Virological analysis in the diagnosis of sudden children death: a medico-legal approach

Infections are considered to be an important cause of unexpected death in children. It has also been assumed that respiratory viruses are involved in the genesis of sudden infant death syndrome (SIDS). The Spanish National Institute of Toxicology and Forensic Sciences act as the forensic reference centre for Spain. We analyse the experience of this centre in the virological study of 64 cases of sudden children death where viral serology, virological cultures, herpesviruses polymerase chain reaction (PCR) and electron microscopy were performed. According to pathological findings, death could only be attributed to an adenovirus infection in one amygdalitis with upper airways stenosis and asphyxia. Human herpes virus 6 (HHV-6) was detected by PCR in one case with pathological findings characteristic of SIDS. Recent infection by respiratory syncytial virus (RSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were also detected. Meanwhile, 85.9% of the cases yielded negative viral results. Twenty-eight infants were finally categorised as SIDS. Pathological findings of infection were detected in 12 patients despite the negativity of viral analyses. Although viral infection is an uncommon cause of sudden children death, a complete microbiological investigation will help to solve the puzzle of SIDS. Definitive guidelines for microbiological analyses need to be updated whilst new pathogens are discovered or new techniques are implemented in order to clarify unsolved cases.     

Suicide by inhalation of carbon monoxide in a residential fire

Fire deaths are usually accidental, but atypical cases of homicide or suicide have been described. In suicide by fire, the only method reported by several authors consists of self-immolation. We present here the unusual case of an adult female who committed suicide by waiting in the living room after setting fire to her bedroom. The autopsy revealed smoke inhalation and the toxicological analysis revealed carboxyhemoglobin levels of 67%. Very few cases of suicide by fire not of the self-immolation type have been reported, and all have been anecdotal. A review of the literature is presented and a new term, "suicide by inhalation of carbon monoxide in a fire," is proposed for such cases.     

Diaphragmatic muscle fibre necrosis in SIDS

Observations of acute muscle fibre necrosis, as seen in 242 sudden infant death syndrome (SIDS) cases is described. The lesion is a focal acute anoxic muscle fibre coagulative necrosis in some cases followed by myocytolysis, central vacuolation, macrophage and phagocytic cell infiltrate, stromal condensation and scarring.     

Control of communicable diseases. Interim final rule with comment period

The Public Health Service Act authorizes the Secretary, in consultation with the Surgeon General, to make and enforce regulations as are necessary to prevent the introduction, transmission or spread of communicable diseases from foreign countries into the States or possessions, or from one State or possession into any other State or possession. The existing regulations are outdated and do not address communicable diseases that currently pose a substantial public health threat. As of April 2, 2003, the World Health Organization (WHO) has reported 2236 cases and 78 deaths related to outbreaks of a severe form of pneumonia of unknown origin in Hong Kong SAR, Vietnam, Guangdong province in southern China, Canada, Singapore, and Thailand, which appears to have spread rapidly. For this reason, the Director General of the World Health Organization (WHO) issued a global alert about cases of atypical pneumonia and recommended that travelers with atypical pneumonia who may be related to these outbreaks be placed into isolation and assessed by quarantine officials. The Centers for Disease Control and Prevention (CDC) is currently investigating 85 suspected cases of the disease in the United States. This is being issued as an interim final rule because this newly-detected disease is likely spread in person-to-person fashion and may have an adverse public health impact if further introduced into the United States.     

Forensic medical evaluation of the morphological alterations of the liver in drug abuse

Application of a morphometric method for investigation of chronic virus hepatitis in drug addicts and persons rejecting drug abuse is described. Chronic hepatitis in narcomania runs with frequent formation of lymphoid follicules in the portal tracts, relatively inactive portal hepatitis in marked lobular component of inflammation, pronounced fibrosis and early formation of micronodular hepatic cirrhosis, proliferation of biliary ducts, high neutrophil, eosinophil and macrophage content in the infiltrate, accumulation of macrophages in the portal tracts by granuloma type. These criteria are recommended for diagnosis of narcomania by morphological findings.     

Approaches to the improvement of forensic medical expertise in the cases of sexual crimes and doubtful gender status

The authors analyzed the results of the forensic medical expertise of the cases of sexual assaults and covert sexual abuse. Special attention is given to the peculiarities of forensic-medical expertise in the cases of veneral diseases and HIV-infection, injuries to sexual organs in women and men. The specific approaches to the examination of corpses in the cases of atypical sexual behavior or a murder supposedly committed for sexual motives are considered.     

Penile strangulation: report of a fatal case

Penile strangulation or entrapment is an unusual entity that requires urgent treatment due to its potential complications. Several cases have been reported in the medical literature, some of them describing serious injuries such as necrosis, gangrene, and amputation of the penis. However, as far as we know, no fatal cases have been described before. We present the death of an adult male secondary to the complications due to penile strangulation with a plastic bottle neck. The time of incarceration was unknown, but according to a witness it could be about 10 to 14 days. The findings of autopsy were penile strangulation, necrosis of the penis, acute pyelonephritis, and bronchopneumonia. The subject's refusal to ask for medical help was the cause of this atypical evolution.     

Black Esophagus: Acute Esophageal Necrosis in Fatal Haloperidol Intoxication

Herein, we present a case of 53‐year‐old psychotic woman with acute esophageal necrosis (black esophagus), who was found lying on the floor in the living room of her flat. Pillboxes of antipsychotic drugs were located in the bin. External examination of the body was unremarkable. On internal examination, we found acute esophageal necrosis. Histologically, there was complete epithelial necrosis with focal involvement of muscularis mucosae, dense infiltrate of leukocytes, and ulcerations without any viable cells. There was no evidence of underlying organic diseases or trauma. Toxicological analysis revealed a fatal blood level of antipsychotics (haloperidol, zotepine, and chlorprothixene). Death of the deceased was attributed to fatal intoxication with three various types of antipsychotics. As far we know, this is the first described association between so‐called black esophagus and fatal blood level of neuroleptics.     

Autoerotic deaths in the literature from 1954 to 2004: a review

Autoerotic death by hanging or ligature is a method of autoeroticism well known by forensic pathologists. In order to analyze autoerotic deaths of nonclassic hanging or ligature type, this paper reviews all published cases of autoerotic deaths from 1954 to 2004, with the exclusion of homicide cases or cases in which the autoerotic activity was not solitary. These articles were obtained through a systematic Medline database search. A total of 408 cases of such deaths has been reported in 57 articles. For each case, the following characteristics are presented here: sex, age, race, method of autoerotic activity, cause of death, and location where the body was found. Autoerotic death practioners were predominantly Caucasian males. Victims were aged from 9 to 77 years and were mainly found in various indoor locations. Most cases were asphyxia by hanging, ligature, plastic bags, chemical substances, or a mixture of these. Still, atypical methods of autoerotic activity leading to death accounted for about 10.3% of cases in the literature and are classified here into five broad categories: electrocution (3.7%), overdressing/body wrapping (1.5%), foreign body insertion (1.2%), atypical asphyxia method (2.9%), and miscellaneous (1.0%). All these atypical methods are further discussed individually.     

Disposition of quetiapine in biological specimens from postmortem cases

Quetiapine is a new atypical antipsychotic that was approved in 1997 by the U.S. Food and Drug Administration for the treatment of schizophrenia. It possesses a high affinity for 5-HT2 receptors and a low affinity for D1 and D2 dopamine receptors. Because quetiapine has only been released recently to the U.S. market, little information exists regarding therapeutic, toxic, and lethal concentrations. This study reports the detection of quetiapine in 13 postmortem cases. Following a basic liquid-liquid extraction, quetiapine was identified and quantitated by capillary gas chromatography with nitrogen phosphorus detection. Confirmation was accomplished by full scan electron impact gas chromatography/mass spectrometry. Heart blood quetiapine concentrations ranged from 0.07 to 18.37 mg/L (N = 12, mean +/- SD = 3.42 +/- 5.67, median 0.62) and femoral blood concentrations ranged from 0.06 to 19.25 mg/L (N = 10. mean +/- SD = 3.89 +/- 6.12, median 0.81). The average heart blood/femoral blood ratio was 1.31 (range 0.55 to 2.57, N = 10). Urine, bile, and gastric contents were assayed in all cases in which they were submitted. In three cases, the cause of death was determined to be quetiapine toxicity. In these cases heart blood concentrations ranged from 0.72 to 18.37 mg/L (N = 3). These data may provide a basis for establishing levels associated with quetiapine toxicity as well as therapeutic concentrations in postmortem specimens.     

Postmortem investigation of lamotrigine concentrations

Lamotrigine is a relatively new anticonvulsant. Therapeutic plasma concentrations generally range from 1 to 4 mg/L, although several studies have shown that good control of epilepsy has been achieved with concentrations reaching 10 mg/L generally, with little toxicity. In overdose, however, the drug has been linked to ECG changes that may suggest a possible arrythmogenic effect and hence cardiac toxicity. Lamotrigine has also been shown to cause encephalopathy and thus neurotoxicity. There is no information concerning postmortem lamotrigine concentrations and their interpretation. We describe lamotrigine concentrations in postmortem specimens including blood, liver, bile, vitreous humour, and urine from eight cases. A high performance liquid chromatography (HPLC) method is described with extraction procedures for the various tissues. Two possible groups were identified. The first being the "broader therapeutic" group with blood concentrations ranging from 0.9 to 7.2 mg/L and corresponding liver concentrations ranging from 16 to 36 mg/kg. The second being a "supratherapeutic" group with blood concentrations ranging from 20 to 39 mg/L and corresponding liver concentrations ranging from 53 to 350 mg/kg. Although none of the eight cases described were attributed to overdose by lamotrigine alone, the cause of death for one of the three cases in the "supratherapeutic" group was given as mixed drug toxicity. Cause of death for the remaining two cases in this group was reported as epilepsy. However, both these cases showed elevated concentrations of lamotrigine and both were co-medicated with valproic acid. Such co-administration has been shown in the literature to lead to elevated lamotrigine concentrations and a reduction in lamotrigine dose has been recommended. With such data, we highlight the importance of monitoring lamotrigine concentrations in cases co-medicated, particularly with valproic acid.     

Fatal intoxication with amisulpride and presentation of organ distribution

Amisulpride is a substituted benzamide used as an atypical antipsychotic drug. It antagonizes dopamine D2 and D3 receptor-mediated effects with greater affinity for the limbic system suggesting better neurological tolerance than classical neuroleptics. However, occasionally amisulpride intoxications associated with seizures, comatose conditions and agitation, hyperthermia, tachycardia, prolongation of the QT interval and extrapyramidal features have been described. A 27-year-old female with a medical history of psychosis and amisulpride therapy was found dead at home. By means of high performance liquid chromatography coupled with mass spectrometry (LC/MS) an amisulpride concentration of 13.4 mg/l was found in the peripheral blood. A lower concentration in the brain and an extremely high concentration in bile can be explained by the polarity and hydrophobic character of the substance. After macroscopic and histological exclusion of other causes of death the results of the toxicological analysis were consistent with the assumption of a fatal amisulpride overdose.     

Fatal Diabetic Ketoacidosis and Antipsychotic Medication

Hyperglycemia and new onset diabetes have been described with certain antipsychotic medications and some of the initial presentations are fatal diabetic ketoacidosis (DKA). We report 17 deaths due to DKA in psychiatric patients treated with second generation antipsychotic medications. Death certificates and toxicology data were searched for DKA and hyperglycemia. We reviewed the medical examiner records which included the autopsy, toxicology, police, and medical examiner investigators' reports. The decedents ranged in age from 32 to 57 years (average 48 years). There were 15 men and two women. The immediate cause of death was DKA in all. The psychiatric disorders included: 10 schizophrenia, three bipolar/schizophrenia, two bipolar, and two major depression. The most frequent atypical antipsychotic medications found were quetiapine and olanzapine followed by risperidone. In 16 deaths, we considered the medication as primary or contributory to the cause of death.     

Atherosclerotic and Hypertensive Cardiovascular Disease are Associated with Death at Sublethal Carboxyhemoglobin Levels: A Postmortem Study

Residential fires are a significant cause for morbidity and mortality in the United States. Death is often the result of soot and smoke inhalation causing carbon monoxide (CO) toxicity. The approximate lethal level of carboxyhemoglobin (COHb) in healthy adults has been well described. However, a significant number of medical examiner cases involve infirmed decedents, often elderly, with complex cardiovascular disease burdens. It is well known that death in these cases will occur at sublethal levels of COHb; however, increased lethality has been largely documented via anecdotal experience and lacks quantification. Fifty-five cases were identified where death resulted from smoke and soot inhalation suffered in a residential fire. The control group, with no cardiovascular disease, had an age-adjusted mean COHb level of 61.6% at the time of death. Presence of hypertensive cardiovascular disease showed a 30% reduction in COHb (age-adjusted mean 43.2%), atherosclerotic disease showed a 33% reduction (age-adjusted mean 41.5%), and combined disease presentation accounted for 41% reduction (age-adjusted mean 36.3%). When controlling for age, atherosclerotic and hypertensive cardiovascular diseases were each associated with statistically significant decreases in COHb (p < 0.01). Increasing age was associated with decreased COHb levels at 2.8% per 10 years of life (p < 0.01), even when modeled with hypertensive and atherosclerotic disease. These findings carry important public health significance, as well as practical significance for the medical examiner when interpreting COHb levels in cases of suspected deaths due to smoke and soot inhalation.     

Pervasive developmental disorders and criminal behaviour: a case control study

The prevalence and pattern of criminal behaviour in a population of 313 former child psychiatric in-patients with pervasive developmental disorders were studied. The patients were divided into three subgroups and compared with 933 matched controls from the general population. Age at follow-up was between 25 years and 59 years. An account of convictions in the nationwide Danish Register of Criminality was used as a measure of criminal behaviour. Among 113 cases with childhood autism, .9% had been convicted. In atypical autism (n=86) and Asperger's syndrome (n=114) the percentages were 8.1% and 18.4%, respectively. The corresponding rate of convictions in the comparison groups was 18.9%, 14.7%, and 19.6% respectively. Particular attention is given to arson in Asperger's syndrome (p= .0009).     

Isoelectric focusing of human hair keratins: correlation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns and effect of cosmetic treatments.

A new isoelectric focusing (IEF) technique in polyacrylamide gels with 6M urea and 1.5% Nonidet P40 has been developed to characterize human hair samples. The phenotypes demonstrated with this procedure has been correlated with the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns described by other authors. The method described can be applied in the forensic science analysis of a single human hair. Using the same IEF technique we have studied the changes in electrophoretic patterns of cosmetically treated hair. The characteristics of the modifications observed and its utility in forensic science work are also discussed in this paper.     

Analysis of drugs of abuse in hair by automated solid-phase extraction, GC/EI/MS and GC ion trap/CI/MS

In our laboratory, analysis of human hair for the detection of drugs of abuse was first performed in 1995. Initially, requests for hair analysis were few, and it is only since 1997 that these analyses have become routine. As demand grew, we developed an automatic solid-phase extraction method; the use of a robot ASPEC allowed us to drop certain fastidious manipulations, and to treat a large number of samples at a time. This method is described, along with analysis by gas-chromatography-mass spectrometry (GC/MS) in selected ion monitoring mode (SIM), for the following drugs: codeine, 6-monoacetylmorphine (6-MAM), morphine, cocaine, methadone, ecstasy (MDMA) and Eve (MDE). This requires prior derivatization with propionic anhydride. The different validation parameters, linearity, repeatability, recovery and detection limits are described, as well as the application of this method to some real cases. Analysis of these cases is also performed by an ion trap GC/MS in chemical ionization mode (GC/IT/CI/MS) in order to demonstrate the usefulness of this technique as a complement to routine analysis. Analysis by GC/IT/CI/MS indeed avoids the risk of false-positive results by the identification of metabolites.     

"Spontaneous" coronary artery dissection. The challenge of detection, the enigma of cause

Sudden death secondary to acute dissection of a coronary artery is a rare, but increasingly recognized, cause of sudden, unexpected death in apparently healthy persons. It has been reported more frequently in women and has been associated with sudden death during the puerperium. It has also been reported that these involved coronary vessels contain increased numbers of eosinophils and often show areas of cystic medial necrosis. In this article, we report a case of sudden death in a 47-year-old white woman due to dissection of the distal segment of her left anterior descending coronary artery. There was marked involvement of the coronary arterial walls with cystic degeneration of the media with accumulation of glycosaminoglycans as demonstrated by Alcian blue staining. There was no eosinophilic infiltrate within the arterial walls. This case is unusual in that this woman's mother and brother both have had aneurysms, which stresses the importance of not only searching carefully for these lesions, but also of obtaining family history in such cases.     

Scanning electron microscopy as an auxiliary method in the study of exhumed bones

Scanning electron microscopy (SEM) has been used in forensic science in many ways. The reports of cases in which SEM has been used as an auxiliary method in the investigation of exhumed bones are rare. In this article, we report an exhumation that was made to determine if a seized weapon could have been used in a homicide. We used SEM to analyze a fracture in the interior of the skull of the victim. The findings described in this article showed us that it is possible to develop new researches in this field.     

Investigation of markers to indicate and distinguish death due to alcoholic ketoacidosis, diabetic ketoacidosis and hyperosmolar hyperglycemic state using post-mortem samples

Data from 191 post-mortem cases where post-mortem blood beta-hydroxybutyrate (βHB) and acetone concentrations and vitreous humor glucose concentrations (where available) had been measured were retrospectively investigated to determine the markers required to identify and distinguish between Alcoholic Ketoacidosis (AKA), Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS). Blood βHB concentrations above 250 μg/mL were considered significant and it was shown to be the preferred marker of ketoacidosis. All cases with significant βHB detected also had acetone present (greater than 2mg/dL) demonstrating that acetone can be used as a marker to identify ketoacidosis and can be used to indicate when βHB measurement is necessary. Vitreous humor glucose concentrations above 6.9 mmol/L were considered high and indicative of hyperglycemia prior to death. Vitreous humor glucose concentrations can be used to distinguish between DKA and ketoacidosis from other causes and to identify deaths due to HHS. The data showed that ketoacidosis can occur without a history of alcoholism or diabetes. Many diabetics are undiagnosed for many years. Therefore, DKA or HHS should be considered in sudden or unexplained deaths and glucose should be routinely measured especially in cases with risk factors for diabetes including obesity, old age, a history of mental health problems or treatment with atypical antipsychotic drugs including clozapine, olanzapine, quetiapine and risperidone.