Antidote treatment for cyanide poisoning with hydroxocobalamin causes bright pink discolouration and chemical-analytical interferences.

Here we report the case of a 70-year-old woman who committed suicide by cyanide poisoning. During resuscitation cares, she underwent an antidote treatment by hydroxocobalamin. Postmortem investigations showed marked bright pink discolouration of organs and fluids, and a lethal cyanide blood concentration of 43 mg/L was detected by toxicological investigation. Discolouration of hypostasis and organs has widely been studied in forensic literature. In our case, we interpreted the unusual pink coloration as the result of the presence of hydroxocobalamin. This substance is a known antidote against cyanide poisoning, indicated because of its efficiency and poor adverse effects. However, its main drawback is to interfere with measurements of many routine biochemical parameters. We have tested the potential influence of this molecule in some routine postmortem investigations. The results are discussed.

Post-mortem β-hydroxybutyrate determination in synovial fluid.

β-hydroxybutyrate concentrations were determined in blood and synovial fluid in a series of medico-legal cases including hypothermia fatalities, individuals found dead in a cold environment and non-hypothermia cases with various, non-traumatic causes of death. Hypothermia was considered to be the cause of death according to circumstantial elements indicating exposure to cold, autopsy findings, biochemical investigation results and exclusion of other causes of death. The intention of this study was to characterize β-hydroxybutyrate distribution in synovial fluid and assess its usefulness for the postmortem diagnosis of antemortem abnormalities in blood β-hydroxybutyrate levels. Unenhanced CT scans, autopsies, histology, neuropathology, toxicology, and biochemistry were systematically performed. Within the limited number of subjects included in the study, the results indicate that abnormalities in antemortem β-hydroxybutyrate blood levels, as may be observed in hypothermia fatalities, are reflected in postmortem synovial fluid values. These preliminary findings notwithstanding, synovial fluid analysis to determine β-hydroxybutyrate is unlikely to be generally applied due to the more invasive collection technique it requires and could be limited to special cases in which biological fluids systematically collected upon autopsy are unavailable.

Early glutathione deficit impairs parvalbumin expression in gaba interneurons and kainate-induced gamma oscillations

An increased oxidative stress and alteration of the antioxidant systems have been observed in schizophrenia. Glutathione (GSH), a major redox regulator, is decreased in patients' cerebrospinal fluid, prefrontal cortex in vivo and striatum post-mortem tissue. Most importantly, there is genetic and functional evidence for the implication of the gene of the glutamate cysteine ligase (GCL) catalytic subunit, the key GSH-synthesizing enzyme. We have developed animal models for a GSH deficit to study the consequences of such deficit on the brain development. A GSH deficit combined with elevated dopamine (DA) during development leads to reduced parvalbumin (PV) expression in a subclass of GABA interneurons in rat anterior cingulate cortex (ACC). Similar changes are observed in postmortem brain tissue of schizophrenic patients. GSH dysregulation increases vulnerability to oxidative stress, that in turn could lead to cortical circuit anomalies in the schizophrenic brain. In the present study, we use a GCL modulatory subunit (GCLM) knock-out (KO) mouse model that presents up to 80% decreased brain GSH levels. During postnatal development, a subgroup of animals from each genotype is exposed to elevated oxidative stress induced by treatment with the DA reuptake inhibitor GBR12909. Results reveal a significant genotype-specific delay International Congress on Schizophrenia Research 136 10. 10. Neuroanatomy, Animal Downloaded from http://schizophreniabulletin.oxfordjournals.org at Bibliotheque Cantonale et Universitaire on June 18, 2010 in cortical PV expression at postnatal day P10 in GCLM-KO mice, as compared to wild-type. This effect seems to be further exaggerated in animals treated with GBR12909 from P5 to P10. At P20, PV expression is no longer significantly reduced in GCLM-KO ACC without GBR but is reduced if GBR is applied from P10 to P20. However, our result show that GCLM-KO mice exhibit increased oxidative stress, cortical altered myelin development as shown by MBP marker, and more specifically impairment of the peri-neuronal net known to modulate PV connectivity. In addition, we also observe a reduced PV expression in the ventro-temporal hippocampus of adult GCLM-KO mice, suggesting that anomalies of the PV interneurons prevail at least in some brain regions throughout the adulthood. Interestingly, the power of kainate-induced gamma oscillations, known to be dependent on proper activation of PV interneuron's, is also lower in hippocampal slices of adult GCLM KO mice. These results suggest that the PV positive GABA interneurons is particularly vulnerable to increased oxidative stress

Organ volume measurements: comparison between MRI and autopsy findings in infants following sudden unexpected death.

OBJECTIVE: To assess the accuracy of a semiautomated 3D volume reconstruction method for organ volume measurement by postmortem MRI. METHODS: This prospective study was approved by the institutional review board and the infants' parents gave their consent. Postmortem MRI was performed in 16 infants (1 month to 1 year of age) at 1.5 T within 48 h of their sudden death. Virtual organ volumes were estimated using the Myrian software. Real volumes were recorded at autopsy by water displacement. The agreement between virtual and real volumes was quantified following the Bland and Altman's method. RESULTS: There was a good agreement between virtual and real volumes for brain (mean difference: -0.03% (-13.6 to +7.1)), liver (+8.3% (-9.6 to +26.2)) and lungs (+5.5% (-26.6 to +37.6)). For kidneys, spleen and thymus, the MRI/autopsy volume ratio was close to 1 (kidney: 0.87±0.1; spleen: 0.99±0.17; thymus: 0.94±0.25), but with a less good agreement. For heart, the MRI/real volume ratio was 1.29±0.76, possibly due to the presence of residual blood within the heart. The virtual volumes of adrenal glands were significantly underestimated (p=0.04), possibly due to their very small size during the first year of life. The percentage of interobserver and intraobserver variation was lower or equal to 10%, but for thymus (15.9% and 12.6%, respectively) and adrenal glands (69% and 25.9%). CONCLUSIONS: Virtual volumetry may provide significant information concerning the macroscopic features of the main organs and help pathologists in sampling organs that are more likely to yield histological findings.

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

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.

Gastrointestinal disease following heart transplantation.

With advances in heart transplantation, a growing number of recipients are at risk of developing gastrointestinal disease. We reviewed our experience with gastrointestinal disease in 92 patients undergoing 93 heart transplants. All had follow-up, with the median time 4.8 years (range 0.5-9.6 years). During the period of the study we progressively adopted a policy of low immunosuppression aiming toward monotherapy with cyclosporine. Nineteen patients (20.6%) developed 28 diseases related to the gastrointestinal tract. Thirteen patients required 18 surgical interventions, five as emergencies: closure of a duodenal ulcer, five cholecystectomies (one with biliary tract drainage), a sigmoid resection for a diverticulitis with a colovesical fistula, a colostomy followed by a colostomy takedown for an iatrogenic colon perforation, appendectomy, two anorectal procedures, and six abdominal wall herniorrhaphies. At the onset of gastrointestinal disease, 8 patients were on standard triple-drug immunosuppression, all of them within 6 months of transplantation; 13 were on double-drug immunosuppression; and 7 were on cyclosporine alone. All the patients with perforations/fistulas were on steroids. Among the 11 infectious or potentially infectious diseases, 10 were on triple- or double-drug immunosuppression. One death, a patient who was on triple-drug immunosuppression, had a postmortem diagnosis of necrotic and hemorrhagic pancreatitis. Except for an incisional hernia following a laparoscopic cholecystectomy, there was no morbidity and, importantly, no septic complications. We concluded that a low immunosuppression policy is likely to be responsible for the low morbidity and mortality of posttransplant gastrointestinal disease, with a lower incidence of viscous perforation/fistula and infectious gastrointestinal disease.

Incidence and outcome of progressive multifocal leukoencephalopathy over 20 years of the Swiss HIV Cohort Study.

BACKGROUND: We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996. METHODS: From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996-2007). RESULTS: The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20-0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04-0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome-defining conditions (P = .007) but similar CD4+ T cell counts (60 vs. 71 cells/microL; P = .25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44-140 days), compared with 90 days (interquartile range, 54-313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8-115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.-60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07-0.50; P < .001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/microL, 0.52; 95% CI, 0.32-0.85; P = .010) and cART use (hazard ratio, 0.37; 95% CI, 0.19-0.75; P = .006). CONCLUSIONS: cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependent on cART use and baseline CD4+ T cell count.

Ketoacidosis and adrenocortical insufficiency.

We herein report an autopsy case involving a 27-year-old Caucasian woman suffering from chronic adrenocortical insufficiency with a background of a polyendocrine disorder. Postmortem biochemistry revealed pathologically decreased aldosterone, cortisol, and dehydroepiandrosterone levels in postmortem serum from femoral blood as well as decreased cortisol and 17-hydroxycorticosteroid in urine. Decreased vitreous sodium and increased 3-beta-hydroxybutyrate and C-reactive protein concentrations were observed. The cause of death was determined to be acute adrenocortical insufficiency. Fasting ketoacidosis was postulated to have precipitated the Addisonian crisis. Traumatic causes of death and third-party involvement were excluded. The case highlights the importance of systematically performing exhaustive postmortem biochemical investigations to formulate appropriate hypothesis regarding the pathophysiological mechanisms involved in the death process.

Marinade with alkaline solutions for the improvement of pork quality

The objective of this work was to evaluate the effects of alkaline solution marinades on the characteristics of pork subjected to post-mortem pH decrease in pig muscle. The pH of carcasses was measured in a commercial slaughterhouse (n = 526), 45 min after slaughtering (pH45) and, then, the carcasses were divided into the groups with pH45<5.7 or pH45>5.7. Ten samples of the longissimus dorsi muscles of each group were collected and distributed in an entirely randomized design, in a 2x4 factorial arrangement, with two conditions (pH45<5.7 or pH45>5.7), and four marinade solutions: TC, no marinade; TM1, sodium bicarbonate and sodium chloride; TM2, sodium tripolyphosphate and sodium chloride; TM3, sodium bicarbonate, sodium tripolyphosphate and sodium chloride. There was no interaction between pH45 of the meat and the marinade treatments. Meat with pH45<5.7 showed higher values for lightness, and for purge loss (PL), exudate loss (EL), cooking loss (CL) and shear force (SF). Marinating increased the pH, reduced the lightness, EL, CL and SF, and improved tenderness, juiciness and flavor of meat. Marinades with solutions containing chloride, bicarbonate, and sodium tripolyphosphate are effective in the improvement of pork quality, making physical characteristics of marinated meat similar to those of fresh pork, as a consequence of accelerated postmortem glycolysis.

Up-regulated 14-3-3β and 14-3-3ζ proteins in prefrontal cortex of subjects with schizophrenia: effect of psychotropic treatment.

14-3-3 is a family of conserved regulatory proteins that bind to a multitude of functionally diverse signalling proteins. Various genetic studies and gene expression and proteomic analyses have involved 14-3-3 proteins in schizophrenia (SZ). On the other hand, studies about the status of these proteins in major depressive disorder (MD) are still missing. Immunoreactivity values of cytosolic 14-3-3β and 14-3-3ζ proteins were evaluated by Western blot in prefrontal cortex (PFC) of subjects with schizophrenia (SZ; n=22), subjects with major depressive disorder (MD; n=21) and age-, gender- and postmortem delay-matched control subjects (n=52). The modulation of 14-3-3β and 14-3-3ζ proteins by psychotropic medication was also assessed. The analysis of both proteins in SZ subjects with respect to matched control subjects showed increased 14-3-3β (Δ=33±10%, p<0.05) and 14-3-3ζ (Δ=29±6%, p<0.05) immunoreactivity in antipsychotic-free but not in antipsychotic-treated SZ subjects. Immunoreactivity values of 14-3-3β and 14-3-3ζ were not altered in MD subjects. These results show the specific up-regulation of 14-3-3β and 14-3-3ζ proteins in PFC of SZ subjects and suggest a possible down-regulation of both proteins by antipsychotic treatment.

Cardioinhibitory reflex due to a karate kick: a case report.

This article describes the case of a 17-year-old adolescent boy who received a foot kick in the trunk area from an expert in karate. He presented with immediate cardiocirculatory arrest. After a prolonged resuscitation, he was transferred to a hospital where he died 5 days later without ever regaining consciousness. Postmortem investigations including autopsy, radiology, histology, toxicology, and postmortem chemistry were performed that showed signs of multiple organ failure, an acute hemorrhage in the region of the celiac plexus, and signs of medical resuscitation. No preexisting disease, particularly those concerning the heart, was objectified. The cause of death was attributed to multiple organ failure after a prolonged cardiocirculatory arrest. Concerning the origin of the cardiac arrest, 2 hypotheses were considered-a cardioinhibitory reflex and a cardiac contusion (commotio cordis). Because of the presence of traumatic lesions in the celiac plexus, the first hypothesis was finally submitted. This case is reported because rare cases of sudden death from celiac reflex are described in the literature where it is almost impossible to find references with accurate documentation. The presented case confirms the importance of detailed documentation of the circumstances and postmortem investigations to establish a diagnosis of death due to cardioinhibitory reflex.

Diagonal ear lobe crease and atherosclerosis: a review of the medical literature and dental implications

In Spain a significant number of individuals die from atherosclerotic disease of the coronary and carotid arteries without having classic risk factors and prodromal symptoms. The diagonal ear lobe crease (DELC) has been characterized in the medical literature as a surrogate marker which can identify high risk patients having occult atherosclerosis. This topic however has not been examined in either the medical or dental literature emanating from Spain. The majority of clinical, angiography and postmortem reports support the premise that DELC is a valuable extravascular physical sign able to distinguish some patients at risk of succumbing to atherosclerosis of the coronary arteries. A minority of studies have however failed to support this hypothesis. More recently reports using B mode ultrasound have also linked DELC to atherosclerosis of the carotid artery and another report has related DELC to the presence of calcified carotid artery atheromas on panoramic radiographs. DELC is readily visible during head and neck cancer screening examinations. In conjunction with the patient"s medical history, vital signs, and panoramic radiograph, the DELC may assist in atherosclerotic risk assessment

Pathomorphological and CT-angiographical characteristics of coronary atherosclerotic plaques in cases of sudden cardiac death.

The goal of this study was to assess the localization and types of thrombosed plaques in cases of sudden cardiac death attributed to coronary artery disease and to evaluate possible correlations with body mass index (BMI) and increased heart weight. This retrospective study was performed on forensic cases for which the cause of death was attributed to coronary artery disease. A complete autopsy and a multi-phase postmortem computed tomography (CT) angiography (MPMCTA) were performed in all cases. Eighty-five cases were selected (mean age, 55.18 ± 11.04 years; 72 men and 13 women). MPMCTA performed prior to autopsy enabled an evaluation of coronary artery perfusion before dissection of the body and helped therefore to guide sampling for histology. An acute coronary thrombosis was found in 57 cases, which included plaque erosion in 26 cases (mean age, 46.73 ± 8.33 years) and rupture or intra-plaque hemorrhage in 31 cases (mean age, 58.23 ± 10.62 years). Erosions were most frequently found in the left anterior descending artery (61.5 %), while only 35.48 % of ruptures were observed in this artery. Chronic coronary pathology was considered as the main cause of death in 28 cases (mean age, 59.64 ± 9.47 years). Sixty-two of the cases (72.94 %) had a BMI in the overweight category (BMI ≥25), with the highest mean BMI in patients with chronic coronary pathology without acute thrombosis found at autopsy. The heart weight was above the predicted reference values in 52 cases (61.18 %). Our results are in accordance with previously published studies on the spatial distribution of vulnerable plaques. We observed a higher percentage of eroded plaques than previously reported. Patients with coronary erosions were significantly younger than those with plaque rupture or those without an acute coronary thrombosis (p values <0.0001). BMI and heart weight were significantly higher for cases without thrombosis in comparison with those with plaque rupture (p values 0.028 and 0.003, respectively). Our results indicating that increased BMI and overweight hearts are associated with chronic ischemic heart disease are compatible with clinical studies. Performing more postmortem studies on forensic autopsies, including modern radiological examinations with MPMCTA, can enhance the detection of vulnerable plaques in living patients and prevent sudden cardiac death.

A case of suicide by self-injection of adrenaline.

Adrenaline (epinephrine) auto-injectors provide life-saving pre-hospital treatment for individuals experiencing anaphylaxis in a community setting. Errors in handling adrenaline auto-injectors, particularly by children and healthcare professionals, have been reported. Reports of adrenaline overdoses are limited in the medical literature. In most of these cases, accidental adrenaline administration results from medical error. Exogenous administration of catecholamine is responsible for cardiovascular and metabolic responses, which may cause supraventricular tachycardia, ventricular dysrhythmias and myocardial ischemia. The authors present a unique autopsy case involving a 34 year-old woman who intentionally self-injected adrenaline using an adrenaline auto-injector as part of a suicide plan. Catecholamines and metanephrines were measured in peripheral and cardiac blood as well as urine and vitreous humor. Based on the results of all postmortem investigations, the cause of death was determined to be cardiac dysrhythmia and cardiac arrest following adrenaline self-injection.

Fatal Cervical Spine Injury From Diving Accident.

Spinal cord injuries result after diving into shallow water, often after incautious jumps head first into water of unknown depth during recreational or sport activities. Mortality is generally due to upper cervical trauma. The authors present a case of a diving-related death in a young woman who underwent medicolegal investigations. The measured water depth at the supposed dive site was 1.40 m. Postmortem radiology and autopsy revealed fractures of the body and the posterior arch of the fifth cervical vertebra, a fracture of the right transverse process of the sixth cervical vertebra and hemorrhages involving the cervical paraspinal muscles. Neuropathology showed a posterior epidural hematoma involving the whole cervical region and a symmetric laceration of the spinal cord located at the fourth and fifth cervical vertebra level, surrounded by multiple petechial hemorrhages. Toxicology revealed the presence of ethanol in both blood and urine samples. The death was attributed to cervical spine fracture (C5-C6), spinal cord contusion, and subsequent drowning. This case highlights the usefulness of postmortem radiology, examination of the deep structures of the neck, toxicology, neuropathology, and a detailed research of signs of drowning to formulate appropriate hypotheses pertaining to the cause and mechanism of death.