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

Purpose

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.

Materials and methods

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.

Results

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.

Conclusions

Multiphase postmortem computed tomography angiography is a useful tool in the postmortem setting for investigating ischemically damaged myocardium.

     

Detection of coronary thrombosis after multi-phase postmortem CT-angiography

The aim of this study was to compare postmortem angiography-based, autopsy-based and histology-based diagnoses of acute coronary thrombosis in a series of medicolegal cases that underwent postmortem angiographies according to multiphase CT-angiography protocol. Our study included 150 medicolegal cases. All cases underwent native CT-scan, postmortem angiography, complete conventional autopsy and histological examination of the main organs and coronary arteries. In 10 out of the 150 investigated cases, postmortem angiographies revealed coronary arterial luminal filling defects and the absence of collateral vessels, suggesting acute coronary thromboses. Radiological findings were confirmed by autopsy and histological examinations in all cases. In 40 out of 150 cases, angiograms revealed complete or incomplete coronary arterial luminal filling defects and the presence of collateral vessels. Histological examinations did not reveal free-floating or non-adherent thrombi in the coronary arteries in any of these cases. Though postmortem angiography examination has not been well-established for the diagnosis of acute coronary thrombosis, luminal filling defects in coronary arteries suggesting acute thromboses can be observed through angiography and subsequently confirmed by autopsy and histological examinations.     

Endocan concentrations in postmortem serum,vitreous humor and urine in victims of lethal hypothermia

Endocan is a soluble molecule secreted from vascular endothelial cells of various organs. Its exact function in humans remains to be elucidated, though it has been postulated that increased tissue expression or serum levels of this molecule may be an indicator of endothelial activation and neovascularization. In the realm of forensic pathology, studies pertaining to endothelial activation following exposure to cold exclusively focused on thrombomodulin, a transmembrane protein specific to endothelial cells. In the study herein described, endocan concentrations were determined in postmortem serum, urine and vitreous humor samples collected during autopsy in a series of cases that underwent medicolegal investigations. A total of 76 autopsy cases were selected and three study groups (hypothermia group, sepsis group and non-hypothermia/non-sepsis group) prospectively formed during the study period. The obtained results seem to indicate that exposure to cold and subsequent death is not distinguished by significant endothelial dysfunction causing enhanced endocan secretion.     

Application of the Cozart DDS system to postmortem screening of drugs of abuse in vitreous humor

The analysis of drugs of abuse in human specimens is essential in forensic medicine. This study evaluated the use of Cozart DDS for postmortem screening of some drugs of abuse in vitreous humor (VH) prior to forensic autopsies. The Cozart DDS is an on-site drug detection system that has been validated for oral fluid. Seventy-one VH specimens were obtained from cadavers. Causes of death included injury, drug poisoning, natural disorders, and traffic accidents. The samples were tested for cannabis, cocaine, opiate, amphetamine, and methamphetamine. Thirty-three of 71 samples were positive for drugs of abuse (42% for cocaine, 28% for cannabis, 26% for opiates, and 3% for methamphetamine). The positive specimens for opiates and methamphetamine were reexamined by gas chromatography-mass spectrometry (GC-MS); benzoylecgonine (cocaine product) was detected by liquid chromatography-tandem mass spectrometry (LC-MS-MS). All positive results for cocaine or its products and opiates by the Cozart test were confirmed by MS analysis, whereas one positive result for methamphetamine was negative by MS. The Cozart DDS system is generally a useful screening test for VH specimens prior to autopsies, because of its simplicity and rapidness.     

The postmortem distribution of ketone bodies between blood,vitreous humor,spinal fluid,and urine

The distribution of the ketone bodies: acetone, acetoacetate, and d-β-hydroxybutyrate, between blood, vitreous humor, spinal fluid, and urine was examined in 105 medico-legal autopsies. The ketone body concentration in the body fluids was determinated by head-space gas chromatography. The correlation between blood and the body fluids could be described with regression lines on the logarithmic-transformed results. The correlation is dependent on the ketone body concentration. The ketone bodies in spinal fluid show the best correlation to blood, followed by vitreous humor, and last urine. The concentration dependence in spinal fluid is mainly due to ketone bodies being metabolized in the brain. The human brain utilizes ketone bodies during normal nutritional state. In vitreous humor, the dependence is mainly due to protein bindings of acetoacetate and β-hydroxybutyrate in blood and the difference in dry matter between blood and vitreous humor.     

Phencyclidine and cannabinoids in vitreous humor

Vitreous humor (VH) is routinely collected at autopsy for the testing of electrolytes and ethanol. In recent years drugs of abuse have been detected in this specimen. In this study the authors assayed 30 VH samples for phencyclidine (PCP) and 50 specimens for cannabinoids. Specimens were screened by immunoassay and then assayed for PCP by GC-FID and cannabinoids by GC/MS. Eighteen (60%) specimens screened positive for PCP using a cutoff of 25ng/mL. Quantitative analysis showed PCP concentrations in VH that screened positive ranged 30-290ng/mL. Corresponding blood concentrations were 50-600ng/mL. VH PCP concentrations in the 12 cases which screened negative were 40-470ng/mL. False negative results were probably due to matrix effects. All VH specimens screened for cannabinoids were negative. Ten negative screening specimens assayed by GC/MS yielded 1 11-nor-9-carboxy-delta-9-tetrahydrocannabinol positive result at 2ng/mL. These data indicated that VH maybe a useful specimen for the detection of PCP but not for cannabinoids.     

High variation in hypoxanthine determination after analytical treatment of vitreous humor samples

In the field of legal medicine the correct determination of the time of death is of great importance because an error in calculating the post-mortem interval (PMI) could be crucial in a criminal investigation. The quantification of hypoxanthine (Hx) concentration in the vitreous humor (VH) as a means to estimate PMI is useful when dealing with a recent time interval of death and has several advantages over other biological matrices. However, due to its viscous nature, VH has to be liquefied prior to its analysis, and the different procedures to liquefy it may cause alterations in Hx concentration, and hence in estimation of PMI. The aim of this study was to determine differences in Hx concentration after applying several pre-analytical treatments to different aliquots of the same VH sample. Enzymatic digestion, sonication, centrifugation and heat were the liquefying methods applied to reduce the viscosity of 105 VH samples. Analysis was performed using solid phase extraction and liquid chromatography in tandem with mass spectrometry. Statistically significant differences in the measured Hx concentrations were found between enzymatic digestion and the other three methods analyzed (sonication, centrifugation, and heat). Additionally, high data dispersion was found under heat treatment but was not observed for centrifugation or sonication, where similar and more moderate results were found. We conclude that high variations in Hx determination are observed when enzymatic digestion or heat treatment is used and we therefore recommend sonication or centrifugation to quantify Hx concentration in the VH.     

Determination of glucose in human vitreous humor

Summary In twenty cases, human vitreous humor glucose concentrations were measured with five different methods in common use. Striking differences in glucose values were obtained by the various analytical procedures. The reasons for these discrepancies remain obscure. Before interpretation of a given vitreous value, therefore, the analytical method employed must be known.

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Zusammenfassung In Glaskörper-Flüssigkeit wurde die Glucose-Konzentration mit fünf verschiedenen Methoden, die im allgemeinen Gebrauch sind, in zwanzig Fällen bestimmt. Es wurden hierbei erhebliche Differenzen in den Glucose-Werten mit den verschiedenen Analysenmethoden erhalten, wobei die Ursachen für die Diskrepanzen unklar sind. Bei der Beurteilung von Glucose Konzentrationen im Glaskörper muß daher die angewandte Bestimmungsmethode berücksichtigt werden.

     

Determination of calcium and magnesium in postmortem human vitreous humor as a test to ascertain the cause and time of death

Summary The concentrations of magnesium and total calcium human vitreous humors obtained postmortem was tested. In the groups of heart disease and asphyxia a correlation between the postmortem interval and calcium or magnesium concentrations was found. There was no correlation between postmortem interval and calcium respectively magnesium in the other causes of death. It seems possible that the analysis of vitreous humor may be useful in both diagnosis and determination of postmortem interval in the cases of heart death and asphyxia.     

Post-mortem biochemistry differences between vitreous humour and cerebrospinal fluid

ABSTRACT

Cerebrospinal fluid (CSF) and vitreous humour (VH) can be biochemically analysed post-mortem. CSF can be aspirated from the ventricular system (VA) and from lumbar puncture (LP), whereas, VH is aspirated from the orbits. This study compared the biochemical constituents between CSF and VH in 20 post-mortem subjects as well as the effect post-mortem interval and subject age have on these variables. VH samples had significantly higher sodium (Na) and chloride (Cl) and lower magnesium (Mg), potassium (K), urea (Ur) and creatinine (Cr) compared with CSF samples. No statistically significant difference was demonstrated with beta-hydroxybutyrate (BHB) and glucose levels in both VH and both CSF samples. Interestingly, some of the differences in the biochemical analysis correlated with age, but none with post-mortem interval. In addition to sampling and pre-analytical sample processing differences, there may also be ante- and post-mortem factors explaining these observations. This study suggests that post-mortem CSF and VH are biochemically different and reference ranges for VH are not recommended for use in CSF samples.     

Fatal metformin overdose: case report and postmortem biochemistry contribution

Metformin is an oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. Lactic acidosis from metformin overdose is a rare complication of metformin therapy and occurs infrequently with therapeutic use. Fatal cases, both accidental and intentional, are extremely rare in clinical practice. Metformin is eliminated by the kidneys, and impaired renal function can result in an increased plasma concentration of the drug. In this report, we describe an autopsy case involving a 70-year-old woman suffering from diabetes mellitus and impaired renal function who received metformin treatment. Metformin concentrations in the peripheral blood collected during hospitalization and femoral blood collected during autopsy were 42 and 47.3 µg/ml, respectively. Lactic acidosis (29.10 mmol/l) was objectified during hospitalization. Furthermore, postmortem biochemistry allowed ketoacidosis to be diagnosed (blood β-hydroxybutyrate, 10,500 µmol/l). Death was attributed to lactic acidosis due to metformin intoxication. Increased plasma concentrations of the drug were attributed to severely impaired renal function. The case emphasizes the usefulness of performing exhaustive toxicology and postmortem biochemistry towards the more complete understanding of the pathophysiological mechanisms that may be involved in the death process.     

Low-dose multidetector-row CT-angiography of abdominal aortic aneurysm after endovascular repair

Purpose

To investigate the possibility of reducing radiation dose exposure while maintaining image quality using multidetector computed tomography angiography (MDCTA) with high-concentration contrast media in patients undergoing follow-up after endovascular aortic repair (EVAR) to treat abdominal aortic aneurysm.

Materials and methods

In this prospective, single center, intra-individual study, patients underwent two consecutive MDCTA scans 6 months apart, one with a standard acquisition protocol (130 mAs/120 kV) and 120 mL of iomeprol 300, and one using a low dose protocol (100 mAs/80 kV) and 90 mL of iomeprol 400. Images acquired during the arterial phase of contrast enhancement were evaluated both qualitatively and quantitatively for image noise and intraluminal contrast enhancement.

Results

Thirty adult patients were prospectively enrolled. Statistically significantly higher attenuation values were measured in the low-dose acquisition protocol compared to the standard protocol, from the suprarenal abdominal aorta to the common femoral artery (p < 0.0001; all vascular segments). Qualitatively, image quality was judged significantly (p = 0.0002) better with the standard protocol than with the low-dose protocol. However, no significant differences were found between the two protocols in terms of contrast-to-noise ratio (CNR) (13.63 ± 6.97 vs. 11.48 ± 8.13; p = 0.1058). An overall dose reduction of up to 74% was observed for the low-dose protocol compared with the standard protocol.

Conclusion

In repeat follow-up examinations of patients undergoing EVAR for abdominal aortic aneurysm, a low-dose radiation exposure acquisition protocol provides substantially reduced radiation exposure while maintaining a constant CNR and good image quality.     

Usefulness of postmortem biochemistry in forensic pathology: illustrative case reports

The aim of this work is to present some practical, postmortem biochemistry applications to illustrate the usefulness of this discipline and reassert the importance of carrying out biochemical investigations as an integral part of the autopsy process. Five case reports are presented pertaining to diabetic ketoacidosis in an adult who was not known to suffer from diabetes and in presence of multiple psychotropic substances; fatal flecainide intoxication in a poor metabolizer also presenting an impaired renal function; diabetic ketoacidosis showing severe postmortem changes; primary aldosteronism presented with intracranial hemorrhage and hypothermia showing severe postmortem changes. The cases herein presented can be considered representative examples of the importance of postmortem biochemistry investigations, which may provide significant information useful in determining the cause of death in routine forensic casework or contribute to understanding the pathophysiological mechanisms involved in the death process.     

The radiodensity of cerebrospinal fluid and vitreous humor as indicator of the time since death

Purpose

After death, a series of changes occur naturally in the human body in a fairly regular pattern. These postmortem changes are detectable on postmortem CT scans (PMCT) and may be useful in estimating the postmortem interval (PMI). The purpose of our study is to correlate the PMCT radiodensities of the cerebrospinal fluid (CSF) and vitreous humor (VH) to the PMI.

Methods

Three patient groups were included: group A consisted of 5 donated cadavers, group B, 100 in-hospital deceased patients, and group C, 12 out-of-hospital forensic cadavers. Group A were scanned every hour for a maximum of 36 h postmortem, and the tympanic temperature was measured prior to each scan. Groups B and C were scanned once after death (PMI range 0.2–63.8 h). Radiodensities of the VH and CSF were measured in Hounsfield units. Correlation between density and PMI was determined using linear regression and the influence of temperature was assessed by a multivariate regression model. Results from group A were validated in groups B and C.

Results

Group A showed increasing radiodensity of the CSF and VH over time (r ² CSF, 0.65). PMI overruled the influence of temperature (r = 0.99 and p = 0.000). Groups B and C showed more diversity, with CSF and VH radiodensities below the mean regression line of Group A. The formula of this upper limit indicated the maximum PMI and was correct for >95 % of the cadavers.

Conclusion

The results of group A showed a significant correlation between CSF radiodensity and PMI. The radiodensities in groups B and C were higher than in group A, therefore the maximum PMI can be estimated with the upper 95 % confidence interval of the correlation line of group A.