Sudden death as a complication of bacterial endocarditis

Three cases are reported to demonstrate the range of possible lesions and wide variation in lethal mechanisms that may be found in cases of unexpected death subsequently shown to be due to bacterial endocarditis. Case 1: A 36-year-old man was found dead on his bedroom floor surrounded by drug paraphernalia. At autopsy, acute myocardial ischemia was present caused by coronary artery ostial occlusion complicating acute bacterial endocarditis of the aortic valve. Case 2: A 54-year-old man with chronic renal failure was found dead in bed at home. At autopsy, a left middle cerebral artery territory cerebral infarct was present due to septic embolization from bacterial endocarditis involving the aortic valve. Case 3: A 23-year-old man was found collapsed in a pool of blood. At autopsy, upper airway hemorrhage from an arteriobronchial fistula was present caused by septic pulmonary infarction from previous endocarditis of a congenital ventricular septal defect. This report demonstrates that bacterial endocarditis may still be a cause of sudden and unexpected death presenting to forensic mortuaries and that the underlying mechanisms may involve complex sequences of pathological changes that compromise vascular function.     

Heroin dependence as a rare cause of symmetrical globus pallidus necrosis

Long-term survival after carbon monoxide intoxication has been accepted for a long time as pathognomonic for elective cerebral tissue damage, especially in cases of isolated symmetrical necrosis of the globus pallidus. The results of old bilateral necrosis in the globus pallidus are described in a case of an acute heroin death after long-term drug abuse. The evaluation of such cerebral changes is discussed as they have to be interpreted as hypoxic or oligemic tissue damage. The different causes of symmetrical necrosis of the globus pallidus that are relevant for legal medicine are compiled and discussed.     

海洛因慢性依赖大鼠神经元一氧化氮合成酶变化

目的 研究海洛因药物滥用致脑神经细胞一氧化氮合成酶(ncNOS)表达的变化及法医学鉴定意义。方法 采用ncNOS免疫组织化学SP法、ncNOS mRNA原位分子杂交及图像分析技术,观察大鼠海洛因慢性依赖和自然戒断大脑皮质、中脑导水管周围灰质和中脑腹侧被盖区神经细胞ncNOS的变化和ncNOSmRNA的表达。结果 实验组神经细胞ncNOS含量和ncNOS mRNA表达比对照组明显增加,阳性细胞数明显增多;自然戒断组较慢性依赖组改变更加明显(P<0.05)。结论 ncNOS在海洛因慢性依赖和戒断中起重要作用,脑神经细胞ncNOS免疫组织化学变化可作为海洛因药物滥用法医学鉴定的形态学依据。     

Cerebral hemorrhage after the consumption of amphetamine

Cerebral hemorrhages are rare complications that occur after the consumption of amphetamine; the mortality rate is estimated at 50 %. It is assumed that cerebral hemorrhages are caused by amphetamine-induced hypertensive crises coinciding with pre-existing vascular alterations (congenital vascular malformations, vasculitis). In the present case report, a 40-year-old man, who is said to have regularly consumed hashish, heroin and speed, died of a massive cerebral hemorrhage located in the region of the basal ganglia shortly after the intravenous administration of amphetamine and heroin. In the course of the post-mortem investigation, neither vascular malformations nor vasculitis could be detected in the brain. Even if the evidence for the existence of such alterations was missing, this does not exclude their presence for certain. Other potential amphetamine-induced vascular alterations are discussed.     

Ruptured cerebral artery aneurysm and bacterial meningitis in a man with osteogenesis imperfecta

This report describes a 38-year-old man with osteogenesis imperfecta who died of a ruptured cerebral artery aneurysm and bacterial meningitis. He had multiple long bone fractures in the past, and approximately 4 months before death, he had surgery to relieve symptoms of basilar impression. The surgery was complicated by a postoperative wound infection. For the next 4 months, he had intermittent headaches and vomiting. He was found dead in his bed at home. At autopsy, he had a ruptured anterior communicating artery aneurysm and bacterial meningitis. Cerebrospinal fluid and blood cultures had growth of Staphylococcus aureus. Osteogenesis imperfecta is a disorder of type I collagen. Type I collagen is present in many tissues, including blood vessels. The etiology of cerebral artery aneurysm formation is multifactorial. Some patients with cerebral artery aneurysms have been shown to have abnormalities in type III collagen. There has not been a reported relationship made between abnormalities in type I collagen and aneurysms. Meningitis can also result in cerebral artery aneurysms, but they are usually due to Aspergillus or Mycobacterium species. The case we report is unique; cerebral artery aneurysm formation may have been due to osteogenesis imperfecta and/or bacterial meningitis.     

Identification of heroin in street doses using 1D-TOCSY nuclear magnetic resonance

Heroin street doses are complex mixtures commonly analyzed in forensic laboratories. Identification of the illicit substance in these street doses is among the primary analytical tasks of a forensic laboratory. We demonstrate that the one-dimensional ID-TOCSY NMR experiment permits identification of heroin in standard mixtures containing up to ten or more different components. This method produces an easily-identified and effective "fingerprint" for heroin within a mixture of other substances. The method has been successfully tested as a tool for identification of heroin in street doses from police casework in Israel. This NMR technique is robust and quick (a measurement can be carried out in 10-15 min), and it does not require any preliminary physical or chemical treatments of the sample to be examined, due to the effective spectroscopic "filtering" of the interfering components. The ID-TOCSY NMR method can potentially be used in combination with additional analytical methods as a routine tool in forensic laboratories to positively identify heroin for court purposes.     

海洛因诱导大脑神经元凋亡的研究

目的观察海洛因有无直接诱导培养大脑神经元凋亡的作用。方法神经元培养取自SD大鼠妊娠的胎鼠大脑皮质,培养7d后分别用不同浓度的海洛因(纯度80%)处理大脑神经元24h。用FDA法分析细胞存活率,Hoechst 33258荧光染色后观察凋亡的形态学改变,再用DNA琼脂糖凝胶电泳分析凋亡的生化特征。结果海洛因可剂量依赖性地降低神经元的存活率;荧光显微镜可见细胞核染为高亮蓝色的典型凋亡小体,其细胞核明显固缩、凝聚和断裂,且随海洛因剂量的增加,出现凋亡小体的细胞明显增多;不同浓度的海洛因处理大脑神经元,电泳图谱显示清晰的DNA梯带。结论海洛因可直接诱导大鼠大脑皮质神经元凋亡。     

Fatal intoxication as a consequence of intranasal administration (snorting) or pulmonary inhalation (smoking) of heroin

In recent years we have noticed an increasing proportion of mortalities resulting from an overdose of heroin that involve routes of administration other than injection. Of 239 cases of fatal heroin intoxication examined at our department during the period 1997-2000, 18 deaths were associated with non-parental administration. Seven of these fatalities were experienced heroin users who had begun to use more sporadically, seven were recreational "party-users", while the remaining four persons had relapsed into heroin use following long periods of abstinence. The median blood morphine concentration of these non-injectors was 0.095 microg/g (range: 0.02-0.67 microg/g), significantly lower than that of the injectors. Concurrent use of alcohol, other illicit drugs and/or pharmaceutical preparations was observed in 17 of the 18 cases. However, there were no statistically significant differences between the victims of heroin intoxication by injection or by other routes with respect to the proportion who had simultaneously consumed alcohol or benzodiazepines. Pathological alterations like lung fibrosis, liver cirrhosis, endocarditis, etc. were not found to play a significant role in any of the 18 mortalities. We conclude that snorting or smoking heroin probably involves a reduced risk of obtaining high blood concentrations of morphine but still constitutes a considerable risk of lethal outcome due to high variability in blood concentrations. Furthermore, decreased tolerance resulting from periods of reduced or sporadic use appears to be an important risk factor in connection with heroin overdosing by snorting or smoking, which indicate that some heroin addicts may inaccurately assume that these routes of administration are safe when resuming their use of heroin after a period of abstinence.     

Heroin body packing: three fatal cases of intestinal perforation

Death from heroin body packing has been well described in the forensic literature. Most fatalities are due to drug leakage and consequent acute heroin toxicity. Recently, drug traffickers have become more sophisticated in their packaging, and the risk of rupture of drug packets is more remote. Though intestinal obstruction is a recognized risk of body packing, rarely has this resulted in death. We describe four cases of heroin body packing presenting to the Regional Medical Examiner Office in New Jersey. Death in three of these cases was due to intestinal obstruction, with resultant intestinal rupture and peritonitis. Toxicologic evaluation in these three cases was negative for opiates or other drugs of abuse. In one case, death was due to acute heroin toxicity, validated by toxicologic analysis. We briefly discuss the differing drug packaging found in these four cases and the ramifications of packaging as it relates to intestinal obstruction.     

Evaluation of human brain damage in fire fatality by quantification of basic fibroblast growth factor (bFGF), glial fibrillary acidic protein (GFAP) and single-stranded DNA (ssDNA) immunoreactivities

Burns and inhalation of toxic gases, including carbon monoxide (CO) and cyanide, which are produced by combustion, are major factors involved in fire death. The present study immunohistochemically investigated basic fibroblast growth factor (bFGF), glial fibrillary acidic protein (GFAP) and single-stranded DNA (ssDNA) in the brains of fire fatalities (n=49) to examine the differences between fatal burns and CO intoxication, compared with those in cardiac deaths (n=24) and mechanical asphyxiation cases (n=23). In acute fire fatality, neuronal ssDNA immunopositivity in the cerebral cortex of the parietal lobe was high in both fatal burns and fatal CO intoxication, but that of the pallidum was higher for CO intoxication than for burns. The number of neurons was decreased in prolonged fire deaths, irrespective of the severity of burns or CO intoxication, but glias were increased in cases of fatal burns. Prolonged deaths due to burns had a higher glial bFGF immunopositivity in the cortex and white matter, higher and lower glial GFAP immunopositivity in the cortex and white matter, respectively, and a low neuronal ssDNA immunopositivity in the cerebral cortex and hippocampus. In prolonged deaths due to CO intoxication, however, glial bFGF and GFAP immunopositivities were low at each site, but neuronal ssDNA immunopositivity showed a higher value. These observations suggest increased cerebral neuronal ssDNA immunopositivity to be a finding of vitality in acute fire death, and a neuronal loss accompanied by active glial responses after severe burns, and a neuronal loss and progressive apoptosis without glial responses after CO intoxication to be characteristic in prolonged death.     

Mycoflora of potential sanitary interest present in illicit heroin

The injection of heroin mixtures poses difficult problems in some cases to both pathologist and toxicologist in evaluating the cause of death. Direct heroin toxicity, allergic or idiosyncratic reactions, and bacterial and mycotic infections are different complications that can be found in these cases. The mycotic profile (mycoflora) present in illicit heroin from street samples (sachets) has been studied. The profile was obtained after incubating the samples at pH5 in 2% and 3% agar-maltose media. Only two samples (nos. 24 and 26) yielded negative results. Twenty-seven taxa were isolated. Penicillium and Aspergillus were the genera most frequently found in the samples. Other genera, such as Cladosporium, Absidia, Rhizopus and Micelia sterilia were also detected. Most of the fungi isolated presented a high allergenic potential and were liable to result in allergic reactions connected with "drug deaths". All the fungi found were commonly present in our environment.     

Heroin fatality due to penile injection

Death due to heroin overdose and/or rapid injection of heroin is a frequent occurrence among opioid addicts. We present an unusual case of heroin fatality due to the injection of the drug in the penis. Blood, urine, bile, and vitreous humor concentrations of morphine were 0.68, 0.49, 0.32 and 0.062 microg/ml, respectively. Ethanol was detected at concentrations of 104, 124, 106, and 94 mg/dl in the blood, urine, bile, and vitreous humor, respectively. The cause of death was determined to be due to heroin and ethanol intoxication.     

海洛因成瘾大鼠心电图及心肌超微结构改变的研究

目的探讨海洛因成瘾大鼠心电图及心肌超微结构的改变,为海洛因对心脏的损害机制提供研究基础。方法建立大鼠海洛因成瘾模型,观察心电图、HE染色及心肌超微结构改变。结果大鼠海洛因成瘾组心电图改变明显,主要表现在心率减慢、P波及T波压低、时间延长,S-T段压低、时间延长,QT间期延长,上述差异有统计学意义(P<0.05),提示心肌损伤、心肌缺血及心室功能下降。电镜改变主要表现在核浓缩,核变小,核膜皱缩,染色质凝集成块,线粒体嵴排列紊乱、消失及空泡变等,提示海洛因可造成心肌细胞超微结构的病理改变。结论海洛因对心肌可造成损害,并且心肌超微结构改变提示心肌凋亡可能是海洛因造成心肌损伤的机制之一。     

Evaluation of human brain damage in fatalities due to extreme environmental temperature by quantification of basic fibroblast growth factor (bFGF), glial fibrillary acidic protein (GFAP), S100β and single-stranded DNA (ssDNA) immunoreactivities

Fatalities due to extreme environmental temperatures involving hypothermia (cold exposure) and hyperthermia (heat stroke) might present with poor or nonspecific morphological pathologies, which are insufficient to establish the cause of death in forensic practice. The present study immunohistochemically investigated basic fibroblast growth factor (bFGF), glial fibrillary acidic protein (GFAP), S100β and single-stranded DNA (ssDNA) in the parietal lobe and hippocampus of the brain in fatalities from hypothermia (n=15) and hyperthermia (n=18), and compared them to those of controls (n=39), including acute death due to ischemic heart disease, mechanical asphyxiation and drowning. In addition, S100β concentration in cerebrospinal fluid (CSF) was measured. Characteristic findings in hypothermia cases were higher glial bFGF immunopositivity in the cerebral cortex and white matter, and higher S100β immunopositivity in the cerebral cortex with a lower CSF S100β concentration. Hyperthermia showed lower glial GFAP and S100β immunopositivities in the white matter, and higher neuronal ssDNA immunopositivity in the cerebral cortex and hippocampus, accompanied by high glial bFGF and S100β immunopositivities in the cerebral cortex. These findings suggest neuroprotective glial responses without marked neuronal or glial damage in fatal hypothermia, and diffuse neuronal apoptosis despite initiation of neuroprotective cortical astrocyte responses, accompanied by glial damage in the white matter, in fatal hyperthermia. These markers may be useful for evaluating brain damage and responses in fatalities due to extreme environmental temperatures.     

自制海洛因标准品在常用有机溶剂中稳定性研究

目的 研发海洛因标准品及优化分析方法,以对云南缴获海洛因样本提纯制备成的自制海洛因对照品在常用有机溶剂中的稳定性进一步研究.方法 采用内标及GC、GC/MS方法,通过对提纯制备的海洛因在5种有机溶剂中冷藏保存后含量的变化,观察海洛因在常用有机溶剂中的稳定性.结果 乙醇、三氯甲烷及乙腈为溶剂的自制海洛因对照品储备液,保存30天时间范围内海洛因含量未发生明显变化;以丙酮作为溶剂的自制海洛因对照品储备液,在7至30天时间范围内,海洛因含量明显升高;以甲醇作为溶剂的自制海洛因对照品储备液,在0小时至30天时间范围内,海洛因含量一直呈明显的下降趋势.结论 乙醇、三氯甲烷及乙腈可以作为海洛因样品储备液溶剂使用,丙酮、甲醇不适合作为海洛因样品储备液溶剂使用.     

Study on the changes of electrocardiogram and ultrastructural in heroin dependence in rats

OBJECTIVE: To study the changes of electrocardiograms (ECG) and myocardial ultrastructure in heroin dependence in rats, in order to reveal the mechanisms of the myocardial injury by heroin. METHODS: Establish heroin addict model in SD mice, investigate the changes in electrocardiograms, HE staining and myocardial ultrastructure. RESULTS: The electrocardiograms of the addict group had prominently changes, main expressions: heart rate decreased, P wave and T wave amplitude reduced and duration increased, S-T reduced and duration increased, QT interval prolongation, these changes indicated that myocardium had been injured, myocardial ischemia, ventricle function declined. These difference was significant (P<0.05) between before inject heroin and after inject heroin. Transformations in the ultrastructure: nuclear concentrate, reduce, nuclear membrane shrink, chromatin agglutinate, mitochondria cristal had disorder formation, disappeared or hollowed, these indicated that heroin could cause pathological changes in myocardial ultrastructure. CONCLUSION: Above-mentioned changes indicated that heroin can injure myocardium, and the changes of myocardial ultrastructure suggested that myocardial apoptosis may be one of the mechanisms of the myocardial injury by heroin.     

Isotopic fractionation of carbon and nitrogen during the illicit processing of cocaine and heroin in South America

The forensic application of stable isotope analysis to cocaine and heroin for geolocation of exhibits must take into account the possible enrichment and/or depletion of 13C and 15N during the illicit manufacturing process. Continuous-flow elemental analysis-isotope ratio mass spectrometry was utilized to measure changes in the stable isotope ratios of carbon and nitrogen for both cocaine (N = 92) and heroin/morphine (N = 81) exhibits derived from illicit manufacturing processes utilized by South American clandestine chemists. In controlled settings in South America, there was no siginficiant carbon isotope fractionation during the conversion of cocaine base to cocaine HCI using current illict methodologies. In contrast, nitrogen isotope fractionation for this conversion was 1 per thousand. There was a kinetic carbon isotope ratio fractionation during the acetylation of Colombian morphine to heroin and as a result heroin exhibits will almost always have more negative delta13C values than the original morphine. There was an isotopic fractionation against 15N during the acetylation of morphine base to heroin base, but this effect was not expressed since all of the heroin base was precipitated during the manufacturing process. However, the clandestine process of converting a single batch of heroin base usually involved two consecutive crops of heroin HCl and the latter crop was isotopically depleted as expected from a Rayleigh distillation process. When heroin was deacetylated to morphine, the morphine produced resulted in delta13C values that were indistinguishable from the original morphine. The kinetic carbon isotope fractionation factor for the South American process of morphine acetylation was -1.8 per thousand, allowing calculation of the delta13C values of the acetic anhydride from deacetylated heroin delta13C values.     

Aspects of forensic medical diagnosis of acute opiate poisoning

The case study is dedicated to morphological changes occurring in the organs and tissues in lethal outcomes due to acute poisoning with narcotic substances; it is also dedicated to the structure of an acute respiratory insufficiency in unexpected "heroin" death and to delayed death after intoxication. The clinical-and-anatomical analysis of the material, involving the immunological, biochemical, chemical and spectral examination data, has been undertaken.     

Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis

In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine. Victims of lethal heroin overdose often present with fairly low blood concentrations of morphine. Reduced tolerance due to abstinence has been proposed to account for this finding. The aim of the present study was to examine the role of abstinence in drug-related deaths by comparing recent and past exposure to opioids using segmental hair analysis with the postmortem blood morphine concentrations in deceased heroin users. The study included 60 deceased drug addicts in the Stockholm area, Sweden. In 32 cases, death was not related to heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most recent hair segment, suggesting a reduced tolerance to opioids. However, the blood morphine levels were similar to those found in the 10 subjects that showed continuous opioid use. Hair and blood analysis disclosed an extensive use of additional drugs that directly or indirectly may influence the opioid system. The results suggest that abstinence is not a critical factor for heroin overdose death. Obviously tolerant subjects die after intake of similar doses. Other factors, particularly polydrug use, seem to be more causally important for these deaths.