A fatal case of amniotic fluid embolism with elevation of serum mast cell tryptase

A case of a 40-year-old female who died of amniotic fluid embolism is presented. This case showed typical histological findings of this syndrome. Postmortem serum of this case showed an elevated tryptase level (67.2ng/ml, normal levels <10ng/ml). Tryptase is a neutral protease of mast cells, and an important indicator of mast cell activation and degranulation. Thus, mast cell activation, a central feature of anaphylaxis, may have been involved in the pathogenetic mechanism of this case.     

实验性兔羊水栓塞肥大细胞类胰蛋白酶的含量变化

目的观察家兔羊水栓塞 (AFE)后肺组织中肥大细胞类胰蛋白酶 (MCT)含量的变化。方法分别于健康怀孕家兔耳缘静脉注入羊水、制造羊水栓塞的动物模型 ;取肺组织进行HE染色和免疫组织化学MCT染色 ,镜下观察AFE兔肺组织中MCT的变化。结果对照组兔肺组织MCT呈弱阳性反应 (平均阳性细胞计数 11 2 5个 ) ,注入羊水组和注入胎盘提取液与羊水混合液组肺组织中MCT呈强阳性反应 (平均阳性细胞计数分别为 3 2 98和 45 5 3个 )。结论在羊水栓塞时兔肺组织MCT含量增加     

类胰蛋白酶及其法医学应用

类胰蛋白酶由肥大细胞表达,以活性形式储存在肥大细胞的脱颗粒中。作为肥大细胞及其脱颗粒的标志,类胰蛋白酶具有多种生物活性,可以促进气道的恢复,调节气道平滑肌细胞的张力和反应性,提高毛细血管的通透性,刺激新生血管的生成,进而启动和加速多种疾病的进程,并与过敏反应、羊水拴塞、注射海洛因过量、外伤致死及SIDS等有关,因而在法医学中有重要的意义。     

Three cases of suspected hyperthermia with remarkable elevation of serum mast cell tryptase

Tryptase is a neutral protease of human mast cells, and an important indicator of mast cell activation and degranulation in anaphylactic events. The elevation of serum mast cell tryptase (SMCT) is used for postmortem diagnosis of anaphylaxis. We have quantified the SMCT levels of 122 forensic autopsy cases with various causes of death and found only three where the SMCT levels were remarkably elevated, with values of 179, 68.9 and 69.4 ng/ml (normal level <13.5 ng/ml). The three cases were suspected to have suffered from hyperthermia, and the deaths did not seem to be related to causes of death where SMCT levels have been reported to be elevated in some cases. Two cases were patients who had been prescribed long-term neuroleptics or antidepressants, and myoglobin was detected immunohistochemically in the renal tubules of both cases. The other case died of heatstroke. A possible mechanism of hyperthermia in SMCT elevation is discussed.     

Ancillary studies in amniotic fluid embolism: a case report and review of the literature

The incidence of amniotic fluid embolism during pregnancy is approximately 1/50,000 and has a mortality rate in excess of 80%. The postmortem diagnosis of amniotic fluid embolism can be challenging for forensic investigators and pathologists. At autopsy, usually signs of disseminated intravascular coagulation suggest an amniotic fluid embolism. A definitive diagnosis of amniotic fluid embolism cannot be made until ancillary studies are performed on the decedent's tissues. We report a case of a 37-year-old G3P2 white female who was 36 weeks gestation when her membranes spontaneously ruptured. She suddenly became breathless, went into cardiogenic shock, and died. The autopsy revealed gross and microscopic findings of amniotic fluid embolism, which was confirmed with ancillary studies consisting of special stains, immunohistochemistry, and a serum tryptase level. The authors hope this case report, including gross and microscopic autopsy findings with procedural and ancillary studies, and review of the literature will help investigators and pathologists in the diagnosis of amniotic fluid embolism.     

损伤皮肤中组胺荧光显微定位定量与损伤时间推断的实验研究

本文应用显微荧光分光光度计法研究大白鼠皮肤创缘组织中组胺的分布和含量,并用甲苯胺蓝法观察创缘肥大细胞形态和数量的变化。结果发现,创缘真皮乳头层出现扩散的细胞外黄色荧光和肥大细胞脱颗粒现象为生前伤的重要特点;组胺荧光分布范围及增多的程度与损伤时间密切相关。从而为损伤时间推断提供了一种新的方法。     

肥大细胞类胰蛋白酶的免疫组化染色观察

目的　观察过敏性休克死亡者咽喉、肺、小肠组织肥大细胞类胰蛋白酶 (MCT) ,探讨过敏性休克死亡法医鉴定的形态学依据。方法　交通事故致严重颅脑损伤死亡者 10例 (对照组 )、明确诊断为过敏性休克死亡者 15例(实验A组 )和羊水栓塞死亡者 8例 (实验B组 )的尸体 ,分别取其咽喉部、肺及小肠组织 ,石蜡切片 ,HE染色及用免疫组化超敏SP法进行MCT染色。结果　实验A组的咽喉部组织充血、水肿 ,咽喉部粘膜下层MCT增多 (MCT颗粒计数为 48 2 3 ) ;实验B组的咽喉部粘膜下层MCT增多 (MCT颗粒计数为 42 72 )。肺间质尤其是小支气管壁及小血管壁上MCT增多 (MCT颗粒计数分别为 46 98和 43 5 0 ) ,小肠粘膜层MCT增多 (MCT颗粒计数分别为 48 2 3和 42 72 )。对照组的咽喉部、肺和小肠MCT颗粒计数较少 ,分别为 7 79、 12 94和 2 0 2 5。实验A组与对照组相比 ,两组具有显著性差异 (P <0 0 1) ;实验A、B组相比 ,两组无显著性差异 (P >0 0 1)。结论　过敏性休克及羊水栓塞死亡的尸体 ,其咽喉部组织、肺组织及胃肠道组织MCT增多。     

人体皮肤索沟局部肥大细胞脱颗粒率的观察

本文观察人体皮肤索沟局部肥大细胞脱颗粒率变化。发现生前皮肤损伤局部脱颗粒率在皮肤受在处及距受压边缘０～１．０ｍｍ区域明显升高（＞４９％），与死后皮肤索沟有显著差异（Ｐ＜０．００１）。作者认为损伤局部肥大细胞脱颗粒率明显升高（＞４９％）可作为人体生前索沟的诊断依据。     

The reaction of lung mast cells to acute barbiturate and bromureide poisoning (author's transl)]

Guinea pigs were poisoned by large oral doses of hypnotics in order to study the effect of bromureides on the mast cell contents of the lungs in comparison to the influence of barbiturate intoxication. The dose of the hypnotics chosen was thus, that all animals died within the first three hours after the beginning of feeding. Then the degranulation of mast cells with decrease of the mast cell number in the lung tissue was merely small in the barbiturate poisoned animals, but very extensive in the animals intoxicated by bromureides. The difference is highly significant. The possible influence of this effect upon the different clinical course of both kinds of intoxication is discussed.     

Hypernatremia due to amniotic fluid embolism during a saline-induced abortion

A case of fatal amniotic fluid embolism leading to hypernatremia during a hypertonic saline-induced abortion is reported. This sequence of events has not, to our knowledge, been previously reported. Hypernatremia as a diagnostic aid for amniotic fluid embolism is discussed.     

Eosinophilic Coronary Periarteritis with Arterial Dissection: The Mast Cell Hypothesis

A subset of coronary arterial dissections is associated with eosinophilic coronary periarteritis (ECPA); however, the pathogenesis of the process remains unclear. Mast cells normally reside in coronary arterial adventitia and are known mediators of eosinophilic inflammatory conditions such as type I hypersensitivity reactions. We report two cases in which coronary arterial dissection with ECPA was detected at autopsy. Tryptase, CD68, CD4, CD8, and CD1a immunohistochemical staining was performed to better characterize inflammation. While eosinophils represented a prominent periadventitial inflammatory cell, there were slightly more lymphocytes: CD4/CD8 ratios were within expected reference ranges. There were moderate numbers of macrophages, and few neutrophils or dendritic cells. Numbers of mast cells in dissected versus nondissected sections were compared: adventitial mast cell densities were threefold higher in dissected portions and showed a trend toward increased degranulation. These findings suggest that mast cells may play a role in orchestrating inflammation in cases of ECPA.     

The effect of ethanol and antabus-antabus-alcohol-reaction on histamin and mast cell. Contents of the lung (author's transl)]

Alcohol--orally given in concentrations from 1 to 4 g/kg body-weight--leads to a reduction of mast cells in the guinea pig lung. At the same time a minor decrease of histamine concentration was observed. The incompatibility reaction with alcohol after disulfiram intake (DAR) shows an additional degranulation oft mast cells of the lungs and decrease of histamine-content. So far, there seems little difference between the influence of disulfiram alone and the DAR. Besides thrombocytes and basophile leucocytes, the mast cells of the lung are responsible for the release of histamine and serotonine during higher alcohol concentrations and alcohol-disulfiram-reactions. We think that the intolerance phenomena of humans after alcohol--f.e. in form of flush-reaction--is at least partly related to the concomitant influence oft mast cell-substances.     

Mast cell tryptase and hemolysis after trauma

BACKGROUND: We have previously found increased mast cell tryptase in accidental deaths due to trauma, indicating that mast cell degranulation had occurred. The present study was designed to confirm the previous observation and to determine if tryptase release after trauma is acute or delayed. Furthermore, the importance of hemolysis and direct trauma to the mast cells was investigated. MATERIALS AND METHODS: Mast cell tryptase was measured in post-mortem blood from the femoral vein in 27 cases of death from trauma and in 27 control cases by means of a commercially available immunoassay. The trauma cases were further classified into groups with single versus multiple trauma, and groups with short survival time (i.e. death at the scene of the accident) versus longer survival time (death in hospital). In five multi-trauma deaths, blood was sampled locally from the sites of crush injury. RESULTS: The mean value of tryptase in femoral vein blood was 35.6+/-34.6 microg/l in the entire trauma group and 14.7+/-6.5 microg/l in the controls (P<0.005). In bloody liquid sampled from crush injuries, tryptase was substantially elevated in all cases, with a mean of 227+/-146 microg/l. In cases with short survival time, tryptase was significantly higher than in those who died after several hours or days in hospital (P<0.001). No statistically significant difference was seen between multi- and single-trauma cases. A correlation between hemolysis in the samples and elevated tryptase was found only in the trauma cases (P<0.05), but experimentally induced hemolysis in vitro was not found to influence the measurements. CONCLUSION: Mast cell tryptase becomes elevated in trauma deaths and this seems to be ascribable either to direct mechanical injury to tissue mast cells and/or to cell lysis. In patients initially surviving severe injuries, the effects of massive release of histamine and other mast cell mediators might be of importance for treatment strategies and prognosis.     

Localization and quantification of histamine in injured skin as parameters for the timing of wounds.

Localization and estimation of the histamine (HA) content in skin wound edges in 86 Sprague-Dawley rats and three cases of human injuries were carried out by a microfluorimetric method specific for this amine which forms a complex with o-phthalaldehyde (OPT). Distribution and density of the mast cells in the same areas were observed at the same time by toluidine blue stain. In all skin specimens with antemortem wounds, both the epidermis and upper dermis exhibit extracellular yellowish fluorescence of the HA-OPT complex. The fluorescent zone spreads in the wound edges with the lapse of time in vital injuries. The HA content increases gradually up to 30 min and then the yellow histamine fluorescence in areas 0-200 microns from the wound edge decreases. None of these features can be observed in normal skin and postmortem-injured skin. Mast cell degranulation can be demonstrated in all antemortem-injured skin. No statistical relationship exists between the number of mast cells and the HA-OPT fluorescence in either ante- or postmortem-injured groups. This study indicates that skin HA microfluorimetry by the OPT method is of practical value for distinguishing ante- from the postmortem wounds and for timing antemortem wounds.     

Retrograde venous cerebral air embolism from disconnected central venous catheter: an experimental model

There are few reported cases of death attributed to retrograde cerebral air embolism from central venous catheter. The pathophysiological mechanism and the necessary conditions are not fully understood, also because of missing experimental data. We performed experimental simulation while working on a possible case of retrograde cerebral air embolism. A hermetic system consisting of two containers connected to each other and to an electric pump by means of rubber hoses was built. In this system, a fluid (water and blood) could continuously flow under conditions similar to those of the common jugular vein. The part of the system representing the jugular vein could be freely positioned at angles between 0 and 90°. A central venous catheter was inserted into this part. After disconnection, the behavior of the air bubbles entering the hose through the tip of the catheter was evaluated at different positions. At angles between 0 and 45°, the air bubbles followed the fluid flow. At angles >45°, the air bubbles showed the tendency to flow upstream; this phenomenon was more evident the more vertically the hose was located. We were able to demonstrate that a retrograde air embolism can be caused by a disconnected catheter and is even more likely if the neck is in a vertical position.     

实验性兔羊水栓塞血浆凝血指标的含量变化

目的观察兔羊水栓塞(AFE)后血浆凝血指标的动态变化。方法采用怀孕家兔制作羊水栓塞动物模型,将不同性质的自身羊水注入兔血循环,分别在羊水注入前、注入后,5min、45min从兔心脏取血,用血凝仪检测血浆中各项凝血指标包括纤维蛋白原定量(FIB)、血浆凝血酶原时间(PT)、凝血酶凝固时间(TT)、活化部分凝血活酶时间(APTT)的动态变化。结果注入羊水后PT、TT、APTT时间显著延长(P<0.01),FIB则显著降低(P<0.01),而对照组无显著变化(P>0.05)。结论凝血指标的动态变化表明羊水栓塞早期有发生DIC的趋势,胎盘提取液中的某些成分可能加重了DIC的严重程度。     

扫描电镜下缢沟的形态特征

作者用光镜和扫描电镜对縊沟进行对比观察,得出如下结论:(1)扫描电镜下縊沟组织的改变具有较恒定的特征,出血及纤维蛋白检出率远较光镜为高;(2)在光镜下生活反应不明显的生前缢沟,在扫描电镜下其表面及断面均可见红细胞及纤维蛋白形成,并包裹红细胞。縊沟部位胶原纤维之间可见散在大小不等的圆球形脂肪样小滴。缢沟部位肥大细胞的形态改变,有助于生前与死后缢沟的鉴别诊断。     

新疆地区66例多类型栓塞死亡法医学尸检分析

总结分析不同类型的栓子(血栓、脂肪、空气、羊水)栓塞致死的一般特点,探讨其法医病理学鉴定要点及注意事项.对2015～2021年在新疆医科大学司法鉴定所鉴定的66例栓塞致死案例进行回顾分析.经过研究分析,导致患者出现栓塞的因素较多,栓塞致死以肺动脉血栓栓塞多见,另外空气栓塞、羊水栓塞和脂肪栓塞也不容忽视,其均能导致呼吸、...     

实验性兔羊水栓塞血浆NO和ET的含量变化

目的观察兔羊水栓塞(AFE)后血浆一氧化氮(NO)、内皮素(ET)含量的动态变化。方法采用怀孕家兔制作羊水栓塞动物模型,将不同性质的自身羊水注入兔血循环,分别在羊水注入前、注入后5min、45min从兔心脏取血,用镉还原法、放射免疫分析(RIA)法分别检测血浆中NO和ET的动态变化。结果注入羊水后ET含量显著增加,NO含量则显著降低,对照组无显著变化。NO与ET含量变化呈显著负相关。结论NO、ET的动态变化在羊水栓塞早期的一过性肺动脉高压及随后发生的DIC等过程中起重要作用。     

A sudden death with lung embolism after inadvertent infusion of zinc oxide shake lotion

A 74-year old woman in postoperative treatment after a colonic surgery died immediately after perfusion of about 1.5 mL of a white emulsion which was believed to contain 1% propofol via cardiac catheter into the right atrium. It was strongly suspected that a syringe with a zinc oxide shake lotion (consisting of 20% ZnO, 20% talc, 25% glycerol and 35% water) which was intended for external treatment had been mistaken for the propofol syringe. During autopsy, an anatomic cause of death could not be found. In order to exclude an intoxication and to determine the significance of the perfusion fluid in this context, toxicological and histological investigations were performed. Propofol and other drugs applied to the patient were found in therapeutic or sub-therapeutic range. However, in comparison to a control case, the zinc concentrations determined by AAS were about 200 times higher in lung tissue, 10 times higher in heart blood and 3–4 times higher in kidney and liver tissue. No increase was seen in venous blood. Histology showed a strong embolism of the lung tissue with birefingent sharp-edged crystals, which were identified as the talcum, and an amorphous component (ZnO). The same embolism was seen to a medium extent also in the brain sections and to a low extent in heart, liver, pancreas and kidney. Pulmonary embolism by talcum and zinc oxide was established as the cause of death which occurred by syringe swap due to insufficient security precautions in the drug administration. The results are discussed in context of pulmonary microembolism cases frequently described for drug addicts after injection of crashed talcum containing tablets.