死后生物化学在糖尿病酮症酸中毒法医学诊断中的应用

糖尿病酮症酸中毒是糖尿病患者一种处于高糖、高酮状态并且导致代谢失代偿的危险并发症。这类死者常规法医学检查无特异性表现,需要进行死后生物化学指标分析。死后生物化学是一种采集死者体液进行生物化学检测,从而判断死者生前的代谢状态进而明确死因的检查方法。本文综述了糖尿病酮症酸中毒死亡的基本情况、法医学检查表现,并着重阐述运用于诊断糖尿病酮症酸中毒的死后生化指标,从而总结糖尿病酮症酸中毒死亡的法医学诊断思路。     

Olanzapine‐Induced Fatal Ketoacidosis with Pneumomediastinum and Subcutaneous Emphysema

We report a case of fatal olanzapine‐induced ketoacidosis in which pneumomediastinum (PM) and subcutaneous emphysema (SE) were detected on postmortem computed tomographic (CT) images. A man in his forties was found in a state of cardiopulmonary arrest with profuse perspiration, and 50 empty capsules of olanzapine (10 mg) and flunitrazepam (1 mg) were found in his room. The major findings of postmortem CT prior to autopsy were PM and SE from the lower half of the face to the height of the first rib. The results of autopsy, biochemical tests, and toxicological analyses indicated the cause of death to be fatal ketoacidosis induced by olanzapine intoxication. No injuries, medical interventions, or particular diseases were evident, suggesting that PM and SE were caused by ketoacidosis. Our findings indicated that toxicological analyses should be performed when PM and SE are detected on CT images.     

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.     

Basal Vacuolization in Renal Tubular Epithelial Cells at Autopsy and Their Relation to Ketoacidosis

Basal vacuolization of renal tubular epithelial cells is a useful postmortem marker for ketoacidosis. To investigate its incidence and relationship to the severity of ketoacidosis, 158 autopsy cases with elevated β‐hydroxybutyrate (>1 mmol/L) over a 7‐year‐period were retrospectively reviewed. Sixty‐eight cases (43%) exhibited basal vacuolizations (vitreous β‐hydroxybutyrate: 1.16–29.35 mmol/L, mean 10.28 mmol/L), and 90 cases (57%) did not (vitreous β‐hydroxybutyrate: 1.03–13.7 mmol/L, mean 2.84 mmol/L). Quantitative analysis revealed on average a fourfold elevation in β‐hydroxybutyrate in cases with basal vacuolizations compared to those without; 10.3% of cases with β‐hydroxybutyrate concentrations between 1.01 and 2.00 mmol/L had basal vacuolizations, and this incidence increased to 33.3% with concentrations between 4.01 and 6.00 mmol/L. A marked increase in incidence to >70% was observed with concentrations >6.00 mmol/L, and basal vacuoles were invariably present (100%) with concentrations >14.01 mmol/L. This study demonstrates that basal vacuolizations are a sensitive marker for significant ketoacidosis and reaffirms its use as an indicator for likely cases of fatal ketoacidosis at autopsy.     

Fatal Diabetic Ketoacidosis—A Potential Complication of MDMA (Ecstasy) Use

A 19‐year‐old woman with insulin‐dependent diabetes mellitus was found dead in bed having allegedly recently taken ecstasy and consumed alcohol. At autopsy, there were microhemorrhages in the brain with subnuclear vacuolization and Armanni–Ebstein changes in renal tubules. Biochemical analyses confirmed diabetic ketoacidosis (vitreous glucose—46.5 mmol/L; β‐OH butyrate—13.86 mmol/L.). Toxicological analyses of blood showed a low level of 3,4‐methylenedioxy‐methamphetamine (MDMA) (0.01 mg/L), with acetone but no alcohol or other common drugs. Death was attributed to diabetic ketoacidosis most likely provoked by mixed MDMA/alcohol ingestion. Although the use of illicit drugs by young individuals with diabetes mellitus is being increasingly recognized, it has been noted that there is minimal information about the relationship between drug use and acute diabetic complications. Toxicological screening of cases of lethal diabetic ketoacidosis in the young may clarify lethal mechanisms in individual cases and also help to determine the extent of this problem.     

Fatal Child Abuse Presenting with Multiple Vertebral and Vascular Trauma

This case study involves the unexplained death of a previously healthy 30‐month‐old child. Reportedly, she was found unresponsive by her foster father following a 2‐hour nap. She was transported to the hospital and died in the emergency room of unknown causes. Blood drawn in the ER showed hemoglobin of 4.3 mg/dL. Postmortem skeletal survey, magnetic resonance imaging (MRI) of the brain, and retinal examinations were negative. The medical examiner assumed jurisdiction of the body. The autopsy showed massive retroperitoneal hemorrhage, transections of the abdominal aorta, and inferior vena cava, and complete tears of the anterior longitudinal ligament of the spine at C5/C6 and L1/L2 with diastases of the vertebral bodies at the corresponding intervertebral disk spaces. The case is believed to be extraordinary due to both the extent of injury that does not match the reported history and the mechanism of vertebral and vascular injuries.     

Utility of Postmortem Vitreous Beta-Hydroxybutyrate Testing for Distinguishing Sudden from Prolonged Deaths and for Diagnosing Ketoacidosis

A retrospective, cross-sectional analysis of vitreous beta-hydroxybutyrate (BHB) on 967 forensic cases over a two-year period was conducted. Cases were sorted into six categories of death: (i) sudden traumatic/non-natural (ST), (ii) sudden natural (SN), (iii) prolonged traumatic/non-natural (PT), (iv) prolonged natural (PN), (v) diabetic ketoacidosis (DKA), and (vi) alcoholic ketoacidosis (AKA). The mean BHB for all cases was 1.67 mmol/L (17.4 mg/dL; range: 0.11–18.02 mmol/L). The numbers of DKA, AKA, PN, PT, SN, and ST deaths were 21, 5, 155, 258, 275, and 253, respectively. Their mean vitreous BHBs were as follows: 11.04 mmol/L (DKA), 8.88 mmol/L (AKA), 1.56 mmol/L (PN), 1.55 mmol/L (PT), 1.26 mmol/L (SN), and 1.38 mmol/L (ST). There was a statistically significant difference between the mean BHBs of the PN and SN death groups (p < 0.001), as well as between those of the PT and ST death groups (p = 0.004). Given the overlapping ranges seen between the prolonged and sudden death groups, the identified differences did not hold clinical significance. In addition, we sought to determine a threshold value for vitreous BHB to definitely diagnose cases of ketoacidosis. BHB threshold concentrations between 2.5 and 5 mmol/L produced sensitivities >92% and specificities >96%. A receiver operator characteristic curve found 3.43 mmol/L to be the optimal cutoff value, demonstrating a specificity of 98.3% and a sensitivity of 96.2%.     

Subway Train‐Related Fatalities in New York City: Accident versus Suicide*

Abstract: We examined the characteristics of subway train‐related fatalities in New York City between Jan. 1, 2003 and May 31, 2007 in order to determine which factors are useful in differentiating accident from suicide. Subway train‐related deaths with homicide and undetermined manners also are included. During this period, there were 211 subway train‐related fatalities. The manners of death were: suicide (n = 111), accident (n = 76), undetermined (n = 20), and homicide (n = 4). The causes of death were blunt trauma (n = 206) and electrocution (n = 5). Torso transection and extremity amputation were more frequent in suicides. Antidepressant medications were more frequently detected in suicides, whereas cocaine and ethanol were more frequent in accidents. However, autopsy findings should be weighed in the context of the entire evaluation along with other circumstantial and investigative findings. In unwitnessed deaths where additional information is unavailable or discrepant, the most appropriate manner of death usually is undetermined.     

Sevoflurane concentrations in blood, brain, and lung after sevoflurane-induced death

Sevoflurane concentrations in blood, brain, and lung were measured in an individual apparently dying from sevoflurane inhalation. Sevoflurane is a volatile nonflammable fluorinated methyl isopropyl ether inhaled anesthetic, chemically related to desflurane and isoflurane. The incidence of abuse of sevoflurane is lower than that of other drugs of abuse possibly due to its inaccessibility to the general public and less pleasurable and addicting effects. The dead subject was an anesthetist found prone in bed holding an empty bottle of sevoflurane (Ultane). Serum, urine, and liver were screened for numerous drugs and metabolites using enzyme immunoassays and gas chromatography-mass spectrometry. Analysis did not reveal presence of any drug, including ethanol, other than sevoflurane. Sevoflurane was determined by headspace gas chromatography and revealed concentrations of 15 microg/mL in blood and 130 mg/kg in brain and lung. Autopsy revealed pulmonary edema and frothing in the lung, pathological findings associated with death by sevoflurane or hypoxia. The cause of death was ruled as sevoflurane toxicity and the manner of death as accident.     

Contribution of Antemortem Computed Tomography Findings to Cause of Death Determination: An Unusual Fatal Stroke

In the case reported here, the antemortem computed tomography scan (CT scan) was essential in the forensic investigation. A 32‐year‐old man was found fully awake with a facial abrasion, after what seemed to be a car accident. He lost consciousness suddenly one hour after initial management. Successive CT scan showed a facial fracture and a metallic foreign body in the carotid canal associated with an occlusion/dissection of the left internal carotid, a pseudoaneurysm, and a carotid‐cavernous fistula. The victim died from a stroke. Autopsy confirmed that the facial abrasion was a gunshot entrance wound, the metallic foreign body being a projectile. Intracranial vascular injuries linked with gunshot wounds are most of the time isolated and due to pelet embolism. The observed vascular injury association has never been described in the existing literature. The CT scan provided a better understanding of the chronology of events that led to death.     

The Interplay Between Diabetes and Pancreatitis: Two Case Reports of Sudden,Natural Deaths and a Review of the Literature

Diabetes mellitus (DM) is a common disease involving insulin resistance or deficit that, when left unchecked, may cause severe hyperglycemia and subsequent end‐organ damage. Acute pancreatitis (AP) is inflammation of the pancreas that can lead to significant morbidity and mortality. AP and DM both account for a significant amount of sudden deaths, and rarely both disease processes may be present in the same decedent, causing some difficulty in wording the cause of death statement. Although much research has been directed at studying the causes and risk factors for AP and DM, there is a complex interplay between these diseases that is not fully understood. This study presents two autopsy cases of sudden, natural deaths that illustrate this interplay, along with a review of the literature. An algorithm for differentiating AP and DM is then discussed in the context of the presented cases as a proposed aid for forensic pathologists in the certification of such deaths.     

抗精神病药物致心源性猝死的机制及其法医学意义

精神障碍患者是由各种原因导致脑功能障碍并伴有一系列功能缺失和寿命缩短的群体,其死亡率为普通人群的2~5倍,且服用抗精神病药物导致猝死的发生率明显高于不服药者。大量案例报道和临床资料的回顾性研究表明,精神障碍患者发生心源性猝死风险与服用APs相关。本文简要介绍APs致心源性猝死的机制和危险因素,以期为法医学鉴定提供参考依据。     

Renal Tubular Epithelial Vacuoles—A Marker for Both Hyperlipidemia and Ketoacidosis at Autopsy

Review of 15 cases of nephrotic syndrome found that eight had significant hyperlipidemia with serum cholesterol levels ranging between 10.59 and 18.60 mmol/L (mean 12.88) and serum triglyceride levels between 2.30 and 9.92 mmol/L (mean 4.58); all of these cases displayed basal lipid vacuolization. Seven of the 15 study cases had normal–mild hyperlipidemia with serum cholesterol levels ranging between 4.71 and 7.54 mmol/L (mean 6.02) and serum triglyceride levels between 0.65 and 4.1 mmol/L (mean 1.57). Six of the seven cases had basal lipid vacuoles (86%). Of these, five cases were hyperlipidemic and one case had borderline hyperlipidemia with a serum cholesterol level of 4.71 mmol/L. Although hyperlipidemia was associated with renal tubular epithelial vacuolization, the vacuoles appeared morphologically different to those found in ketoacidosis. This study has shown that while hyperlipidemia in isolation may result in basal lipid vacuolization within renal tubular epithelial cells, the phenotype differs from that observed in ketoacidosis.     

Fat Transfer and Fatal Macroembolization

Fat embolism is usually associated with long bone fractures or other trauma. The diagnosis is usually clinical, and in most cases, emboli are not fatal and not usually seen on gross examination. At the Los Angeles County Coroner's Office, we autopsied the victim of fatal macroscopic fat embolization to the lungs. The patient died during buttock enhancement surgery when fat from liposuction was injected into her buttocks. Fat embolism from liposuction and fat injection is reportedly rare, and macroscopic embolization is rarer still. Varicose veins can occur in the area of the sciatic notch and are known to cause painful sciatica symptoms. We suggest them as a potential conduit for macroscopic fat to reach the lungs. Simple pre‐operative questioning for sciatica symptoms and possible radiologic study to rule out sciatic varices seem prudent before undertaking buttock‐enhancing surgery. Careful fat injection with pre‐aspiration is always advised.     

Fatal Drowning Accident and Undiagnosed Hydrocephalus

Abstract: Bodies found in water present several diagnostic challenges for the forensic examiner, such as the identification of the time and mechanism of death, the postmortem submersion time, and above all the circumstances of drowning. We report the case of a 33‐year‐old security guard found dead in Venice, in the water of the lagoon, who at autopsy presented a previously undiagnosed hydrocephalus with macrocephaly. The victim remained asymptomatic until 2 months before death and had never undergone a neurological or radiological examination. In the article, we emphasize the need to perform a thorough autopsy in all suspected drownings, discuss the etiopathogenesis of the neurological disease and hypothesize a possible relationship between the hydrocephalus and the drowning accident. Finally, we discuss the major clinical and forensic implications of macrocephaly and hydrocephalus in adults.     

Disopyramide and Mianserin Intoxication: A Unique Fatal Case – Review of the Literature

Lethal occurrence is exceptional after disopyramide or mianserin poisoning. A case of intentional lethal intoxication with these drugs was reported, as well as a review of the literature. Pre‐ and postmortem blood concentrations of disopyramide or mianserin were assessed in a woman who died from acute cardiac failure after ingestion. The premortem blood concentration of disopyramide alone was considered lethal, and a toxic premortem concentration of mianserin was observed that may have increased cardiovascular failure induced by disopyramide because the metabolism of both drugs is mediated via cytochrome P450. Moreover, it was shown that the postmortem redistribution of disopyramide was limited, as pre‐ and postmortem concentrations were 48 and 65 mg/L, respectively. As regards mianserin, redistribution was observed after death with pre‐ and portmortem concentrations at 0.23 and 0.79 mg/L, respectively. This case illustrates that if postmortem blood concentration of disopyramide is known, the premortem concentration can be deduced.     

Clinical and Autopsy Characteristics of Fatal Methamphetamine Toxicity in Australia

Characteristics of death attributed solely to methamphetamine toxicity (MT, n = 93) by forensic pathologists were examined and compared to cases of multiple drug toxicity (MDT, n = 634). The mean age of MT cases was 36.7 years, and 86.0% were male. Strenuous activity was reported in 12.9%. The most common witness observations were: collapse (60.3%), difficulty in breathing (36.2%), and hyperthermia (27.6%). MT cases had higher blood methamphetamine (0.54 vs. 0.11 mg/L) and amphetamine (0.04 vs. 0.02 mg/L) concentrations and lower likelihoods for opioids (12.5% vs. 80.9%), hypnosedatives (27.3 vs. 60.7%), antidepressants (14.8 vs. 29.8%), and antipsychotics (9.1 vs. 19.7%). MT cases had significantly heavier hearts than MDT cases (423.4 vs. 385.8 g) and were more likely to have cardiomegaly (37.1 vs. 20.4%) and replacement fibrosis (25.7 vs. 14.5%). The clinical picture was of a sudden cardiac event in a middle‐aged man with a high methamphetamine concentration. Cardiovascular signs of heavy methamphetamine use are frequently seen.     

Postmortem detection of isopropanol in ketoacidosis

Isopropanol (IPA) detected in deaths because of diabetic ketoacidosis (DKA) or alcoholic ketoacidosis (AKA) may cause concern for IPA poisoning. This study addressed this concern in a 15-year retrospective review of 260 deaths in which concentrations of acetone and IPA, as well as their ratios, were compared in DKA (175 cases), AKA (79 cases), and IPA intoxication (six cases). The results demonstrated the frequency of detecting IPA in ketoacidosis when there was no evidence of IPA ingestion. IPA was detectable in 77% of DKA cases with quantifiable concentrations averaging 15.1 ± 13.0 mg/dL; 52% of AKA cases with quantifiable concentrations averaging 18.5 ± 22.1 mg/dL; and in cases of IPA intoxication, averaging 326 ± 260 mg/dL. There was weak correlation of IPA production with postmortem interval in DKA only (r = -0.48). Although IPA concentrations were much higher with ingestion, potentially toxic concentrations were achievable in DKA without known ingestion.     

Psychotropic Medication Experiences of Incarcerated Women: A Qualitative Inquiry into Conundrums of Access and Identity

The study examines narrative data from in-depth, semi-structured interviews with 25 women in a medium security prison with the hope of deepening the knowledge base related to women’s beliefs about their mental health problems, mental health care during incarceration, and especially their experiences with psychotropic medication. The findings highlight the functional role of psychotropic medication in the lives of incarcerated women, while also emphasizing problems with limited access to prescribers, preferred medications, and other forms of mental health treatment. Trauma, substance use, and the impact of medication use on sense of self all emerged as interfacing with quality of life.     

An Uncommon Accident and Unusual Cause of Death—A Fatal Domestic Ram Attack

Domestic animal attacks are not common; their fatal attacks are even rarer. Herein, a case of a 78‐year‐old woman attacked by a ram is presented. She sustained multiple head and chest injuries. The autopsy findings and the inspection of the scene revealed that the fatal aortic injury had been caused by direct force from the front, which subsequently caused a powerful anteroposterior chest compression, resulting in an incomplete tear by flexion and compression of the aortic arch. The aortic dissection propagated in both an ante‐ and retrograde direction, with intact adventitia. However, due to a rise in pressure in the formed false lumen, dissection propagated downward to the base of the heart, and further into the subepicardial adipose tissue, forming a subepicardial hematoma. This hematoma gradually compressed the proximal sections of the coronary arteries, impairing their filling, and producing a myocardial ischemia. In addition, circulation had probably been already disturbed by the right‐sided pneumothorax, as well as a possible pneumomediastinum.