Comparative evaluation of postmortem serum concentrations of neopterin and C-reactive protein

The cellular immune response is accompanied by the release of neopterin. The level of neopterin in serum is increased in patients suffering from viral infections, autoimmune diseases, systemic inflammation, allograft rejection and malignant diseases, while that of C-reactive protein (CRP) is known to rise during inflammatory diseases and traumas. To investigate postmortem neopterin and CRP concentrations with regard to the cause of death, we examined cardiac and peripheral blood samples in 474 autopsy cases without advanced decomposition (0-96 years of age, 343 males and 131 females), 2.8 h to 3 days (median, 18.0 h) after death. Survival time was 0.1 h to 5 months (median, 3.0 h) for traumatic death, and 0.1-1, 440 h (median, 2.5 h) for natural death. In autopsied subjects, neopterin concentrations were higher than the clinical reference, independent of the time after death, and depended on the survival time. In cases of acute and subacute death due to trauma, the neopterin level in right heart blood was mildly to moderately elevated (about 50-200 nmol/l) except for sharp instrument injury, whereas the CRP concentration usually remained low (<1 mg/dl). However, a moderate rise in the CRP level (around 1-10 mg/dl) was observed in fatal cases of hypothermia (cold exposure). Markedly elevated serum CRP and neopterin levels (>10 mg/dl and >500 nmol/l, respectively) were detected in cases of delayed death due to trauma involving systemic inflammatory response syndrome (SIRS) and of fatal bacterial infections. For sepsis, the serum CRP level was markedly elevated but the neopterin level was low in some cases. Fatal viral infections usually resulted in a marked elevation in the serum neopterin level (>500 nmol/l) with a mild to moderate rise in the CRP level. Combined analyses of neopterin and CRP may be useful to investigate viral infections and delayed traumatic death involving SIRS to support pathological findings.     

Carbon monoxide poisoning without cherry-red livor

Carbon monoxide (CO) poisoning typically causes so-called cherry-red livor of the skin and viscera. The authors report a case of CO poisoning in which cherry-red livor did not develop. The decedent was a 75-year-old white man who was found dead in his car during a cold winter. Blood CO saturation was 86%. The death was attributed to CO poisoning, and the manner of death was designated suicide. The curious absence of cherry-red livor was studied. The decedent's tissue and blood specimens were tested at different temperatures. There was no tendency for either type of specimen to develop cherry-red color at cold or warm temperatures. The antemortem response of the skin to cold possibly sequestered CO-saturated blood in the cadaver. As regards the viscera, there are other proteins to which CO can bond, and possibly these proteins contribute to the development of visceral cherry-red livor. In this case, the absence of cherry-red livor could have led to misclassification of the cause and manner of death. The medicolegal and social consequences of such misclassification can be significant, and psychiatric history, which may be useful to surviving family members, could be lost.     

Time of death of victims found in cold water environment

Limited data is available on the application of post-mortem temperature methods to non-standard conditions, especially in problematic real life cases in which the body of the victim is found in cold water environment. Here we present our experience on two cases with known post-mortem times. A 14-year-old girl (rectal temperature 15.5 degrees C) was found assaulted and drowned after a rainy cold night (+5 degrees C) in wet clothing (four layers) at the bottom of a shallow ditch, lying in non-flowing water. The post-mortem time turned out to be 15-16 h. Four days later, at the same time in the morning, after a cold (+/- 0 degrees C) night, a young man (rectal temperature 10.8 degrees C) was found drowned in a shallow cold drain (+4 degrees C) wearing similar clothing (four layers) and being exposed to almost similar environmental and weather conditions, except of flow (7.7 l/s or 0.3 m/s) in the drain. The post-mortem time was deduced to be 10-12 h. We tested the applicability of five practical methods to estimate time of death. Henssge's temperature-time of death nomogram method with correction factors was the most versatile and gave also most accurate results, although there is limited data on choosing of correction factors. In the first case, the right correction factor was close to 1.0 (recommended 1.1-1.2), suggesting that wet clothing acted like dry clothing in slowing down body cooling. In the second case, the right correction factor was between 0.3 and 0.5, similar to the recommended 0.35 for naked bodies in flowing water.     

Sudden death after a cold drink: case report

We report a case of sudden cardiac death in a 12-year-old boy after rapid ingestion of a frozen slurry drink. The cause of death was determined to be a cardiac arrhythmia secondary to a previously undiagnosed cardiac rhabdomyoma with associated myocardial scarring. Ingestion of cold liquids has been associated with syncope, but not sudden cardiac death. In this case, bradycardia induced by cold-induced vasovagal reflex may have precipitated the terminal arrhythmia. Ingestion of cold liquids should be considered a potential trigger for fatal cardiac arrhythmias in patients with underlying heart disease.     

Massive systemic fat embolism detected by postmortem imaging and biopsy*

Postmortem computed tomography (pmCT) and pmCT angiography (pmCTA) provide a minimally invasive method to determine the cause of death. Postmortem image-guided biopsy allows for precise sampling of histological specimens. This case study describes the findings of lethal systemic fat embolism (FE) on whole-body unenhanced pmCT, pmCTA, and image-guided biopsy, with autopsy and histopathologic correlation. Unenhanced pmCT revealed a distinct fat level on top of sedimented layers of corpuscular blood particles and serum in the arterial system and pulmonary trunk. Subsequent pmCTA showed reproducible results, and image-guided biopsy confirmed fatal FE. pm CT/pmCTA combined with image-guided biopsy established the cause of death as right heart failure as a result of systemic fatal FE prior to autopsy. All imaging findings were consistent with traditional autopsy and histological specimens. This unique case demonstrates new imaging findings in massive, fatal FE and highlights that postmortem imaging, supplemented by image-guided biopsy, may detect the cause of death prior to traditional autopsy.     

Lowered cold tolerance in cold-acclimated and non-acclimated guinea pigs treated with diazepam

The effects of the clinically most commonly used minor tranquilizer, diazepam, on the survival time and on the mechanism of death in non-acclimated and cold-acclimated guinea pigs in severe cold exposure (-20 degrees C) were studied. Cold acclimation for 2 months increased the average survival time from 4 h to 10 h. The lowest rectal temperature at death (14.6 degrees C) was seen in the cold-acclimated animals. Diazepam at a dose of 5 or 15 mg/kg i.p. 30 min before the beginning of the exposure reduced dose-dependently the cold endurance of both cold-acclimated and non-acclimated guinea pigs. The serum glucose and free fatty acid concentrations were low in the animals with the long survival time. Histological studies of liver, kidney, and adrenal glands showed no specific changes. Exposure seemed to increase the frequency of contraction bands and to decrease focally the intensity of beta-hydroxybutyrate dehydrogenase reaction in the myocardium, which indicates a mild hypoxic lesion of the muscle cells.     

The elevation of serum creatine phosphokinase (CPK) at induced hypothermia

The creatine phosphokinase (CPK) elevation of induced hypothermia was elaborated. CPK elevation is a remarkable sign of death due to cold exposure. It appears that the results of the animal experiment indicate that the method could be useful in forensic medical practice as well.     

对冻死尸体血糖变化的研究

用分光光度计对10具冻死尸体、50具非冻死尸体、50名健康体检人的血糖及5只家兔冻死前后的血糖分别进行测定,测得的数据用统计学“方差分析”方法处理,结果为健康人男、女的血糖浓度、健康人与非冻死尸体血糖的浓度差异无显著性;冻死与非冻死血糖的浓度、冻死与健康人血糖的浓度差异有高度显著性;家兔在冻前与冻死后血糖浓度的差异有高度的显著性。结论为冻死尸体血糖明显升高,可以做为法医确定冻死的佐证之一。     

Effects of acute cold exposure on blood-brain barrier permeability in acute and chronic hyperglycemic rats

These experiments were carried out to study, the effects of cold exposure on the permeability of blood-brain barrier (BBB) in hyperglycemic rats. The integrity of the BBB was investigated using Evans blue albumin (EBA) extravasation. Serum glucose levels in hyperglycemic rats were significantly higher than that obtained from normoglycemic rats (P < 0.05). Mean arterial blood pressure in hypothermic groups significantly dropped into lower levels, than that obtained in normothermic groups (P < 0.05). The EBA extravasation to the cerebellum in the group of cold exposure+acute hyperglycemia significantly increased compared with the values obtained from the cold exposure group (P < 0.05). The EBA extravasation to the brain regions of diabetic rats exposed to cold increased more than that in normotermic control rats (P < 0.05), but did not exceed the levels in cold controls. The result of this study suggests that, acute hyperglycemia superimposed upon the permeability of BBB in the rat exposed to cold, only in selected regions of the brain, especially the cerebellum, and this result could be an important factor to explain the mechanisms of death related with hyperglycemia+cold exposure in forensic medicine.     

On an accident by liquid nitrogen — histological changes of skin in cold

Two young researchers were found lying beside 3 Dewar flasks for liquid nitrogen in a cold experimental room of a university. They were sent to a hospital but died 1.5 h after cardiopulmonary resuscitation. One of the cadavers had dark red discoloration of the skin on the left arm at autopsy. By the histological investigation of the discolored region karyopyknosis and vacuolation of the keratinocytes were noticeably observed in the epidermis. In addition, hyperemia and edematous changes were seen. Hemoglobin (Hb) was not immunodetected in the skin tissue except intravascular erythrocytes. Therefore, these histological findings of the discolored skin can indicate that the skin damage was produced by cold due to liquid nitrogen before death. The cause of death was asphyxia due to oxygen deficiency. There were few autopsy findings which showed the participation of liquid nitrogen in the accident. But, the histological findings of the discolored region demonstrate that liquid nitrogen was involved in this accident.     

Sudden death in a 35-year-old man with occult malformation of the brain and aseptic meningitis

A 35-year-old man was found dead by his wife. He was reported to have had symptoms of a common cold the week preceding his death. The medicolegal autopsy yielded signs of central dysregulation (ectasia of the urinary bladder and rectum, dystelectasis of the lungs) together with marked brain edema and fresh bite marks on the tongue. The cause of death was presumed to be lethal epileptic seizure. Neuropathologic examination revealed neuronal nodular heterotopia as well as discrete lymphocytic meningitis (aseptic meningitis). The death was most probably caused by the combination of the meningitis with the occult malformation, leading to a lowered seizure threshold and subsequent lethal seizure. The morphologic findings of this case are presented, and the probable mechanisms of death are discussed.     

Diagnostics of hypothermia in death after cold temperature was over

The prevalence and morphological peculiarities of signs, which are most typical of factors of hypothermia in death due directly to cold and in death after the low-temperature factor is over, as well as the related therapeutic-and-resuscitation measures, were studied. A significantly decreasing detection frequency and a decreasing pronouncement degree of a majority of the basic diagnostic criteria applicable to supercooling were established for the second variant of than atogenesis. Possible reasons of their pathomorphism are defined. The derived regularities need to be duly taken into consideration in order to ensure an objective diagnosis of supercooling in expertise of cold injury received under appropriate conditions.     

Possible role of pseudoephedrine and other over-the-counter cold medications in the deaths of very young children

The Philadelphia Medical Examiners Office has reported a series of 15 deaths between February 1999 and June 2005 of infants and toddlers 16 months and younger in which drugs commonly found in over-the-counter (OTC) cold medications were present. A total of 10 different drugs were detected: pseudoephedrine, dextromethorphan, acetaminophen, brompheniramine, carbinoxamine, chlorpheniramine, ethanol, doxylamine and the anticonvulsants, phenobarbital, and phenytoin. The drugs were confirmed and quantified by gas chromatography (GC)-mass spectrometry, with the exception of ethanol, which was analyzed by headspace GC and of phenobarbital and phenytoin that were quantified by GC with a nitrogen phosphorus detector. The most predominant drug was pseudoephedrine, which was found in all of the cases (blood concentration, n=14, range=0.10-17.0 mg/L, mean=3.34 mg/L) and was the sole drug detected in three cases. Acetaminophen was detected in blood from each of the five cases with sufficient sample. Other drugs (with frequency of detection) were dextromethorphan (five cases), carbinoxamine (four cases), chlorpheniramine (two cases) and brompheniramine, doxylamine, and ethanol (one case each). In the majority of the cases, toxicity from drugs found in easily available OTC medications was listed either as the direct cause of death or as a contributory factor. The manner of death was determined to be natural in only two of the cases. This postmortem study supports previous evidence that the administration of OTC cold medications to infants may, under some circumstances, be an unsafe practice and in some cases may even be fatal. The treating physicians and the general public need to be made more aware of the dangers of using OTC cold medications to treat very young children so that these types of tragedies might be avoided.     

An unusual case of accidental hypothermia due to cold water immersion

Accidental deaths due to hypothermia most commonly result from exposure to low environmental temperature. Generally, a cold climatic condition is present in a severe environmental setting. A case report is presented of a 58-year-old man who died from accidental hypothermia associated with immersion in cold water while on a farm during warm weather. The importance of an adequate death scene investigation is discussed.     

The eye as a chemical indicator of environmental temperature at the time of death

Vitreous humor chemistry profiles were reviewed on 133 autopsied cases in which death occurred outdoors during a six-year period, to determine whether environmental temperature at the time of death influenced chemistry values obtained at autopsy. The glucose concentration and total carbon dioxide content varied inversely with temperature. Values were significantly higher in the winter than the summer months. The mean glucose level was higher in deaths caused by cold exposure than in other deaths occurring in the cold, but individual cases could not be distinguished on the basis of chemistry values. Potassium levels tended to be slightly lower in winter. It was noted that chemistry studies could be used to help determine whether a body found outdoors in winter actually died in a different, warmer environment.     

离体人肝细胞核DNA含量死后变化的图像分析研究

目的应用图像分析技术研究人肝细胞DNA降解与死亡时间的关系。方法选取18例已知死亡时间的人体肝脏,在死后4~36h内每小时进行细胞学涂片、Feu lgen-Vans染色,应用图像分析系统研究肝细胞核平均灰度、平均光度、积分光密度等参数在死后的变化规律。结果在4~36h内随死亡时间的延长,肝细胞核的平均灰度逐渐上升,平均光度、积分光密度逐渐下降,获得了36h内3个参数变化的回归方程。结论肝细胞核的平均灰度、平均光度和积分光密度均与死亡时间有明显的相关性,可望用于推断早期人体死亡时间。     

Method for determining if a corpse has been frozen: measuring the activity of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD).

Accidental deaths by exposure to the cold have figured in many publications, whereas the freezing of the corpse is not well known. The study which we have reported was motivated by an observation of homicide in which ignorance of the fact that the body had been frozen was responsible for an underestimation of the time since death. It proved that measuring the activity of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) could reveal that the body had been frozen.     

人脾脏细胞核DNA含量与死亡时间关系的图像分析

目的研究人脾脏细胞DNA含量改变与死亡时间的关系。方法选取36例已知死亡时间的人体脾脏,在死后5～36h内逐时进行细胞学涂片、Feulgen Vans染色观察,并用图像分析系统,测定脾脏细胞核积分光密度、平均灰度等灰度参数,所得数据用SPSS软件分析。结果在5～36h内平均光密度、积分光密度、平均灰度均值均与死亡时间显著性相关,并得出对应的回归方程,其中平均光密度、积分光密度随死亡时间的延长而逐渐减小、平均灰度逐渐增大。结论人脾脏细胞核DNA含量改变呈现一定规律,与死亡时间明显相关。     

Death caused by myocarditis in Wayne County, Michigan: a 9-year retrospective study

This paper reviews 72 cases of death caused by myocarditis between the years 1996 and 2004, autopsied at the Office of the Wayne County Medical Examiner in Michigan. Myocarditis as a cause of sudden and unexpected death represented 1.3% of all natural deaths in Wayne County during said period. The year 1999 contained the highest number of deaths of this cause (18), where the average number of myocarditis deaths was 8 per year for this 9-year span. In this study, each case was reviewed based on information gathered from investigative, autopsy, and toxicology reports. Significantly, 58% of these cases were male, and 63.4% were African American. Myocarditis caused death in every age group between 7 months and 67 years, but adults between the ages of 19 and 67 were most significantly affected (75%). Flu and/or cold were the most common symptoms experienced in the days directly proceeding death (28%), followed by shortness of breath (17%) and sudden collapse (15%). Sixty-nine percent of these 72 cases were pronounced dead after ACLS (advanced cardiac life support) protocol by emergency medical services or hospital attendants. Cardiomegaly was observed in 24 cases of adults aged 19 or older (54%), and flabby/soft myocardial tissue was observed grossly in 16% of all 72 cases.