant to be generalizable, we discuss an existing large body of scientific literature showing the difficulties, limitations and some relevant medico-legal questions regarding BAC determinations in postmortem samples and their interpretation, particularly in the context of plausible in vitro ethanol production. The key conclusion is that evaluating a postmortem BAC is a complex and multifactorial process that always deserves a thorough analysis and a careful interpretation. Copyright © 2017 Elsevier B.V. All rights reserved.

Survival and Intra-Nuclear Trafficking of Burkholderia pseudomallei: Strategies of Evasion from Immune Surveillance?

PubMed

Vadivelu, Jamuna; Vellasamy, Kumutha Malar; Thimma, Jaikumar; Mariappan, Vanitha; Kang, Wen-Tyng; Choh, Leang-Chung; Shankar, Esaki M; Wong, Kum Thong

2017-01-01

During infection, successful bacterial clearance is achieved via the host immune system acting in conjunction with appropriate antibiotic therapy. However, it still remains a tip of the iceberg as to where persistent pathogens namely, Burkholderia pseudomallei (B. pseudomallei) reside/hide to escape from host immune sensors and antimicrobial pressure. We used transmission electron microscopy (TEM) to investigate post-mortem tissue sections of patients with clinical melioidosis to identify the localisation of a recently identified gut microbiome, B. pseudomallei within host cells. The intranuclear presence of B. pseudomallei was confirmed using transmission electron microscopy (TEM) of experimentally infected guinea pig spleen tissues and Live Z-stack, and ImageJ analysis of fluorescence microscopy analysis of in vitro infection of A549 human lung epithelial cells. TEM investigations revealed intranuclear localization of B. pseudomallei in cells of infected human lung and guinea pig spleen tissues. We also found that B. pseudomallei induced actin polymerization following infection of A549 human lung epithelial cells. Infected A549 lung epithelial cells using 3D-Laser scanning confocal microscopy (LSCM) and immunofluorescence microscopy confirmed the intranuclear localization of B. pseudomallei. B. pseudomallei was found within the nuclear compartment of host cells. The nucleus may play a role as an occult or transient niche for persistence of intracellular pathogens, potentially leading to recurrrent episodes or recrudescence of infection.

Survival and Intra-Nuclear Trafficking of Burkholderia pseudomallei: Strategies of Evasion from Immune Surveillance?

PubMed Central

Vadivelu, Jamuna; Vellasamy, Kumutha Malar; Thimma, Jaikumar; Mariappan, Vanitha; Kang, Wen-Tyng; Choh, Leang-Chung; Wong, Kum Thong

2017-01-01

Background During infection, successful bacterial clearance is achieved via the host immune system acting in conjunction with appropriate antibiotic therapy. However, it still remains a tip of the iceberg as to where persistent pathogens namely, Burkholderia pseudomallei (B. pseudomallei) reside/hide to escape from host immune sensors and antimicrobial pressure. Methods We used transmission electron microscopy (TEM) to investigate post-mortem tissue sections of patients with clinical melioidosis to identify the localisation of a recently identified gut microbiome, B. pseudomallei within host cells. The intranuclear presence of B. pseudomallei was confirmed using transmission electron microscopy (TEM) of experimentally infected guinea pig spleen tissues and Live Z-stack, and ImageJ analysis of fluorescence microscopy analysis of in vitro infection of A549 human lung epithelial cells. Results TEM investigations revealed intranuclear localization of B. pseudomallei in cells of infected human lung and guinea pig spleen tissues. We also found that B. pseudomallei induced actin polymerization following infection of A549 human lung epithelial cells. Infected A549 lung epithelial cells using 3D-Laser scanning confocal microscopy (LSCM) and immunofluorescence microscopy confirmed the intranuclear localization of B. pseudomallei. Conclusion B. pseudomallei was found within the nuclear compartment of host cells. The nucleus may play a role as an occult or transient niche for persistence of intracellular pathogens, potentially leading to recurrrent episodes or recrudescence of infection. PMID:28045926

A novel approach to determine post mortem interval using neutron radiography.

PubMed

Bilheux, Hassina Z; Cekanova, Maria; Vass, Arpad A; Nichols, Trent L; Bilheux, Jean C; Donnell, Robert L; Finochiarro, Vincenzo

2015-06-01

One of the most difficult challenges in forensic research is to objectively determine the post-mortem interval (PMI). The accuracy of PMI is critical for determining the timeline of events surrounding a death. Most PMI techniques rely on gross morphological changes of cadavers that are highly sensitive to taphonomic factors. Recent studies have demonstrated that even exhumed individuals exposed to the same environmental conditions with similar PMIs can present different stages of decomposition. After death, tissue undergoes sequential changes consisting of organic and inorganic phase variations, as well as a gradual reduction of tissue water content. Hydrogen (H) is the primary contributor to neutron radiography (NR) contrast in biological specimens because (1) it is the most abundant element in biological tissues and (2) its nucleus scatters thermal and cold neutrons more strongly than any other atomic nucleus. These contrast differences can be advantageous in a forensic context to determine small changes in hydrogen concentrations. Neutron radiography of decaying canine tissues was performed to evaluate the PMI by measuring the changes in H content. In this study, dog cadavers were used as a model for human cadavers. Canine tissues and cadavers were exposed to controlled (laboratory settings, at the University of Tennessee, College of Veterinary Medicine) and uncontrolled (University of Tennessee Anthropology Research Facility) environmental conditions, respectively. Neutron radiographs were supplemented with photographs and histology data to assess the decompositional stages of cadavers. Results demonstrated that the increase in neutron transmission likely corresponded to a decrease in hydrogen content in the tissue, which was correlated with the decay time of the tissue. Tissues depleted in hydrogen were brighter in the neutron transmission radiographs of skeletal muscles, lung, and bone, under controlled conditions. Over a period of 10 days, changes in neutron transmission through lung and muscle were found to be higher than bone by 8.3%, 7.0%, and 2.0%, respectively. Results measured during uncontrolled conditions were more difficult to assess and further studies are necessary. In conclusion, neutron radiography may be used to detect changes in hydrogen abundance that can be correlated with the post-mortem interval. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Changes in Vickers hardness during the decomposition of bone: Possibilities for forensic anthropology.

PubMed

Walden, Steven J; Evans, Sam L; Mulville, Jacqui

2017-01-01

The purpose of this study was to determine how the Vickers hardness (HV) of bone varies during soft tissue putrefaction. This has possible forensic applications, notably for determining the postmortem interval. Experimental porcine bone samples were decomposed in surface and burial deposition scenarios over a period of 6 months. Although the Vickers hardness varied widely, it was found that when transverse axial hardness was subtracted from longitudinal axial hardness, the difference showed correlations with three distinct phases of soft tissue putrefaction. The ratio of transverse axial hardness to longitudinal axial hardness showed a similar correlation. A difference of 10 or greater in HV with soft tissue present and signs of minimal decomposition, was associated with a decomposition period of 250 cumulative cooling degree days or less. A difference of 10 (+/- standard error of mean at a 95% confidence interval) or greater in HV associated with marked decomposition indicated a decomposition period of 1450 cumulative cooling degree days or more. A difference of -7 to +8 (+/- standard error of mean at a 95% confidence interval) was thus associated with 250 to 1450 cumulative cooling degree days' decomposition. The ratio of transverse axial HV to longitudinal HV, ranging from 2.42 to 1.54, is a more reliable indicator in this context and is preferable to using negative integers These differences may have potential as an indicator of postmortem interval and thus the time of body deposition in the forensic context. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations.

PubMed

Lax, Nichola Z; Alston, Charlotte L; Schon, Katherine; Park, Soo-Mi; Krishnakumar, Deepa; He, Langping; Falkous, Gavin; Ogilvy-Stuart, Amanda; Lees, Christoph; King, Rosalind H; Hargreaves, Iain P; Brown, Garry K; McFarland, Robert; Dean, Andrew F; Taylor, Robert W

2015-07-01

Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Enzyme histochemistry of postmortem tissues revealed a near-global cytochrome c oxidase-deficiency; assessment of respiratory chain enzyme activities confirmed severe deficiencies involving complexes I, III, and IV. Molecular genetic studies revealed 2 RARS2 gene mutations: a c.1A>G, p.? variant predicted to abolish the initiator methionine, and a deep intronic c.613-3927C>T variant causing skipping of exons 6-8 in the mature RARS2 transcript. Neuropathologic investigation included low brain weights, small brainstem and cerebellum, deep cerebral white matter pathology, pontine nucleus neuron loss (in 1 sibling), and peripheral nerve pathology. Mitochondrial respiratory chain immunohistochemistry in brain tissues confirmed an absence of complexes I and IV immunoreactivity with sparing of mitochondrial numbers. These cases expand the clinical spectrum of RARS2 mutations, including antenatal features and widespread mitochondrial respiratory chain deficiencies in postmortem brain tissues.

Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations

PubMed Central

Lax, Nichola Z.; Alston, Charlotte L.; Schon, Katherine; Park, Soo-Mi; Krishnakumar, Deepa; He, Langping; Falkous, Gavin; Ogilvy-Stuart, Amanda; Lees, Christoph; King, Rosalind H.; Hargreaves, Iain P.; Brown, Garry K.; McFarland, Robert; Dean, Andrew F.; Taylor, Robert W.

2015-01-01

Abstract Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Enzyme histochemistry of postmortem tissues revealed a near-global cytochrome c oxidase-deficiency; assessment of respiratory chain enzyme activities confirmed severe deficiencies involving complexes I, III, and IV. Molecular genetic studies revealed 2 RARS2 gene mutations: a c.1A>G, p.? variant predicted to abolish the initiator methionine, and a deep intronic c.613-3927C>T variant causing skipping of exons 6–8 in the mature RARS2 transcript. Neuropathologic investigation included low brain weights, small brainstem and cerebellum, deep cerebral white matter pathology, pontine nucleus neuron loss (in 1 sibling), and peripheral nerve pathology. Mitochondrial respiratory chain immunohistochemistry in brain tissues confirmed an absence of complexes I and IV immunoreactivity with sparing of mitochondrial numbers. These cases expand the clinical spectrum of RARS2 mutations, including antenatal features and widespread mitochondrial respiratory chain deficiencies in postmortem brain tissues. PMID:26083569

[The application of X-ray imaging in forensic medicine].

PubMed

Kučerová, Stěpánka; Safr, Miroslav; Ublová, Michaela; Urbanová, Petra; Hejna, Petr

2014-07-01

X-ray is the most common, basic and essential imaging method used in forensic medicine. It serves to display and localize the foreign objects in the body and helps to detect various traumatic and pathological changes. X-ray imaging is valuable in anthropological assessment of an individual. X-ray allows non-invasive evaluation of important findings before the autopsy and thus selection of the optimal strategy for dissection. Basic indications for postmortem X-ray imaging in forensic medicine include gunshot and explosive fatalities (identification and localization of projectiles or other components of ammunition, visualization of secondary missiles), sharp force injuries (air embolism, identification of the weapon) and motor vehicle related deaths. The method is also helpful for complex injury evaluation in abused victims or in persons where abuse is suspected. Finally, X-ray imaging still remains the gold standard method for identification of unknown deceased. With time modern imaging methods, especially computed tomography and magnetic resonance imaging, are more and more applied in forensic medicine. Their application extends possibilities of the visualization the bony structures toward a more detailed imaging of soft tissues and internal organs. The application of modern imaging methods in postmortem body investigation is known as digital or virtual autopsy. At present digital postmortem imaging is considered as a bloodless alternative to the conventional autopsy.

Studies with a reconstituted muscle glycolytic system. The rate and extent of glycolysis in simulated post-mortem conditions

PubMed Central

Scopes, Robert K.

1974-01-01

The reconstituted glycolytic system described previously (Scopes, 1973) was used to simulate post-mortem glycolytic metabolism in muscle. The effects of the following factors have been investigated: ATPase (adenosine triphosphatase) amount, AMP deaminase amount, percentage of the phosphorylase in the a form and the effect of diluting the glycolytic enzyme complex as a whole. It was confirmed that the rate of metabolism was solely dependent on the amount of ATPase present and that various concentrations of the glycolytic enzymes had no effect over a wide range encompassing the variation found in anatomically different muscles. The extent of metabolism, represented by the value of the `ultimate' pH, depended markedly on the amount of phosphorylase in the a form; as little as 1% of the a form resulted in a considerably lower pH than in its absence. To a lesser extent the amount of AMP deaminase also affected the ultimate pH, but this was probably only significant for comparisons of genetically distinct muscles with widely differing amounts of AMP deaminase. The reconstituted system behaved almost identically with regard to post-mortem glycolytic metabolism compared with intact muscle tissue. It is concluded that the controlling effectors found with the reconstituted system apply to intact muscle also. PMID:4280304

Skin analysis following dermal exposure to kerosene in rats: the effects of postmortem exposure and fire.

PubMed

Hieda, Yoko; Tsujino, Yoshio; Xue, Yuying; Takayama, Koji; Fujihara, Junko; Kimura, Kojiro; Dekio, Satoshi

2004-02-01

To evaluate the usefulness of skin analysis for the forensic examination of cases involving postmortem dermal exposure to kerosene and/or fire, an experimental study using rats was performed. Rats received dermal exposure to kerosene before or after death, and the effect of fire was determined by burning an area of exposed skin after death. Kerosene concentrations in skin and blood were determined by gas chromatography-mass spectrometry and microscopic observation was performed for skin samples. No differences were observed in skin kerosene levels between antemortem and postmortem exposure. Kerosene concentrations in mildly burned skin where the stratum corneum (SC) was retained were approximately 84% compared to those in non-burned exposed skin, whereas concentrations in severely burned skin where the SC was almost completely burned off were 28% of non-burned skin. Even in non-exposed control skin 14% of the original kerosene concentrations could be detected, which was considered to be caused by contamination during the experimental protocol combined with kerosene's property of a high affinity for the SC. These results suggest that (1) skin analysis is useful in estimating the type of petroleum product involved in crimes or accidents even for postmortem exposure, (2) whether the SC is retained or not primarily determined the kerosene levels in burned skin, and (3) attention must be paid to evaluate the results obtained from skin samples in the light of the circumstances surrounding the case.

Light scatter on the surface of AcrySof intraocular lenses: part I. Analysis of lenses retrieved from pseudophakic postmortem human eyes.

PubMed

Yaguchi, Shigeo; Nishihara, Hitoshi; Kambhiranond, Waraporn; Stanley, Daniel; Apple, David J

2008-01-01

To investigate the cause of light scatter measured on the surface of AcrySof intraocular lenses (Alcon Laboratories, Inc., Fort Worth, TX) retrieved from pseudophakic postmortem human eyes. Ten intraocular lenses (Alcon AcrySofModel MA60BM) were retrieved postmortem and analyzed for light scatter before and after removal of surface-bound biofilms. Six of the 10 lenses exhibited light scatter that was clearly above baseline levels. In these 6 lenses, both peak and average pixel density were reduced by approximately 80% after surface cleaning. The current study demonstrates that a coating deposited in vivo on the lens surface is responsible for the light scatter observed when incident light is applied.

Identification of exhumed remains of fire tragedy victims using conventional methods and autosomal/Y-chromosomal short tandem repeat DNA profiling.

PubMed

Calacal, Gayvelline C; Delfin, Frederick C; Tan, Michelle Music M; Roewer, Lutz; Magtanong, Danilo L; Lara, Myra C; Fortun, Raquel dR; De Ungria, Maria Corazon A

2005-09-01

In a fire tragedy in Manila in December 1998, one of the worst tragic incidents which resulted in the reported death of 23 children, identity could not be established initially resulting in the burial of still unidentified bodies. Underscoring the importance of identifying each of the human remains, the bodies were exhumed 3 months after the tragedy. We describe here our work, which was the first national case handled by local laboratories wherein conventional and molecular-based techniques were successfully applied in forensic identification. The study reports analysis of DNA obtained from skeletal remains exposed to conditions of burning, burial, and exhumation. DNA typing methods using autosomal and Y-chromosomal short tandem repeat (Y-STR) markers reinforced postmortem examinations using conventional identification techniques. The strategy resulted in the identification of 18 out of the 21 human remains analyzed, overcoming challenges encountered due to the absence of established procedures for the recovery of mass disaster remains. There was incomplete antemortem information to match the postmortem data obtained from the remains of 3 female child victims. Two victims were readily identified due to the availability of antemortem tissues. In the absence of this biologic material, parentage testing was performed using reference blood samples collected from parents and relatives. Data on patrilineal lineage based on common Y-STR haplotypes augmented autosomal DNA typing, particularly in deficiency cases.

Photoacoustic imaging in both soft and hard biological tissue

NASA Astrophysics Data System (ADS)

Li, T.; Dewhurst, R. J.

2010-03-01

To date, most Photoacoustic (PA) imaging results have been from soft biotissues. In this study, a PA imaging system with a near-infrared pulsed laser source has been applied to obtain 2-D and 3-D images from both soft tissue and post-mortem dental samples. Imaging results showed that the PA technique has the potential to image human oral disease, such as early-stage teeth decay. For non-invasive photoacoustic imaging, the induced temperature and pressure rises within biotissues should not cause physical damage to the tissue. Several simulations based on the thermoelastic effect have been applied to predict initial temperature and pressure fields within a tooth sample. Predicted initial temperature and pressure rises are below corresponding safety limits.

Effects of antemortem ingestion of ethanol on insect successional patterns and development of Phormia regina (Diptera: Calliphoridae).

PubMed

Tabor, Kimberly L; Fell, Richard D; Brewster, Carlyle C; Pelzer, Kevin; Behonick, George S

2005-05-01

The effects of antemortem ingestion of ethanol by domestic pigs, Sus scrofa L., on postmortem insect successional patterns and the development of Phormia regina (Meigen) were studied during summer 2003 in Blacksburg, VA. Insect samples were collected from the carcasses of ethanol-treated and untreated pigs for 10 d postmortem during two successional studies. In total, 32 insect taxa were collected during the two studies, with 29 and 27 taxa observed on the carcasses of ethanol-treated and untreated pigs, respectively. The earliest arrivers to both carcass types were dipterans. This group was represented by six families, with P. regina and Phaenicia coeruleiviridis (Macquart) being the most common calliphorids. Beetles in six families were collected on the carcasses of ethanol-treated pigs, but only three of the families were collected on carcasses of the untreated pigs. Permutation analyses to test the null hypothesis of no similarity between successional patterns of insect taxa from carcasses of ethanol-treated and untreated pigs showed that the successional patterns were similar between carcass types in the first (P = 0.003) and the second (P = 0.01) studies. The results of the development study of P. regina maggots in the field show that there was a significant difference between the distributions of length for maggots reared on loin tissue from ethanol-treated and untreated pigs. Maggots that fed on tissue from ethanol-treated pigs took approximately 11.9 h longer to reach the pupal stage than maggots that fed on tissue from untreated pigs. The longer developmental time for maggots on tissue from ethanol-treated pigs was due mainly to the longer postfeeding period of the third instar.

HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer

PubMed Central

Rose, Rebecca; Lamers, Susanna L.; Nolan, David J.; Maidji, Ekaterina; Faria, N. R.; Pybus, Oliver G.; Dollar, James J.; Maruniak, Samuel A.; McAvoy, Andrew C.; Salemi, Marco; Stoddart, Cheryl A.; Singer, Elyse J.

2016-01-01

ABSTRACT While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV+ cART-treated (cART+) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART+ and cART-naive (cART−) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA+ cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. IMPORTANCE Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV+ cART+ individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies. PMID:27466425

HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

PubMed

Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

2016-10-15

While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV(+) cART(+) individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid-Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder.

PubMed

Ruzicka, W Brad; Subburaju, Sivan; Benes, Francine M

2015-06-01

Dysfunction related to γ-aminobutyric acid (GABA)-ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8 patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. Methylation levels at 1308 GAD1 regulatory network-associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. A total of 146 differentially methylated positions with a false detection rate lower than 0.05 were identified across all 6 groups (2 circuit locations in each of 3 diagnostic categories), and 54 differentially methylated regions with P < .01 were identified in single-group comparisons. Methylation changes were enriched in MSX1, CCND2, and DAXX at specific loci within the hippocampus of patients with schizophrenia and bipolar disorder. This work demonstrates diagnosis- and circuit-specific DNA methylation changes at a subset of GAD1 regulatory network genes in the human hippocampus in schizophrenia and bipolar disorder. These genes participate in chromatin regulation and cell cycle control, supporting the concept that the established GABAergic dysfunction in these disorders is related to disruption of GABAergic interneuron physiology at specific circuit locations within the human hippocampus.

Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid–Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder

PubMed Central

Ruzicka, W. Brad; Subburaju, Sivan; Benes, Francine M.

2017-01-01

IMPORTANCE Dysfunction related to γ-aminobutyric acid (GABA)–ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. OBJECTIVE To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. DESIGN, SETTING, AND PARTICIPANTS This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont,Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. MAIN OUTCOMES AND MEASURES Methylation levels at 1308 GAD1 regulatory network–associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. RESULTS A total of 146 differentially methylated positions with a false detection rate lower than 0.05 were identified across all 6 groups (2 circuit locations in each of 3 diagnostic categories), and 54 differentially methylated regions with P < .01 were identified in single-group comparisons. Methylation changes were enriched in MSX1, CCND2, and DAXX at specific loci within the hippocampus of patients with schizophrenia and bipolar disorder. CONCLUSIONS AND RELEVANCE This work demonstrates diagnosis- and circuit-specific DNA methylation changes at a subset of GAD1 regulatory network genes in the human hippocampus in schizophrenia and bipolar disorder. These genes participate in chromatin regulation and cell cycle control, supporting the concept that the established GABAergic dysfunction in these disorders is related to disruption of GABAergic interneuron physiology at specific circuit locations within the human hippocampus. PMID:25738424

[Establishment of the Mathematical Model for PMI Estimation Using FTIR Spectroscopy and Data Mining Method].

PubMed

Wang, L; Qin, X C; Lin, H C; Deng, K F; Luo, Y W; Sun, Q R; Du, Q X; Wang, Z Y; Tuo, Y; Sun, J H

2018-02-01

To analyse the relationship between Fourier transform infrared （FTIR） spectrum of rat's spleen tissue and postmortem interval （PMI） for PMI estimation using FTIR spectroscopy combined with data mining method. Rats were sacrificed by cervical dislocation, and the cadavers were placed at 20 ℃. The FTIR spectrum data of rats' spleen tissues were taken and measured at different time points. After pretreatment, the data was analysed by data mining method. The absorption peak intensity of rat's spleen tissue spectrum changed with the PMI, while the absorption peak position was unchanged. The results of principal component analysis （PCA） showed that the cumulative contribution rate of the first three principal components was 96%. There was an obvious clustering tendency for the spectrum sample at each time point. The methods of partial least squares discriminant analysis （PLS-DA） and support vector machine classification （SVMC） effectively divided the spectrum samples with different PMI into four categories （0-24 h, 48-72 h, 96-120 h and 144-168 h）. The determination coefficient （ R ²） of the PMI estimation model established by PLS regression analysis was 0.96, and the root mean square error of calibration （RMSEC） and root mean square error of cross validation （RMSECV） were 9.90 h and 11.39 h respectively. In prediction set, the R ² was 0.97, and the root mean square error of prediction （RMSEP） was 10.49 h. The FTIR spectrum of the rat's spleen tissue can be effectively analyzed qualitatively and quantitatively by the combination of FTIR spectroscopy and data mining method, and the classification and PLS regression models can be established for PMI estimation. Copyright© by the Editorial Department of Journal of Forensic Medicine.

The criminal justice system's considerations of so-called near-virtual autopsies: the East Midlands experience.

PubMed

Jeffery, A; Raj, V; Morgan, B; West, K; Rutty, G N

2011-08-01

While several research groups champion the potential for postmortem CT (PMCT) to replace the invasive postmortem (PM), many questions still remain. Perhaps the two most important questions are whether PMCT can provide the same level of information as an invasive PM, and arguably more importantly, can it meet the needs of the end users of the PM report. Through a comparative analysis of invasive post-mortem and CT findings and a questionnaire based qualitative thematic analysis, the authors have sought to answer these questions. Here, the authors show that PMCT is good at providing accurate causes of death and that the interpretation of cases is not significantly altered by the absence of histology. The authors show that in straightforward trauma deaths such as road traffic incidents, there exists the potential for the replacement of the invasive PM by PMCT examination. However, as yet, PMCT cannot provide all of the information that is expected by the criminal justice system in complex forensic cases.

A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project.

PubMed

Carithers, Latarsha J; Ardlie, Kristin; Barcus, Mary; Branton, Philip A; Britton, Angela; Buia, Stephen A; Compton, Carolyn C; DeLuca, David S; Peter-Demchok, Joanne; Gelfand, Ellen T; Guan, Ping; Korzeniewski, Greg E; Lockhart, Nicole C; Rabiner, Chana A; Rao, Abhi K; Robinson, Karna L; Roche, Nancy V; Sawyer, Sherilyn J; Segrè, Ayellet V; Shive, Charles E; Smith, Anna M; Sobin, Leslie H; Undale, Anita H; Valentino, Kimberly M; Vaught, Jim; Young, Taylor R; Moore, Helen M

2015-10-01

The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community.

Cementum as a source of DNA in challenging forensic cases.

PubMed

Mansour, Hussam; Krebs, Oliver; Sperhake, Jan Peter; Augustin, Christa; Koehne, Till; Amling, Michael; Püschel, Klaus

2018-02-01

Each forensic case is characterized by its own uniqueness. Deficient forensic cases require additional sources of human identifiers to assure the identity. We report on two different cases illustrating the role of teeth in answering challenging forensic questions. The first case involves identification of an adipocere male found in a car submersed in water for approximately 2 years. The second scenario, which involves paternity DNA testing of an exhumed body, was performed approximately 2.8 years post-mortem. The difficulty in anticipating the degradation of the DNA is one of the main obstacles. DNA profiling of dental tissues, DNA quantification by using real-time PCR (PowerQuant™ System/Promega) and a histological dental examination have been performed to address the encountered impediments of adverse post-mortem changes. Our results demonstrate that despite the adverse environmental conditions, a successful STR profile of DNA isolated from the root of teeth can be generated with respect to tooth type and apportion. We conclude that cementocytes are a fruitful source of DNA. Cementum resists DNA degradation in comparison to other tissues with respect to the intra- and inter-individual variation of histological and anatomical structures. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Neuronal nuclei isolation from human postmortem brain tissue.

PubMed

Matevossian, Anouch; Akbarian, Schahram

2008-10-01

Neurons in the human brain become postmitotic largely during prenatal development, and thus maintain their nuclei throughout the full lifespan. However, little is known about changes in neuronal chromatin and nuclear organization during the course of development and aging, or in chronic neuropsychiatric disease. However, to date most chromatin and DNA based assays (other than FISH) lack single cell resolution. To this end, the considerable cellular heterogeneity of brain tissue poses a significant limitation, because typically various subpopulations of neurons are intermingled with different types of glia and other non-neuronal cells. One possible solution would be to grow cell-type specific cultures, but most CNS cells, including neurons, are ex vivo sustainable, at best, for only a few weeks and thus would provide an incomplete model for epigenetic mechanisms potentially operating across the full lifespan. Here, we provide a protocol to extract and purify nuclei from frozen (never fixed) human postmortem brain. The method involves extraction of nuclei in hypotonic lysis buffer, followed by ultracentrifugation and immunotagging with anti-NeuN antibody. Labeled neuronal nuclei are then collected separately using fluorescence-activated sorting. This method should be applicable to any brain region in a wide range of species and suitable for chromatin immunoprecipitation studies with site- and modification-specific anti-histone antibodies, and for DNA methylation and other assays.

ELEVATED GAMMA-AMINOBUTYRIC ACID LEVELS IN CHRONIC SCHIZOPHRENIA

PubMed Central

Öngür, Dost; Prescot, Andrew P.; McCarthy, Julie; Cohen, Bruce M.; Renshaw, Perry F.

2010-01-01

Background Despite widely-replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy controls in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC). Methods 21 schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy controls (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7cc voxels and analyzed using LCModel. Results We found elevations in GABA/Cr in the schizophrenia group compared with controls (F(1,65)=4.149, p=0.046) in both brain areas (15.5% elevation in ACC, 11.9% in POC). We also found a positive correlation between GABA/Cr and Glu/Cr which was not accounted for by %GM or brain region. Conclusions We found elevated GABA/Cr in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. PMID:20598290

Ultrasonographic findings in goats with contagious caprine pleuropneumonia caused by Mycoplasma capricolum subsp. capripneumoniae.

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd

2017-08-22

In goats, contagious caprine pleuropneumonia (CCPP) is a cause of major economic losses in Africa, Asia and in the Middle East. There is no information emphasising the importance of diagnostic ultrasound in goats with CCPP caused by Mycoplasma capricolum subsp. capripneumoniae (Mccp). This study was designed to describe the ultrasonographic findings in goats with CCPP caused by Mccp and to correlate ultrasonographic with post-mortem findings. To this end, 55 goats with CCPP were examined. Twenty-five healthy adult goats were used as a control group. Major clinical findings included harried, painful respiration, dyspnoea and mouth breathing. On ultrasonography, a liver-like echotexture was imaged in 13 goats. Upon post-mortem examination, all 13 goats exhibited unilateral pulmonary consolidation. Seven goats had a unilateral hypoechoic pleural effusion. At necropsy, the related lung was consolidated and the pleural fluid appeared turbid and greenish. Pleural abscessiation detected in five goats was confirmed post-mortem. Twenty-eight goats had a bright, fibrinous matrix extending over the chest wall containing numerous anechoic fluid pockets with medial displacement and compression of lung tissue. Echogenic tags imaged floating in the fluid were found upon post-mortem examination to be fibrin. In two goats, a consolidated right parenchyma was imaged together with hypoechoic pericardial effusions with echogenic tags covering the epicardium. At necropsy, the right lung was consolidated in three goats and fibrin threads were found covering the epicardium and pericardium. In goats with CCPP, the extension and the severity of the pulmonary changes could not be verified with clinical certainty in most cases, whereas this was possible most of the time with sonography, thus making the prognosis easier. Ultrasonographic examination of the pleurae and the lungs helped in the detection of various lesions.

Quantification of interstitial fluid on whole body CT: comparison with whole body autopsy.

PubMed

Lo Gullo, Roberto; Mishra, Shelly; Lira, Diego A; Padole, Atul; Otrakji, Alexi; Khawaja, Ranish Deedar Ali; Pourjabbar, Sarvenaz; Singh, Sarabjeet; Shepard, Jo-Anne O; Digumarthy, Subba R; Kalra, Mannudeep K; Stone, James R

2015-12-01

Interstitial fluid accumulation can occur in pleural, pericardial, and peritoneal spaces, and subcutaneous tissue planes. The purpose of the study was to assess if whole body CT examination in a postmortem setting could help determine the presence and severity of third space fluid accumulation in the body. Our study included 41 human cadavers (mean age 61 years, 25 males and 16 females) who had whole-body postmortem CT prior to autopsy. All bodies were maintained in the morgue in the time interval between death and autopsy. Two radiologists reviewed the whole-body CT examinations independently to grade third space fluid in the pleura, pericardium, peritoneum, and subcutaneous space using a 5-point grading system. Qualitative CT grading for third space fluid was correlated with the amount of fluid found on autopsy and the quantitative CT fluid volume, estimated using a dedicated software program (Volume, Syngo Explorer, Siemens Healthcare). Moderate and severe peripheral edema was seen in 16/41 and 7/41 cadavers respectively. It is not possible to quantify anasarca at autopsy. Correlation between imaging data for third space fluid and the quantity of fluid found during autopsy was 0.83 for pleural effusion, 0.4 for pericardial effusion and 0.9 for ascites. The degree of anasarca was significantly correlated with the severity of ascites (p < 0.0001) but not with pleural or pericardial effusion. There was strong correlation between volumetric estimation and qualitative grading for anasarca (p < 0.0001) and pleural effusion (p < 0.0001). Postmortem CT can help in accurate detection and quantification of third space fluid accumulation. The quantity of ascitic fluid on postmortem CT can predict the extent of anasarca.

Optical clearing of the dura mater using glycerol: a reversible process to aid the post-mortem investigation of infant head injury.

PubMed

Cheshire, Emma C; Malcomson, Roger D G; Joseph, Shiju; Biggs, Mike J B; Adlam, David; Rutty, Guy N

2015-09-01

In cases of suspected abusive head trauma, a thorough and systematic study of the cranium and its contents is essential, preferably using the best available methods for observing the brain and its coverings. Building upon recent developments in skull bone removal techniques in infant autopsies, we have assessed the use of two optical clearing agents (OCAs), glycerol and mannitol, on pediatric dura mater in an attempt to increase the transparency of this tissue and thereby enhance the post-mortem assessment of infant head injuries, particularly subdural hematomas. Extracorporeal testing revealed glycerol to be the more effective OCA. Therefore, in situ investigations were commenced using glycerol during 33 pediatric post-mortem examinations. An increase in the transparency of the dura was observed in 32 of the 33 cases, within 1 min of application of the OCA. In a 2 year old with cerebral palsy, only partial optical clearance of the dura was seen, most likely due to a significantly atrophic brain, prominent gelatinous leptomeninges, and abnormally thickened dura. This technique allowed for detection of minimal amounts of subdural bleeding over the convexities, before dissection of the dura, avoiding post-mortem blood spillage from artifactually disrupted bridging veins. Optical clearing of the dura aided in the evaluation of patterns of subdural hemorrhage in three cases of non-accidental head injury, three cases of peri-natal head injury and one case of overlaying, apparently resulting in minor crush injury to the head. We have demonstrated that glycerol is an effective and easy-to-use OCA to effect the readily reversible optical clearing of human infant calvarial dura at autopsy.

Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects.

PubMed

Lintas, Carla; Sacco, Roberto; Persico, Antonio M

2016-01-01

Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.

Noninvasive Determination of Bone Mechanical Properties using Vibration Response: A Refined Model and Validation in vivo

NASA Technical Reports Server (NTRS)

Roberts, S. G.; Hutchinson, T. M.; Arnaud, S. B.; Steele, C. R.; Kiratli, B. J.; Martin, R. B.

1996-01-01

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical Response Tissue Analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(MRTA) and theoretical EI values for padded aluminum rods was R(exp 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal Bone Mineral Density (BMD) measurements were also made. The relationship between E(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(exp 2) = 0.947) and better than that using the older model (R(exp 2) = 0.645). EI(MRTA) and BMD are also highly correlated (R(exp 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(exp 2) = 0.915 and R(exp 2) = 0.894, respectively). This is the first biological validation of a non-invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

Noninvasive Determination of Bone Mechanical Properties Using Vibration Response: A Refined Model and Validation in vivo

NASA Technical Reports Server (NTRS)

Roberts, S. G.; Hutchinson, T. M.; Arnaud, S. B.; Kiratli, B. J; Steele, C. R.

1996-01-01

Accurate non-invasive mechanical measurement of long bones is made difficult by the masking effect of surrounding soft tissues. Mechanical response tissue analysis (MRTA) offers a method for separating the effects of the soft tissue and bone; however, a direct validation has been lacking. A theoretical analysis of wave propagation through the compressed tissue revealed a strong mass effect dependent on the relative accelerations of the probe and bone. The previous mathematical model of the bone and overlying tissue system was reconfigured to incorporate the theoretical finding. This newer model (six-parameter) was used to interpret results using MRTA to determine bone cross-sectional bending stiffness, EI(sub MRTA). The relationship between EI(sub MRTA) and theoretical EI values for padded aluminum rods was R(sup 2) = 0.999. A biological validation followed using monkey tibias. Each bone was tested in vivo with the MRTA instrument. Postmortem, the same tibias were excised and tested to failure in three-point bending to determine EI(sub 3-PT) and maximum load. Diaphyseal bone mineral density (BMD) measurements were also made. The relationship between EI(sub 3-PT) and in vivo EI(sub MRTA) using the six-parameter model is strong (R(sup 2) = 0.947) and better than that using the older model (R(sup 2) = 0.645). EI(sub MRTA) and BMD are also highly correlated (R(sup 2) = 0.853). MRTA measurements in vivo and BMD ex vivo are both good predictors of scaled maximum strength (R(sup 2) = 0.915 and R(sup 2) = 0.894, respectively). This is the first biological validation of a non- invasive mechanical measurement of bone by comparison to actual values. The MRTA technique has potential clinical value for assessing long-bone mechanical properties.

Chronic impedance spectroscopy of an endovascular stent-electrode array

NASA Astrophysics Data System (ADS)

Opie, Nicholas L.; John, Sam E.; Rind, Gil S.; Ronayne, Stephen M.; Grayden, David B.; Burkitt, Anthony N.; May, Clive N.; O'Brien, Terence J.; Oxley, Thomas J.

2016-08-01

Objective. Recently, we reported a minimally invasive stent-electrode array capable of recording neural signals from within a blood vessel. We now investigate the use of electrochemical impedance spectroscopy (EIS) measurements to infer changes occurring to the electrode-tissue interface from devices implanted in a cohort of sheep for up to 190 days. Approach. In a cohort of 15 sheep, endovascular stent-electrode arrays were implanted in the superior sagittal sinus overlying the motor cortex for up to 190 days. EIS was performed routinely to quantify viable electrodes for up to 91 days. An equivalent circuit model (ECM) was developed from the in vivo measurements to characterize the electrode-tissue interface changes occurring to the electrodes chronically implanted within a blood vessel. Post-mortem histological assessment of stent and electrode incorporation into the wall of the cortical vessels was compared to the electrical impedance measurements. Main results. EIS could be used to infer electrode viability and was consistent with x-ray analysis performed in vivo, and post-mortem evaluation. Viable electrodes exhibited consistent 1 kHz impedances across the 91 day measurement period, with the peak resistance frequency for the acquired data also stable over time. There was a significant change in 100 Hz phase angles, increasing from -67.8° ± 8.8° at day 0 to -43.8° ± 0.8° at day 91, which was observed to stabilize after eight days. ECM’s modeled to the data suggested this change was due to an increase in the capacitance of the electrode-tissue interface. This was supported by histological assessment with >85% of the implanted stent struts covered with neointima and incorporated into the blood vessel within two weeks. Conclusion. This work demonstrated that EIS could be used to determine the viability of electrode implanted chronically within a blood vessel. Impedance measurements alone were not observed to be a useful predictor of alterations occurring at the electrode tissue interface. However, measurement of 100 Hz phase angles was in good agreement with the capacitive changes predicted by the ECM and consistent with suggestions that this represents protein absorption on the electrode surface. 100 Hz phase angles stabilized after 8 days, consistent with histologically assessed samples. Significance. These findings demonstrate the potential application of this technology for use as a chronic neural recording system and indicate the importance of conducting EIS as a measure to identify viable electrodes and changes occurring at the electrode-tissue interface.

Determination of formic acid tissue and fluid concentrations in three fatalities due to methanol poisoning.

PubMed

Hantson, P; Haufroid, V; Mahieu, P

2000-12-01

Three fatalities caused by methanol ingestion are reported. Admission blood methanol concentrations ranged from 0.28 to 4.6 g/L. Two patients had been admitted after a significant delay (>20 hours), and one patient was observed within 90 minutes following ingestion. Formic acid levels were determined in blood samples at admission and ranged from 302 to 680 mg/L. The patients died 44, 55, and 82 hours after poisoning. Formic acid determinations in postmortem tissues were performed by a gas chromatograph method. The authors found great variability in formic acid distribution among the patients and among organs.

Diagnosis of myocardial ischemia combining multiphase postmortem CT-angiography, histology, and postmortem biochemistry.

PubMed

Vanhaebost, Jessica; Ducrot, Kewin; de Froidmont, Sébastien; Scarpelli, Maria Pia; Egger, Coraline; Baumann, Pia; Schmit, Gregory; Grabherr, Silke; Palmiere, Cristian

2017-02-01

The aim of this study was to assess whether the identification of pathological myocardial enhancement at multiphase postmortem computed tomography angiography was correlated with increased levels of troponin T and I in postmortem serum from femoral blood as well as morphological findings of myocardial ischemia. We further aimed to investigate whether autopsy cases characterized by increased troponin T and I concentrations as well as morphological findings of myocardial ischemia were also characterized by pathological myocardial enhancement at multiphase postmortem computed tomography angiography. Two different approaches were used. In one, 40 forensic autopsy cases that had pathological enhancement of the myocardium (mean Hounsfield units ≥95) observed at postmortem angiography were retrospectively selected. In the second approach, 40 forensic autopsy cases that had a cause of death attributed to acute myocardial ischemia were retrospectively selected. The preliminary results seem to indicate that the identification of a pathological enhancement of the myocardium at postmortem angiography is associated with the presence of increased levels of cardiac troponins in postmortem serum and morphological findings of ischemia. Analogously, a pathological enhancement of the myocardium at postmortem angiography can be retrospectively found in the great majority of autopsy cases characterized by increased cardiac troponin levels in postmortem serum and morphological findings of myocardial ischemia. Multiphase postmortem computed tomography angiography is a useful tool in the postmortem setting for investigating ischemically damaged myocardium.

Imaging of oxygen and hypoxia in cell and tissue samples.

PubMed

Papkovsky, Dmitri B; Dmitriev, Ruslan I

2018-05-14

Molecular oxygen (O 2 ) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O 2 concentration, state of decreased O 2 (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O 2 levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include fluorescent hypoxia stains, fluorescent protein reporter systems, phosphorescent probes and nanosensors of different types. These techniques allow high-resolution mapping of O 2 gradients in live or post-mortem tissue, in 2D or 3D, qualitatively or quantitatively. They enable control and monitoring of oxygenation conditions and their correlation with other biomarkers of cell and tissue function. Comparison of these techniques and corresponding imaging setups, their analytical capabilities and typical applications are given.

CE-TOF MS-based metabolomic profiling revealed characteristic metabolic pathways in postmortem porcine fast and slow type muscles.

PubMed

Muroya, Susumu; Oe, Mika; Nakajima, Ikuyo; Ojima, Koichi; Chikuni, Koichi

2014-12-01

To determine key compounds and metabolic pathways associated with meat quality, we profiled metabolites in postmortem porcine longissimus lumborum (LL) and vastus intermedius (VI) muscles with different aging times by global metabolomics using capillary electrophoresis-time of flight mass spectrometry. Loading analyses of the principal component analysis showed that hydrophilic amino acids and β-alanine-related compounds contributed to the muscle type positively and negatively, respectively, whereas glycolytic and ATP degradation products contributed to aging time. At 168h postmortem, LL samples were characterized by abundance of combinations of amino acids, dipeptides, and glycolytic products, whereas the VI samples were characterized by abundance of both sulfur-containing compounds and amino acids. The AMP and inosine contents in the VI were approx. 10 times higher than those in the LL at 4h postmortem, suggesting different rates of inosine 5'-monophosphate (IMP) accumulation by adenylate kinase 7 and 5'-nucleotidase, and subsequent different production levels of IMP and hypoxanthine between these two porcine muscles. Copyright © 2014 Elsevier Ltd. All rights reserved.

Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease

PubMed Central

Ho Kim, Jae; Franck, Julien; Kang, Taewook; Heinsen, Helmut; Ravid, Rivka; Ferrer, Isidro; Hee Cheon, Mi; Lee, Joo-Yong; Shin Yoo, Jong; Steinbusch, Harry W; Salzet, Michel; Fournier, Isabelle; Mok Park, Young

2015-01-01

Alzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis. PMID:26059363

Trace elements during primordial plexiform network formation in human cerebral organoids

PubMed Central

Sartore, Rafaela C.; Cardoso, Simone C.; Lages, Yury V.M.; Paraguassu, Julia M.; Stelling, Mariana P.; Madeiro da Costa, Rodrigo F.; Guimaraes, Marilia Z.; Pérez, Carlos A.

2017-01-01

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development in vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood. PMID:28194309

Dutch guideline for clinical foetal-neonatal and paediatric post-mortem radiology, including a review of literature.

PubMed

Sonnemans, L J P; Vester, M E M; Kolsteren, E E M; Erwich, J J H M; Nikkels, P G J; Kint, P A M; van Rijn, R R; Klein, W M

2018-06-01

Clinical post-mortem radiology is a relatively new field of expertise and not common practice in most hospitals yet. With the declining numbers of autopsies and increasing demand for quality control of clinical care, post-mortem radiology can offer a solution, or at least be complementary. A working group consisting of radiologists, pathologists and other clinical medical specialists reviewed and evaluated the literature on the diagnostic value of post-mortem conventional radiography (CR), ultrasonography, computed tomography (PMCT), magnetic resonance imaging (PMMRI), and minimally invasive autopsy (MIA). Evidence tables were built and subsequently a Dutch national evidence-based guideline for post-mortem radiology was developed. We present this evaluation of the radiological modalities in a clinical post-mortem setting, including MIA, as well as the recently published Dutch guidelines for post-mortem radiology in foetuses, neonates, and children. In general, for post-mortem radiology modalities, PMMRI is the modality of choice in foetuses, neonates, and infants, whereas PMCT is advised in older children. There is a limited role for post-mortem CR and ultrasonography. In most cases, conventional autopsy will remain the diagnostic method of choice. Based on a literature review and clinical expertise, an evidence-based guideline was developed for post-mortem radiology of foetal, neonatal, and paediatric patients. What is Known: • Post-mortem investigations serve as a quality check for the provided health care and are important for reliable epidemiological registration. • Post-mortem radiology, sometimes combined with minimally invasive techniques, is considered as an adjunct or alternative to autopsy. What is New: • We present the Dutch guidelines for post-mortem radiology in foetuses, neonates and children. • Autopsy remains the reference standard, however minimal invasive autopsy with a skeletal survey, post-mortem computed tomography, or post-mortem magnetic resonance imaging can be complementary thereof.

Application of Fourier transform infrared spectroscopy with chemometrics on postmortem interval estimation based on pericardial fluids.

PubMed

Zhang, Ji; Li, Bing; Wang, Qi; Wei, Xin; Feng, Weibo; Chen, Yijiu; Huang, Ping; Wang, Zhenyuan

2017-12-21

Postmortem interval (PMI) evaluation remains a challenge in the forensic community due to the lack of efficient methods. Studies have focused on chemical analysis of biofluids for PMI estimation; however, no reports using spectroscopic methods in pericardial fluid (PF) are available. In this study, Fourier transform infrared (FTIR) spectroscopy with attenuated total reflectance (ATR) accessory was applied to collect comprehensive biochemical information from rabbit PF at different PMIs. The PMI-dependent spectral signature was determined by two-dimensional (2D) correlation analysis. The partial least square (PLS) and nu-support vector machine (nu-SVM) models were then established based on the acquired spectral dataset. Spectral variables associated with amide I, amide II, COO - , C-H bending, and C-O or C-OH vibrations arising from proteins, polypeptides, amino acids and carbohydrates, respectively, were susceptible to PMI in 2D correlation analysis. Moreover, the nu-SVM model appeared to achieve a more satisfactory prediction than the PLS model in calibration; the reliability of both models was determined in an external validation set. The study shows the possibility of application of ATR-FTIR methods in postmortem interval estimation using PF samples.

Identification of pulmonary edema in forensic autopsy cases of fatal anaphylactic shock using Fourier transform infrared microspectroscopy.

PubMed

Lin, Hancheng; Luo, Yiwen; Wang, Lei; Deng, Kaifei; Sun, Qiran; Fang, Ruoxi; Wei, Xin; Zha, Shuai; Wang, Zhenyuan; Huang, Ping

2018-03-01

Anaphylaxis is a rapid allergic reaction that may cause sudden death. Currently, postmortem diagnosis of anaphylactic shock is sometimes difficult and often achieved through exclusion. The aim of our study was to investigate whether Fourier transform infrared (FTIR) microspectroscopy combined with pattern recognition methods would be complementary to traditional methods and provide a more accurate postmortem diagnosis of fatal anaphylactic shock. First, the results of spectral peak area analysis showed that the pulmonary edema fluid of the fatal anaphylactic shock group was richer in protein components than the control group, which included mechanical asphyxia, brain injury, and acute cardiac death. Subsequently, principle component analysis (PCA) was performed and showed that the anaphylactic shock group contained more turn and α-helix protein structures as well as less tyrosine-rich proteins than the control group. Ultimately, a partial least-square discriminant analysis (PLS-DA) model combined with a variables selection method called the genetic algorithm (GA) was built and demonstrated good separation between these two groups. This pilot study demonstrates that FTIR microspectroscopy has the potential to be an effective aid for postmortem diagnosis of fatal anaphylactic shock.

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review.

PubMed

Bévalot, Fabien; Cartiser, Nathalie; Bottinelli, Charline; Fanton, Laurent; Guitton, Jérôme

2016-01-01

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

A role for iron and oxygen chemistry in preserving soft tissues, cells and molecules from deep time.

PubMed

Schweitzer, Mary H; Zheng, Wenxia; Cleland, Timothy P; Goodwin, Mark B; Boatman, Elizabeth; Theil, Elizabeth; Marcus, Matthew A; Fakra, Sirine C

2014-01-22

The persistence of original soft tissues in Mesozoic fossil bone is not explained by current chemical degradation models. We identified iron particles (goethite-αFeO(OH)) associated with soft tissues recovered from two Mesozoic dinosaurs, using transmission electron microscopy, electron energy loss spectroscopy, micro-X-ray diffraction and Fe micro-X-ray absorption near-edge structure. Iron chelators increased fossil tissue immunoreactivity to multiple antibodies dramatically, suggesting a role for iron in both preserving and masking proteins in fossil tissues. Haemoglobin (HB) increased tissue stability more than 200-fold, from approximately 3 days to more than two years at room temperature (25°C) in an ostrich blood vessel model developed to test post-mortem 'tissue fixation' by cross-linking or peroxidation. HB-induced solution hypoxia coupled with iron chelation enhances preservation as follows: HB + O2 > HB - O2 > -O2 > +O2. The well-known O2/haeme interactions in the chemistry of life, such as respiration and bioenergetics, are complemented by O2/haeme interactions in the preservation of fossil soft tissues.

A role for iron and oxygen chemistry in preserving soft tissues, cells and molecules from deep time

PubMed Central

Schweitzer, Mary H.; Zheng, Wenxia; Cleland, Timothy P.; Goodwin, Mark B.; Boatman, Elizabeth; Theil, Elizabeth; Marcus, Matthew A.; Fakra, Sirine C.

2014-01-01

The persistence of original soft tissues in Mesozoic fossil bone is not explained by current chemical degradation models. We identified iron particles (goethite-αFeO(OH)) associated with soft tissues recovered from two Mesozoic dinosaurs, using transmission electron microscopy, electron energy loss spectroscopy, micro-X-ray diffraction and Fe micro-X-ray absorption near-edge structure. Iron chelators increased fossil tissue immunoreactivity to multiple antibodies dramatically, suggesting a role for iron in both preserving and masking proteins in fossil tissues. Haemoglobin (HB) increased tissue stability more than 200-fold, from approximately 3 days to more than two years at room temperature (25°C) in an ostrich blood vessel model developed to test post-mortem ‘tissue fixation’ by cross-linking or peroxidation. HB-induced solution hypoxia coupled with iron chelation enhances preservation as follows: HB + O2 > HB − O2 > −O2 ≫ +O2. The well-known O2/haeme interactions in the chemistry of life, such as respiration and bioenergetics, are complemented by O2/haeme interactions in the preservation of fossil soft tissues. PMID:24285202

Postmortem Tissue Distribution of Acetyl Fentanyl, Fentanyl and their Respective Nor-Metabolites Analyzed by Ultrahigh Performance Liquid Chromatography with Tandem Mass Spectrometry

PubMed Central

Poklis, Justin; Poklis, Alphonse; Wolf, Carl; Mainland, Mary; Hair, Laura; Devers, Kelly; Chrostowski, Leszek; Arbefeville, Elise; Merves, Michele; Pearson, Julia

2015-01-01

In the last two years, an epidemic of fatal narcotic overdose cases has occurred in the Tampa area of Florida. Fourteen of these deaths involved fentanyl and/or the new designer drug, acetyl fentanyl. Victim demographics, case histories, toxicology findings and causes and manners of death, as well as, disposition of fentanyl derivatives and their nor-metabolites in postmortem heart blood, peripheral blood, bile, brain, liver, urine and vitreous humor are presented. In the cases involving only acetyl fentanyl (without fentanyl, n=4), the average peripheral blood acetyl fentanyl concentration was 0.467 mg/L (range 0.31 to .60 mg/L) and average acetyl norfentanyl concentration was 0.053 mg/L (range 0.002 to 0.086 mg/L). In the cases involving fentanyl (without acetyl fentanyl, n=7), the average peripheral blood fentanyl concentration was 0.012 mg/L (range 0.004 to 0.027 mg/L) and average norfentanyl blood concentration was 0.001 mg/L (range 0.0002 to 0.003 mg/L). In the cases involving both acetyl fentanyl and fentanyl (n=3), the average peripheral blood acetyl fentanyl concentration was 0.008 mg/L (range 0.006 to 0.012 mg/L), the average peripheral blood acetyl norfentanyl concentration was 0.001 mg/L (range 0.001 to 0.002 mg/L), the average peripheral blood fentanyl concentration was 0.018 mg/L (range 0.015 to 0.021 mg/L) and the average peripheral blood norfentanyl concentration was 0.002 mg/L (range 0.001 mg/L to 0.003 mg/L). Based on the toxicology results, it is evident that when fentanyl and/or acetyl fentanyl were present, they contributed to the cause of death. A novel ultrahigh performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS) method to identify and quantify acetyl fentanyl, acetyl norfentanyl, fentanyl and norfentanyl in postmortem fluids and tissues is also presented. PMID:26583960

Multi-site evaluation of the LN34 pan-lyssavirus real-time RT-PCR assay for post-mortem rabies diagnostics

PubMed Central

Dettinger, Lisa; Powell, James W.; Seiders, Melanie; Condori, Rene Edgar Condori; Griesser, Richard; Okogi, Kenneth; Carlos, Maria; Pesko, Kendra; Breckenridge, Mike; Simon, Edson Michael M.; Chu, Maria Yna Joyce V.; Davis, April D.; Brunt, Scott J.; Orciari, Lillian; Yager, Pamela; Carson, William C.; Hartloge, Claire; Saliki, Jeremiah T.; Deldari, Mojgan; Hsieh, Kristina; Wadhwa, Ashutosh; Wilkins, Kimberly; Rabideau, Patricia; Gruhn, Nina; Cadet, Rolain; Isloor, Shrikrishna; Nath, Sujith S.; Joseph, Tomy; Gao, Jinxin; Wallace, Ryan; Reynolds, Mary; Olson, Victoria A.

2018-01-01

Rabies is a fatal zoonotic disease that requires fast, accurate diagnosis to prevent disease in an exposed individual. The current gold standard for post-mortem diagnosis of human and animal rabies is the direct fluorescent antibody (DFA) test. While the DFA test has proven sensitive and reliable, it requires high quality antibody conjugates, a skilled technician, a fluorescence microscope and diagnostic specimen of sufficient quality. The LN34 pan-lyssavirus real-time RT-PCR assay represents a strong candidate for rabies post-mortem diagnostics due to its ability to detect RNA across the diverse Lyssavirus genus, its high sensitivity, its potential for use with deteriorated tissues, and its simple, easy to implement design. Here, we present data from a multi-site evaluation of the LN34 assay in 14 laboratories. A total of 2,978 samples (1,049 DFA positive) from Africa, the Americas, Asia, Europe, and the Middle East were tested. The LN34 assay exhibited low variability in repeatability and reproducibility studies and was capable of detecting viral RNA in fresh, frozen, archived, deteriorated and formalin-fixed brain tissue. The LN34 assay displayed high diagnostic specificity (99.68%) and sensitivity (99.90%) when compared to the DFA test, and no DFA positive samples were negative by the LN34 assay. The LN34 assay produced definitive findings for 80 samples that were inconclusive or untestable by DFA; 29 were positive. Five samples were inconclusive by the LN34 assay, and only one sample was inconclusive by both tests. Furthermore, use of the LN34 assay led to the identification of one false negative and 11 false positive DFA results. Together, these results demonstrate the reliability and robustness of the LN34 assay and support a role for the LN34 assay in improving rabies diagnostics and surveillance. PMID:29768505

[The 2009 performance report of the German cornea banks].

PubMed

Schrage, N; Reinhard, T; Seitz, B; Hermel, M; Böhringer, D; Reinshagen, H

2011-03-01

In Germany, human tissue for corneal and amniotic transplantation is supplied by 27 cornea banks. The Section for Tissue Transplantation and Biotechnology of the German Ophthalmological Society records the cornea banks' activities by means of an annual questionnaire. In 2009, a total of 4,818 corneal grafts were processed by 21 responding cornea banks, and 57% were deemed suitable for transplantation. This ratio is slightly higher than the European average. In addition, German cornea banks released 1,257 amniotic grafts in 2009. German cornea banks are currently facing new regulatory issues due to updated legislation regarding tissue transplantation. Recent updates in European law have limited the cutoff time for postmortem blood sampling to 24 h, and this regulation may lead to a significant reduction in potential donors.

Interacting partners of macrophage-secreted cathepsin B contribute to HIV-induced neuronal apoptosis

PubMed Central

CANTRES-ROSARIO, Yisel M.; HERNANDEZ, Natalia; NEGRON, Karla; PEREZ-LASPIUR, Juliana; LESZYK, John; SHAFFER, Scott A.; MELENDEZ, Loyda M.

2015-01-01

Objective HIV-1 infection of macrophages increases cathepsin B secretion and induces neuronal apoptosis, but the molecular mechanism remains unclear. Design We identified macrophage secreted cathepsin B protein interactions extracellularly and their contribution to neuronal death in vitro. Methods Cathepsin B was immunoprecipitated from monocyte-derived macrophage supernatants after 12 days post-infection. The cathepsin B interactome was quantified by label-free tandem mass spectrometry and compared to uninfected supernatants. Proteins identified were validated by western blot. Neurons were exposed to macrophage-conditioned media in presence or absence of antibodies against cathepsin B and interacting proteins. Apoptosis was measured using TUNEL labeling. Immunohistochemistry of post-mortem brain tissue samples from healthy, HIV-infected, and Alzheimer’s disease patients was performed to observe the ex vivo expression of the proteins identified. Results Nine proteins co-immunoprecipitated differentially with cathepsin B between uninfected and HIV-infected macrophages. Serum amyloid p component (SAPC) -cathepsin B interaction increased in HIV-infected macrophage supernatants, while matrix metalloprotease 9 (MMP-9) -cathepsin B interaction decreased. Pre-treatment of HIV-infected macrophage-conditioned media with antibodies against cathepsin B and SAPC decreased neuronal apoptosis. The addition of MMP-9 antibodies was not protective. SAPC was over-expressed in post-mortem brain tissue from HIV-positive neurocognitive impaired patients compared to HIV positive with normal cognition and healthy controls, while MMP-9 expression was similar in all tissues. Conclusions Inhibiting SAPC-cathepsin B interaction protects against HIV–induced neuronal death and may help to find alternative treatments for HIV-associated neurocognitive disorders. PMID:26208400

The HSPB8-BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases.

PubMed

Seidel, K; Vinet, J; Dunnen, W F A den; Brunt, E R; Meister, M; Boncoraglio, A; Zijlstra, M P; Boddeke, H W G M; Rüb, U; Kampinga, H H; Carra, S

2012-02-01

HSPB8 is a small heat shock protein that forms a complex with the co-chaperone BAG3. Overexpression of the HSPB8-BAG3 complex in cells stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, whose accumulation is a hallmark of many neurodegenerative disorders. HSPB8-BAG3 could thus play a protective role in protein aggregation diseases and might be specifically upregulated in response to aggregate-prone protein-mediated toxicity. Here we analysed HSPB8-BAG3 expression levels in post-mortem human brain tissue from patients suffering of the following protein conformation disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Western blotting and immunohistochemistry techniques were used to analyse HSPB8 and BAG3 expression levels in fibroblasts from SCA3 patients and post-mortem brain tissues, respectively. In all diseases investigated, we observed a strong upregulation of HSPB8 and a moderate upregulation of BAG3 specifically in astrocytes in the cerebral areas affected by neuronal damage and degeneration. Intriguingly, no significant change in the HSPB8-BAG3 expression levels was observed within neurones, irrespective of their localization or of the presence of proteinaceous aggregates. We propose that the upregulation of HSPB8 and BAG3 may enhance the ability of astrocytes to clear aggregated proteins released from neurones and cellular debris, maintain the local tissue homeostasis and/or participate in the cytoskeletal remodelling that astrocytes undergo during astrogliosis. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

From Death to Death Certificate: What do the Dead say?

PubMed

Gill, James R

2017-03-01

This is an overview of medicolegal death investigation and death certification. Postmortem toxicological analysis, particularly for ethanol and drugs of abuse, plays a large role in the forensic investigation of natural and unnatural deaths. Postmortem drug concentrations must be interpreted in light of the autopsy findings and circumstances. Interpretations of drug and ethanol concentrations are important for death certification, but they also may be important for other stakeholders such as police, attorneys, public health practitioners, and the next-of-kin.

Forensic Imaging for Causal Investigation of Death

PubMed Central

Sassenberg, Alina; Schlemmer, Heinz-Peter; Yen, Kathrin

2014-01-01

A 63-year-old man was found in the street after overrun by a car. Postmortem CT revealed multiple bone fractures, but surprisingly all without any relevant hemorrhage which would have been expected under such circumstances. A round radiopaque formation was found in the duodenum, which was reminiscent of ingested tablets. The toxicological analysis revealed high concentrations of zopiclone and alcohol. By combining radiologic and forensic results, zopiclone and alcohol intoxication were concluded as the cause of death, followed by a postmortem overrun accident. PMID:24644410

A field study of culling and mortality in beef cows from western Canada.

PubMed

Waldner, Cheryl L; Kennedy, Richard I; Rosengren, Leigh; Clark, Edward G

2009-05-01

The objectives were to describe the pattern of losses through culling, sales of breeding stock, mortality, and disappearance, and to characterize the causes of mortality of cows and replacement heifers of breeding age from Western Canadian beef herds. Cows and replacement heifers from 203 herds were observed for a 1-year period starting June 1, 2001. Veterinarians examined dead animals on-farm using a standard postmortem protocol. The incidence of culling in cows and replacements heifers was 14.3 per 100 cow-years at risk, and the frequencies of sales for breeding stock, mortality, and cows reported missing per cow-years at risk were 4.0, 1.1, and 0.4, respectively. During the study, 355 animals died or were euthanized, 209 were examined postmortem, and the requested tissues were submitted for histopathologic examination from 184. A cause of death was determined for 70% (128/184) of the cows with complete gross postmortem and histopathologic examinations. Hardware disease (traumatic reticuloperitonitis), malignant neoplasia (cancer), calving-associated injury, rumen tympany (bloat), myopathy, and pneumonia accounted for 56% (72/128) of the animals where a cause of death was determined. Twenty-three other causes of death accounted for the remaining 44% (56/128). Factors relating to cow nutrition accounted for 25% of the deaths, emphasizing the importance of feeding management as a determinant of cow health in western Canada.

Post-mortem CT: Hounsfield unit profiles obtained in the lungs with respect to the cause of death assessment.

PubMed

Schober, Daniel; Schwendener, Nicole; Zech, Wolf-Dieter; Jackowski, Christian

2017-01-01

Segmentation of the lungs using post-mortem computed tomography (PMCT) data was so far not feasible due to post-mortem changes such as internal livores. Recently, an Osirix plug-in has been developed allowing automatically segmenting lungs also in PMCT data. The aim of this study was to investigate if the Hounsfield unit (HU) profiles obtained in PMCT data of the segmented lung tissue present with specific behaviour in relation to the cause of death. In 105 PMCT data sets of forensic cases, the entire lung volumes were segmented using the Mia Lite plug-in on Osirix. HU profiles of the lungs were generated and correlated to cause of death groups as assessed after forensic autopsy (cardiac death, fatal haemorrhage, craniocerebral injury, intoxication, drowning, hypothermia, hanging and suffocation). Especially cardiac death cases, intoxication cases, fatal haemorrhage cases and hypothermia cases showed very specific HU profiles. In drowning, the profiles showed two different behaviours representing wet and dry drowning. HU profiles rather varied in craniocerebral injury cases, hanging cases as well as in suffocation cases. HU profiles of the lungs segmented from PMCT data may support the cause of death diagnosis as they represent specific morphological changes in the lungs such as oedema, congestion or blood loss. Especially in cardiac death, intoxication, fatal haemorrhage, hypothermia and drowning cases, HU profiles may be very supportive for the forensic pathologist.

Development of a novel anisotropic self-inflating tissue expander: in vivo submucoperiosteal performance in the porcine hard palate.

PubMed

Swan, Marc C; Bucknall, David G; Czernuszka, Jan T; Pigott, David W; Goodacre, Timothy E E

2012-01-01

The advent of self-inflating hydrogel tissue expanders heralded a significant advance in the reconstructive potential of this technique. Their use, however, is limited by their uncontrolled isotropic (i.e., uniform in all directions) expansion. Anisotropy (i.e., directional dependence) was achieved by annealing a hydrogel copolymer of poly(methyl methacrylate-co-vinyl pyrrolidone) under a compressive load for a specified time period. The expansion ratio is dictated by the percentage of vinyl pyrrolidone content and the degree of compression. The expansion rate is modified by incorporating the polymer within a silicone membrane. The in vivo efficacy of differing prototype devices was investigated in juvenile pigs under United Kingdom Home Office Licence. The devices were implanted within a submucoperiosteal pocket in a total of six porcine palates; all were euthanized by 6 weeks after implantation. A longitudinal volumetric assessment of the expanded tissue was conducted, in addition to postmortem analysis of the bony and mucoperiosteal palatal elements. Uncoated devices caused excessive soft-tissue expansion that resulted in mucoperiosteal ulceration, thus necessitating animal euthanasia. The silicone-coated devices produced controlled soft-tissue expansion over the 6-week study period. There was a statistically significant increase in the volume of expanded soft tissue with no evidence of a significant acute inflammatory response to the implant, although peri-implant capsule formation was observed. Attenuation of the bony palatal shelf was noted. A unique anisotropic hydrogel device capable of controlled expansion has been developed that addresses a number of the shortcomings of the technology hitherto available.

What can imaging tell us about physiology? Lung growth and regional mechanical strain.

PubMed

Hsia, Connie C W; Tawhai, Merryn H

2012-09-01

The interplay of mechanical forces transduces diverse physico-biochemical processes to influence lung morphogenesis, growth, maturation, remodeling and repair. Because tissue stress is difficult to measure in vivo, mechano-sensitive responses are commonly inferred from global changes in lung volume, shape, or compliance and correlated with structural changes in tissue blocks sampled from postmortem-fixed lungs. Recent advances in noninvasive volumetric imaging technology, nonrigid image registration, and deformation analysis provide valuable tools for the quantitative analysis of in vivo regional anatomy and air and tissue-blood distributions and when combined with transpulmonary pressure measurements, allow characterization of regional mechanical function, e.g., displacement, strain, shear, within and among intact lobes, as well as between the lung and the components of its container-rib cage, diaphragm, and mediastinum-thereby yielding new insights into the inter-related metrics of mechanical stress-strain and growth/remodeling. Here, we review the state-of-the-art imaging applications for mapping asymmetric heterogeneous physical interactions within the thorax and how these interactions permit as well as constrain lung growth, remodeling, and compensation during development and following pneumonectomy to illustrate how advanced imaging could facilitate the understanding of physiology and pathophysiology. Functional imaging promises to facilitate the formulation of realistic computational models of lung growth that integrate mechano-sensitive events over multiple spatial and temporal scales to accurately describe in vivo physiology and pathophysiology. Improved computational models in turn could enhance our ability to predict regional as well as global responses to experimental and therapeutic interventions.

Chemical imaging analysis of the brain with X-ray methods

NASA Astrophysics Data System (ADS)

Collingwood, Joanna F.; Adams, Freddy

2017-04-01

Cells employ various metal and metalloid ions to augment the structure and the function of proteins and to assist with vital biological processes. In the brain they mediate biochemical processes, and disrupted metabolism of metals may be a contributing factor in neurodegenerative disorders. In this tutorial review we will discuss the particular role of X-ray methods for elemental imaging analysis of accumulated metal species and metal-containing compounds in biological materials, in the context of post-mortem brain tissue. X-rays have the advantage that they have a short wavelength and can penetrate through a thick biological sample. Many of the X-ray microscopy techniques that provide the greatest sensitivity and specificity for trace metal concentrations in biological materials are emerging at synchrotron X-ray facilities. Here, the extremely high flux available across a wide range of soft and hard X-rays, combined with state-of-the-art focusing techniques and ultra-sensitive detectors, makes it viable to undertake direct imaging of a number of elements in brain tissue. The different methods for synchrotron imaging of metals in brain tissues at regional, cellular, and sub-cellular spatial resolution are discussed. Methods covered include X-ray fluorescence for elemental imaging, X-ray absorption spectrometry for speciation imaging, X-ray diffraction for structural imaging, phase contrast for enhanced contrast imaging and scanning transmission X-ray microscopy for spectromicroscopy. Two- and three-dimensional (confocal and tomographic) imaging methods are considered as well as the correlation of X-ray microscopy with other imaging tools.

Tissue distribution of molidone in a multidrug overdose.

PubMed

Flammia, Dwight D; Bateman, Henry R; Saady, Joseph J; Christensen, Erik D

2004-09-01

Molindone hydrochloride (Moban) is a dihydroindolone compound dissimilar in structure to other antipsychotic drugs (i.e., phenothiazines, butyrophenones, dibenzepines, and thioxanthenes). The antipsychotic (or neuroleptic) activity of molindone makes it particularly useful in the treatment of schizophrenia. There are a few published cases which report the tissue distribution of molindone in the human body. We report the analysis of molindone in postmortem samples using a solvent mixture (toluene/hexane/isoamyl alcohol) base extract followed by an acid (0.5M H(2)SO(4)) wash. Molindone was identified by gas chromatography-mass spectrometry (m/z 100, 176, 276) and quantitated using a gas chromatograph and nitrogen-phosphorus detector. The range of linearity was 0.1 mg/L to 5.0 mg/L. We report our findings of molindone concentrations in blood, liver, bile, gastric, and urine as follows: 6 mg/L in blood; 26 mg/kg in liver; 23.1 mg/L in bile; 1200 mg/L in gastric; and 37.3 mg/L in urine. Vitreous lithium (5.9 mmol/L) was determined by flame atomic absorption spectrometry. The medical examiner listed the cause of death as a combined drug overdose of molindone and lithium. The tissue results are compared with another case and the pharmacology of molindone is presented.

Postmortem computed tomography in victims of military air mishaps: radiological-pathological correlation of CT findings.

PubMed

Levy, Gad; Goldstein, Liav; Blachar, Arye; Apter, Sara; Barenboim, Erez; Bar-Dayan, Yaron; Shamis, Ari; Atar, Eli

2007-10-01

A thorough medical inquiry is included in every aviation mishap investigation. While the gold standard of this investigation is a forensic pathology examination, numerous reports stress the important role of computed tomography in the postmortem evaluation of trauma victims. To characterize the findings identified by postmortem CT and compare its performance to conventional autopsy in victims of military aviation mishaps, we analyzed seven postmortem CT examinations. Musculoskeletal injuries accounted for 57.8% of the traumatic findings identified by postmortem CT. The most frequent findings were fractures of the rib (47%), skull (9.6%) and facial bones (8.6%). Abnormally located air accounted for 24% of findings, for which CT was superior (3.5% detected by autopsy, 100% by postmortem CT, P < 0.001). The performance of autopsy in detecting injuries was superior (autopsy detected 85.8% of all injuries, postmortem CT detected 53.9%, P < 0.001), especially in the detection of superficial lesions (100% detected by autopsy, 10.5% by postmortem CT, P < 0.001) and solid organ injuries (100% by autopsy, 18.5% by postmortem CT, P < 0.001). Performance in the detection of musculoskeletal injuries was similar (91.3% for autopsy, 90.3% for postmortem CT, P = not significant). Postmortem CT and autopsy have distinct performance profiles, and although the first cannot replace the latter it is a useful complementary examination.

The involvement of dityrosine crosslinking in α-synuclein assembly and deposition in Lewy Bodies in Parkinson’s disease

PubMed Central

Al-Hilaly, Youssra K.; Biasetti, Luca; Blakeman, Ben J. F.; Pollack, Saskia J.; Zibaee, Shahin; Abdul-Sada, Alaa; Thorpe, Julian R.; Xue, Wei-Feng; Serpell, Louise C.

2016-01-01

Parkinson’s disease (PD) is characterized by intracellular, insoluble Lewy bodies composed of highly stable α-synuclein (α-syn) amyloid fibrils. α-synuclein is an intrinsically disordered protein that has the capacity to assemble to form β-sheet rich fibrils. Oxidiative stress and metal rich environments have been implicated in triggering assembly. Here, we have explored the composition of Lewy bodies in post-mortem tissue using electron microscopy and immunogold labeling and revealed dityrosine crosslinks in Lewy bodies in brain tissue from PD patients. In vitro, we show that dityrosine cross-links in α-syn are formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress by fluorescence and confirmed using mass-spectrometry. A covalently cross-linked dimer isolated by SDS-PAGE and mass analysis showed that dityrosine dimer was formed via the coupling of Y39-Y39 to give a homo dimer peptide that may play a key role in formation of oligomeric and seeds for fibril formation. Atomic force microscopy analysis reveals that the covalent dityrosine contributes to the stabilization of α-syn assemblies. Thus, the presence of oxidative stress induced dityrosine could play an important role in assembly and toxicity of α-syn in PD. PMID:27982082

Estimation of perimortal percent carboxy-heme in nonstandard postmortem specimens using analysis of carbon monoxide by GC/MS and iron by flame atomic absorption spectrophotometry.

PubMed

Middleberg, R A; Easterling, D E; Zelonis, S F; Rieders, F; Rieders, M F

1993-01-01

In decomposed, formalin-fixed, embalmed, exhumed, and some fire-dried cases in which normal blood is unavailable, the usual methods for determination of carboxyhemoglobin saturation frequently fail. To address these specimens, a method utilizing both gas chromatography/mass spectrometric (GC/MS) determination of carbon monoxide (CO) and flame atomic absorption spectrophotometry (FAAS) determination of iron (Fe), in the same specimen, was developed. The method is reported here, along with its application to seven pertinent forsensic death investigations. The CO analytical methodology involves acid liberation of the gas from the specimen aliquot in a headspace vial. After heating and equilibrating, a sample of the headspace vapor is injected into the GC/MS system with a gastight syringe. Quantitation is achieved by standard addition comparison utilizing the ideal gas law equation. Iron is quantified by FAAS analysis of the same aliquot used for the CO determination, following nitric acid digestion. The concentration is determined by comparison to a standard curve. A formula for determining the minimum percent carboxy-heme saturation was derived by using the ratio of the amount of CO to the amount of Fe in the aliquot analyzed. Tissue types analyzed include spleen, liver, muscle, dried blood, and unspecified decomposed tissue.

Fungal infection in neural tissue of patients with amyotrophic lateral sclerosis.

PubMed

Alonso, Ruth; Pisa, Diana; Fernández-Fernández, Ana M; Rábano, Alberto; Carrasco, Luis

2017-12-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and the main cause of motor neuron pathology. The etiology of the disease remains unknown, and no effective therapy exists to halt the disease or improve the quality of life. Here, we provide compelling evidence for the existence of fungal infection in ALS. Immunohistochemistry analysis using a battery of antifungal antibodies revealed fungal structures such as yeast and hyphae in the motor cortex, the medulla and the spinal cord, in eleven patients with ALS. Some fungal structures were localized intracellularly and even intranuclearly, indicating that this infection is not the result of post-mortem colonization. By contrast, this burden of fungal infection cannot be observed in several CNS areas of control subjects. PCR analysis and next generation sequencing of DNA extracted from frozen neural tissue identified a variety of fungal genera including Candida, Malassezia, Fusarium, Botrytis, Trichoderma and Cryptococcus. Overall, our present observations provide strong evidence for mixed fungal infections in ALS patients. The exact mixed infection varies from patient to patient consistent with the different evolution and severity of symptoms in each ALS patient. These novel findings provide a logical explanation for the neuropathological observations of this disease, such as neuroinflammation and elevated chitinase levels, and could help to implement appropriate therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

[Legal aspects of post-mortem radiology in the Netherlands].

PubMed

Venderink, W; Dute, J C J

2016-01-01

In the Netherlands, the application of post-mortem radiology (virtual autopsy) is on the rise. Contrary to conventional autopsy, with post-mortem radiology the body remains intact. There is uncertainty concerning the legal admissibility of post-mortem radiology, since the Dutch Corpse Disposal Act does not contain any specific regulations for this technique. Autopsy and post-mortem radiology differ significantly from a technical aspect, but these differences do not have far-reaching legal consequences from a legal perspective. Even though the body remains intact during post-mortem radiology, the bodily integrity of a deceased person is breached if it would be applied without previously obtained consent. This permission can only be obtained after the relatives are fully informed about the proposed activity. In this respect, it is not relevant which technique is used, be it post-mortem radiology or autopsy. Therefore, the other legal conditions for post-mortem radiology are essentially identical to those for autopsy.

Association of progressive outer retinal necrosis and varicella zoster encephalitis in a patient with AIDS.

PubMed Central

van den Horn, G J; Meenken, C; Troost, D

1996-01-01

BACKGROUND: A patient with AIDS who developed the clinical picture of bilateral progressive outer retinal necrosis (PORN) in combination with varicella zoster encephalitis is described. The picture developed more than 2 years after an episode of ophthalmic zoster infection, and following intermittent exposure to oral acyclovir because of recurrent episodes of cutaneous herpes simplex infection. METHODS: Aqueous humour, obtained by paracentesis of the anterior chamber, was analysed using immunofluorescence and polymerase chain reaction (PCR). Postmortem analysis of eye and brain tissue was performed by using conventional techniques and in situ hybridisation. RESULTS: While conventional techniques all failed to detect a causative agent, analysis of the aqueous humour using PCR, and histological examination of necropsy specimens from eyes and brain using in situ hybridisation were conclusive for the diagnosis varicella zoster virus (VZV) infection. CONCLUSION: This case documents the presumed association of PORN and VZV encephalitis in a severely immunocompromised AIDS patient. Images PMID:8976726

Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery.

PubMed

Gizaw, Solomon T; Ohashi, Tetsu; Tanaka, Masakazu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2016-08-01

Understanding of the significance of posttranslational glycosylation in Alzheimer's disease (AD) is of growing importance for the investigation of the pathogenesis of AD as well as discovery research of the disease-specific serum biomarkers. We designed a standard protocol for the glycoblotting combined with MALDI-TOFMS to perform rapid and quantitative profiling of the glycan parts of glycoproteins (N-glycans) and glycosphingolipids (GSLs) using human AD's post-mortem samples such as brain tissues (dissected cerebral cortices such as frontal, parietal, occipital, and temporal domains), serum and cerebrospinal fluid (CSF). The structural profiles of the major N-glycans released from glycoproteins and the total expression levels of the glycans were found to be mostly similar between the brain tissues of the AD patients and those of the normal control group. In contrast, the expression levels of the serum and CSF protein N-glycans such as bisect-type and multiply branched glycoforms were increased significantly in AD patient group. In addition, the levels of some gangliosides such as GM1, GM2 and GM3 appeared to alter in the AD patient brain and serum samples when compared with the normal control groups. Alteration of the expression levels of major N- and GSL-glycans in human brain tissues, serum and CSF of AD patients can be monitored quantitatively by means of the glycoblotting-based standard protocols. The changes in the expression levels of the glycans derived from the human post-mortem samples uncovered by the standardized glycoblotting method provides potential serum biomarkers in central nervous system disorders and can contribute to the insight into the molecular mechanisms in the pathogenesis of neurodegenerative diseases and future drug discovery. Most importantly, the present preliminary trials using human post-mortem samples of AD patients suggest that large-scale serum glycomics cohort by means of various-types of human AD patients as well as the normal control sera can facilitate the discovery research of highly sensitive and reliable serum biomarkers for an early diagnosis of AD. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

Validity of Postmortem Glycated Hemoglobin to Determine Status of Diabetes Mellitus in Corneal Donors.

PubMed

Soper, Mark C; Marcovina, Santica M; Hoover, Caroline K; Calhoun, Peter M; McCoy, Kristen E; Stoeger, Christopher G; Schmidt, Gregory A; Arafah, Baha M; Price, Marianne O; Szczotka-Flynn, Loretta B; Lass, Jonathan H

2017-08-01

To examine the stability of postmortem glycated hemoglobin (HbA1c) measurement and its relationship to premortem glycemia. Postmortem blood samples were obtained from 32 donors (8 known diabetic) and shipped on ice to a central laboratory to examine the stability of HbA1c measurements during the first 9 postmortem days. Thirty-nine other suspected diabetic donors underwent comparison of premortem and postmortem HbA1c measurements. Postmortem HbA1c measurements remained stable after 9 postmortem days (all measurements within ±0.2% from baseline with a mean difference of 0.02% ± 0.10%). Of the premortem measurements obtained within 90 days before death, 79% were within ±1.0% of the postmortem measurements compared with 40% for measurements more than 90 days apart. Three of the postmortem HbA1c measurements exceeded 6.5% (considered a threshold for diabetes diagnosis), although the medical histories did not indicate any previous diabetes diagnosis. Postmortem HbA1c testing is feasible with current eye bank procedures and is reflective of glycemic control of donors during 90 days before death. HbA1c testing could potentially be a useful adjunct to review of the medical history and records for donor assessment for endothelial keratoplasty suitability and long-term graft success.

Effects of postmortem aging and USDA quality grade on Warner-Bratzler shear force values of seventeen individual beef muscles.

PubMed

Gruber, S L; Tatum, J D; Scanga, J A; Chapman, P L; Smith, G C; Belk, K E

2006-12-01

Forty USDA Select and 40 upper two-thirds USDA Choice beef carcasses were used to determine the effects of postmortem aging on tenderness of 17 individual beef muscles. Biceps femoris-long head, complexus, gluteus medius, infraspinatus, longissimus dorsi, psoas major, rectus femoris, semimembranosus, semitendinosus, serratus ventralis, spinalis dorsi, supraspinatus, tensor fasciae latae, teres major, triceps brachii-long head, vastus lateralis, and vastus medialis muscles were removed from each carcass. Seven steaks (2.54-cm thick) were cut from every muscle, and each steak was assigned to one of the following postmortem aging periods: 2, 4, 6, 10, 14, 21, or 28 d postmortem. After completion of the designated aging period, steaks were removed from storage (2 degrees C, never frozen), cooked to a peak internal temperature of 71 degrees C, and evaluated using Warner-Bratzler shear force (WBSF). Analysis of WBSF revealed a 3-way interaction (P = 0.004) among individual muscle, USDA quality grade, and postmortem aging period. With the exception of the Select teres major, WBSF of all muscles (both quality grades) decreased with increasing time of postmortem storage. Nonlinear regression was used to characterize the extent (aging response) and rate of decrease in WBSF from 2 through 28 d postmortem for each muscle within each quality grade. In general, WBSF of upper two-thirds Choice muscles decreased more rapidly from 2 to 10 d postmortem than did corresponding Select muscles. Muscles that had greater aging responses generally had greater 2-d WBSF values. The upper two-thirds Choice psoas major, serratus ventralis, and vastus lateralis muscles required similar aging times to complete a majority of the aging response (< or =0.1 kg of aging response remaining) compared with analogous Select muscles. The upper two-thirds Choice complexus, gluteus medius, semitendinosus, triceps brachii-long head, and vastus medialis muscles required 4 to 6 d less time to complete a majority of the aging response than did comparable Select muscles. Aging times for Select biceps femoris-long head, infraspinatus, longissimus dorsi, rectus femoris, semimembranosus, spinalis dorsi, supraspinatus, and tensor fasciae latae muscles were > or =7 d longer than those for corresponding upper two-thirds Choice muscles. Results from this study suggest that muscle-to-muscle tenderness differences depend on quality grade and aging time and that postmortem aging should be managed with respect to individual muscle and USDA quality grade.

p62 Pathology Model in the Rat Substantia Nigra with Filamentous Inclusions and Progressive Neurodegeneration

PubMed Central

Jackson, Kasey L.; Lin, Wen-Lang; Miriyala, Sumitra; Dayton, Robert D.; Panchatcharam, Manikandan; McCarthy, Kevin J.; Castanedes-Casey, Monica; Dickson, Dennis W.; Klein, Ronald L.

2017-01-01

One of the proteins most frequently found in neuropathological lesions is the ubiquitin binding protein p62 (sequestosome 1). Post-mortem analysis of p62 is a defining diagnostic marker in several neurodegenerative diseases including amyotrophic lateral sclerosis and inclusion body myositis. Since p62 functions in protein degradation pathways including autophagy, the build-up of p62-positive inclusions suggests defects in protein clearance. p62 was expressed unilaterally in the rat substantia nigra with an adeno-associated virus vector (AAV9) in order to study p62 neuropathology. Inclusions formed within neurons from several days to several weeks after gene transfer. By electron microscopy, the inclusions were found to contain packed 10 nm thick filaments, and mitochondria cristae structure was disrupted, resulting in the formation of empty spaces. In corollary cell culture transfections, p62 clearly impaired mitochondrial function. To probe for potential effects on macroautophagy, we co-expressed p62 with a double fluorescent tagged reporter for the autophagosome protein LC3 in the rat. p62 induced a dramatic and specific dissociation of the two tags. By 12 weeks, a rotational behavior phenotype manifested, consistent with a significant loss of dopaminergic neurons analyzed post-mortem. p62 overexpression resulted in a progressive and robust pathology model with neuronal inclusions and neurodegeneration. p62 gene transfer could be a novel methodological probe to disrupt mitochondrial function or autophagy in the brain and other tissues in vivo. PMID:28076378

p62 Pathology Model in the Rat Substantia Nigra with Filamentous Inclusions and Progressive Neurodegeneration.

PubMed

Jackson, Kasey L; Lin, Wen-Lang; Miriyala, Sumitra; Dayton, Robert D; Panchatcharam, Manikandan; McCarthy, Kevin J; Castanedes-Casey, Monica; Dickson, Dennis W; Klein, Ronald L

2017-01-01

One of the proteins most frequently found in neuropathological lesions is the ubiquitin binding protein p62 (sequestosome 1). Post-mortem analysis of p62 is a defining diagnostic marker in several neurodegenerative diseases including amyotrophic lateral sclerosis and inclusion body myositis. Since p62 functions in protein degradation pathways including autophagy, the build-up of p62-positive inclusions suggests defects in protein clearance. p62 was expressed unilaterally in the rat substantia nigra with an adeno-associated virus vector (AAV9) in order to study p62 neuropathology. Inclusions formed within neurons from several days to several weeks after gene transfer. By electron microscopy, the inclusions were found to contain packed 10 nm thick filaments, and mitochondria cristae structure was disrupted, resulting in the formation of empty spaces. In corollary cell culture transfections, p62 clearly impaired mitochondrial function. To probe for potential effects on macroautophagy, we co-expressed p62 with a double fluorescent tagged reporter for the autophagosome protein LC3 in the rat. p62 induced a dramatic and specific dissociation of the two tags. By 12 weeks, a rotational behavior phenotype manifested, consistent with a significant loss of dopaminergic neurons analyzed post-mortem. p62 overexpression resulted in a progressive and robust pathology model with neuronal inclusions and neurodegeneration. p62 gene transfer could be a novel methodological probe to disrupt mitochondrial function or autophagy in the brain and other tissues in vivo.

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

Volatile substance abuse--post-mortem diagnosis.

PubMed

Wille, Sarah M R; Lambert, Willy E E

2004-06-10

A substantial number of children and adolescents world-wide abuse volatile substances with the intention to experience an euphoric state of consciousness. Although the ratio of deaths to nonfatal inhalation escapades is low, it is an important and preventable cause of death in young people. In the analytical investigation of volatile substances proper sample collection, storage and handling are important in view of the volatile nature of the compounds. Volatile organic compounds in post-mortem matrices such as blood, urine and tissues are generally determined by gas chromatography after extracting the compounds with methods such as static and dynamic headspace or even with pulse-heating and solvent extraction. In post-mortem cases, metabolites in urine seem less relevant, however, trichloroethanol and trichloroacetic acid were determined in several cases. When interpreting qualitative and quantitative results, researchers should be aware of false conclusions. The main reason why scepticism is necessary is the occurrence of losses of analytes during sampling, sample handling and storage, which results in false quantitation.

Deaths Associated With Brotizolam Poisoning From a Single Drug Overdose: Four Reported Cases.

PubMed

Sakai, Kentaro; Saito, Kazuyuki; Takada, Aya; Hikiji, Wakako; Kikuchi, Yosuke; Fukunaga, Tatsushige

2018-03-01

Brotizolam is a short-acting hypnotic in the benzodiazepine family, and fatal poisonings by an overdose of brotizolam are rare. This report describes 4 cases of deaths associated with brotizolam poisoning from a single drug overdose. The ages ranged from 51 to 90 years, and the postmortem interval between death and tissue sampling was 1.5 to 2.5 days. These deaths were classified as 1 homicide and 3 suicides. The concentration of the brotizolam ranged from 0.05 to 0.21 mg/L in the blood samples. Ethanol, which could cause mild alcohol intoxication, was detected in the blood samples from 2 cases. Postmortem examinations did not find any significant pathologic conditions, except for a case of death by drowning in a bathtub due to brotizolam poisoning. These 4 cases suggest that a brotizolam overdose should not be underestimated in terms of its fatal effects, particularly when situations involve alcohol intoxication, injury subsequent to the poisoning, or underlying medical conditions including aging.

CYP2C19 variant mitigates Alzheimer disease pathophysiology in vivo and postmortem.

PubMed

Benedet, Andréa L; Yu, Lei; Labbe, Aurélie; Mathotaarachchi, Sulantha; Pascoal, Tharick A; Shin, Monica; Kang, Min-Su; Gauthier, Serge; Rouleau, Guy A; Poirier, Judes; Bennett, David A; Rosa-Neto, Pedro

2018-02-01

To verify whether CYP polymorphisms are associated with amyloid-β (Aβ) pathology across the spectrum of clinical Alzheimer disease using in vivo and postmortem data from 2 independent cohorts. A candidate-gene approach tested the association between 5 genes (28 single nucleotide polymorphisms) and Aβ load measured in vivo by the global [ 18 F]florbetapir PET standardized uptake value ratio (SUVR) in 338 Alzheimer's Disease Neuroimaging Initiative participants. Significant results were then tested using plasma Aβ and CSF Aβ and Aβ/phosphorylated tau (Aβ/p-tau) ratio in the same cohort. The significant association was also generalized to postmortem Aβ load measurement in the Rush Religious Orders Study/Memory and Aging Project cohorts. In addition, global cognition was used as a phenotype in the analysis in both cohorts. Analysis of Aβ PET identified a variant in the CYP2C19 gene (rs4388808; p = 0.0006), in which carriers of the minor allele (MA) had a lower global SUVR. A voxel-wise analysis revealed that the variant is associated with a lower Aβ load in the frontal, inferior temporal, and posterior cingulate cortices. MA carriers also had higher CSF Aβ ( p = 0.003) and Aβ/p-tau ratio ( p = 0.02) but had no association with Aβ plasma levels. In postmortem brains, MA carriers had a lower Aβ load ( p = 0.03). Global cognition was higher in MA carriers, which was found to be mediated by Aβ. Together, these findings point to an association between CYP2C19 polymorphism and Aβ pathology, suggesting a protective effect of the MA of rs4388808. Despite the several possibilities in which CYP2C19 affects brain Aβ, the biological mechanism by which this genetic variation may act as a protective factor merits further investigation.

Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers.

PubMed

Aljakna, Aleksandra; Fracasso, Tony; Sabatasso, Sara

2018-03-01

Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.

Elevated gamma-aminobutyric acid levels in chronic schizophrenia.

PubMed

Ongür, Dost; Prescot, Andrew P; McCarthy, Julie; Cohen, Bruce M; Renshaw, Perry F

2010-10-01

Despite widely replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy control subjects in the anterior cingulate cortex and parieto-occipital cortex. Twenty-one schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy control subjects (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7-mL voxels and analyzed using LCModel. We found elevations in GABA/creatine in the schizophrenia group compared with control subjects [F(1,65) = 4.149, p = .046] in both brain areas (15.5% elevation in anterior cingulate cortex, 11.9% in parieto-occipital cortex). We also found a positive correlation between GABA/creatine and glutamate/creatine, which was not accounted for by % GM or brain region. We found elevated GABA/creatinine in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Karyotype versus microarray testing for genetic abnormalities after stillbirth.

PubMed

Reddy, Uma M; Page, Grier P; Saade, George R; Silver, Robert M; Thorsten, Vanessa R; Parker, Corette B; Pinar, Halit; Willinger, Marian; Stoll, Barbara J; Heim-Hall, Josefine; Varner, Michael W; Goldenberg, Robert L; Bukowski, Radek; Wapner, Ronald J; Drews-Botsch, Carolyn D; O'Brien, Barbara M; Dudley, Donald J; Levy, Brynn

2012-12-06

Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants. The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery. In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P=0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P=0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P=0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies. Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

GrinLine identification using digital imaging and Adobe Photoshop.

PubMed

Bollinger, Susan A; Brumit, Paula C; Schrader, Bruce A; Senn, David R

2009-03-01

The purpose of this study was to outline a method by which an antemortem photograph of a victim can be critically compared with a postmortem photograph in an effort to facilitate the identification process. Ten subjects, between 27 and 55 years old provided historical pictures of themselves exhibiting a broad smile showing anterior teeth to some extent (a grin). These photos were termed "antemortem" for the purpose of the study. A digital camera was used to take a current photo of each subject's grin. These photos represented the "postmortem" images. A single subject's "postmortem" photo set was randomly selected to be the "unknown victim." These combined data of the unknown and the 10 antemortem subjects were digitally stored and, using Adobe Photoshop software, the images were sized and oriented for comparative analysis. The goal was to devise a technique that could facilitate the accurate determination of which "antemortem" subject was the "unknown." The generation of antemortem digital overlays of the teeth visible in a grin and the comparison of those overlays to the images of the postmortem dentition is the foundation of the technique. The comparisons made using the GrinLine Identification Technique may assist medical examiners and coroners in making identifications or exclusions.

The use of postmortem computed tomography in the diagnosis of intentional medication overdose.

PubMed

Burke, Michael P; O'Donnell, Chris; Bassed, Richard

2012-09-01

The recognition of a well defined basal layer of radio dense material on the postmortem computed tomography (CT) images, in the setting of typical scene findings of an intentional medication overdose and unremarkable external examination of the deceased's body can, in certain circumstances, permit such cases to be managed without routine full autopsy examination. Preliminary toxicological analysis can be targeted to such cases to provide further supportive evidence of intentional medication overdose. In cases where the scene findings are ambiguous or have been contaminated the postmortem CT images may alert the pathologist of the possibility of overdose in an otherwise apparently natural death. We reviewed 61 cases of documented intentional therapeutic medication overdose and 61 control cases. In the majority of the cases of confirmed intentional therapeutic medication overdose the CT images showed no diagnostic features. However, in many cases a well defined basal layer of radio-opaque material was clearly seen to line the gastric mucosa. The postmortem CT pattern which we believe to be highly suggestive of intentional medication overdose must be differentiated from other causes of increased radio density in the stomach which include CT artefacts.

Study on the apoptosis mediated by cytochrome c and factors that affect the activation of bovine longissimus muscle during postmortem aging.

PubMed

Zhang, Jiaying; Yu, Qunli; Han, Ling; Chen, Cheng; Li, Hang; Han, Guangxing

2017-06-01

This study investigates whether bovine longissimus muscle cell apoptosis occurs during postmortem aging and whether apoptosis is dependent on the mitochondria pathway. This study also determines the apoptosis process mediated by cytochrome c after its release from mitochondria and the factors that affect the activation processes. Results indicate that apoptotic nuclei were detected at 12 h postmortem. Cytochrome c release from the mitochondria to the cytoplasm activated the caspase-9 and caspase-3 at early postmortem aging and the activation of caspase-9 occurs before the activation of caspase-3. The pH level decreased during the first 48 h postmortem, whereas the mitochondria membrane permeability increased from 6 to 12 h. Results demonstrate that an apoptosis process of bovine muscle occurred during postmortem aging. Apoptosis was dependent on the mitochondria pathway and occurred at early postmortem aging. Increased mitochondria membrane permeability and low pH are necessary conditions for the release of cytochrome c during postmortem aging.

Association between diabetes mellitus, hypothyroidism or hyperadrenocorticism, and atherosclerosis in dogs.

PubMed

Hess, Rebecka S; Kass, Philip H; Van Winkle, Thomas J

2003-01-01

The objective of this study was to determine whether dogs with atherosclerosis are more likely to have concurrent diabetes mellitus, hypothyroidism, or hyperadrenocorticism than dogs that do not have atherosclerosis. A retrospective mortality prevalence case-control study was performed. The study group included 30 dogs with histopathological evidence of atherosclerosis. The control group included 142 dogs with results of a complete postmortem examination, a final postmortem examination diagnosis of neoplasia, and no histopathological evidence of atherosclerosis. Control dogs were frequency matched for age and year in which the postmortem examination was performed. Proportionate changes in the prevalence of diabetes mellitus, hypothyroidism, and hyperadrenocorticism were calculated by exact prevalence odds ratios (POR), 95% confidence intervals (95% CI), and P values. Multiple logistic regression analysis was used to examine the combined effects of prevalence determinants while controlling for age and year of postmortem examination. Dogs with atherosclerosis were over 53 times more likely to have concurrent diabetes mellitus than dogs without atherosclerosis (POR = 53.6; 95% CI, 4.6-627.5; P = .002) and over 51 times more likely to have concurrent hypothyroidism than dogs without atherosclerosis (POR = 51.1; 95% CI, 14.5-180.1; P < .001). Dogs with atherosclerosis were not found to be more likely to have concurrent hyperadrenocorticism than dogs that did not have atherosclerosis (POR = 1.8; 95% CI, 0.2-17.6; P = .59). Diabetes mellitus and hypothyroidism, but not hyperadrenocorticism, are more prevalent in dogs with atherosclerosis compared to dogs without atherosclerosis on postmortem examination.

Interpretation of postmortem vitreous concentrations of sodium and chloride.

PubMed

Zilg, B; Alkass, K; Berg, S; Druid, H

2016-06-01

Vitreous fluid can be used to analyze sodium and chloride levels in deceased persons, but it remains unclear to what extent such results can be used to diagnose antemortem sodium or chloride imbalances. In this study we present vitreous sodium and chloride levels from more than 3000 cases. We show that vitreous sodium and chloride levels both decrease with approximately 2.2mmol/L per day after death. Since potassium is a well-established marker for postmortem interval (PMI) and easily can be analyzed along with sodium and chloride, we have correlated sodium and chloride levels with the potassium levels and present postmortem reference ranges relative the potassium levels. We found that virtually all cases outside the reference range show signs of antemortem hypo- or hypernatremia. Vitreous sodium or chloride levels can be the only means to diagnose cases of water or salt intoxication, beer potomania or dehydration. We further show that postmortem vitreous sodium and chloride strongly correlate and in practice can be used interchangeably if analysis of one of the ions fails. It has been suggested that vitreous sodium and chloride levels can be used to diagnose drowning or to distinguish saltwater from freshwater drowning. Our results show that in cases of freshwater drowning, vitreous sodium levels are decreased, but that this mainly is an effect of postmortem diffusion between the eye and surrounding water rather than due to the drowning process, since the decrease in sodium levels correlates with immersion time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and ∆ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs

PubMed Central

Schaefer, Nadine; Kettner, Mattias; Laschke, Matthias W.; Schlote, Julia; Ewald, Andreas H.; Menger, Michael D.; Maurer, Hans H.; Schmidt, Peter H.

2017-01-01

Background: Synthetic cannabinoids (SCs) have become an increasing issue in forensic toxicology. Controlled human studies evaluating pharmacokinetic data of SCs are lacking and only few animal studies have been published. Thus, an interpretation of analytical results found in intoxicated or poisoned individuals is difficult. Therefore, the distribution of two selected SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4) as well as ∆9-tetrahydrocannabinol (THC) as reference were examined in pigs. Methods: Pigs (n = 6 per drug) received a single intravenous 200 µg/kg BW dose of JWH-210, RCS-4, or THC. Six hours after administration, the animals were exsanguinated and relevant organs, important body fluids such as bile, and tissues such as muscle and adipose tissue, as well as the bradytrophic specimens dura and vitreous humor were collected. After hydrolysis and solid phase extraction, analysis was performed by LC-MS/MS. To overcome matrix effects of the LC-MS/MS analysis, a standard addition method was applied for quantification. Results: The parent compounds could be detected in every analyzed specimen with the exception of THC that was not present in dura and vitreous humor. Moderate concentrations were present in brain, the site of biological effect. Metabolite concentrations were highest in tissues involved in metabolism and/or elimination. Conclusions: Besides kidneys and lungs routinely analyzed in postmortem toxicology, brain, adipose, and muscle tissue could serve as alternative sources, particularly if other specimens are not available. Bile fluid is the most appropriate specimen for SCs and THC metabolites detection. PMID:27834143

Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and Δ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs.

PubMed

Schaefer, Nadine; Kettner, Mattias; Laschke, Matthias W; Schlote, Julia; Ewald, Andreas H; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H

2017-01-01

Synthetic cannabinoids (SCs) have become an increasing issue in forensic toxicology. Controlled human studies evaluating pharmacokinetic data of SCs are lacking and only few animal studies have been published. Thus, an interpretation of analytical results found in intoxicated or poisoned individuals is difficult. Therefore, the distribution of two selected SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1- pentyl-indol-3-yl)methanone (RCS-4) as well as Δ9-tetrahydrocannabinol (THC) as reference were examined in pigs. Pigs (n = 6 per drug) received a single intravenous 200 μg/kg BW dose of JWH-210, RCS- 4, or THC. Six hours after administration, the animals were exsanguinated and relevant organs, important body fluids such as bile, and tissues such as muscle and adipose tissue, as well as the bradytrophic specimens dura and vitreous humor were collected. After hydrolysis and solid phase extraction, analysis was performed by LC-MS/MS. To overcome matrix effects of the LC-MS/MS analysis, a standard addition method was applied for quantification. The parent compounds could be detected in every analyzed specimen with the exception of THC that was not present in dura and vitreous humor. Moderate concentrations were present in brain, the site of biological effect. Metabolite concentrations were highest in tissues involved in metabolism and/or elimination Conclusions: Besides kidneys and lungs routinely analyzed in postmortem toxicology, brain, adipose, and muscle tissue could serve as alternative sources, particularly if other specimens are not available. Bile fluid is the most appropriate specimen for SCs and THC metabolites detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cell Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function

PubMed Central

Dai, Bo; Huang, Wei; Xu, Meifeng; Millard, Ronald W.; Gao, Mei Hua; Hammond, H. Kirk; Menick, Donald R.; Ashraf, Muhammad; Wang, Yigang

2012-01-01

Objectives The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium. Background Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery. Methods In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell–derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis-related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein–positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed. Results In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein–positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis. Conclusions Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function. PMID:22051336

Analytical separations of mammalian decomposition products for forensic science: a review.

PubMed

Swann, L M; Forbes, S L; Lewis, S W

2010-12-03

The study of mammalian soft tissue decomposition is an emerging area in forensic science, with a major focus of the research being the use of various chemical and biological methods to study the fate of human remains in the environment. Decomposition of mammalian soft tissue is a postmortem process that, depending on environmental conditions and physiological factors, will proceed until complete disintegration of the tissue. The major stages of decomposition involve complex reactions which result in the chemical breakdown of the body's main constituents; lipids, proteins, and carbohydrates. The first step to understanding this chemistry is identifying the compounds present in decomposition fluids and determining when they are produced. This paper provides an overview of decomposition chemistry and reviews recent advances in this area utilising analytical separation science. Copyright © 2010 Elsevier B.V. All rights reserved.

Use of Cardiac Injury Markers in the Postmortem Diagnosis of Sudden Cardiac Death.

PubMed

Carvajal-Zarrabal, Octavio; Hayward-Jones, Patricia M; Nolasco-Hipolito, Cirilo; Barradas-Dermitz, Dulce Ma; Calderón-Garcidueñas, Ana Laura; López-Amador, Noé

2017-09-01

In the daily practice of forensic pathology, sudden cardiac death (SCD) is a diagnostic challenge. Our aim was to determine the usefulness of blood biomarkers [creatine kinase CK-MB, myoglobin, troponins I and T (cTn-I and T), and lactate dehydrogenase] measured by immunoassay technique, in the postmortem diagnosis of SCD. Two groups were compared, 20 corpses with SCD and 8 controls. Statistical significance was determined by variance analysis procedures, with a post hoc Tukey multiple range test for comparison of means (p < 0.05). SCD cases showed significantly higher levels (p < 0.05) of cTn-T and cTn-I compared to the control group. Although only cases within the first 8 h of postmortem interval were included, and the control group consisted mainly of violent death cases, our results suggest that blood troponin levels may be useful to support a diagnosis of SCD. © 2017 American Academy of Forensic Sciences.

Volumetric analysis of the diagonal band of Broca in patients with schizophrenia and affective disorders: A post-mortem study.

PubMed

Brisch, Ralf; Bernstein, Hans-Gert; Dobrowolny, Henrik; Krzyżanowska, Marta; Jankowski, Zbigniew; Bogerts, Bernhard; Gos, Tomasz

2016-05-01

The human diagonal band of Broca is connected to other parts of the limbic system, such as the hippocampus, that are involved in the pathology of schizophrenia. This study aimed to characterize the volume and anterior-to-posterior distance of the human diagonal band of Broca (vertical limb) from post-mortem brains obtained from three groups: healthy control subjects (N = 17), patients with schizophrenia (N = 26), and patients with affective disorders (N = 12). There were no significant differences in the volume or anterior-to-posterior distance in the patients with schizophrenia or affective disorders compared with the healthy control subjects. To date, this is the first post-mortem investigation measuring the volume and the anterior-to-posterior distance of the diagonal band of Broca (vertical limb) in patients with schizophrenia or affective disorders compared with healthy control subjects. © 2015 Wiley Periodicals, Inc.

Difficulties in distinguishing between an atlas fracture and a congenital posterior atlas arch defect in postmortem analysis.

PubMed

Sanchis-Gimeno, Juan A; Blanco-Perez, Esther; Aparicio, Luis; Martinez-Soriano, Francisco; Martinez-Sanjuan, Vicente

2014-09-01

We found one atlas from a sample of 148 skeletons (0.67%) that presented different anatomical variations which made it difficult to determine whether the vertebra had an atlas fracture, an unusual Type B posterior atlas arch defect, or a combination of both. We carried out a stereomicroscopy, radiographic, and computerized tomography scan study that revealed that the dry atlas we found presented a very uncommon congenital Type B posterior atlas arch defect, simulating a fracture. In short, the present paper has revealed that differentiating Type B posterior atlas arch defects from fractures in post-mortem dry vertebrae is more difficult than expected. Thus we believe that it can be easier than expected to mistake Type B posterior arch defects for fractures and vice versa in postmortem studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Correlation of X-ray computed tomography with quantitative nuclear magnetic resonance methods for pre-clinical measurement of adipose and lean tissues in living mice.

PubMed

Metzinger, Matthew N; Miramontes, Bernadette; Zhou, Peng; Liu, Yueying; Chapman, Sarah; Sun, Lucy; Sasser, Todd A; Duffield, Giles E; Stack, M Sharon; Leevy, W Matthew

2014-10-08

Numerous obesity studies have coupled murine models with non-invasive methods to quantify body composition in longitudinal experiments, including X-ray computed tomography (CT) or quantitative nuclear magnetic resonance (QMR). Both microCT and QMR have been separately validated with invasive techniques of adipose tissue quantification, like post-mortem fat extraction and measurement. Here we report a head-to-head study of both protocols using oil phantoms and mouse populations to determine the parameters that best align CT data with that from QMR. First, an in vitro analysis of oil/water mixtures was used to calibrate and assess the overall accuracy of microCT vs. QMR data. Next, experiments were conducted with two cohorts of living mice (either homogenous or heterogeneous by sex, age and genetic backgrounds) to assess the microCT imaging technique for adipose tissue segmentation and quantification relative to QMR. Adipose mass values were obtained from microCT data with three different resolutions, after which the data were analyzed with different filter and segmentation settings. Strong linearity was noted between the adipose mass values obtained with microCT and QMR, with optimal parameters and scan conditions reported herein. Lean tissue (muscle, internal organs) was also segmented and quantified using the microCT method relative to the analogous QMR values. Overall, the rigorous calibration and validation of the microCT method for murine body composition, relative to QMR, ensures its validity for segmentation, quantification and visualization of both adipose and lean tissues.

Banking for the future: an Australian experience in brain banking.

PubMed

Sarris, M; Garrick, T M; Sheedy, D; Harper, C G

2002-06-01

The New South Wales (NSW) Tissue Resource Centre (TRC) has been set up to provide Australian and international researchers with fixed and frozen brain tissue from cases that are well characterised, both clinically and pathologically, for projects related to neuropsychiatric and alcohol-related disorders. A daily review of the Department of Forensic Medicine provides initial information regarding a potential collection. If the case adheres to the strict inclusion criteria, the pathologist performing the postmortem examination is approached regarding retention of the brain tissue. The next of kin of the deceased is then contacted requesting permission to retain the brain for medical research. Cases are also obtained through donor programmes, where donors are assessed and consent to donate their brain during life. Once the brain is removed at autopsy, the brain is photographed, weighed and the volume determined, the brainstem and cerebellum are removed. The two hemispheres are divided, one hemisphere is fresh frozen and one fixed (randomised). Prior to freezing, the hemisphere is sliced into 1-cm coronal slices and a set of critical area blocks is taken. All frozen tissues are kept bagged at -80 degrees C. The other hemisphere is fixed in 15% buffered formalin for 2 weeks, embedded in agar and sliced at 3-mm intervals in the coronal plane. Tissue blocks from these slices are used for neuropathological analysis to exclude any other pathology. The TRC currently has 230 cases of both fixed and frozen material that has proven useful in a range of techniques in many research projects. These techniques include quantitative analyses of brain regions using neuropathological, neurochemical, neuropharmacological and gene expression assays.

Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

PubMed

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ 11 C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

The shear modulus of the human vocal fold, preliminary results from 20 larynxes.

PubMed

Goodyer, Eric; Hemmerich, Sandra; Müller, Frank; Kobler, James B; Hess, Markus

2007-01-01

Quantification of the elastic properties of the human vocal fold provides invaluable data for researchers deriving mathematical models of phonation, developing tissue engineering therapies, and as normative data for comparison between healthy and scarred tissue. This study measured the shear modulus of excised cadaver vocal folds from 20 subjects. Twenty freshly excised human larynxes were evaluated less than four days post-mortem. They were split along the saggital plane and mounted without tension. Shear modulus was obtained by two different methods. For method 1 cyclical shear stress was applied transversely to the mid-membranous portion of the vocal fold, and shear modulus derived by applying a simple shear model. For method 2 the apparatus was configured as an indentometer, and shear modulus obtained from the stress/strain data by applying an established analytical technique. Method 1 shear model for male larynxes yielded a range from 246 to 3,356 Pa, with a mean value of 1,008 and SD of 380. The range for female larynxes was 286-3,332 Pa, with a mean value of 1,237 and SD of 768. Method 2 indentometer model for male larynxes yielded a range from 552 to 2,741 Pa, with a mean value of 1,000 and SD of 460. The range for female larynxes was 509-1,989 Pa, with a mean value of 1,332 and SD of 428. We have successfully demonstrated two methodologies that are capable of directly measuring the shear modulus of the human vocal fold, without dissecting out the vocal fold cover tissue. The sample size of nine female and 11 male larynxes is too small to validate a general conclusion. The high degree of variability in this small cohort of subjects indicates that factors such as age, health status, and post-mortem delay may be significant; and that there is range of 'normality' for vocal fold tissue.

Statistical evaluation of time-dependent metabolite concentrations: estimation of post-mortem intervals based on in situ 1H-MRS of the brain.

PubMed

Scheurer, Eva; Ith, Michael; Dietrich, Daniel; Kreis, Roland; Hüsler, Jürg; Dirnhofer, Richard; Boesch, Chris

2005-05-01

Knowledge of the time interval from death (post-mortem interval, PMI) has an enormous legal, criminological and psychological impact. Aiming to find an objective method for the determination of PMIs in forensic medicine, 1H-MR spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain metabolite concentrations after death. Following the characterization of newly observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915-920), the full set of acquired spectra was analyzed statistically to provide a quantitative estimation of PMIs with their respective confidence limits. In a first step, analytical mathematical functions are proposed to describe the time courses of 10 metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the inverted functions are used to predict PMIs based on the measured metabolite concentrations. Individual PMIs calculated from five different metabolites are then pooled, being weighted by their inverse variances. The predicted PMIs from all individual examinations in the sheep model are compared with known true times. In addition, four human cases with forensically estimated PMIs are compared with predictions based on single in situ MRS measurements. Interpretation of the individual sheep examinations gave a good correlation up to 250 h post-mortem, demonstrating that the predicted PMIs are consistent with the data used to generate the model. Comparison of the estimated PMIs with the forensically determined PMIs in the four human cases shows an adequate correlation. Current PMI estimations based on forensic methods typically suffer from uncertainties in the order of days to weeks without mathematically defined confidence information. In turn, a single 1H-MRS measurement of brain tissue in situ results in PMIs with defined and favorable confidence intervals in the range of hours, thus offering a quantitative and objective method for the determination of PMIs. Copyright 2004 John Wiley & Sons, Ltd.

An assessment of advance relatives approach for brain death organ donation.

PubMed

Michaut, Carine; Baumann, Antoine; Gregoire, Hélène; Laviale, Corinne; Audibert, Gérard; Ducrocq, Xavier

2017-01-01

Advance announcement of forthcoming brain death has developed to enable intensivists and organ procurement organisation coordinators to more appropriately, and separately from each other, explain to relatives brain death and the subsequent post-mortem organ donation opportunity. Research aim: The aim was to assess how potentially involved healthcare professionals perceived ethical issues surrounding the strategy of advance approach. A multi-centre opinion survey using an anonymous self-administered questionnaire was conducted in the six-member hospitals of the publicly funded East of France regional organ and tissue procurement network called 'Prélor'. The study population comprised 460 physicians and nurses in the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Units and the Emergency Departments. Ethical considerations: The project was approved by the board of the Lorraine University Diploma in Medical Ethics and the Prélor Network administrators. A slight majority of 53.5% of respondents had previously participated in an advance relatives approach: 83% of the physicians and 42% of the nurses. A majority of healthcare professionals (68%) think that the main justification for advance relatives approach is the comprehensive care of the dying patient and the research of his or her most likely opinion (74%). The misunderstanding of the related issues by relatives is an obstacle for 47% of healthcare professionals and 51% think that the answer given by the relatives regarding the most likely opinion of the person regarding post-mortem organ donation really corresponds to the person opinion in only 50% of the cases or less. Time given by advance approach should be employed to help and enable relatives to authentically bear the values and interests of the potential donor in the post-mortem organ donation discussion. Nurses' attendance of advance relatives approach seems necessary to enable them to optimally support the families facing death and post-mortem organ donation issues.

Cloning endangered gray wolves (Canis lupus) from somatic cells collected postmortem.

PubMed

Oh, H J; Kim, M K; Jang, G; Kim, H J; Hong, S G; Park, J E; Park, K; Park, C; Sohn, S H; Kim, D Y; Shin, N S; Lee, B C

2008-09-01

The objective of the present study was to investigate whether nuclear transfer of postmortem wolf somatic cells into enucleated dog oocytes, is a feasible method to produce a cloned wolf. In vivo-matured oocytes (from domestic dogs) were enucleated and fused with somatic cells derived from culture of tissue obtained from a male gray wolf 6h after death. The reconstructed embryos were activated and transferred into the oviducts of naturally synchronous domestic bitches. Overall, 372 reconstructed embryos were transferred to 17 recipient dogs; four recipients (23.5%) were confirmed pregnant (ultrasonographically) 23-25 d after embryo transfer. One recipient spontaneously delivered two dead pups and three recipients delivered, by cesarean section, four cloned wolf pups, weighing 450, 190, 300, and 490g, respectively. The pup that weighed 190g died within 12h after birth. The six cloned wolf pups were genetically identical to the donor wolf, and their mitochondrial DNA originated from the oocyte donors. The three live wolf pups had a normal wolf karyotype (78, XY), and the amount of telomeric DNA, assessed by quantitative fluorescence in situ hybridization, was similar to, or lower than, that of the nuclear donor. In conclusion, the present study demonstrated the successful cloning of an endangered male gray wolf via interspecies transfer of somatic cells, isolated postmortem from a wolf, and transferred into enucleated dog oocytes. Therefore, somatic cell nuclear transfer has potential for preservation of canine species in extreme situations, including sudden death.

Essentials of forensic post-mortem MR imaging in adults.

PubMed

Ruder, T D; Thali, M J; Hatch, G M

2014-04-01

Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion-recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as "forensic sentinel sign". If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system.

Perinatal postmortems: what is important to parents and how do they decide?

PubMed

Breeze, Andrew C G; Statham, Helen; Hackett, Gerald A; Jessop, Flora A; Lees, Christoph C

2012-03-01

Falling consent rates for postmortems, regardless of age of death, have been widely reported in recent years. The aim of this study was to explore parental attitudes to, and decision-making about, a perinatal postmortem after termination for fetal abnormality, late miscarriage, or stillbirth. A prospective self-completion questionnaire was given to 35 women and their partners. The participants had experienced second or third trimester pregnancy loss in a single fetal medicine and delivery unit in the United Kingdom and were making decisions about having a postmortem. They were asked to complete a questionnaire about their attitudes to, and expectations of, a perinatal postmortem. Thirty-one questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Parents of nine babies (53%) said they would agree to a full postmortem, of three babies to a limited postmortem, and of four babies to an external examination only; one couple were undecided. The most important issues for the parents in this study that related to their decisions about a postmortem centered on the need for information, both for future planning and about what had happened. Moderately important issues related to altruism, which is, improving medical knowledge and helping other parents experiencing similar bereavement. Among the lowest scoring issues were potential barriers, such as concerns about cultural or religious acceptability of a postmortem, funeral delays, and what would happen to the baby's body. Bereaved parents who participated in this study, where postmortem consent rates were relatively high, thought that their need for knowledge eclipsed assumed barriers when deciding whether or not to have a postmortem for their baby. © 2012, Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc.

[Morphological findings in fatal cases of hantavirus cardiopulmonary syndrome. Report of 7 autopsies].

PubMed

Guzmán G, Pablo; Tapia E, Oscar; Villaseca H, Miguel; Araya O, Juan; Antonio P, Lilia; Lee O, Bolívar; Roa S, Juan

2010-10-01

Hantavirus cardiopulmonary syndrome (HCPS) is an acute infectious disease characterized by sudden cardiorespiratory failure and high mortality, caused by a RNA virus of the genus Hantavirus, family Bunyaviridae, 15% of Chilean cases have been detected in the Araucania Region. To determine in fatal cases of HCPS, clinical and morphological characteristics. Descriptive-retrospective analysis of seven fatal cases with postmortem study of HCPS, attended between 1997 and 2009 at the Hospital of Temuco, Chile. Cases were young patients from rural areas, and presented as an illness of progressive respiratory failure, with leukocytosis, thrombocytopenia and bilateral interstitial pulmonary infiltrates. Main morphological findings were marked intersticial and intraalveolar pulmonary edema, with minimal epithelial injury and mononuclear cell intersticial infiltrate and mild edematous intersticial inflamatory process. Epidemiological, clinical and laboratory background allow to suspect HCPS. In fatal cases, the autopsy makes possible to discard other similar pathologies and provide tissue for confirmation of the disease.

Method of azimuthally stable Mueller-matrix diagnostics of blood plasma polycrystalline films in cancer diagnostics

NASA Astrophysics Data System (ADS)

Ushenko, Yu. A.; Prysyazhnyuk, V. P.; Gavrylyak, M. S.; Gorsky, M. P.; Bachinskiy, V. T.; Vanchuliak, O. Ya.

2015-02-01

A new information optical technique of diagnostics of the structure of polycrystalline films of blood plasma is proposed. The model of Mueller-matrix description of mechanisms of optical anisotropy of such objects as optical activity, birefringence, as well as linear and circular dichroism is suggested. The ensemble of informationally topical azimuthally stable Mueller-matrix invariants is determined. Within the statistical analysis of such parameters distributions the objective criteria of differentiation of films of blood plasma taken from healthy and patients with liver cirrhosis were determined. From the point of view of probative medicine the operational characteristics (sensitivity, specificity and accuracy) of the information-optical method of Mueller-matrix mapping of polycrystalline films of blood plasma were found and its efficiency in diagnostics of liver cirrhosis was demonstrated. Prospects of application of the method in experimental medicine to differentiate postmortem changes of the myocardial tissue was examined.

Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders

PubMed Central

Hagihara, Hideo; Catts, Vibeke S; Katayama, Yuta; Shoji, Hirotaka; Takagi, Tsuyoshi; Huang, Freesia L; Nakao, Akito; Mori, Yasuo; Huang, Kuo-Ping; Ishii, Shunsuke; Graef, Isabella A; Nakayama, Keiichi I; Shannon Weickert, Cynthia; Miyakawa, Tsuyoshi

2018-01-01

Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder. PMID:28776581

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

Fatal intoxication with tianeptine (Stablon).

PubMed

Proença, Paula; Teixeira, Helena; Pinheiro, João; Monsanto, Paula V; Vieira, Duarte Nuno

2007-08-06

Tianeptine (Stablon), although structurally similar to tricyclic antidepressants, acts by enhancing the reuptake of serotonin. A fatal case is presented involving a 26-year-old man, found lying in bed with a "mushroom of foam" around his mouth. Empty blister packs of Stablon and a suicide note were found next to the body. A liquid-liquid extraction procedure with n-hexane: ethyl acetate and n-hexane: 2-propanol, followed by LC-DAD-MS analysis, using positive mode electrospray ionization was performed. The detection limit was 0.001 microg/mL. The toxicological results revealed the following tianeptine concentrations in the post-mortem samples: blood 5.1 microg/mL; urine 2.0 microg/mL; liver 23 microg/g; stomach contents 22 mg. Femoral blood analyses also revealed an ethanol concentration of 0.53 g/L. The present method was also developed and validated for the other post-mortem specimens, since no previous published data had confirmed the post-mortem distribution of tianeptine. The absence of other suitable direct causes of death (macroscopic or histological) and the positive results achieved with the toxicological analysis led the pathologist to rule that death was due to an intoxication caused by the suicidal ingestion of tianeptine in combination with alcohol.

Occlusive mycotic tracheobronchitis and systemic Alphaherpesvirus coinfection in a free-living striped dolphin Stenella coeruleoalba in Italy.

PubMed

Grattarola, Carla; Giorda, Federica; Iulini, Barbara; Pautasso, Alessandra; Ballardini, Marco; Zoppi, Simona; Marsili, Letizia; Peletto, Simone; Masoero, Loretta; Varello, Katia; Garibaldi, Fulvio; Scaglione, Frine E; Di Guardo, Giovanni; Dondo, Alessandro; Goria, Maria; Serracca, Laura; Mignone, Walter; Casalone, Cristina

2018-01-31

A juvenile female striped dolphin Stenella coeruleoalba live stranded on 4 March 2016 at Alassio, western Ligurian Sea coast, Italy. The dolphin died shortly after stranding, and a complete postmortem examination was performed. Necropsy revealed severe tracheal occlusion and unilateral bronchial stenosis with luminal accumulation of abundant green-yellow mucous-gelatinous material. Histological features suggestive of tracheobronchial aspergillosis were observed. Cultures of lung tissue and tracheo-bronchial exudate isolated Aspergillus fumigatus, identified by a Microseq D2 LSUrDNA fungal sequencing kit. A pan-Herpesvirus nested-PCR assay on frozen samples obtained from multiple organs was positive. Phylogenetic analysis on the partial DNA polymerase gene revealed that the striped dolphin isolate was closely related to known cetacean Alphaherpesvirus sequences from the same host species. Attempted virus isolation was unsuccessful. The tissue levels of different persistent organic pollutants and the toxicological stress, evaluated using a theoretical model, showed a severely impaired immune response. This study reports the first case of occlusive mycotic tracheobronchitis in a free-living cetacean and the first molecular identification of an Alphaherpesvirus in a free-ranging striped dolphin stranded on the coast of Italy.

Sequencing CYP2D6 for the detection of poor-metabolizers in post-mortem blood samples with tramadol.

PubMed

Fonseca, Suzana; Amorim, António; Costa, Heloísa Afonso; Franco, João; Porto, Maria João; Santos, Jorge Costa; Dias, Mário

2016-08-01

Tramadol concentrations and analgesic effect are dependent on the CYP2D6 enzymatic activity. It is well known that some genetic polymorphisms are responsible for the variability in the expression of this enzyme and in the individual drug response. The detection of allelic variants described as non-functional can be useful to explain some circumstances of death in the study of post-mortem cases with tramadol. A Sanger sequencing methodology was developed for the detection of genetic variants that cause absent or reduced CYP2D6 activity, such as *3, *4, *6, *8, *10 and *12 alleles. This methodology, as well as the GC/MS method for the detection and quantification of tramadol and its main metabolites in blood samples was fully validated in accordance with international guidelines. Both methodologies were successfully applied to 100 post-mortem blood samples and the relation between toxicological and genetic results evaluated. Tramadol metabolism, expressed as its metabolites concentration ratio (N-desmethyltramadol/O-desmethyltramadol), has been shown to be correlated with the poor-metabolizer phenotype based on genetic characterization. It was also demonstrated the importance of enzyme inhibitors identification in toxicological analysis. According to our knowledge, this is the first study where a CYP2D6 sequencing methodology is validated and applied to post-mortem samples, in Portugal. The developed methodology allows the data collection of post-mortem cases, which is of primordial importance to enhance the application of these genetic tools to forensic toxicology and pathology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The role of post-mortem investigations in determining the cause of sudden unexpected death in infancy.

PubMed

Weber, M A; Ashworth, M T; Risdon, R A; Hartley, J C; Malone, M; Sebire, N J

2008-12-01

Several autopsy protocols have been suggested for investigating sudden unexpected deaths in infancy (SUDI). The aim of this study is to provide data on the utility of such post-mortem investigations from a large paediatric autopsy series to inform future policy. Retrospective analysis of >1500 consecutive post-mortem examinations carried out by specialist paediatric pathologists at a single centre during a 10-year period according to a common autopsy protocol that included the use of detailed ancillary investigations. SUDI was defined as the sudden unexpected death of an infant aged from 7 to 365 days. All data capture and cause of death classification were carried out according to defined criteria. Of 1516 paediatric post-mortem examinations, 546 presented as SUDI. In 202 infants (37%), death was explained by the autopsy findings. The other 344 cases (63%) remained unexplained. Of the explained deaths, over half (58%) were infective, most commonly due to pneumonia (22%). The component of the post-mortem examination that primarily determined the final cause of death was histological examination in 92 infants (46%), macroscopic examination in 61 (30%), microbiological investigations in 38 (19%) and clinical history in 10 (5%). This constitutes the largest single-institution autopsy study of SUDI. Ten years on from the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) SUDI studies, the ascertainment of a cause of death at autopsy has improved. However, with almost two thirds of SUDI remaining unexplained, alternative and/or additional diagnostic techniques are required to improve detection rates of identifiable causes of death at autopsy.

What can imaging tell us about physiology? Lung growth and regional mechanical strain

PubMed Central

Tawhai, Merryn H.

2012-01-01

The interplay of mechanical forces transduces diverse physico-biochemical processes to influence lung morphogenesis, growth, maturation, remodeling and repair. Because tissue stress is difficult to measure in vivo, mechano-sensitive responses are commonly inferred from global changes in lung volume, shape, or compliance and correlated with structural changes in tissue blocks sampled from postmortem-fixed lungs. Recent advances in noninvasive volumetric imaging technology, nonrigid image registration, and deformation analysis provide valuable tools for the quantitative analysis of in vivo regional anatomy and air and tissue-blood distributions and when combined with transpulmonary pressure measurements, allow characterization of regional mechanical function, e.g., displacement, strain, shear, within and among intact lobes, as well as between the lung and the components of its container—rib cage, diaphragm, and mediastinum—thereby yielding new insights into the inter-related metrics of mechanical stress-strain and growth/remodeling. Here, we review the state-of-the-art imaging applications for mapping asymmetric heterogeneous physical interactions within the thorax and how these interactions permit as well as constrain lung growth, remodeling, and compensation during development and following pneumonectomy to illustrate how advanced imaging could facilitate the understanding of physiology and pathophysiology. Functional imaging promises to facilitate the formulation of realistic computational models of lung growth that integrate mechano-sensitive events over multiple spatial and temporal scales to accurately describe in vivo physiology and pathophysiology. Improved computational models in turn could enhance our ability to predict regional as well as global responses to experimental and therapeutic interventions. PMID:22582216

Ovarian teratoma displaying a wide variety of tissue components in a broiler chicken (Gallus Domesticus): morphological heterogeneity of pluripotential germ cell during tumorigenesis.

PubMed

Ohfuji, S

2016-01-01

Spontaneous ovarian teratoma was found in a seven-week-old female Chunky broiler chicken that was slaughtered for food. On post-mortem inspection, a spherical tumor mass attaching to a juvenile ovary was found in the abdominal cavity. Histopathologically, the tumor was comprised of immature mesenchymal stroma and a variety of mature tissue elements of mesodermal and ectodermal origin. In addition, there were multiple indistinguishable tissue elements, which showed no malignant cytological features but were unidentifiable as to corresponding embryological layer of origin. These heterogeneous teratoma tissues consisted of a variety of glandular, cystic, duct-like, and tubular structures, some of which exhibited a lining by a mixture of both keratinizing/non-keratinizing stratified squamous epithelial cells and cuboidal/columnar epithelial cells. The ovarian tetatoma was considered a benign and congenital one. The highly diverse differentiation of the teratoma might have manifested a morphological aspect of intrinsic character of the pluripotential germ cells during tumorigenesis.

Characterization of postmortem biochemical changes in rabbit plasma using ATR-FTIR combined with chemometrics: A preliminary study

NASA Astrophysics Data System (ADS)

Zhang, Ji; Li, Bing; Wang, Qi; Li, Chengzhi; Zhang, Yinming; Lin, Hancheng; Wang, Zhenyuan

2017-02-01

Postmortem interval (PMI) determination is one of the most challenging tasks in forensic medicine due to a lack of accurate and reliable methods. It is especially difficult for late PMI determination. Although many attempts with various types of body fluids based on chemical methods have been made to solve this problem, few investigations are focused on blood samples. In this study, we employed an attenuated total reflection (ATR)-Fourier transform infrared (FTIR) technique coupled with principle component analysis (PCA) to monitor biochemical changes in rabbit plasma with increasing PMI. Partial least square (PLS) model was used based on the spectral data for PMI prediction in an independent sample set. Our results revealed that postmortem chemical changes in compositions of the plasma were time-dependent, and various components including proteins, lipids and nucleic acids contributed to the discrimination of the samples at different time points. A satisfactory prediction within 48 h postmortem was performed by the combined PLS model with a good fitting between actual and predicted PMI of 0.984 and with an error of ± 1.92 h. In consideration of the simplicity and portability of ATR-FTIR, our preliminary study provides an experimental and theoretical basis for application of this technique in forensic practice.

Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru

PubMed Central

Eza, Dominique; Cerrillo, Gustavo; Moore, David A.J.; Castro, Cecilia; Ticona, Eduardo; Morales, Domingo; Cabanillas, Jose; Barrantes, Fernando; Alfaro, Alejandro; Benavides, Alejandro; Rafael, Arturo; Valladares, Gilberto; Arevalo, Fernando; Evans, Carlton A.; Gilman, Robert H.

2010-01-01

There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed. PMID:16979302

Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru.

PubMed

Eza, Dominique; Cerrillo, Gustavo; Moore, David A J; Castro, Cecilia; Ticona, Eduardo; Morales, Domingo; Cabanillas, Jose; Barrantes, Fernando; Alfaro, Alejandro; Benavides, Alejandro; Rafael, Arturo; Valladares, Gilberto; Arevalo, Fernando; Evans, Carlton A; Gilman, Robert H

2006-01-01

There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed.

Post-Mortem Pathological Examination of Two Patients after Intraaneurysmal Embolization Using Guglielmi Detachable Coils

PubMed Central

Nakahara, T.; Sakamoto, S.; Hamasaki, O.; Sakoda, K.

2003-01-01

Summary We report the histological findings in two patients treated using Guglielmi detachable coils with almost complete occlusion of the aneurysms. Autopsies of these patients were performed one week and one year after GDC embolization respectively. In one aneurysm that was obtained at autopsy one week after embolization, the histological findings revealed coils and an unorganized thrombus-filled aneurysm sac; an incomplete cell-lining on the luminal side of fibrin thrombi in the region of the neck of the aneurysm was recognized. In the other aneurysm in which autopsy was performed one year after embolization, an organized fibrous tissue at the margin of the aneurysmal wall and vascular granulation tissue at the center of the aneurysm were observed. There is a single layer of endothelium covering fibrous tissue in the neck of the aneurysm. We discuss the healing process after GDC treatment. PMID:20591231

Differences in Relative Levels of 88 microRNAs in Various Regions of the Normal Adult Human Brain.

PubMed

Filatova, Elena V; Alieva, Anelya; Shadrina, Maria I; Slominsky, Petr A

2017-08-16

Since the discovery of microRNAs (miRNAs) in the 1990s, our knowledge about their biology has grown considerably. The increasing number of studies addressing the role of miRNAs in development and in various diseases emphasizes the need for a comprehensive catalogue of accurate sequence, expression and conservation information regarding the large number of miRNAs proposed recently in all organs and tissues. The objective of this study was to provide data on the levels of miRNA expression in 15 tissues of the normal human brain. We conducted an analysis of the relative levels of 88 of the most abundantly expressed and best characterized miRNA derived postmortem from well-characterized samples of various regions of the brains from five normal individuals. The cluster analysis revealed some differences in the relative levels of these miRNAs among the brain regions studied. Such diversity can be explained by different functioning of these brain regions. We hope that the data from the current study are a resource that will be useful to our colleagues in this exciting field, as more hypotheses will be generated and tested with regard to small noncoding RNA in the human brain in healthy and disease states. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study

PubMed Central

Paul, Soumen; Zhang, Dali; Mzengeza, Shadreck; Ko, Ji Hyun

2016-01-01

ABSTRACT 2–18F‐fluorodeoxy‐D‐glucose (FDG) is a glucose analog that is taken up by cells and phosphorylated. The amount of FDG accumulated by cells is a measure of the rate of glycolysis, which reflects cellular activity. As the levels and actions of the neuromodulator adenosine are dynamically regulated by neuronal activity, this study was designed to test whether endogenous adenosine affects tissue accumulation of FDG as assessed by positron emission tomography (PET) or by postmortem analysis of tissue radioactivity. Rats were given an intraperitoneal injection of the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropyl‐xanthine (DPCPX, 3 mg/kg), the adenosine kinase inhibitor ABT‐702 (3 mg/kg), or vehicle 10 minutes prior to an intravenous injection of FDG (15.4 ± 0.7 MBq per rat). Rats were then subjected to a 15 minute static PET scan. Reconstructed images were normalized to FDG PET template for rats and standard uptake values (SUVs) were calculated. To examine the regional effect of active treatment compared to vehicle, statistical parametric mapping analysis was performed. Whole‐brain FDG uptake was not affected by drug treatment. Significant regional hypometabolism was detected, particularly in cerebellum, of DPCPX‐ and ABT‐702 treated rats, relative to vehicle‐treated rats. Thus, endogenous adenosine can affect FDG accumulation although this effect is modest in quiescent rats. PMID:27082948

MRI Estimates of Brain Iron Concentration in Normal Aging Using Quantitative Susceptibility Mapping

PubMed Central

Bilgic, Berkin; Pfefferbaum, Adolf; Rohlfing, Torsten; Sullivan, Edith V.; Adalsteinsson, Elfar

2011-01-01

Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ1 and ℓ2 norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5T and 3.0T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ1-regularized QSM versus FDRI and ℓ2-regularized QSM versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths. PMID:21925274

Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies

PubMed Central

van Kesteren, C F M G; Gremmels, H; de Witte, L D; Hol, E M; Van Gool, A R; Falkai, P G; Kahn, R S; Sommer, I E C

2017-01-01

Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories. Our pooled estimate on cellular level showed a significant increase in the density of microglia (P=0.0028) in the brains of schizophrenia patients compared with controls, albeit with substantial heterogeneity between studies. Meta-regression on brain regions demonstrated this increase was most consistently observed in the temporal cortex. Densities of macroglia (astrocytes and oligodendrocytes) did not differ significantly between schizophrenia patients and healthy controls. The results of postmortem histology are paralleled on the molecular level, where we observed an overall increase in expression of proinflammatory genes on transcript and protein level (P=0.0052) in patients, while anti-inflammatory gene expression levels were not different between schizophrenia and controls. The results of this meta-analysis strengthen the hypothesis that components of the immune system are involved in the pathogenesis of schizophrenia. PMID:28350400

[Post-mortem examination prior to cremation--an instrument to verify the quality of medical post-mortems and uncover non-natural deaths?].

PubMed

Germerott, Tanja; Todt, Melanie; Bode-Jänisch, Stefanie; Albrecht, Knut; Breitmeier, Dirk

2012-01-01

The external post-mortem examination, its deficient quality and possible causes have been the subject of numerous political and professional discussions. The external post-mortem examination is the basis for the decision whether further criminal investigations are required to clarify the cause of death. It is thus an essential instrument to ensure legal certainty. Before cremation, a second external post-mortem examination is performed by a public medical officer to make sure that errors of the first post-mortem are corrected. In the present study, cases were retrospectively analyzed in which a forensic autopsy had been ordered on the basis of the results of the post-mortem examination performed before cremation. The entries on the death certificate regarding the manner and cause of death were compared with the autopsy results. Between 1998 and 2007, 387 autopsies were ordered after external examination before cremation. In 55 cases (14.2%), the autopsy revealed a non-natural death, although a natural death had been attested on the death certificate. In descending order, a wrong manner of death was attested by clinicians, general practitioners and emergency physicians. With regard to the place where the first external post-mortem had been performed the lowest error rate was seen in nursing homes. Concerning the cause of death, discrepancies between the first post-mortem and autopsy were found in 59.4% of the cases. In this respect, general practitioners and clinicians were ranking first, whereas in nursing homes the cause of death was wrongly assessed in over 70% of cases. At present, the medical post-mortem does not meet the required quality standards, especially with regard to legal certainty. Determination of the cause of death on the basis of the external post-mortem examination is a challenging task even for the experienced medical examiner. As to the categorization of the manner of death it has to be stated that non-natural deaths are often not recognized or that the possibility to certify a death as unclear is not sufficiently used. As a result, it seems important to demand intensive, qualified, additional training in external post-mortem examinations for physicians.

Usefulness of 2D fusion of postmortem CT and antemortem chest radiography studies for human identification.

PubMed

Shinkawa, Norihiro; Hirai, Toshinori; Nishii, Ryuichi; Yukawa, Nobuhiro

2017-06-01

To determine the feasibility of human identification through the two-dimensional (2D) fusion of postmortem computed tomography (PMCT) and antemortem chest radiography. The study population consisted of 15 subjects who had undergone chest radiography studies more than 12 months before death. Fused images in which a chest radiograph was fused with a PMCT image were obtained for those subjects using a workstation, and the minimum distance gaps between corresponding anatomical landmarks (located at soft tissue and bone sites) in the images obtained with the two modalities were calculated. For each fused image, the mean of all these minimum distance gaps was recorded as the mean distance gap (MDG). For each subject, the MDG obtained for the same-subject fused image (i.e., where both of the images that were fused derived from that subject) was compared with the MDGs for different-subject fused images (i.e., where only one of the images that were fused derived from that subject; the other image derived from a different subject) in order to determine whether same-subject fused images can be reliably distinguished from different-subject fused images. The MDGs of the same-subject fused images were found to be significantly smaller than the MDGs of the different-subject fused images (p < 0.01). When bone landmarks were used, the same-subject fused image was found to be the fused image with the lowest MDG for 33.3% of the subjects, the fused image with the lowest or second-lowest MDG for 73.3% of the subjects, and the fused image with the lowest, second-lowest, or third-lowest MDG for 86.7% of the subjects. The application of bone landmarks rather than soft-tissue landmarks made it significantly more likely that, for each subject, the same-subject fused image would have the lowest MDG (or one of the lowest MDGs) of all the fused images compared (p < 0.05). The 2D fusion of antemortem chest radiography and postmortem CT images may assist in human identification.

Earliest Directly-Dated Human Skull-Cups

PubMed Central

Bello, Silvia M.; Parfitt, Simon A.; Stringer, Chris B.

2011-01-01

Background The use of human braincases as drinking cups and containers has extensive historic and ethnographic documentation, but archaeological examples are extremely rare. In the Upper Palaeolithic of western Europe, cut-marked and broken human bones are widespread in the Magdalenian (∼15 to 12,000 years BP) and skull-cup preparation is an element of this tradition. Principal Findings Here we describe the post-mortem processing of human heads at the Upper Palaeolithic site of Gough's Cave (Somerset, England) and identify a range of modifications associated with the production of skull-cups. New analyses of human remains from Gough's Cave demonstrate the skilled post-mortem manipulation of human bodies. Results of the research suggest the processing of cadavers for the consumption of body tissues (bone marrow), accompanied by meticulous shaping of cranial vaults. The distribution of cut-marks and percussion features indicates that the skulls were scrupulously 'cleaned' of any soft tissues, and subsequently modified by controlled removal of the facial region and breakage of the cranial base along a sub-horizontal plane. The vaults were also ‘retouched’, possibly to make the broken edges more regular. This manipulation suggests the shaping of skulls to produce skull-cups. Conclusions Three skull-cups have been identified amongst the human bones from Gough's Cave. New ultrafiltered radiocarbon determinations provide direct dates of about 14,700 cal BP, making these the oldest directly dated skull-cups and the only examples known from the British Isles. PMID:21359211

17O Relaxation Times in the Rat Brain at 16.4T

PubMed Central

Wiesner, Hannes M.; Balla, Dávid Z.; Shajan, G.; Scheffler, Klaus; Uğurbil, Kâmil; Chen, Wei; Uludağ, Kâmil; Pohmann, Rolf

2015-01-01

Purpose Measurement of the cerebral metabolic rate of oxygen (CMRO2) via direct imaging of the 17O signal can be a valuable tool in neuroscientific research. However, knowledge of the longitudinal and transverse relaxation times of different brain tissue types is required, which is difficult to obtain because of the low sensitivity of natural abundance H217O measurements. Methods Using the improved sensitivity at a field strength of 16.4 T, relaxation time measurements in the rat brain were performed in vivo and postmortem with relatively high spatial resolutions, using a chemical shift imaging sequence. Results In vivo relaxation times of rat brain were found to be T1 = 6.84 ± 0.67 ms and T2* = 1.77 ± 0.04 ms. Postmortem H217O relaxometry at enriched concentrations after inhalation of 17O2 showed similar T2* values for gray (1.87 ± 0.04 ms) and white matter, significantly longer than muscle (1.27 ± 0.05 ms) and shorter than CSF (2.30 ± 0.16 ms). Conclusion Relaxation times of brain H217O were measured for the first time in vivo in different types of tissues with high spatial resolution. Since the relaxation times of H217O are expected to be independent of field strength, our results should help in optimizing the acquisition parameters for experiments also at other MRI field strengths. PMID:26098931

Renal involvement in fatal cases of chikungunya virus infection.

PubMed

Mercado, Marcela; Acosta-Reyes, Jorge; Parra, Edgar; Guzmán, Luis; Beltrán, Mauricio; Gasque, Philippe; Mejía-García, Carlos; Viasus, Diego

2018-06-01

Information regarding physiopathology and complications in fatal cases of chikungunya virus (CHIKV) is scarce. The aim of this study was to describe the frequency and severity of renal complications in fatal cases associated with CHIKV infection based on the clinical and histopathological features from post-mortem tissue biopsies. This retrospective study included fatal cases associated with CHIKV infection occurring from September 2014 through October 2015, reported to National System for Public Health Surveillance (SIVIGILA) and laboratory-confirmed by the National Institute of Health of Colombia. Medical records from 13 patients were available. Information was collected on history, physical examination, and haematological, biochemical, radiological, and virologic investigation reports. Diagnosis of CHIKV infection was performed by positive CHIKV-PCR on post-mortem tissue in 10 cases, positive CHIKV-PCR in serum in 6 cases and anti-CHIKV virus IgM in 2 cases. Only 3 cases were children (≤5 years old). Four cases had underlying diseases, mainly systemic arterial hypertension. The median value of creatinine at admission was 2.8 mg/dL (interquartile range 1.52-4.51). During hospitalization, 9 cases required ICU admission, 8 vasopressor support and 6 mechanical ventilation. Kidney histopathological findings were mainly acute interstitial nephritis (11 cases), congestion/oedema glomerular (10 cases) and acute tubular necrosis (5 cases). Renal impairment in fatal cases of CHIKV infection is frequent and related mainly to acute interstitial nephritis. These data demonstrate evidence of acquired kidney injuries during CHIKV infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Cardiac troponin T determination by a highly sensitive assay in postmortem serum and pericardial fluid.

PubMed

González-Herrera, Lucas; Valenzuela, Aurora; Ramos, Valentín; Blázquez, Antonia; Villanueva, Enrique

2016-06-01

The main objective of this study was to test, for the first time, a highly sensitive cardiac troponin T (cTnThs) assay in postmortem serum and pericardial fluid and to evaluate cardiac troponin T (cTnT) levels and their stability after death at different postmortem intervals, in an attempt to determine the viability of the cTnThs assay in the postmortem diagnosis of the cause of death. cTnT levels were determined in serum and pericardial fluid samples taken from 58 cadavers at known postmortem intervals, whose causes of death were categorized into the following groups: (1) sudden cardiac deaths, (2) multiple trauma, (3) mechanical asphyxia, and (4) other natural deaths. cTnT was determined by inmunoassay, using the Troponin T highly sensitive STAT assay (Roche(®)). Average cTnT levels measured by a highly sensitive assay in postmortem serum were markedly higher than clinical serum levels. Moreover, similar results, higher cTnT levels in postmortem pericardial fluid, were obtained when compared to levels found in pericardial fluid taken from two living patients during coronary artery bypass surgery. cTnT levels in both postmortem fluids remained stable for up to 34 h after death. No differences in cTnT levels in either postmortem fluid by sex and age were detected. Levels of cTnT found in pericardial fluid in the other natural deaths group were significantly lower than the cTnT levels found in that postmortem fluid from any of the other causes of death groups. It is therefore reasonable to conclude that determination of cTnT by a highly sensitive assay in pericardial fluid can provide forensic pathologists with a complementary test to the diagnosis of cause of death.

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

PubMed

Feikin, Daniel R; Hammitt, Laura L; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G

2017-06-15

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Maggot development during morgue storage and its effect on estimating the post-mortem interval.

PubMed

Huntington, Timothy E; Higley, Leon G; Baxendale, Frederick P

2007-03-01

When insect evidence is obtained during autopsy, forensic entomologists make decisions regarding the effects of low-temperature (-1 degrees C to 4 degrees C) storage of the body and associated insects when estimating the post-mortem interval (PMI). To determine the effects of storage in a morgue cooler on the temperature of maggot masses, temperatures inside and outside of body bags containing a human cadaver and porcine cadavers (seven replicates) were measured during storage. Temperatures remained significantly higher (p<0.05) inside of the body bags relative to the cooler, and remained at levels sufficient for maggot feeding and development. If the assumption that no insect development takes place during preautopsy refrigeration is made, potential error rates in PMI estimation of 8.6-12.8% occur. The potential for blow fly larvae to undergo significant development while being stored in the morgue is a possibility that forensic entomologists should consider during an investigation involving samples collected from autopsy. Case and experimental evidence also demonstrate that substantial tissue loss can occur from maggot feeding during morgue storage.

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms.

PubMed

Figueroa-Romero, Claudia; Hur, Junguk; Lunn, J Simon; Paez-Colasante, Ximena; Bender, Diane E; Yung, Raymond; Sakowski, Stacey A; Feldman, Eva L

2016-03-01

Amyotrophic lateral sclerosis is a late-onset and terminal neurodegenerative disease. The majority of cases are sporadic with unknown causes and only a small number of cases are genetically linked. Recent evidence suggests that post-transcriptional regulation and epigenetic mechanisms, such as microRNAs, underlie the onset and progression of neurodegenerative disorders; therefore, altered microRNA expression may result in the dysregulation of key genes and biological pathways that contribute to the development of sporadic amyotrophic lateral sclerosis. Using systems biology analyses on postmortem human spinal cord tissue, we identified dysregulated mature microRNAs and their potential targets previously implicated in functional process and pathways associated with the pathogenesis of ALS. Furthermore, we report a global reduction of mature microRNAs, alterations in microRNA processing, and support for a role of the nucleotide binding protein, TAR DNA binding protein 43, in regulating sporadic amyotrophic lateral sclerosis-associated microRNAs, thereby offering a potential underlying mechanism for sporadic amyotrophic lateral sclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective investigation of chronic wasting disease of cervids at the Toronto Zoo, 1973–2003

PubMed Central

Dubé, Caroline; Mehren, Kay G.; Barker, Ian K.; Peart, Brian L.; Balachandran, Aru

2006-01-01

The occurrence of chronic wasting disease (CWD) at the Toronto Zoo was investigated retrospectively, based on an examination of management, animal health, and postmortem records, and immunohistochemical studies. Records of animal movements, clinical signs, and postmortem findings were examined for all cervids 1973–2003. All available samples of fixed, wax-embedded lymphoid or central nervous system tissue from cervids that died at the Toronto Zoo from 1973 to 2003, > 12 months of age, were tested, using prion protein immunostaining. Chronic wasting disease prion antigen was detected in 8 of 105 animals tested: 7 mule deer and 1 black-tailed deer. The most likely method of introduction was the importation of CWD-infected animals from a zoo in the United States. Animal-to-animal contact and environmental contamination were the most likely methods of spread of CWD at the zoo. No mule deer left the Toronto Zoo site, and the last animal with CWD died in 1981. Historic findings and ongoing testing of cervids indicate that the Toronto Zoo collection has very low risk of currently being infected with CWD. PMID:17217088

Poisoning: fact or fiction?

PubMed

Flanagan, Robert J

2012-01-01

Analytical toxicology is a complex discipline. Simply detecting a poison in a biological sample does not necessarily mean that the individual from whom the sample was obtained had been poisoned. An analysis can prove exposure and perhaps give an indication of the magnitude of exposure, but the results have to be placed in proper context. Even if sampling was ante-mortem an analysis does not necessarily prove the effects that the drug or poison had on the victim immediately before or at the time of sampling. Tolerance is one big issue, the mechanism of exposure (how the drug got into the body) is another, and of course with post-mortem work there are always additional considerations such as site of sample collection and the possibility of post-mortem change in analyte concentration. There are also questions of quality and reliability, and whether a particular analysis and the interpretation placed upon the result are appropriate in a particular case.

Investigating the Postmortem Molecular Biology of Cartilage and its Potential Forensic Applications.

PubMed

Bolton, Shawna N; Whitehead, Michael P; Dudhia, Jayesh; Baldwin, Timothy C; Sutton, Raul

2015-07-01

This study investigated the postmortem molecular changes that articular cartilage undergoes following burial. Fresh pig trotters were interred in 30-cm-deep graves at two distinct locations exhibiting dissimilar soil environments for up to 42 days. Extracts of the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joint cartilage from trotters disinterred weekly over 6 weeks were analyzed by Western blot against the monoclonal antibody 2-B-6 to assess aggrecan degradation. In both soil conditions, aggrecan degradation by-products of decreasing molecular size and complexity were observed up to 21 days postmortem. Degradation products were undetected after this time and coincided with MCP/MTP joint exposure to the soil environment. These results show that cartilage proteoglycans undergo an ordered molecular breakdown, the analysis of which may have forensic applications. This model may prove useful for use as a human model and for forensic investigations concerning crimes against animals and the mortality of endangered species. © 2015 American Academy of Forensic Sciences.

CYP2C19 variant mitigates Alzheimer disease pathophysiology in vivo and postmortem

PubMed Central

Benedet, Andréa L.; Yu, Lei; Labbe, Aurélie; Mathotaarachchi, Sulantha; Pascoal, Tharick A.; Shin, Monica; Kang, Min-Su; Gauthier, Serge; Rouleau, Guy A.; Poirier, Judes; Bennett, David A.

2018-01-01

Objective To verify whether CYP polymorphisms are associated with amyloid-β (Aβ) pathology across the spectrum of clinical Alzheimer disease using in vivo and postmortem data from 2 independent cohorts. Methods A candidate-gene approach tested the association between 5 genes (28 single nucleotide polymorphisms) and Aβ load measured in vivo by the global [18F]florbetapir PET standardized uptake value ratio (SUVR) in 338 Alzheimer's Disease Neuroimaging Initiative participants. Significant results were then tested using plasma Aβ and CSF Aβ and Aβ/phosphorylated tau (Aβ/p-tau) ratio in the same cohort. The significant association was also generalized to postmortem Aβ load measurement in the Rush Religious Orders Study/Memory and Aging Project cohorts. In addition, global cognition was used as a phenotype in the analysis in both cohorts. Results Analysis of Aβ PET identified a variant in the CYP2C19 gene (rs4388808; p = 0.0006), in which carriers of the minor allele (MA) had a lower global SUVR. A voxel-wise analysis revealed that the variant is associated with a lower Aβ load in the frontal, inferior temporal, and posterior cingulate cortices. MA carriers also had higher CSF Aβ (p = 0.003) and Aβ/p-tau ratio (p = 0.02) but had no association with Aβ plasma levels. In postmortem brains, MA carriers had a lower Aβ load (p = 0.03). Global cognition was higher in MA carriers, which was found to be mediated by Aβ. Conclusions Together, these findings point to an association between CYP2C19 polymorphism and Aβ pathology, suggesting a protective effect of the MA of rs4388808. Despite the several possibilities in which CYP2C19 affects brain Aβ, the biological mechanism by which this genetic variation may act as a protective factor merits further investigation. PMID:29473050

Adverse events, toxicity and post-mortem data on duloxetine: case reports and literature survey.

PubMed

Vey, Eric L; Kovelman, Inna

2010-05-01

Duloxetine, a dual acting norepinephrine serotonin reuptake inhibitor, is a relatively new pharmacologic agent utilized in the treatment of depression, as well as diabetic neuropathic pain, fibromyalgia, and female stress urinary incontinence. This expanding scope of usage will inevitably lead to its eventual appearance during routine post-mortem toxicologic assays. Currently there is a paucity of post-mortem toxicologic data concerning duloxetine. The current report provides six additional case reports of post-mortem duloxetine levels, along with a review of duloxetine's pharmacokinetics, and the toxicologic manifestations which have been reported in the literature. The post-mortem levels reported, including the highest level recorded to date, are integrated with previously published reports to generate a foundation for a nascent guide to the interpretation of post-mortem duloxetine levels that could be encountered during routine post-mortem toxicologic analyses, and establish a basis upon which the establishment of toxic and lethal thresholds for this compound can be further elucidated with greater clarity. Copyright (c) 2010 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Influence of Post-Mortem Sperm Recovery Method and Extender on Unstored and Refrigerated Rooster Sperm Variables.

PubMed

Villaverde-Morcillo, S; Esteso, M C; Castaño, C; Santiago-Moreno, J

2016-02-01

Many post-mortem sperm collection techniques have been described for mammalian species, but their use in birds is scarce. This paper compares the efficacy of two post-mortem sperm retrieval techniques - the flushing and float-out methods - in the collection of rooster sperm, in conjunction with the use of two extenders, i.e., L&R-84 medium and Lake 7.1 medium. To determine whether the protective effects of these extenders against refrigeration are different for post-mortem and ejaculated sperm, pooled ejaculated samples (procured via the massage technique) were also diluted in the above extenders. Post-mortem and ejaculated sperm variables were assessed immediately at room temperature (0 h), and after refrigeration at 5°C for 24 and 48 h. The flushing method retrieved more sperm than the float-out method (596.5 ± 75.4 million sperm vs 341.0 ± 87.6 million sperm; p < 0.05); indeed, the number retrieved by the former method was similar to that obtained by massage-induced ejaculation (630.3 ± 78.2 million sperm). For sperm collected by all methods, the L&R-84 medium provided an advantage in terms of sperm motility variables at 0 h. In the refrigerated sperm samples, however, the Lake 7.1 medium was associated with higher percentages of viable sperm, and had a greater protective effect (p < 0.05) with respect to most motility variables. In conclusion, the flushing method is recommended for collecting sperm from dead birds. If this sperm needs to be refrigerated at 5°C until analysis, Lake 7.1 medium is recommended as an extender. © 2015 Blackwell Verlag GmbH.

Effect of postmortem sampling technique on the clinical significance of autopsy blood cultures.

PubMed

Hove, M; Pencil, S D

1998-02-01

Our objective was to investigate the value of postmortem autopsy blood cultures performed with an iodine-subclavian technique relative to the classical method of atrial heat searing and antemortem blood cultures. The study consisted of a prospective autopsy series with each case serving as its own control relative to subsequent testing, and a retrospective survey of patients coming to autopsy who had both autopsy blood cultures and premortem blood cultures. A busy academic autopsy service (600 cases per year) at University of Texas Medical Branch Hospitals, Galveston, Texas, served as the setting for this work. The incidence of non-clinically relevant (false-positive) culture results were compared using different methods for collecting blood samples in a prospective series of 38 adult autopsy specimens. One hundred eleven adult autopsy specimens in which both postmortem and antemortem blood cultures were obtained were studied retrospectively. For both studies, positive culture results were scored as either clinically relevant or false positives based on analysis of the autopsy findings and the clinical summary. The rate of false-positive culture results obtained by an iodine-subclavian technique from blood drawn soon after death were statistically significantly lower (13%) than using the classical method of obtaining blood through the atrium after heat searing at the time of the autopsy (34%) in the same set of autopsy subjects. When autopsy results were compared with subjects' antemortem blood culture results, there was no significant difference in the rate of non-clinically relevant culture results in a paired retrospective series of antemortem blood cultures and postmortem blood cultures using the iodine-subclavian postmortem method (11.7% v 13.5%). The results indicate that autopsy blood cultures obtained using the iodine-subclavian technique have reliability equivalent to that of antemortem blood cultures.

Effects of postmortem storage temperature on sea bass (Dicentrarchus labrax) muscle protein degradation: analysis by 2-D DIGE and MS.

PubMed

Terova, Genciana; Addis, Maria Filippa; Preziosa, Elena; Pisanu, Salvatore; Pagnozzi, Daniela; Biosa, Grazia; Gornati, Rosalba; Bernardini, Giovanni; Roggio, Tonina; Saroglia, Marco

2011-07-01

Storage conditions are known to be important for postmortem deterioration of fish muscle, and temperature is one of the factors with the strongest impact on this process. In order to shed light on the influence of temperature on the status of sea bass (Dicentrarchus labrax) muscle proteins during postmortem storage, a 2-D DIGE and mass spectrometry study was performed on fish kept at either 1 or 18°C for 5 days. As expected, the greatest alterations in sea bass filet protein composition were observed upon postmortem storage at 18°C, with distinct changes appearing in the 2-D protein profile after 5 days of storage at this temperature. In particular, degradation of the myofibrillar protein myosin heavy chain and of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, among the most abundant muscle proteins, could be clearly observed upon storage at higher temperatures. Although to a lesser extent, however, several proteins were observed to vary in abundance also upon storage for 5 days at 1°C. In particular, one of the most interesting observations was the rapid and significant decrease in the abundance of nucleoside diphosphate kinase B and phosphoglycerate mutase 2, which was observed also at low storage temperatures and appeared to be temperature-independent. The results of this study offer new knowledge on changes occurring in sea bass muscle proteins during postmortem storage at different temperatures and provide indications on protein degradation trends that might be useful for monitoring freshness of fish and quality of storage conditions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analytical Challenge in Postmortem Toxicology Applied to a Human Body Found into a Lake after Three Years Immersion.

PubMed

Morini, Luca; Vignali, Claudia; Tricomi, Paolo; Groppi, Angelo

2015-09-01

The body of a 30-year-old woman was found in Como lake at a depth of about 120 meters in her own car after 3 years of immersion. The aim of this study was to evaluate psychoactive drugs as well as alcohol biomarkers in biological matrices. The following analyses were initially performed: GC-MS systematic toxicological analysis on biological fluids and tissues; GC-MS analysis of drugs of abuse on pubic hair; direct ethanol metabolite determination in pubic hair by LC-MS/MS. After 7 years, the samples, that had been stored at -20°C, were re-analyzed and submitted to an LC-MS/MS targeted screening method, using multiple reaction monitoring mode. These analyses detected citalopram (150-3000 ng/mL), desmethylcitalopram (50-2300 ng/mL), clotiapine (20-65 ng/mL), and ethyl glucuronide (97 pg/mg). The methods showed an acceptable reproducibility, and the concentrations of citalopram and desmethylcitalopram calculated through the two analytical techniques did not significantly differ in biological fluids. © 2015 American Academy of Forensic Sciences.

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

PubMed

Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

2018-03-01

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Essentials of forensic post-mortem MR imaging in adults

PubMed Central

Ruder, T D; Thali, M J; Hatch, G M

2014-01-01

Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion–recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as “forensic sentinel sign”. If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system. PMID:24191122

Diagnosis of Vitality in Skin Wounds in the Ligature Marks Resulting From Suicide Hanging.

PubMed

Legaz Pérez, Isabel; Falcón, Maria; Gimenez, M; Diaz, F Martínez; Pérez-Cárceles, M D; Osuna, E; Nuno-Vieira, D; Luna, A

2017-09-01

Ascertaining the vital origin of skin wounds is one of the most challenging problems in forensic pathology. The forensic literature describes biomarkers and methods for differentiating vital and postmortem wounds, although no clear conclusions have been reached. The aim of this study was to characterize human vital wounds by analyzing the concentrations of metallic ions and the expression of P-selectin and cathepsin D in skin wounds in the ligature marks in a cohort of suicidal hangings for which vitality was previously demonstrated.A total of 71 skin wounds were analyzed within a postmortem interval of 19 to 36 hours. The concentration of Fe, Zn, Mg, and Ca and the expression of P-selectin and cathepsin D were analyzed together and separately. The majority of autopsied suicidal hangings were men (86%) with complete hanging mode (60.7%) in which there was a high frequency of subcutaneous injuries (78.3%). High concentrations of Ca and Mg compared with Fe and Zn were found. Ca and Zn concentrations decreased, and Fe concentration increased with the seriousness of the injury. A high percentage of moderately negative expression of both proteins was correlated with subcutaneous injury and low or medium concentrations of Fe.In conclusion, the joint study of metallic ions and proteins allows to characterize and to differentiate an injured vital wound of noninjured skin, especially when the damage in the tissue affects to the majority of the structures of the skin, but these results will need to be complemented with other biomarkers in time-controlled samples to further help in the differentiation of vital and postmortem wounds.

Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years.

PubMed

Ranginwala, Najeeb A; Hynan, Linda S; Weiner, Myron F; White, Charles L

2008-05-01

To examine the impact of newer neuropathological techniques on the power of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria for Alzheimer disease (AD) to detect AD at later postmortem study. We examined clinical and postmortem diagnoses of persons evaluated postmortem with thioflavin-S staining for plaques and tangles and immunohistochemical staining techniques for alpha synuclein, uhiquitin, and tau protein. Alzheimer Disease Center. Clinically evaluated persons for whom tissue diagnosis was available. Of 313 evaluees, 166 met criteria for probable AD. An additional 59 subjects had clinical diagnoses that included AD, e.g., possible AD, Lewy body variant of AD, AD and Parkinsonism, and mixed AD and vascular dementia. Of the 166 probable AD cases, 147 of 166 (88.6%) met pathologic criteria for AD. When all five AD groups were combined, 194 of 225 subjects (86.2%) met pathologic criteria for AD. There were five cases diagnosed pathologically as tangle-only dementia, which was considered a variant of AD. A pathologic diagnosis of Lewy body variant of AD was made in 56 (17.9%) of cases, including 44 of 313 (14.1%) cases diagnosed as probable or possible AD. Pure dementia with Lewy bodies was seen in 13 (4.2%). There were 9 (2.9%) cases of mixed AD and vascular dementia, and 37 (11.4%) cases of frontotemporal dementia. McKhann et al. criteria for probable and possible AD are valid for AD but do not exclude additional Lewy body pathology.

Hematocrit Measurement with R2* and Quantitative Susceptibility Mapping in Postmortem Brain.

PubMed

Walsh, A J; Sun, H; Emery, D J; Wilman, A H

2018-05-24

Noninvasive venous oxygenation quantification with MR imaging will improve the neurophysiologic investigation and the understanding of the pathophysiology in neurologic diseases. Available MR imaging methods are limited by sensitivity to flow and often require assumptions of the hematocrit level. In situ postmortem imaging enables evaluation of methods in a fully deoxygenated environment without flow artifacts, allowing direct calculation of hematocrit. This study compares 2 venous oxygenation quantification methods in in situ postmortem subjects. Transverse relaxation (R2*) mapping and quantitative susceptibility mapping were performed on a whole-body 4.7T MR imaging system. Intravenous measurements in major draining intracranial veins were compared between the 2 methods in 3 postmortem subjects. The quantitative susceptibility mapping technique was also applied in 10 healthy control subjects and compared with reference venous oxygenation values. In 2 early postmortem subjects, R2* mapping and quantitative susceptibility mapping measurements within intracranial veins had a significant and strong correlation ( R 2 = 0.805, P = .004 and R 2 = 0.836, P = .02). Higher R2* and susceptibility values were consistently demonstrated within gravitationally dependent venous segments during the early postmortem period. Hematocrit ranged from 0.102 to 0.580 in postmortem subjects, with R2* and susceptibility as large as 291 seconds -1 and 1.75 ppm, respectively. Measurements of R2* and quantitative susceptibility mapping within large intracranial draining veins have a high correlation in early postmortem subjects. This study supports the use of quantitative susceptibility mapping for evaluation of in vivo venous oxygenation and postmortem hematocrit concentrations. © 2018 by American Journal of Neuroradiology.

A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

PubMed Central

Logotheti, Marianthi; Papadodima, Olga; Venizelos, Nikolaos; Chatziioannou, Aristotelis; Kolisis, Fragiskos

2013-01-01

Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets. PMID:23554570

The formation of inflammatory demyelinated lesions in cerebral white matter

PubMed Central

Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

2016-01-01

Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

The formation of inflammatory demyelinated lesions in cerebral white matter.

PubMed

Maggi, Pietro; Macri, Sheila M Cummings; Gaitán, María I; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L; Ellis, Mary; Wu, Tianxia; Silva, Afonso C; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S

2014-10-01

Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. On average, BBB permeability increased 3.5-fold (p < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (p < 0.0001). This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. © 2014 American Neurological Association.

[Research Progress of Carrion-breeding Phorid Flies for Post-mortem Interval Estimation in Forensic Medicine].

PubMed

Li, L; Feng, D X; Wu, J

2016-10-01

It is a difficult problem of forensic medicine to accurately estimate the post-mortem interval. Entomological approach has been regarded as an effective way to estimate the post-mortem interval. The developmental biology of carrion-breeding flies has an important position at the post-mortem interval estimation. Phorid flies are tiny and occur as the main or even the only insect evidence in relatively enclosed environments. This paper reviews the research progress of carrion-breeding phorid flies for estimating post-mortem interval in forensic medicine which includes their roles, species identification and age determination of immatures. Copyright© by the Editorial Department of Journal of Forensic Medicine.

Anatomically Realistic Three-Dimensional Meshes of the Pelvic Floor & Anal Canal for Finite Element Analysis

PubMed Central

Noakes, Kimberley F.; Bissett, Ian P.; Pullan, Andrew J.; Cheng, Leo K.

2014-01-01

Three anatomically realistic meshes, suitable for finite element analysis, of the pelvic floor and anal canal regions have been developed to provide a framework with which to examine the mechanics, via finite element analysis of normal function within the pelvic floor. Two cadaver-based meshes were produced using the Visible Human Project (male and female) cryosection data sets, and a third mesh was produced based on MR image data from a live subject. The Visible Man (VM) mesh included 10 different pelvic structures while the Visible Woman and MRI meshes contained 14 and 13 structures respectively. Each image set was digitized and then finite element meshes were created using an iterative fitting procedure with smoothing constraints calculated from ‘L’-curves. These weights produced accurate geometric meshes of each pelvic structure with average Root Mean Square (RMS) fitting errors of less than 1.15 mm. The Visible Human cadaveric data provided high resolution images, however, the cadaveric meshes lacked the normal dynamic form of living tissue and suffered from artifacts related to postmortem changes. The lower resolution MRI mesh was able to accurately portray structure of the living subject and paves the way for dynamic, functional modeling. PMID:18317929

Application of contrast media in post-mortem imaging (CT and MRI).

PubMed

Grabherr, Silke; Grimm, Jochen; Baumann, Pia; Mangin, Patrice

2015-09-01

The application of contrast media in post-mortem radiology differs from clinical approaches in living patients. Post-mortem changes in the vascular system and the absence of blood flow lead to specific problems that have to be considered for the performance of post-mortem angiography. In addition, interpreting the images is challenging due to technique-related and post-mortem artefacts that have to be known and that are specific for each applied technique. Although the idea of injecting contrast media is old, classic methods are not simply transferable to modern radiological techniques in forensic medicine, as they are mostly dedicated to single-organ studies or applicable only shortly after death. With the introduction of modern imaging techniques, such as post-mortem computed tomography (PMCT) and post-mortem magnetic resonance (PMMR), to forensic death investigations, intensive research started to explore their advantages and limitations compared to conventional autopsy. PMCT has already become a routine investigation in several centres, and different techniques have been developed to better visualise the vascular system and organ parenchyma in PMCT. In contrast, the use of PMMR is still limited due to practical issues, and research is now starting in the field of PMMR angiography. This article gives an overview of the problems in post-mortem contrast media application, the various classic and modern techniques, and the issues to consider by using different media.

Injury-related mortality in South Africa: a retrospective descriptive study of postmortem investigations.

PubMed

Matzopoulos, Richard; Prinsloo, Megan; Pillay-van Wyk, Victoria; Gwebushe, Nomonde; Mathews, Shanaaz; Martin, Lorna J; Laubscher, Ria; Abrahams, Naeemah; Msemburi, William; Lombard, Carl; Bradshaw, Debbie

2015-05-01

To investigate injury-related mortality in South Africa using a nationally representative sample and compare the results with previous estimates. We conducted a retrospective descriptive study of medico-legal postmortem investigation data from mortuaries using a multistage random sample, stratified by urban and non-urban areas and mortuary size. We calculated age-specific and age-standardized mortality rates for external causes of death. Postmortem reports revealed 52,493 injury-related deaths in 2009 (95% confidence interval, CI: 46,930-58,057). Almost half (25,499) were intentionally inflicted. Age-standardized mortality rates per 100,000 population were as follows: all injuries: 109.0 (95% CI: 97.1-121.0); homicide 38.4 (95% CI: 33.8-43.0; suicide 13.4 (95% CI: 11.6-15.2) and road-traffic injury 36.1 (95% CI: 30.9-41.3). Using postmortem reports, we found more than three times as many deaths from homicide and road-traffic injury than had been recorded by vital registration for this period. The homicide rate was similar to the estimate for South Africa from a global analysis, but road-traffic and suicide rates were almost fourfold higher. This is the first nationally representative sample of injury-related mortality in South Africa. It provides more accurate estimates and cause-specific profiles that are not available from other sources.

Back-scattered electron imaging of a non-vertebral case of hypervitaminosis A in a cat.

PubMed

Franch, J; Pastor, J; Franch, B; Durall, I; Manzanares, M C

2000-03-01

We describe a clinical case of hypervitaminosis A in a cat. The main lesions were bony fusions of both the hip and stifle joints, without spinal involvement. A post-mortem study using back-scattered scanning electron microscopy (BEI-SEM) revealed that exostoses had formed around the joints without articular surface involvement. The more recently formed areas of bony proliferation were composed mainly of chondroid tissue surrounded by different degrees of woven bone. As the bony reaction occurred, remodelling of the trabeculae was observed which lead to progressive substitution of chondroid tissue by woven bone surrounded by apposition of lamellar bone. No traces of calcified cartilage were observed in any of the bone sections evaluated. Copyright 2000 European Society of Feline Medicine.

Paranoid Schizophrenia is Characterized by Increased CB1 Receptor Binding in the Dorsolateral Prefrontal Cortex

PubMed Central

Dalton, Victoria S; Long, Leonora E; Weickert, Cyndi Shannon; Zavitsanou, Katerina

2011-01-01

A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB1 receptor (CB1R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB1R ligand [3H] CP 55 940 and CB1R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB1R expression. There was a main effect of diagnosis on [3H] CP 55 940 binding quantified across all layers of the DLPFC (F(2,71)=3.740, p=0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB1R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67)=6.048, p=0.004) with paranoid SCZ patients differing significantly from the control (p=0.004) and from the non-paranoid group (p=0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB1R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ. PMID:21471953

Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex.

PubMed

Dalton, Victoria S; Long, Leonora E; Weickert, Cyndi Shannon; Zavitsanou, Katerina

2011-07-01

A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB(1) receptor (CB(1)R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB(1)R ligand [(3)H] CP 55,940 and CB(1)R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB(1)R expression. There was a main effect of diagnosis on [(3)H] CP 55,940 binding quantified across all layers of the DLPFC (F(2,71) = 3.740, p = 0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB(1)R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67) = 6.048, p = 0.004) with paranoid SCZ patients differing significantly from the control (p = 0.004) and from the non-paranoid group (p = 0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB(1)R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ.

Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder.

PubMed

Chandley, Michelle J; Szebeni, Katalin; Szebeni, Attila; Crawford, Jessica; Stockmeier, Craig A; Turecki, Gustavo; Miguel-Hidalgo, Jose Javier; Ordway, Gregory A

2013-07-01

Norepinephrine and glutamate are among several neurotransmitters implicated in the neuropathology of major depressive disorder (MDD). Glia deficits have also been demonstrated in people with MDD, and glia are critical modulators of central glutamatergic transmission. We studied glia in men with MDD in the region of the brain (locus coeruleus; LC) where noradrenergic neuronal cell bodies reside and receive glutamatergic input. The expression of 3 glutamate-related genes (SLC1A3, SLC1A2, GLUL) concentrated in glia and a glia gene (GFAP) were measured in postmortem tissues from men with MDD and from paired psychiatrically healthy controls. Initial gene expression analysis of RNA isolated from homogenized tissue (n = 9-10 pairs) containing the LC were followed by detailed analysis of gene expressions in astrocytes and oligodendrocytes (n = 6-7 pairs) laser captured from the LC region. We assessed protein changes in GFAP using immunohistochemistry and immunoblotting (n = 7-14 pairs). Astrocytes, but not oligodendrocytes, demonstrated robust reductions in the expression of SLC1A3 and SLC1A2, whereas GLUL expression was unchanged. GFAP expression was lower in astrocytes, and we confirmed reduced GFAP protein in the LC using immunostaining methods. Reduced expression of protein products of SLC1A3 and SLC1A2 could not be confirmed because of insufficient amounts of LC tissue for these assays. Whether gene expression abnormalities were associated with only MDD and not with suicide could not be confirmed because most of the decedents who had MDD died by suicide. Major depressive disorder is associated with unhealthy astrocytes in the noradrenergic LC, characterized here by a reduction in astrocyte glutamate transporter expression. These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD.

Different Statistical Approaches to Investigate Porcine Muscle Metabolome Profiles to Highlight New Biomarkers for Pork Quality Assessment

PubMed Central

Welzenbach, Julia; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tholen, Ernst; Große-Brinkhaus, Christine

2016-01-01

The aim of this study was to elucidate the underlying biochemical processes to identify potential key molecules of meat quality traits drip loss, pH of meat 1 h post-mortem (pH1), pH in meat 24 h post-mortem (pH24) and meat color. An untargeted metabolomics approach detected the profiles of 393 annotated and 1,600 unknown metabolites in 97 Duroc × Pietrain pigs. Despite obvious differences regarding the statistical approaches, the four applied methods, namely correlation analysis, principal component analysis, weighted network analysis (WNA) and random forest regression (RFR), revealed mainly concordant results. Our findings lead to the conclusion that meat quality traits pH1, pH24 and color are strongly influenced by processes of post-mortem energy metabolism like glycolysis and pentose phosphate pathway, whereas drip loss is significantly associated with metabolites of lipid metabolism. In case of drip loss, RFR was the most suitable method to identify reliable biomarkers and to predict the phenotype based on metabolites. On the other hand, WNA provides the best parameters to investigate the metabolite interactions and to clarify the complex molecular background of meat quality traits. In summary, it was possible to attain findings on the interaction of meat quality traits and their underlying biochemical processes. The detected key metabolites might be better indicators of meat quality especially of drip loss than the measured phenotype itself and potentially might be used as bio indicators. PMID:26919205

A new model for the estimation of time of death from vitreous potassium levels corrected for age and temperature.

PubMed

Zilg, B; Bernard, S; Alkass, K; Berg, S; Druid, H

2015-09-01

Analysis of potassium concentration in the vitreous fluid of the eye is frequently used by forensic pathologists to estimate the postmortem interval (PMI), particularly when other methods commonly used in the early phase of an investigation can no longer be applied. The postmortem rise in vitreous potassium has been recognized for several decades and is readily explained by a diffusion of potassium from surrounding cells into the vitreous fluid. However, there is no consensus regarding the mathematical equation that best describes this increase. The existing models assume a linear increase, but different slopes and starting points have been proposed. In this study, vitreous potassium levels, and a number of factors that may influence these levels, were examined in 462 cases with known postmortem intervals that ranged from 2h to 17 days. We found that the postmortem rise in potassium followed a non-linear curve and that decedent age and ambient temperature influenced the variability by 16% and 5%, respectively. A long duration of agony and a high alcohol level at the time of death contributed less than 1% variability, and evaluation of additional possible factors revealed no detectable impact on the rise of vitreous potassium. Two equations were subsequently generated, one that represents the best fit of the potassium concentrations alone, and a second that represents potassium concentrations with correction for decedent age and/or ambient temperature. The former was associated with narrow confidence intervals in the early postmortem phase, but the intervals gradually increased with longer PMIs. For the latter equation, the confidence intervals were reduced at all PMIs. Therefore, the model that best describes the observed postmortem rise in vitreous potassium levels includes potassium concentration, decedent age, and ambient temperature. Furthermore, the precision of these equations, particularly for long PMIs, is expected to gradually improve by adjusting the constants as more reference data are added over time. A web application that facilitates this calculation process and allows for such future modifications has been developed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pericardial fluid is suitable as an alternative specimen for the measurement of β-hydroxybutyrate within 96 h after death.

PubMed

Mizutani, Tatsushi; Yoshimoto, Takashi; Ishii, Akira

2018-05-21

We examined postmortem β-hydroxybutyrate (BHB) levels in the body fluids obtained from 253 forensic autopsy cases whose causes of death were determined. Postmortem changes of BHB levels according to postmortem intervals (PMI) in various body fluids (plasma, urine, vitreous humor, and pericardial fluids) were investigated to determine appropriate alternative specimens as plasma samples. Our study has indicated the following points: 1) the BHB levels in plasma specimens from three sampling sites showed no significant differences, 2) postmortem changes of BHB levels in plasma and pericardial fluids could be negligible within 96 h PMI, while urine and vitreous humor BHB levels showed postmortem changes, and 3) pericardial fluid would thus be most suitable as an alternative to plasma in postmortem BHB level. We have also proposed that BHB levels could be applicable for the diagnosis of metabolic disorders in forensic autopsy. Copyright © 2018 Elsevier B.V. All rights reserved.

The difficult task of assessing perimortem and postmortem fractures on the skeleton: a blind text on 210 fractures of known origin.

PubMed

Cappella, Annalisa; Amadasi, Alberto; Castoldi, Elisa; Mazzarelli, Debora; Gaudio, Daniel; Cattaneo, Cristina

2014-11-01

The distinction between perimortem and postmortem fractures is an important challenge for forensic anthropology. Such a crucial task is presently based on macro-morphological criteria widely accepted in the scientific community. However, several limits affect these parameters which have not yet been investigated thoroughly. This study aims at highlighting the pitfalls and errors in evaluating perimortem or postmortem fractures. Two trained forensic anthropologists were asked to classify 210 fractures of known origin in four skeletons (three victims of blunt force trauma and one natural death) as perimortem, postmortem, or dubious, twice in 6 months in order to assess intraobserver error also. Results show large errors, ranging from 14.8 to 37% for perimortem fractures and from 5.5 to 14.8% for postmortem ones; more than 80% of errors concerned trabecular bone. This supports the need for more objective and reliable criteria for a correct assessment of peri- and postmortem bone fractures. © 2014 American Academy of Forensic Sciences.

Co-registration of In-Vivo Human MRI Brain Images to Postmortem Histological Microscopic Images

PubMed Central

Singh, M.; Rajagopalan, A.; Kim, T.-S.; Hwang, D.; Chui, H.; Zhang, X.-L.; Lee, A.-Y.; Zarow, C.

2009-01-01

Certain features such as small vascular lesions seen in human MRI are detected reliably only in postmortem histological samples by microscopic imaging. Co-registration of these microscopically detected features to their corresponding locations in the in-vivo images would be of great benefit to understanding the MRI signatures of specific diseases. Using non-linear Polynomial transformation, we report a method to co-register in-vivo MRIs to microscopic images of histological samples drawn off the postmortem brain. The approach utilizes digital photographs of postmortem slices as an intermediate reference to co-register the MRIs to microscopy. The overall procedure is challenging due to gross structural deformations in the postmortem brain during extraction and subsequent distortions in the histological preparations. Hemispheres of the brain were co-registered separately to mitigate these effects. Approaches relying on matching single-slices, multiple-slices and entire volumes in conjunction with different similarity measures suggested that using four slices at a time in combination with two sequential measures, Pearson correlation coefficient followed by mutual information, produced the best MRI-postmortem co-registration according to a voxel mismatch count. The accuracy of the overall registration was evaluated by measuring the 3D Euclidean distance between the locations of microscopically identified lesions on postmortem slices and their MRI-postmortem co-registered locations. The results show a mean 3D displacement of 5.1 ± 2.0 mm between the in-vivo MRI and microscopically determined locations for 21 vascular lesions in 11 subjects. PMID:19169415

Quantitative measurement of intact alpha-synuclein proteoforms from post-mortem control and Parkinson's disease brain tissue by intact protein mass spectrometry.

PubMed

Kellie, John F; Higgs, Richard E; Ryder, John W; Major, Anthony; Beach, Thomas G; Adler, Charles H; Merchant, Kalpana; Knierman, Michael D

2014-07-23

A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).

Lifelike Vascular Reperfusion of a Thiel-Embalmed Pig Model and Evaluation as a Surgical Training Tool.

PubMed

Willaert, Wouter; Tozzi, Francesca; Van Hoof, Tom; Ceelen, Wim; Pattyn, Piet; D''Herde, Katharina

2016-01-01

Vascular reperfusion of Thiel cadavers can aid surgical and anatomical instruction. This study investigated whether ideal embalming circumstances provide lifelike vascular flow, enabling surgical practice and enhancing anatomical reality. Pressure-controlled pump-driven administration of blue embalming solution was assessed directly postmortem in a pig model (n = 4). Investigation of subsequent pump-driven vascular injection of red paraffinum perliquidum (PP) included assessment of flow parameters, intracorporeal distribution, anatomical alterations, and feasibility for surgical training. The microscopic distribution of PP was analyzed in pump-embalmed pig and gravity-embalmed human small intestines. Embalming lasted 50-105 min, and maximum arterial pressure was 65 mm Hg. During embalming, the following consecutive alterations were observed: arterial filling, organ coloration, venous perfusion, and further tissue coloration during the next weeks. Most organs were adequately preserved. PP generated low arterial pressures (<30 mm Hg) and drained through the venous cannula. Generally, realistic reperfusion and preservation of original anatomy were observed, but leakage in the pleural, abdominal, and retroperitoneal cavities occurred, and computed tomography showed edematous spleen and liver. Reduction of arterial flow rates after venous drainage is a prerequisite to prevent anatomical deformation, allowing simulation of various surgeries. In pump-embalmed pig small intestines, PP flowed from artery to vein through the capillaries without extravasation. In contrast, arterioles were blocked in gravity-embalmed human tissues. In a pig model, immediate postmortem pressure-controlled pump embalming generates ideal circumstances for (micro)vascular reperfusion with PP, permitting lifelike anatomy instruction and surgical training. © 2016 S. Karger AG, Basel.

Ultralow-field and spin-locking relaxation dispersion in postmortem pig brain.

PubMed

Dong, Hui; Hwang, Seong-Min; Wendland, Michael; You, Lixing; Clarke, John; Inglis, Ben

2017-12-01

To investigate tissue-specific differences, a quantitative comparison was made between relaxation dispersion in postmortem pig brain measured at ultralow fields (ULF) and spin locking at 7 tesla (T). The goal was to determine whether ULF-MRI has potential advantages for in vivo human brain imaging. Separate specimens of gray matter and white matter were investigated using an ULF-MRI system with superconducting quantum interference device (SQUID) signal detection to measure T1ULF at fields from 58.7 to 235.0 μT and using a commercial MRI scanner to measure T1ρ7T at spin-locking fields from 5.0 to 235.0 μT. At matched field strengths, T1ρ7T is 50 to 100% longer than T1ULF. Furthermore, dispersion in T1ULF is close to linear between 58.7 and 235 µT, whereas dispersion in T1ρ7T is highly nonlinear over the same range. A subtle elbow in the T1ULF dispersion at approximately 140 µT is tentatively attributed to the local dipolar field of macromolecules. It is suggested that different relaxation mechanisms dominate each method and that ULF-MRI has a fundamentally different sensitivity to the macromolecular structure of neural tissue. Ultralow-field MRI may offer distinct, quantitative advantages for human brain imaging, while simultaneously avoiding the severe heating limitation imposed on high-field spin locking. Magn Reson Med 78:2342-2351, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Temporal/compartmental changes in viral RNA and neuronal injury in a primate model of NeuroAIDS.

PubMed

González, R Gilberto; Fell, Robert; He, Julian; Campbell, Jennifer; Burdo, Tricia H; Autissier, Patrick; Annamalai, Lakshmanan; Taheri, Faramarz; Parker, Termara; Lifson, Jeffrey D; Halpern, Elkan F; Vangel, Mark; Masliah, Eliezer; Westmoreland, Susan V; Williams, Kenneth C; Ratai, Eva-Maria

2018-01-01

Despite the advent of highly active anti-retroviral therapy HIV-associated neurocognitive disorders (HAND) continue to be a significant problem. Furthermore, the precise pathogenesis of this neurodegeneration is still unclear. The objective of this study was to examine the relationship between infection by the simian immunodeficiency virus (SIV) and neuronal injury in the rhesus macaque using in vivo and postmortem sampling techniques. The effect of SIV infection in 23 adult rhesus macaques was investigated using an accelerated NeuroAIDS model. Disease progression was modulated either with combination anti-retroviral therapy (cART, 4 animals) or minocycline (7 animals). Twelve animals remained untreated. Viral loads were monitored in the blood and cerebral spinal fluid, as were levels of activated monocytes in the blood. Neuronal injury was monitored in vivo using magnetic resonance spectroscopy. Viral RNA was quantified in brain tissue of each animal postmortem using reverse transcription polymerase chain reaction (RT-PCR), and neuronal injury was assessed by immunohistochemistry. Without treatment, viral RNA in plasma, cerebral spinal fluid, and brain tissue appears to reach a plateau. Neuronal injury was highly correlated both to plasma viral levels and a subset of infected/activated monocytes (CD14+CD16+), which are known to traffic the virus into the brain. Treatment with either cART or minocycline decreased brain viral levels and partially reversed alterations in in vivo and immunohistochemical markers for neuronal injury. These findings suggest there is significant turnover of replicating virus within the brain and the severity of neuronal injury is directly related to the brain viral load.

ASTROCYTE PATHOLOGY IN MAJOR DEPRESSIVE DISORDER: INSIGHTS FROM HUMAN POSTMORTEM BRAIN TISSUE

PubMed Central

Rajkowska, Grazyna; Stockmeier, Craig A.

2013-01-01

The present paper reviews astrocyte pathology in major depressive disorder (MDD) and proposes that reductions in astrocytes and related markers are key features in the pathology of MDD. Astrocytes are the most numerous and versatile of all types of glial cells. They are crucial to the neuronal microenvironment by regulating glucose metabolism, neurotransmitter uptake (particularly for glutamate), synaptic development and maturation and the blood brain barrier. Pathology of astrocytes has been consistently noted in MDD as well as in rodent models of depressive-like behavior. This review summarizes evidence from human postmortem tissue showing alterations in the expression of protein and mRNA for astrocyte markers such as glial fibrillary acidic protein (GFAP), gap junction proteins (connexin 40 and 43), the water channel aquaporin-4 (AQP4), a calcium-binding protein S100B and glutamatergic markers including the excitatory amino acid transporters 1 and 2 (EAAT1, EAAT2) and glutamine synthetase. Moreover, preclinical studies are presented that demonstrate the involvement of GFAP and astrocytes in animal models of stress and depressive-like behavior and the influence of different classes of antidepressant medications on astrocytes. In light of the various astrocyte deficits noted in MDD, astrocytes may be novel targets for the action of antidepressant medications. Possible functional consequences of altered expression of astrocytic markers in MDD are also discussed. Finally, the unique pattern of cell pathology in MDD, characterized by prominent reductions in the density of astrocytes and in the expression of their markers without obvious neuronal loss, is contrasted with that found in other neuropsychiatric and neurodegenerative disorders. PMID:23469922

An audit of the contribution to post-mortem examination diagnosis of individual analyte results obtained from biochemical analysis of the vitreous.

PubMed

Mitchell, Rebecca; Charlwood, Cheryl; Thomas, Sunethra Devika; Bellis, Maria; Langlois, Neil E I

2013-12-01

Biochemical analysis of the vitreous humor from the eye is an accepted accessory test for post-mortem investigation of cause of death. Modern biochemical analyzers allow testing of a range of analytes from a sample. However, it is not clear which analytes should be requested in order to prevent unnecessary testing (and expense). The means and standard deviation of the values obtained from analysis of the vitreous humor for sodium, potassium, chloride, osmolality, glucose, ketones (β-hydroxybutyrate), creatinine, urea, calcium, lactate, and ammonia were calculated from which the contribution of each analyte was reviewed in the context of post-mortem findings and final cause of death. For sodium 32 cases were regarded as high (more than one standard deviation above the mean), from which 9 contributed to post-mortem diagnosis [drowning (4), heat related death (2), diabetic hyperglycemia (2), and dehydration (1)], but 25 low values (greater than one standard deviation below the mean) made no contribution. For chloride 29 high values contributed to 4 cases--3 drowning and 1 heat-related, but these were all previously identified by a high sodium level. There were 29 high and 35 low potassium values, none of which contributed to determining the final cause of death. Of 22 high values of creatinine, 12 contributed to a diagnosis of renal failure. From 32 high values of urea, 18 contributed to 16 cases of renal failure (2 associated with diabetic hyperglycemia), 1 heat-related death, and one case with dehydration. Osmolarity contributed to 12 cases (5 heat-related, 4 diabetes, 2 renal failure, and 1 dehydration) from 36 high values. There was no contribution from 32 high values and 19 low values of calcium and there was no contribution from 4 high and 2 low values of ammonia. There were 11 high values of glucose, which contributed to the diagnosis of 6 cases of diabetic hyperglycemia and 21 high ketone levels contributed to 8 cases: 4 diabetic ketosis, 3 hypothermia, 3 ketosis of unknown cause, and 2 alcohol related deaths. A high lactate was identified in 25 cases, which contributed to 1 case with a diagnosis of metformin toxicity (1), but none of the 22 low lactate values contributed. The results of this audit have been used to reduce vitreous biochemistry test requests for sodium, osmolality, glucose, ketones, urea, and creatinine in most cases. Critical appraisal of each part of the post-mortem process should be undertaken to provide evidence to justify any investigative methods used in an autopsy.

Magnetic resonance imaging of the rat Harderian gland

PubMed Central

Sbarbati, Andrea; Calderan, Laura; Nicolato, Elena; Marzola, Pasquina; Lunati, Ernesto; Donatella, Benati; Bernardi, Paolo; Osculati, Francesco

2002-01-01

The intra-orbital lachrymal gland (Harderian gland, or HG) of the female rat was studied by magnetic resonance imaging (MRI) to evaluate whether MRI can be used to visualize the gland in vivo and localized-1H-spectroscopy detect its lipid content. The results were correlated with post-mortem anatomical sections, and with light and electron microscopy. On MRI, HG presented as a mass located between the ocular bulb and the orbit. In strongly T2W sequences the secretory structures had a reduced signal while intraparenchymal connective tissue was visible. T2-quantitative maps values of HG (60.12 ± 8.15 ms, mean ± SD) were different from other tissues (i.e. muscular tissue, T2 = 44.79 ± 3.43 ms and olfactory bulb, T2 = 79.26 ± 4.25 ms). In contrast-enhanced-MRI, HG had a signal-intensity-drop of 0.074 ± 0.072 (mean ± SD), after injection of AMI-25, significantly different from the muscle (0.17 ± 0.10). Localized MRI spectra gave a large part of the signal originating from fat protons, but with a significant percentage from water protons. At light and electron microscopy the lipid deposition appeared to be composed of low-density material filling a large part of the cytoplasm, and the porphyrin aggregates were easily recognizable. The data demonstrate that an in vivo study of the HG was feasible and that high-field MRI allowed analysis of the gross anatomy detecting the lipid content of the gland. PMID:12363274

Incidence of disorders of spermatogenesis in middle aged finnish men, 1981-91: two necropsy series.

PubMed Central

Pajarinen, J.; Laippala, P.; Penttila, A.; Karhunen, P. J.

1997-01-01

OBJECTIVE: To investigate if the incidence of disorders of spermatogenesis and testicular tissue morphology have changed in middle aged Finnish men over 10 years. DESIGN: Two necropsy series completed in 1981 and in 1991. SETTING: Department of Forensic Medicine, University of Helsinki, Finland. SUBJECTS: 528 men, aged 35 to 69 years, subjected to medicolegal necropsy. MAIN OUTCOME MEASURES: Scoring of spermatogenesis and morphometric analysis of testicular tissue components. Individual risk factors for testicular disorders obtained by postmortem blind interviews with acquaintances. RESULTS: Normal spermatogenesis was found in 41.7% of the men (mean age 53.1 years). Between 1981 and 1991, the ratio of normal spermatogenesis decreased significantly (odds ratio 3.5; 95% confidence interval 2.5 to 5.1) from 56.4% to 26.9%, with a parallel increase in the incidence of partial and complete spermatogenic arrest (2.1; 1.4 to 2.9 and 2.9; 1.7 to 5.0, respectively). During this period, the size of seminiferous tubules decreased, the amount of fibrotic tissue increased, and the weight of testicles decreased significantly. Alterations in testicular characteristics over time could not be explained by changes in body mass index, smoking, alcohol drinking, or exposure to drugs. CONCLUSIONS: The incidence of normal spermatogenesis decreased among middle aged Finnish men from 1981 to 1991, and the incidence of disorders of spermatogenesis and pathological alterations in testicles increased. Deteriorating spermatogenesis may thus be one important factor in the explanation of declining sperm counts observed worldwide. PMID:9001473

A novel Tc-99m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine hindlimb ischemia model.

PubMed

Hyoun Kim, Myoung; Kim, Seul-Gi; Guhn Kim, Chang; Kim, Dae-Weung

2017-03-01

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Portraying the Dead.

ERIC Educational Resources Information Center

Ruby, Jay

1989-01-01

Explores custom of post-mortem photography. Describes practice of post-mortem photography in 19th century America and traces changes in post-mortem photography in the 20th century. Discusses value of photographs in mourning process and suggests more thorough examination of the place of death-related photographs in grief management. (Author/NB)

The Relationship Between the Changes in Local Stiffness of Chicken Myofibril and the Tenderness of Muscle During Postmortem Aging

NASA Astrophysics Data System (ADS)

Iwasaki, T.; Hasegawa, Y.; Yamamoto, K.; Nakamura, K.

We have investigated that the relationship between the stiffness of myofibrils and the tenderness of muscle during postmortem aging. The stiffness (elasticity) of A and I bands as well as Z-line of chicken myofibrils during postmortem aging were measured by atomic force microscope. The stiffness of all regions increased till 12 hr of postmortem, then it decreased to 96 hr. This tendency was the same as the changes of shear force value of whole muscle during postmortem aging. The elasticity of the Z-line of chicken myofibrils treated with calcium ions in the presence of protease inhibitor decreased with treating time. This indicates that the nonenzymatic structural changes of myofibrils is one of the causes of meat tenderization.

Development of a consensus approach for return of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project.

PubMed

Lockhart, Nicole C; Weil, Carol J; Carithers, Latarsha J; Koester, Susan E; Little, A Roger; Volpi, Simona; Moore, Helen M; Berkman, Benjamin E

2018-06-14

The active debate about the return of incidental or secondary findings in research has primarily focused on return to research participants, or in some cases, family members. Particular attention has been paid to return of genomic findings. Yet, research may generate other types of findings that warrant consideration for return, including findings related to the pathology of donated biospecimens. In the case of deceased biospecimen donors who are also organ and/or tissue transplant donors, pathology incidental findings may be relevant not to family members, but to potential organ or tissue transplant recipients. This paper will describe the ethical implications of pathology incidental findings in the Genotype-Tissue Expression (GTEx) project, the process for developing a consensus approach as to if/when such findings should be returned, possible implications for other research projects collecting postmortem tissues and how the scenario encountered in GTEx fits into the larger return of results/incidental findings debate. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mycobacterium avium subsp. avium in lymph nodes and diaphragms of pigs from one infected herd in the Czech Republic.

PubMed

Kriz, Petr; Kaevska, Marija; Slana, Iva; Bartejsova, Iva; Pavlik, Ivo

2014-01-01

This study was performed on 40 finished pigs from one herd naturally infected with Mycobacterium avium subsp. avium. The aim was to investigate the presence and amount of M. a. avium in samples of lymph nodes and diaphragm tissues collected during routine postmortem inspection using the triplex quantitative real time PCR (qPCR) method. We collected, in total, 107 samples: various lymph nodes affected by gross tuberculosis (TB)-like lesions from 17 pig carcasses, as well as samples of head and mesenteric lymph nodes from 23 carcasses without TB-like lesions. Samples of diaphragm tissues were collected from all carcasses. M. a. avium was detected in one or more tissue samples collected from half of the slaughtered pigs tested. Samples of diaphragm tissues of three pigs with detected TB-like lesions contained M. a. avium (10(2) to 10(3) cells per g of sample); the organism was not detected in diaphragm tissues from pigs without TB-like lesions. The qPCR method may be useful for quantification of M. a. avium in pigs for the purposes of foodborne risk assessment.

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

PubMed Central

Weickert, Cynthia Shannon; Sheedy, Donna; Rothmond, Debora A.; Dedova, Irina; Fung, Samantha; Garrick, Therese; Wong, Jenny; Harding, Antony J.; Sivagnanansundaram, Sinthuja; Hunt, Clare; Duncan, Carlotta; Sundqvist, Nina; Tsai, Shan-Yuan; Anand, Jasna; Draganic, Daren; Harper, Clive

2010-01-01

Objective To conduct postmortem human brain research into the neuropathological basis of schizophrenia, it is critical to establish cohorts that are well-characterised and well-matched. Our objective was to determine if specimen characteristics, including: diagnosis, age, postmortem interval (PMI), brain acidity (pH), and/or the agonal state of the subject at death related to RNA quality, and to determine the most appropriate reference gene mRNAs. Methods We selected a matched cohort of 74 cases (37 schizophrenia / schizoaffective disorder cases and 37 controls cases). Middle frontal gyrus tissue was pulverised, tissue pH was measured, RNA isolated for cDNA from each case, and RNA integrity number (RIN) measurements were assessed. Using RT-PCR, we measured nine housekeeper genes and calculated a geomean in each diagnostic group. Results We found that the RINs were very good (mean 7.3) and all nine housekeeper control genes were significantly correlated with RIN. Seven of nine housekeeper genes were also correlated with pH, and two clinical variables, agonal state and duration of illness did have an effect on some control mRNAs. No major impact of PMI or freezer time on housekeeper mRNAs was detected. Our results show that people with schizophrenia had significantly less PPIA, and SDHA and tended to have less GUSB and B2M mRNA suggesting that these control genes may not be good candidates for normalisation. Conclusions In our cohort, less than 10% variability in RIN values was detected and the diagnostic groups were well matched overall. Our cohort was adequately powered (0.80–0.90) to detect mRNA differences (25%) due to disease. Our study suggests that multiple factors should be considered in mRNA expression studies of human brain tissues. When schizophrenia cases are adequately matched to control cases subtle differences in gene expression can be reliably detected. PMID:20073568

Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

PubMed Central

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration. PMID:28713239

Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela

2011-11-18

Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount ofmore » mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.« less

Postmortem redistribution of tramadol and O-desmethyltramadol.

PubMed

Costa, Isabel; Oliveira, Ana; Guedes de Pinho, Paula; Teixeira, Helena Maria; Moreira, Roxana; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

2013-01-01

Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its efficacy and safety. Although tramadol induces less adverse effects compared with other opioids, an increased number of documented cases of dependence, abuse, intentional overdose or intoxication have been described. In fatal intoxication, the interpretation of the probable cause of death often relies on the measurement of the tramadol concentration in blood. However, postmortem redistribution (PMR) may affect the results and therefore bias the autopsy report. In the present study, the postmortem cardiac and femoral blood samples from 15 cases of fatal tramadol intoxication were obtained to assess the PMR of tramadol and its main active metabolite, O-desmethyltramadol (M1). Toxicological analysis was performed by the gas chromatography-electron impact-mass spectrometry (GC-EI-MS) method, previously developed and validated for the quantification of both analytes. The cardiac-to-femoral blood ratios of 1.40 and 1.28 were obtained for tramadol and M1, respectively. Results were compared with those in the literature and it was possible to conclude that femoral blood should be considered for quantitative interpretations in fatal cases of tramadol intoxication.

Multimodal assessment of spatial distribution of drug-tracer uptake by brain tissue after intra-arterial injections

NASA Astrophysics Data System (ADS)

Singh-Moon, Rajinder; Chaudhuri, Durba; Wang, Mei; Straubinger, Robert; Bigio, Irving J.; Joshi, Shailendra

2014-02-01

It is challenging to track the rapid changes in drug concentrations after intra-arterial (IA) administration to elucidate the pharmacokinetics of this method of drug delivery. Traditional pharmacokinetic parameters (such as protein binding) that are highly relevant to intravenous (IV) administration do not seem to apply to IA injections. Regional drug delivery is affected by the biomechanics of drug injection, resting blood flow, and local tissue extraction. In-vivo and ex-vivo, optical methods for spatial mapping of drug deposition can assist in visualizing drug distributions and aid in the screening of potential drugs and carrier candidates. We present a multimodal approach for the assessment of drug distribution in postmortem tissue specimens using diffuse reflectance spectroscopy, multispectral imaging, and confocal microscopy and demonstrate feasibility of distinguishing route of administration advantages of liposome-dye conjugate delivery. The results of this study suggest that insight on drug dynamics gained by this aggregated approach can be used to help screen and/or optimize potential drug candidates and drug delivery protocols.

SyMRI of the Brain

PubMed Central

Hagiwara, Akifumi; Warntjes, Marcel; Hori, Masaaki; Andica, Christina; Nakazawa, Misaki; Kumamaru, Kanako Kunishima; Abe, Osamu; Aoki, Shigeki

2017-01-01

Abstract Conventional magnetic resonance images are usually evaluated using the image signal contrast between tissues and not based on their absolute signal intensities. Quantification of tissue parameters, such as relaxation rates and proton density, would provide an absolute scale; however, these methods have mainly been performed in a research setting. The development of rapid quantification, with scan times in the order of 6 minutes for full head coverage, has provided the prerequisites for clinical use. The aim of this review article was to introduce a specific quantification method and synthesis of contrast-weighted images based on the acquired absolute values, and to present automatic segmentation of brain tissues and measurement of myelin based on the quantitative values, along with application of these techniques to various brain diseases. The entire technique is referred to as “SyMRI” in this review. SyMRI has shown promising results in previous studies when used for multiple sclerosis, brain metastases, Sturge-Weber syndrome, idiopathic normal pressure hydrocephalus, meningitis, and postmortem imaging. PMID:28257339

Detection and Heterogeneity of Herpesviruses Causing Pacheco's Disease in Parrots

PubMed Central

Tomaszewski, Elizabeth; Wilson, Van G.; Wigle, William L.; Phalen, David N.

2001-01-01

Pacheco's disease (PD) is a common, often fatal, disease of parrots. We cloned a virus isolate from a parrot that had characteristic lesions of PD. Three viral clones were partially sequenced, demonstrating that this virus was an alphaherpesvirus most closely related to the gallid herpesvirus 1. Five primer sets were developed from these sequences. The primer sets were used with PCR to screen tissues or tissue culture media suspected to contain viruses from 54 outbreaks of PD. The primer sets amplified DNA from all but one sample. Ten amplification patterns were detected, indicating that PD is caused by a genetically heterogeneous population of viruses. A single genetic variant (psittacid herpesvirus variant 1) amplified with all primer sets and was the most common virus variant (62.7%). A single primer set (23F) amplified DNA from all of the positive samples, suggesting that PCR could be used as a rapid postmortem assay for these viruses. PCR was found to be significantly more sensitive than tissue culture for the detection of psittacid herpesviruses. PMID:11158102

High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.

PubMed

Seiriki, Kaoru; Kasai, Atsushi; Hashimoto, Takeshi; Schulze, Wiebke; Niu, Misaki; Yamaguchi, Shun; Nakazawa, Takanobu; Inoue, Ken-Ichi; Uezono, Shiori; Takada, Masahiko; Naka, Yuichiro; Igarashi, Hisato; Tanuma, Masato; Waschek, James A; Ago, Yukio; Tanaka, Kenji F; Hayata-Takano, Atsuko; Nagayasu, Kazuki; Shintani, Norihito; Hashimoto, Ryota; Kunii, Yasuto; Hino, Mizuki; Matsumoto, Junya; Yabe, Hirooki; Nagai, Takeharu; Fujita, Katsumasa; Matsuda, Toshio; Takuma, Kazuhiro; Baba, Akemichi; Hashimoto, Hitoshi

2017-06-21

Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Isolation and molecular characterization of Toxoplasma gondii in a colony of captive black-capped squirrel monkeys (Saimiri boliviensis).

PubMed

Pardini, L; Dellarupe, A; Bacigalupe, D; Quiroga, M A; Moré, G; Rambeaud, M; Basso, W; Unzaga, J M; Schares, G; Venturini, M C

2015-12-01

Toxoplasmosis is commonly asymptomatic; however, it can be a fatal multisystemic disease in some animal species, such as New World monkeys. An outbreak of acute fatal toxoplasmosis was reported in a colony of black-capped squirrel monkeys (Saimiri boliviensis) from the zoo of La Plata, Argentina. Post-mortem examination of two monkeys revealed macroscopical and microscopical lesions compatible with acute toxoplasmosis. The presence of Toxoplasma gondii was confirmed by immunohistochemistry on monkey tissues, bioassay in mice and PCR using the specific primers B22-B23. By PCR-RFLP analysis, T. gondii isolated in mice, deriving from both monkeys, showed the same restriction pattern, with most markers showing a type III restriction pattern, except for C22-8 (type II) and C29-2 (type I). To our knowledge this is the first report of fatal toxoplasmosis in S. boliviensis caused by a non-canonical or atypical genotype of T. gondii. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Potential use of hydrocarbons for aging Lucilia sericata blowfly larvae to establish the postmortem interval.

PubMed

Moore, Hannah E; Adam, Craig D; Drijfhout, Falko P

2013-03-01

Previous studies on Diptera have shown the potential for the use of cuticular hydrocarbons' analysis in the determination of larval age and hence the postmortem interval (PMI) for an associated cadaver. In this work, hydrocarbon compounds, extracted daily until pupation from the cuticle of the blowfly Lucilia sericata (Diptera: Calliphoridae), have been analyzed using gas chromatography-mass spectrometry (GC-MS). The results show distinguishing features within the hydrocarbon profile over the period of the larvae life cycle, with significant chemical changes occurring from the younger larvae to the postfeeding larvae. Further interpretation of the chromatograms using principal component analysis revealed a strong correlation between the magnitudes of particular principal components and time. This outcome suggests that, under the conditions of this study, the cuticular hydrocarbons evolve in a systematic fashion with time, thus supporting the potential for GC-MS analysis as a tool for establishing PMI where such a species is present. © 2012 American Academy of Forensic Sciences.

Accuracy and usefulness of the AVOXimeter 4000 as routine analysis of carboxyhemoglobin.

PubMed

Fujihara, Junko; Kinoshita, Hiroshi; Tanaka, Naoko; Yasuda, Toshihiro; Takeshita, Haruo

2013-07-01

The measurement of blood carboxyhemoglobin (CO-Hb) is important to determine the cause of death. The AVOXimeter 4000 (AVOX), a portable CO-oximeter, has the advantages of a low purchase price and operating cost, ease of operation, and rapid results. Little information is available on the usefulness of AVOX in the forensic sample, and the previous study investigated only six samples. Therefore, in this study, we confirmed the usefulness of the AVOX through a comparison of its results with data previously obtained using the double wavelength spectrophotometric method in autopsies. Regression analysis was performed between CO-Hb levels measured by the AVOX and those measured by the conventional double wavelength spectrophotometric method in postmortem blood samples: a significant correlation was observed. This study suggests the usefulness of the AVOX to analyze postmortem blood, and the AVOX is suitable for routine forensic analysis and can be applied at the crime scene. © 2013 American Academy of Forensic Sciences.

Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross-Isseroff, R.; Dillon, K.A.; Fieldust, S.J.

In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measuredmore » by autoradiography.« less

Post-mortem review of fentanyl-related overdose deaths among identified drug users in Southern Bavaria, Germany, 2005-2014.

PubMed

Sinicina, Inga; Sachs, Hans; Keil, Wolfgang

2017-11-01

Two decades ago, there were only single case reports on deaths in Europe following the consumption of illicitly manufactured fentanyl by problem drug users. Today, lethal fentanyl intoxication is now no longer a rarity. Since 2005, a rapid increase of lethal fentanyl-related intoxications in the drug scene has been observed at the Institute of Legal Medicine, Ludwig Maximilians University, Munich. We hypothesized that this rise is the result of the launch of fentanyl matrix patches in Germany in 2004, their broad acceptance, their diversion from the regulated supply chain, and incautious prescription by medical care providers. Post-mortem toxicological reports were reviewed for lethal fentanyl-related intoxications between 2004 und 2014. Blood and tissue samples were tested by GC/MS or LC-MS/MS. The results of police investigations, autopsy reports, and the database of the Institute of Legal Medicine, LMU, were analysed to identify problem drug users and to detect the source of fentanyl as well as the routes of administration. Between 2005 and 2014, 242 overdose victims with post-mortem toxicological detection of fentanyl were found. In the majority of cases, fentanyl matrix patches were the source of fentanyl. The onset of fentanyl-related deaths coincided with the launch of transdermal fentanyl matrix patches in Germany in 2004. Several approaches, such as providing drug users with information on the possible risks of fentanyl consumption, education of medical caregivers, and also monitoring of the prescription of fentanyl patches, are required to reduce the number of fentanyl-related deaths in drug addicts. Copyright © 2017 Elsevier B.V. All rights reserved.

Injury-related mortality in South Africa: a retrospective descriptive study of postmortem investigations

PubMed Central

Prinsloo, Megan; Pillay-van Wyk, Victoria; Gwebushe, Nomonde; Mathews, Shanaaz; Martin, Lorna J; Laubscher, Ria; Abrahams, Naeemah; Msemburi, William; Lombard, Carl; Bradshaw, Debbie

2015-01-01

Abstract Objective To investigate injury-related mortality in South Africa using a nationally representative sample and compare the results with previous estimates. Methods We conducted a retrospective descriptive study of medico-legal postmortem investigation data from mortuaries using a multistage random sample, stratified by urban and non-urban areas and mortuary size. We calculated age-specific and age-standardized mortality rates for external causes of death. Findings Postmortem reports revealed 52 493 injury-related deaths in 2009 (95% confidence interval, CI: 46 930–58 057). Almost half (25 499) were intentionally inflicted. Age-standardized mortality rates per 100 000 population were as follows: all injuries: 109.0 (95% CI: 97.1–121.0); homicide 38.4 (95% CI: 33.8–43.0; suicide 13.4 (95% CI: 11.6–15.2) and road-traffic injury 36.1 (95% CI: 30.9–41.3). Using postmortem reports, we found more than three times as many deaths from homicide and road-traffic injury than had been recorded by vital registration for this period. The homicide rate was similar to the estimate for South Africa from a global analysis, but road-traffic and suicide rates were almost fourfold higher. Conclusion This is the first nationally representative sample of injury-related mortality in South Africa. It provides more accurate estimates and cause-specific profiles that are not available from other sources. PMID:26229201

Utility of Postmortem Autopsy via Whole-Body Imaging: Initial Observations Comparing MDCT and 3.0T MRI Findings with Autopsy Findings

PubMed Central

Cha, Jang Gyu; Kim, Dong Hun; Kim, Dae Ho; Paik, Sang Hyun; Park, Jai Soung; Park, Seong Jin; Lee, Hae Kyung; Hong, Hyun Sook; Choi, Duek Lin; Chung, Nak Eun; Lee, Bong Woo; Seo, Joong Seok

2010-01-01

Objective We prospectively compared whole-body multidetector computed tomography (MDCT) and 3.0T magnetic resonance (MR) images with autopsy findings. Materials and Methods Five cadavers were subjected to whole-body, 16-channel MDCT and 3.0T MR imaging within two hours before an autopsy. A radiologist classified the MDCT and 3.0T MRI findings into major and minor findings, which were compared with autopsy findings. Results Most of the imaging findings, pertaining to head and neck, heart and vascular, chest, abdomen, spine, and musculoskeletal lesions, corresponded to autopsy findings. The causes of death that were determined on the bases of MDCT and 3.0T MRI findings were consistent with the autopsy findings in four of five cases. CT was useful in diagnosing fatal hemorrhage and pneumothorax, as well as determining the shapes and characteristics of the fractures and the direction of external force. MRI was effective in evaluating and tracing the route of a metallic object, soft tissue lesions, chronicity of hemorrhage, and bone bruises. Conclusion A postmortem MDCT combined with MRI is a potentially powerful tool, providing noninvasive and objective measurements for forensic investigations. PMID:20592923

Extrahepatic biliary atresia in a border collie.

PubMed

Schulze, C; Rothuizen, J; van Sluijs, F J; Hazewinkel, H A; van den Ingh, T S

2000-01-01

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.

Effect of postmortem aging on marination performance of broiler breast pectoralis major categorized by color lightness

USDA-ARS?s Scientific Manuscript database

The objective was to evaluate the effect of postmortem aging on marinade uptake and retention by early-deboned chicken breast fillets with different color lightness. Effects of marination on product yield and muscle shear force were also determined. Early deboned (2 h postmortem) broiler butterflies...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

9 CFR 355.41 - Antemortem and postmortem inspection for mules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Animal Food, Mule Meat By-Product § 355.41 Antemortem and postmortem inspection for mules. (a)(1) An... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Antemortem and postmortem inspection for mules. 355.41 Section 355.41 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE...

Estimation of postmortem interval through albumin in CSF by simple dye binding method.

PubMed

Parmar, Ankita K; Menon, Shobhana K

2015-12-01

Estimation of postmortem interval is a very important question in some medicolegal investigations. For the precise estimation of postmortem interval, there is a need of a method which can give accurate estimation. Bromocresol green (BCG) is a simple dye binding method and widely used in routine practice. Application of this method in forensic practice may bring revolutionary changes. In this study, cerebrospinal fluid was aspirated from cisternal puncture from 100 autopsies. A study was carried out on concentration of albumin with respect to postmortem interval. After death, albumin present in CSF undergoes changes, after 72 h of death, concentration of albumin has become 0.012 mM, and this decrease was linear from 2 h to 72 h. An important relationship was found between albumin concentration and postmortem interval with an error of ± 1-4h. The study concludes that CSF albumin can be a useful and significant parameter in estimation of postmortem interval. Copyright © 2015 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.

Prediction of brain deformations and risk of traumatic brain injury due to closed-head impact: quantitative analysis of the effects of boundary conditions and brain tissue constitutive model.

PubMed

Wang, Fang; Han, Yong; Wang, Bingyu; Peng, Qian; Huang, Xiaoqun; Miller, Karol; Wittek, Adam

2018-05-12

In this study, we investigate the effects of modelling choices for the brain-skull interface (layers of tissues between the brain and skull that determine boundary conditions for the brain) and the constitutive model of brain parenchyma on the brain responses under violent impact as predicted using computational biomechanics model. We used the head/brain model from Total HUman Model for Safety (THUMS)-extensively validated finite element model of the human body that has been applied in numerous injury biomechanics studies. The computations were conducted using a well-established nonlinear explicit dynamics finite element code LS-DYNA. We employed four approaches for modelling the brain-skull interface and four constitutive models for the brain tissue in the numerical simulations of the experiments on post-mortem human subjects exposed to violent impacts reported in the literature. The brain-skull interface models included direct representation of the brain meninges and cerebrospinal fluid, outer brain surface rigidly attached to the skull, frictionless sliding contact between the brain and skull, and a layer of spring-type cohesive elements between the brain and skull. We considered Ogden hyperviscoelastic, Mooney-Rivlin hyperviscoelastic, neo-Hookean hyperviscoelastic and linear viscoelastic constitutive models of the brain tissue. Our study indicates that the predicted deformations within the brain and related brain injury criteria are strongly affected by both the approach of modelling the brain-skull interface and the constitutive model of the brain parenchyma tissues. The results suggest that accurate prediction of deformations within the brain and risk of brain injury due to violent impact using computational biomechanics models may require representation of the meninges and subarachnoidal space with cerebrospinal fluid in the model and application of hyperviscoelastic (preferably Ogden-type) constitutive model for the brain tissue.

Differential Decomposition Among Pig, Rabbit, and Human Remains.

PubMed

Dautartas, Angela; Kenyhercz, Michael W; Vidoli, Giovanna M; Meadows Jantz, Lee; Mundorff, Amy; Steadman, Dawnie Wolfe

2018-03-30

While nonhuman animal remains are often utilized in forensic research to develop methods to estimate the postmortem interval, systematic studies that directly validate animals as proxies for human decomposition are lacking. The current project compared decomposition rates among pigs, rabbits, and humans at the University of Tennessee's Anthropology Research Facility across three seasonal trials that spanned nearly 2 years. The Total Body Score (TBS) method was applied to quantify decomposition changes and calculate the postmortem interval (PMI) in accumulated degree days (ADD). Decomposition trajectories were analyzed by comparing the estimated and actual ADD for each seasonal trial and by fuzzy cluster analysis. The cluster analysis demonstrated that the rabbits formed one group while pigs and humans, although more similar to each other than either to rabbits, still showed important differences in decomposition patterns. The decomposition trends show that neither nonhuman model captured the pattern, rate, and variability of human decomposition. © 2018 American Academy of Forensic Sciences.

[External post-mortem examination].

PubMed

Hartwig, S

2016-09-01

The external post-mortem examination in Germany is a non-delegable medical duty for determination of death, identity of the deceased, cause of death, manner of death, time of death and notifiable infectious diseases. Within the framework of rescue service missions the physician is limited to ascertaining that death has occurred. The determination of death must be reliable and is automatically followed by a complete external post-mortem examination of the body, if necessary by another physician. The certain signs of death are livor mortis, rigor mortis and putrefaction. Reliable features for the occurrence of death are injuries which are not compatible with life and brain death. The external post-mortem examination is the basis for the decision on whether further criminal investigations are necessary. The external post-mortem examination and the accompanying death certification must always be meticulously carried out.

Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC-MS/MS in Postmortem Casework.

PubMed

Mohr, Amanda L A; Friscia, Melissa; Papsun, Donna; Kacinko, Sherri L; Buzby, David; Logan, Barry K

2016-11-01

Following series of synthetic cannabinoid and synthetic cathinone derivatives, the illicit drug market has begun to see increased incidence of synthetic opioids including fentanyl and its derivatives, and other chemically unrelated opioid agonists including AH-7921 and MT-45. Among the most frequently encountered compounds in postmortem casework have been furanyl fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylfuran-2-carboxamide, Fu-F) and U-47700 (trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide). Both drugs have been reported to be present in the heroin supply and to be gaining popularity among recreational opioid users, but were initially developed by pharmaceutical companies in the 1970s as candidates for development as potential analgesic therapeutic agents. A method was developed and validated for the analysis of U-47700, U-50488 and furanyl fentanyl in blood specimens. A total of 20 postmortem cases, initially believed to be heroin or other opioid-related drug overdoses, were submitted for quantitative analysis. The analytical range for U-47770 and U-50488 was 1-500 and 1-100 ng/mL for furanyl fentanyl. The limit of detection was 0.5 ng/mL for all compounds. Within the scope of the method, U-47700 was the only confirmed drug in 11 of the cases, 5 cases were confirmed for both U-47700 and furanyl fentanyl, and 3 cases were confirmed only for furanyl fentanyl. The mean and median blood concentrations for U-47700 were 253 ng/mL (±150) and 247 ng/mL, respectively, range 17-490 ng/mL. The mean and median blood concentrations for furanyl fentanyl were 26 ng/mL (±28) and 12.9 ng/mL, respectively, range 2.5-76 ng/mL. Given the widespread geographical distribution and increase in prevalence in postmortem casework, toxicology testing should be expanded to include testing for "designer opioids" in cases with histories consistent with opioid overdose but with no traditional opioids present or insufficient quantities to account for death. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Causes and manners of death among users of heroin, methadone, amphetamine, and cannabis in relation to postmortem chemical tests for illegal drugs.

PubMed

Eksborg, Staffan; Rajs, Jovan

2008-01-01

A 12-year medicolegal investigation of deceased illegal drug users (ILDU) in Stockholm, Sweden, classified on the basis of postmortem chemical tests, showed noticeable variations in causes and manners of death as well as in the distribution of suicide methods. This study offers objective information about connection between the postmortem findings of illegal drugs and the causes and manners of death of their users. However, further studies, comparing prevalence of drug use in general population and at the postmortem tests, are needed for more detailed elucidation of this connection.

The Anatomy of Amnesia: Neurohistological Analysis of Three New Cases

ERIC Educational Resources Information Center

Gold, Jeffrey J.; Squire, Larry R.

2006-01-01

The most useful information about the anatomy of human memory comes from cases where there has been extensive neuropsychological testing followed by detailed post-mortem neurohistological analysis. To our knowledge, only eight such cases have been reported (four with medial temporal lobe damage and four with diencephalic damage). Here we present…

A case of nontraumatic gas gangrene in a common marmoset (Callithrix jacchus).

PubMed

Yasuda, Masahiko; Inoue, Takashi; Ueno, Masami; Morita, Hanako; Hayashimoto, Nobuhito; Kawai, Kenji; Itoh, Toshio

2016-01-01

The common marmoset is widely used in neuroscience and regenerative medicine research. However, information concerning common marmoset disorders, particularly infectious diseases, is scarce. Here, we report a case of a female common marmoset that died suddenly due to gas gangrene. The animal presented with gaseous abdominal distention at postmortem, and Clostridium perfringens type A was isolated from several tissues. Vacuoles, a Gram-positive bacteremia and intravascular hemolysis were observed microscopically in the muscles, liver and lungs. On the basis of these findings, we diagnosed nontraumatic gas gangrene caused by Clostridium perfringens type A in this common marmoset.

A case of nontraumatic gas gangrene in a common marmoset (Callithrix jacchus)

PubMed Central

YASUDA, Masahiko; INOUE, Takashi; UENO, Masami; MORITA, Hanako; HAYASHIMOTO, Nobuhito; KAWAI, Kenji; ITOH, Toshio

2015-01-01

The common marmoset is widely used in neuroscience and regenerative medicine research. However, information concerning common marmoset disorders, particularly infectious diseases, is scarce. Here, we report a case of a female common marmoset that died suddenly due to gas gangrene. The animal presented with gaseous abdominal distention at postmortem, and Clostridium perfringens type A was isolated from several tissues. Vacuoles, a Gram-positive bacteremia and intravascular hemolysis were observed microscopically in the muscles, liver and lungs. On the basis of these findings, we diagnosed nontraumatic gas gangrene caused by Clostridium perfringens type A in this common marmoset. PMID:26156080

Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

PubMed

Choi, Jeong-Won; Lee, Hyun-Kyoung; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Kyoung-Ki; Lee, Myoung-Heon; Oem, Jae-Ku

2014-12-01

A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing.

"Body property": challenging the ethical barriers in organ transplantation to protect individual autonomy.

PubMed

Dunham, Charles C

2008-01-01

One of two articles related to the current organ shortage, this article advocates the need for legislation to recognize organs and tissues separated from the body as a distinct category of personal property. After addressing the legislative history of organ procurement and psychological barriers to donor consent, the article examines the importance of separating the lifetime rights of ownership in our own bodies from postmortem rights. Ultimately, the author proposes a futures market approach to this problem in which individuals before death, or surviving family members after death, are permitted sell the decedent's organs in a private contract.

Brainstem pathology in spasmodic dysphonia

PubMed Central

Simonyan, Kristina; Ludlow, Christy L.; Vortmeyer, Alexander O.

2009-01-01

Spasmodic dysphonia (SD) is a primary focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speech production. We examined two rare cases of postmortem brainstem tissue from SD patients compared to four controls. In SD patients, small clusters of inflammation were found in the reticular formation surrounding solitary tract, spinal trigeminal and ambigual nuclei, inferior olive and pyramids. Mild neuronal degeneration and depigmentation were observed in the substantia nigra and locus coeruleus. No abnormal protein accumulations and no demyelination or axonal degeneration were found. These neuropathological findings may provide insights into the pathophysiology of SD. PMID:19795469

Supplementation of glycerol or fructose via drinking water to grazing lambs on tissue glycogen level and lipogenesis.

PubMed

Volpi-Lagreca, G; Duckett, S K

2017-06-01

Lambs ( = 18; 40.1 ± 7.4 kg BW) were used to assess supplementation of glycerol or fructose via drinking water on growth, tissue glycogen levels, postmortem glycolysis, and lipogenesis. Lambs were blocked by BW and allocated to alfalfa paddocks (2 lambs/paddock and 3 paddocks/treatment). Each paddock within a block was assigned randomly to drinking water treatments for 30 d: 1) control (CON), 2) 120 g fructose/L of drinking water (FRU), or 3) 120 g glycerol/L of drinking water (GLY). Lambs grazed alfalfa with free access to water treatments for 28 d and then were fasted in indoor pens for a final 2 d with access to only water treatments. Data were analyzed using the MIXED procedure of SAS with water treatment and time (when appropriate) in the model. During the 28-d grazing period, ADG was greater ( < 0.05) for GLY than for CON or FRU. During the 2-d fasting period, BW shrink was lower ( < 0.05) for GLY compared with CON or FRU. Hot carcass weight was greater ( < 0.05) for GLY than for FRU. The interaction for glycogen content × postmortem time was significant ( = 0.003) in LM and semitendinosus (ST) muscles. Glycogen content in the LM was greater ( < 0.05) for GLY at 2 and 3 h and for FRU at 1 h postmortem compared with CON. Glycogen content in ST did not differ between treatments ( > 0.05). Liver glycogen content was over 14-fold greater ( < 0.05) for GLY compared with FRU or CON. Liver free glucose was greater ( < 0.05) for GLY than for CON, whereas liver lipid content was higher ( < 0.05) for CON than for GLY. Supplementation with GLY increased ( < 0.05) odd-chain fatty acids in LM, subcutaneous fat (SQ), and the liver. Stearic acid (C18:0) concentrations were reduced in LM ( = 0.064) and subcutaneous adipose tissue (SQ; = 0.018), whereas oleic acid (C18:1 -9) concentration tended to be increased ( = 0.066) in SQ with FRU and GLY. Linolenic acid (C18:3 -3) was reduced ( = 0.031) and all long-chain -3 fatty acid (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) concentrations were increased ( < 0.05) with FRU and GLY compared with CON. Glycerol supplementation upregulated ( < 0.05) stearoyl-CoA desaturate () and fatty acid synthase () mRNA by over 40-fold in the SQ and 5-fold in the liver. Glycerol supplementation also upregulated ( < 0.05) glucose transporters and glycogen branching enzyme in the liver. Overall, glycerol supplementation improved growth, reduced BW shrink during fasting, increased glycogen content in muscle and the liver, and stimulated de novo lipogenesis.

Optimised laser microdissection of the human ocular surface epithelial regions for microarray studies

PubMed Central

2013-01-01

Background The most important challenge of performing insitu transcriptional profiling of the human ocular surface epithelial regions is obtaining samples in sufficient amounts, without contamination from adjacent tissue, as the region of interest is microscopic and closely apposed to other tissues regions. We have effectively collected ocular surface (OS) epithelial tissue samples from the Limbal Epithelial Crypt (LEC), limbus, cornea and conjunctiva of post-mortem cadaver eyes with laser microdissection (LMD) technique for gene expression studies with spotted oligonucleotide microarrays and Gene 1.0 ST arrays. Methods Human donor eyes (4 pairs for spotted oligonucleotide microarrays, 3 pairs for Gene 1.0 ST arrays) consented for research were included in this study with due ethical approval of the Nottingham Research Ethics Committee. Eye retrieval was performed within 36 hours of post-mortem period. The dissected corneoscleral buttons were immersed in OCT media and frozen in liquid nitrogen and stored at −80°C till further use. Microscopic tissue sections of interest were taken on PALM slides and stained with Toluidine Blue for laser microdissection with PALM microbeam systems. Optimisation of the laser microdissection technique was crucial for efficient and cost effective sample collection. Results The starting concentration of RNA as stipulated by the protocol of microarray platforms was taken as the cut-off concentration of RNA samples in our studies. The area of LMD tissue processed for spotted oligonucleotide microarray study ranged from 86,253 μm2 in LEC to 392,887 μm2 in LEC stroma. The RNA concentration of the LMD samples ranged from 22 to 92 pg/μl. The recommended starting concentration of the RNA samples used for Gene 1.0 ST arrays was 6 ng/5 μl. To achieve the desired RNA concentration the area of ocular surface epithelial tissue sample processed for the Gene 1.0 ST array experiments was approximately 100,0000 μm2 to 130,0000 μm2. RNA concentration of these samples ranged from 10.88 ng/12 μl to 25.8 ng/12 μl, with the RNA integrity numbers (RIN) for these samples from 3.3 to 7.9. RNA samples with RIN values below 2, that had failed to amplify satisfactorily were discarded. Conclusions The optimised protocol for sample collection and laser microdissection improved the RNA yield of the insitu ocular surface epithelial regions for effective microarray studies on spotted oligonucleotide and affymetrix platforms. PMID:24160452

Running a postmortem service--a business case and clinical experience.

PubMed

Cohen, Marta C; Whitby, Elspeth; Fink, Michelle A; Collett, Jacquelene M; Offiah, Amaka C

2015-04-01

The purpose of the postmortem examination is to offer answers to explain the cause and manner of death. In the case of perinatal, infant and paediatric postmortem examinations, the goal is to identify unsuspected associated features, to describe pathogenic mechanisms and new conditions, and to evaluate the clinical management and diagnosis. Additionally, the postmortem examination is useful to counsel families regarding the probability of recurrence in future pregnancies and to inform family planning. Worldwide the rate of paediatric autopsy examinations has significantly declined during the last few decades. Religious objections to postmortem dissection and organ retention scandals in the United Kingdom provided some of the impetus for a search for non-invasive alternatives to the traditional autopsy; however, until recently, imaging studies remained an adjunct to, rather than a replacement for, the traditional autopsy. In 2012, Sheffield Children's Hospital National Health Service Foundation Trust set up the service provision of minimally invasive fetal, perinatal and neonatal autopsy, while a postmortem imaging service has been running in Melbourne, Australia, since 2008. Here we summarise the essentials of a business case and practical British and Australian experiences in terms of the pathological and radiologic aspects of setting up a minimally invasive clinical service in the United Kingdom and of developing a clinical postmortem imaging service as a complementary tool to the traditional autopsy in Australia.

[The theory of postmortem rigidity: the history and an original concept].

PubMed

Kil'diushov, E M; Tumanov, É V; Sokolova, Z Iu

2012-01-01

The original theory of postmortem rigidity has been developed and substantiated based on the concept of postmortem muscular contracture. It is postulated that the unrestricted growth of Ca2+ concentration in myoplasm of contractile cells during the immediate postmortal period brings the actin-myosine complex to the force generation state without subsequent relaxation.

Postmortem aging and freezing and thawing storage enhance ability of early deboned chicken pectoralis major muscle to hold added salt water

USDA-ARS?s Scientific Manuscript database

The effects of postdeboning aging and frozen storage on water-holding capacity (WHC) of chicken breast pectoralis major muscle were investigated. Broiler breast muscle was removed from carcasses either early postmortem (2 h) or later postmortem (24 h). Treatments included: no postdeboning aging; 1-...

Meat quality and rigor mortis development in broiler chickens with gas-induced anoxia and postmortem electrical stimulation.

PubMed

Sams, A R; Dzuik, C S

1999-10-01

This study was conducted to evaluate the combined rigor-accelerating effects of postmortem electrical stimulation (ES) and argon-induced anoxia (Ar) of broiler chickens. One hundred broilers were processed in the following treatments: untreated controls, ES, Ar, or Ar with ES (Ar + ES). Breast fillets were harvested at 1 h postmortem for all treatments or at 1 and 6 h postmortem for the control carcasses. Fillets were sampled for pH and ratio of inosine to adenosine (R-value) and were then individually quick frozen (IQF) or aged on ice (AOI) until 24 h postmortem. Color was measured in the AOI fillets at 24 h postmortem. All fillets were then cooked and evaluated for Allo-Kramer shear value. The Ar treatment accelerated the normal pH decline, whereas the ES and AR + ES treatments yielded even lower pH values at 1 h postmortem. The Ar + ES treatment had a greater R-value than the ES treatment, which was greater than either the Ar or 1-h controls, which, in turn, were not different from each other. The ES treatment had the lowest L* value, and ES, Ar, and Ar + ES produced significantly higher a* values than the 1-h controls. For the IQF fillets, the ES and Ar + ES treatments were not different in shear value but were lower than Ar, which was lower than the 1-h controls. The same was true for the AOI fillets except that the ES and the Ar treatments were not different. These results indicated that although ES and Ar had rigor-accelerating and tenderizing effects, ES seemed to be more effective than Ar; there was little enhancement when Ar was added to the ES treatment and fillets were deboned at 1 h postmortem.

Rigor mortis at the myocardium investigated by post-mortem magnetic resonance imaging.

PubMed

Bonzon, Jérôme; Schön, Corinna A; Schwendener, Nicole; Zech, Wolf-Dieter; Kara, Levent; Persson, Anders; Jackowski, Christian

2015-12-01

Post-mortem cardiac MR exams present with different contraction appearances of the left ventricle in cardiac short axis images. It was hypothesized that the grade of post-mortem contraction may be related to the post-mortem interval (PMI) or cause of death and a phenomenon caused by internal rigor mortis that may give further insights in the circumstances of death. The cardiac contraction grade was investigated in 71 post-mortem cardiac MR exams (mean age at death 52 y, range 12-89 y; 48 males, 23 females). In cardiac short axis images the left ventricular lumen volume as well as the left ventricular myocardial volume were assessed by manual segmentation. The quotient of both (LVQ) represents the grade of myocardial contraction. LVQ was correlated to the PMI, sex, age, cardiac weight, body mass and height, cause of death and pericardial tamponade when present. In cardiac causes of death a separate correlation was investigated for acute myocardial infarction cases and arrhythmic deaths. LVQ values ranged from 1.99 (maximum dilatation) to 42.91 (maximum contraction) with a mean of 15.13. LVQ decreased slightly with increasing PMI, however without significant correlation. Pericardial tamponade positively correlated with higher LVQ values. Variables such as sex, age, body mass and height, cardiac weight and cause of death did not correlate with LVQ values. There was no difference in LVQ values for myocardial infarction without tamponade and arrhythmic deaths. Based on the observation in our investigated cases, the phenomenon of post-mortem myocardial contraction cannot be explained by the influence of the investigated variables, except for pericardial tamponade cases. Further research addressing post-mortem myocardial contraction has to focus on other, less obvious factors, which may influence the early post-mortem phase too. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Search for fungi-specific metabolites of four model drugs in postmortem blood as potential indicators of postmortem fungal metabolism.

PubMed

Martínez-Ramírez, Jorge A; Strien, Juliane; Walther, Grit; Peters, Frank T

2016-05-01

Fungi colonizing cadavers are capable of drug metabolism and may thus change the metabolite pattern or concentration of drugs in forensic postmortem samples. The purpose of this study was to check for the presence of such changes by searching fungi-specific metabolites of four model drugs (amitriptyline, metoprolol, mirtazapine, and zolpidem) in decomposed postmortem blood samples from 33 cases involving these drugs. After isolation and identification of fungal strains present in the samples, each isolate was incubated in Sabouraud medium at 25°C for up to 120h with each model drug. One part of the supernatants was directly analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), another after liquid-liquid extraction with chlorobutane and concentration. From 21 out of 33 decomposed postmortem blood samples (64%) a total of 30 different strains could be isolated, one from the class of Ascomycete and the rest belonging to 15 species from 8 different genera (number of species): Aspergillus (2), Botrytis (1), Candida (8), Fusarium (1), Mucor (1), Penicillium (1), and Rodothorula (1). In the in vitro studies, these microorganisms were found capable of N-demethylation and N-oxidation of amitriptyline and mirtazapine, O-demethylation followed by side chain oxidation of metoprolol as well as hydroxylation of all four-model drugs. In two of the postmortem blood samples, from which the fungi Aspergillus jensenii, Candida parapsilosis. and Mucor circinelloides had been isolated, a fungi-specific hydroxy zolpidem metabolite was detected. The presence of this metabolite in postmortem samples likely indicates postmortem fungal biodegradation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Postmortem examination of Australian sea snakes ( Hydrophiinae): Anatomy and common pathologic conditions.

PubMed

Gillett, Amber K; Ploeg, Richard; Flint, Mark; Mills, Paul C

2017-09-01

There is limited published information about disease in wild sea snakes and no standardized guideline for postmortem examination of sea snakes. Identifying causes of morbidity and mortality of marine vertebrate species has been pivotal to understanding disease factors implicated in stranding events and assisting with the formulation of conservation plans. Additionally, postmortem findings can provide valuable information on life history traits and the ecology of these reclusive species. Sick, moribund, or dead sea snakes are intermittently washed ashore along Australian and international beaches and provide an opportunity to examine a subset of the population and identify causes of population decline. We present an illustrated description of sea snake anatomy and describe a systematic approach to postmortem examination of sea snakes. We describe common pathologic conditions identified from clinical and postmortem examinations of stranded Australian sea snakes from southeast Queensland. Notable pathologic conditions include traumatic injury, inflammatory conditions, parasitic infections, and neoplasia.

Gene expression changes with age in skin, adipose tissue, blood and brain.

PubMed

Glass, Daniel; Viñuela, Ana; Davies, Matthew N; Ramasamy, Adaikalavan; Parts, Leopold; Knowles, David; Brown, Andrew A; Hedman, Asa K; Small, Kerrin S; Buil, Alfonso; Grundberg, Elin; Nica, Alexandra C; Di Meglio, Paola; Nestle, Frank O; Ryten, Mina; Durbin, Richard; McCarthy, Mark I; Deloukas, Panagiotis; Dermitzakis, Emmanouil T; Weale, Michael E; Bataille, Veronique; Spector, Tim D

2013-07-26

Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.

Postmortem aging can significantly enhance water-holding capacity of broiler pectoralis major muscle measured by the salt-induced swelling/centrifuge method

USDA-ARS?s Scientific Manuscript database

Water-holding capacity (WHC) is one of the most important functional properties of fresh meat and can be significantly affected by postmortem muscle changes. Two experiments were carried out to evaluate the effects of postmortem aging on WHC of broiler pectoralis (p.) major muscle indicated with % s...

Best-practices approach to determination of blood alcohol concentration (BAC) at specific time points: Combination of ante-mortem alcohol pharmacokinetic modeling and post-mortem alcohol generation and transport considerations.

PubMed

Cowan, Dallas M; Maskrey, Joshua R; Fung, Ernest S; Woods, Tyler A; Stabryla, Lisa M; Scott, Paul K; Finley, Brent L

2016-07-01

Alcohol concentrations in biological matrices offer information regarding an individual's intoxication level at a given time. In forensic cases, the alcohol concentration in the blood (BAC) at the time of death is sometimes used interchangeably with the BAC measured post-mortem, without consideration for alcohol concentration changes in the body after death. However, post-mortem factors must be taken into account for accurate forensic determination of BAC prior to death to avoid incorrect conclusions. The main objective of this work was to describe best practices for relating ante-mortem and post-mortem alcohol concentrations, using a combination of modeling, empirical data and other qualitative considerations. The Widmark modeling approach is a best practices method for superimposing multiple alcohol doses ingested at various times with alcohol elimination rate adjustments based on individual body factors. We combined the selected ante-mortem model with a suggestion for an approach used to roughly estimate changes in BAC post-mortem, and then analyzed the available data on post-mortem alcohol production in human bodies and potential markers for alcohol production through decomposition and putrefaction. Hypothetical cases provide best practice approaches as an example for determining alcohol concentration in biological matrices ante-mortem, as well as potential issues encountered with quantitative post-mortem approaches. This study provides information for standardizing BAC determination in forensic toxicology, while minimizing real world case uncertainties. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

PubMed

Reynolds, A M; McEvoy, R D

1988-04-01

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Erratum: Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue.

PubMed

Love, Seth; Chalmers, Katy; Ince, Paul; Esiri, Margaret; Attems, Johannes; Kalaria, Raj; Jellinger, Kurt; Yamada, Masahito; McCarron, Mark; Minett, Thais; Matthews, Fiona; Greenberg, Steven; Mann, David; Kehoe, Patrick Gavin

2015-01-01

In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each centre) and high inter-rater reliability was demonstrated. Stage two used the results of the three-centre assessment to validate the protocol by investigating previously described associations between APOE genotype (previously determined), and both CAA and vasculopathy. Association of capillary CAA with or without arteriolar CAA with APOE ε4 was confirmed. However APOE ε2 was also found to be a strong risk factor for the development of CAA, not only in AD but also in elderly non-demented controls. Further validation of this protocol and scoring scheme is encouraged, to aid its wider adoption to facilitate collaborative and replication studies of CAA.[This corrects the article on p. 19 in vol. 3, PMID: 24754000.].

Differential and brain region-specific regulation of Rap-1 and Epac in depressed suicide victims.

PubMed

Dwivedi, Yogesh; Mondal, Amal C; Rizavi, Hooriyah S; Faludi, Gabor; Palkovits, Miklos; Sarosi, Andrea; Conley, Robert R; Pandey, Ghanshyam N

2006-06-01

Depression is a major public health problem. Despite many years of research, the molecular mechanisms associated with depression remain unclear. Rap-1, activated in response to many extracellular stimuli, is one of the major substrates of protein kinase A, which participates in myriad physiologic functions in the brain, including cell survival and synaptic plasticity. Rap-1 is also activated directly by cyclic adenosine monophosphate through Epac, and thus participates in mediating physiologic functions independent of protein kinase A. To examine whether the pathogenesis of depression is associated with altered activation and expression of Rap-1, as well as expression of Epac, in depressed suicide victims. Postmortem study. Tissues were obtained from the Lenhossek Human Brain Program, Semmelweis University, Budapest, Hungary, and the Brain Collection Program of the Maryland Psychiatric Research Center, Baltimore. Postmortem brains of 28 depressed suicide victims and 28 nonpsychiatric control subjects. Examination of brain tissues. Rap-1 activation as well as messenger RNA and protein levels of Rap-1 and Epac in prefrontal cortex, hippocampus, and cerebellum. Rap-1 activation was significantly reduced (P<.001) in prefrontal cortex and hippocampus in the suicide group. This was associated with significant reductions in Rap-1 messenger RNA and protein levels (P<.001). In contrast, protein level of only Epac-2 (P<.001) but not Epac-1 (P = .89) was significantly increased in prefrontal cortex and hippocampus of these subjects. These changes were present whether the 2 cohorts were analyzed together or separately. None of the measures showed any significant change in cerebellum in the suicide group. Given the importance of Rap-1 in neuroprotection and synaptic plasticity, our findings of differential regulation of Rap-1 and Epac between brain regions suggest the relevance of these molecules in the pathophysiology of depression.

Neural space and biomechanical integrity of the developing cervical spine in compression.

PubMed

Nuckley, David J; Van Nausdle, Joseph A; Eck, Michael P; Ching, Randal P

2007-03-15

A factorial study design was used to examine the biomechanical and neuroprotective integrity of the cervical spine throughout maturation using a postmortem baboon model. To investigate changes with spinal development that affect the neuroprotective ability of the cervical spine in compressive loading. Child spinal cord injuries claim and debilitate thousands of children in the United States each year. Many of these injuries are diagnostically and mechanistically difficult to classify, treat, and prevent. Biomechanical studies on maturing spinal tissues have identified decreased stiffness and tolerance characteristics for children compared with adults. Unfortunately, while neurologic deficit typically dictates functional outcome, no previous studies have examined the neuroprotective role of the pediatric cervical spine. Twenty-two postmortem baboon cervical spines across the developmental age spectrum were tested. Two functional spinal unit segments (Oc-C2, C3-C5, and C6-T1) were instrumented with transducers to measure dynamic changes in the spinal canal. These tissues were compressed to 70% strain dynamically, and the resultant mechanics and spinal canal occlusions were recorded. Classic injury patterns were observed in all of the specimens tested. The compressive mechanics exhibited a significant age relationship (P < 0.0001). Furthermore, while the peak-percent spinal canal occlusion was not age dependent, the percent occlusion just before failure did demonstrate a significant decrease with advancing age (P = 0.0001). The neuroprotective ability of the cervical spine preceding failure appears to be age dependent, where the young spine can produce greater spinal canal occlusions without failure than its adult counterpart. The overall percent of the spinal canal occluded during a compression injury was not age dependent; however, these data reveal the neuroprotective ability of the child spine to be more sensitive as an injury predictor than the biomechanical fracture data.

Investigation of polymerase chain reaction assays to improve detection of bacterial involvement in bovine respiratory disease.

PubMed

Bell, Colin J; Blackburn, Paul; Elliott, Mark; Patterson, Tony I A P; Ellison, Sean; Lahuerta-Marin, Angela; Ball, Hywel J

2014-09-01

Bovine respiratory disease (BRD) causes severe economic losses to the cattle farming industry worldwide. The major bacterial organisms contributing to the BRD complex are Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, Pasteurella multocida, and Trueperella pyogenes. The postmortem detection of these organisms in pneumonic lung tissue is generally conducted using standard culture-based techniques where the presence of therapeutic antibiotics in the tissue can inhibit bacterial isolation. In the current study, conventional and real-time polymerase chain reaction (PCR) assays were used to assess the prevalence of these 5 organisms in grossly pneumonic lung samples from 150 animals submitted for postmortem examination, and the results were compared with those obtained using culture techniques. Mannheimia haemolytica was detected in 51 cases (34%) by PCR and in 33 cases (22%) by culture, H. somni was detected in 35 cases (23.3%) by PCR and in 6 cases (4%) by culture, Myc. bovis was detected in 53 cases (35.3%) by PCR and in 29 cases (19.3%) by culture, P. multocida was detected in 50 cases (33.3%) by PCR and in 31 cases (20.7%) by culture, and T. pyogenes was detected in 42 cases (28%) by PCR and in 31 cases (20.7%) by culture, with all differences being statistically significant. The PCR assays indicated positive results for 111 cases (74%) whereas 82 cases (54.6%) were culture positive. The PCR assays have demonstrated a significantly higher rate of detection of all 5 organisms in cases of pneumonia in cattle in Northern Ireland than was detected by current standard procedures. © 2014 The Author(s).