Techniques and criteria in pathologic and forensic-medical diagnostics in sudden unexpected infant and perinatal death.
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For each case of sudden infant and perinatal death, a full review of clinical and epidemiologic data and a complete necropsy study were performed according to the necropsy protocol devised by the Institute of Pathology, University of Milan, Milan, Italy (available at: http://users.unimi.it/~pathol/sids_e.html). Histopathologic examination of unexpected late fetal and neonatal death and SIDS cases allowed us to identify frequent alterations, mainly congenital, of the autonomic nervous system, modulating respiratory, cardiovascular, arousal, and upper digestive activities. The data and arguments presented herein provide a brief survey tending to open, rather than conclude, a far-reaching subject and to motivate medicolegal specialists and pathologists to perform more in-depth study. (+info)
Investigation of an LC-MS-MS (QTrap) method for the rapid screening and identification of drugs in postmortem toxicology whole blood samples.
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The QTrap liquid chromatography-tandem mass spectrometry (LC-MS-MS) by Applied Biosystems was investigated as an adjund to enzyme immunoassay (EIA) for the rapid detection of drugs in blood. Thus, a procedure used to identify drugs in whole blood by EIA was extended to LC-MS-MS analysis. A multiple reaction monitoring (MRM) database of over 100 drugs was constructed to analyze for those drugs commonly observed in postmortem toxicology cases. The QTrap method provided for a scan time of only 2.8 s to produce both an MRM and an enhanced product ion scan. Various validation and developmental steps of the method are presented, as well as a concordance study as a final means of validation. This study was conducted to compare the effectiveness of the QTrap versus conventional extraction methods and gas chromatography-MS for the identification of drugs in 95 postmortem samples. The more than 400 drug results in this study showed 100% concordance between the two techniques. (+info)
Investigation of fatalities due to acute gasoline poisoning.
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This paper presents a simple, rapid, reliable, and validated method suited for forensic examination of gasoline in biological samples. The proposed methodology has been applied to the investigation of four fatal cases due to gasoline poisoning that occurred in Spain in 2003 and 2004. Case histories and pathological and toxicological findings are described in order to illustrate the danger of gasoline exposure under several circumstances. Gasoline's tissular distribution, its quantitative toxicological significance, and the possible mechanisms leading to death are also discussed. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography (GC) with flame-ionization detection, and confirmation was performed using GC-mass spectrometry in total ion chromatogram mode. m,p-Xylene peak was selected to estimate gasoline in all biological samples. Gasoline analytical methodology was validated at five concentration levels from 1 to 100 mg/L. The method provided extraction recoveries between 77.6% and 98.3%. The limit of detection was 0.3 mg/L, and the limit of quantitation was 1.0 mg/L. The linearity of the blood calibration curves was excellent with r2 values of > 0.997. Intraday and interday precisions had a coefficient of variation < or = 5.4% in all cases. Cases 1 and 2 consist of the accidental inhalation of gasoline vapor inside a small enclosed space. Case 3 is a death by recreational gasoline inhalation in a male adolescent. Heart blood concentrations were 28.4, 18.0, and 38.3 mg/L, respectively; liver concentrations were 41.4, 52.9, and 124.2 mg/kg, respectively; and lung concentrations were 5.6, 8.4, and 39.3 mg/kg, respectively. Case 4 was an accidental death due to gasoline ingestion of a woman with senile dementia. Peripheral blood concentration was 122.4 mg/L, the highest in our experience. Because pathological findings were consistent with other reports of gasoline intoxication and constituents of gasoline were found in the body, cause of death was attributed to acute gasoline intoxication. As a rule, this kind of poisoning offers little difficulty in diagnosis because there is a history of exposure, and the odor usually clings to the clothes, skin, or gastric contents. However, anatomic autopsy findings will be nonspecific and therefore toxicological analysis is necessary. There is a paucity of recent references regarding analytical and toxicological data, and this article provides evidence about toxic concentrations and is a useful adjunct to the postmortem toxicological interpretation of fatalities if the decedent has been involved in gasoline use. (+info)
Methylation of 3,4-methylenedioxymethamphetamine in formalin-fixed human liver tissue.
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3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a commonly consumed recreational drug. As is the case with most secondary amines, MDMA reacts with formaldehyde under acidic conditions to form tertiary amines. This reaction is likely to occur in formalin-fixed tissue. In formalin solutions, MDMA is methylated producing 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDA). MDDA standard was synthesized by treating methylenedioxyamphetamine HCl in formaldehyde solution. Structure confirmation was by electrospray ionization-mass spectrometry (MS) and MS-MS. Randomly chosen human liver pieces (100-200 mg) were injected with 2 microg of MDMA HCl. The liver pieces in centrifuge tubes were covered with 200 microL of formalin solution (20% v/v), held at room temperature for 24 h, and then homogenized. The resulting suspension was sonicated for 5 min and then centrifuged. Controls consisted of substitution of 200 microL of water in place of formalin solution. Supernatant aliquots (10 mciroL) were added to 500 microL of 0.1% formic acid in acetonitrile for MS analysis. Positive ion electrospray spectra recorded in MS, MS2, and MS3 modes were used to confirm the presence of methylated MDMA. Liver tissue containing added MDMA HCl but not treated with formalin did not show a detectable level of methylated MDMA. (+info)
Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose.
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We report a case involving a fatal intoxication with loperamide (Imodium). Loperamide is a synthetic opioid of the phenyl piperidine class used as an over-the-counter antidiarrheal. It exerts its effects through interaction with micro-opiate receptors in the intestine to reduce peristalsis. Loperamide lacks the typical euphoric opiate effects when administered at recommended doses. Both loperamide and its major metabolite, N-desmethylloperamide, were isolated by liquid-liquid extraction into n-butyl chloride from alkalinized samples. Extracts were analyzed by liquid chromatography-electrospray-mass spectrometry in selected-ion-monitoring mode. Rapid separation of the drug, metabolite, and internal standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8-microm particle diameter. The mobile phase consisted of 0.1% formic acid in deionized water (60%) and acetonitrile (40%) at a flow rate of 0.5 mL/min. Heart blood concentrations for loperamide and its metabolite were 1.2 mg/L and 3.3 mg/L, respectively. In contrast, reported peak plasma concentrations of loperamide after administration of recommended daily doses of 16 mg did not exceed 0.012 mg/L in controlled trials. Because the heart blood ethanol concentration was 0.08 g/dL, the medical examiner ruled that the cause of death was loperamide and ethanol intoxication, and the manner of death as undetermined. (+info)
Use of the histopathology in the differential diagnosis of drowning in fresh and salty water: an experimental model establishment in rats.
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PURPOSE: To develop a method of differential diagnosis to drowning, due to analysis of the alveolar macrophages quantitative, in rats submitted to induced drowning in fresh water and salty water. METHODS: Were used 15 male adult rats Wistar EPM-1, weight 360g (SD=21,3), randomized in three groups: G1--Control; G2--Fresh water; G3--Salty water, each one with n=5. The animals have been anesthetized and tracheostomized to insert a cannula inside the trachea, for drowning induction. The lungs have been removed, weighed, prepared for histology and colored by immunohistochemistry. The macrophages have been counted in both lungs (right and left) of each animal. The statistical test used was ANOVA (SPSS.10) with p<0,05. RESULTS: The amount of macrophages was G3>G2>G1 with p=0,0001 in each comparison. The weight of lungs of G3 and G2 was higher than G1, with p>0,0001, however G3 and G2 do not possess difference statistics in the weight of lungs. CONCLUSION: The developed diagnostic method was efficient in rats. The results, if expanded, will be able to assist the Forensic Pathology for technique of low cost and high trustworthiness. (+info)
The international criminal tribunal for the former Yugoslavia (ICTY) and the forensic pathologist: ethical considerations.
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Since 1991, war crimes in the former Yugoslavia have been the subject of several international medico-legal investigations of mass graves within the framework of inquiries led by the International Criminal Tribunal for the former Yugoslavia (ICTY). Forensic pathologists involved in the ICTY missions could be subjected to ethical tensions due to the difficulties of the missions, the emergent conflicts between forensic scientists of the investigating teams and the original nature of the ICTY proceedings. In order to study the nature of such ethical tensions, we sent a questionnaire to 65 forensic pathologists who have been involved in the ICTY missions. The rate of response was 38%. The majority of forensic pathologists questioned (n=18) did not know how the medico-legal data was exploited by the ICTY. Three of them have been subjected to pressures. Three of them were aware of mass grave sites knowingly not investigated by the ICTY. Fifteen considered that the ICTY respected the elementary rules of the law and four of them questioned the impartiality of the justice led by the ICTY. Two conflicting types of ethics can be drawn from these results: conviction ethics, which are shared by most of the forensic pathologists questioned, and responsibility ethics. In the former, the forensic pathologist completely agrees with the need for an international war crimes tribunal, even if such justice can be challenged regarding the respect of human rights and impartiality. In the latter, he or she needs to conduct him or herself in ways that do not infringe impartiality. As medical deontology duty requires impartiality ethics, discursive ethics are needed to ease ethical tensions and to suggest ethical guidelines. Alternatives to international justice, through a truth and reconciliation commission and by way of humanitarian missions combining victims' identification with forensic investigations for historical purposes, could be considered. (+info)
Forensic visualization of foreign matter in human tissue by near-infrared spectral imaging: methodology and data mining strategies.
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BACKGROUND: Rapidity of data acquisition, high image fidelity and large field of view are of tremendous value when looking for chemical contaminants or for the proverbial "needle in the haystack" - in this case foreign inclusions in histologic sections of biopsy or autopsy tissues. Near infrared chemical imaging is one of three chemical imaging techniques (NIR, MIR and Raman) based on vibrational spectroscopy, and provides distinct technical advantages for this application. METHODS: We have chosen to utilize and evaluate near infrared (NIR) imaging for studies of foreign materials in tissue because the experimental configuration is relatively simple, data collection is rapid, and large sample areas can be screened with high image fidelity and spatial resolution. RESULTS: We have shown that NIR imaging can readily find and identify silicone gel inclusions in biological tissue samples. Additionally, preliminary results indicate that spectral signatures in the data set are also potentially sensitive to structural changes in the surrounding tissue that may be induced by the foreign body. CONCLUSIONS: NIR chemical imaging is a powerful, non-destructive tool for localization and identifying foreign contaminants in biological tissue. Preliminary results indicate that NIR imaging is also sensitive enough to differentiate tissue types (perhaps based on collagen structural differences), and provide data on the spatial localization of these components. (+info)