Delayed elimination in humans after ingestion of colchicine: Two fatal cases of colchicine poisoning

Colchicine has been widely used in the treatment of acute gout over the years, but it has a narrow therapeutic index, and overdose can be life threatening. A method using ultra-high-performance liquid chromatography–tandem mass spectrometry system was applied in two fatal cases of colchicine poisoning in this study to the determination of colchicine in blood. In case 1, a 19-year-old man suffered from depression and ingested 160 colchicine tablets (each 0.5 mg). The concentration of colchicine in his blood samples showed a fluctuating trend and kept above the therapeutic steady-state concentration for 5 days. In case 2, a 70-year-old female patient with a history of gout and chronic colchicine intake ingested five times the usual dose of colchicine (5 mg) and died after 12 days of medical care, with 5 ng/mL of colchicine in her blood sample. Our findings suggest that the delayed elimination and accumulation in humans after colchicine overdose could keep the concentration of colchicine maintaining above the therapeutic steady-state concentration for many days before dying, probably along with a fluctuating trend.     

Colchicine Extract Suicidal Lethal Poisoning Confirmation Using High‐Resolution Accurate Mass Spectrometry: A Case Study

A case of suspected acute and lethal intoxication caused by colchicine has been reported. The woman was hospitalized after her suspicion of suicidal poisoning by a rare autumn crocus (Colchicum autumnale). Suspected colchicine poisoning was confirmed using a novel UHPLC method with a modern reversed‐phase stationary phase with a sub 2‐micron superficial porous particle size combined with a QTOF mass spectrometer. Sample preparation procedure included the addition of propiverine as internal standard, protein precipitation using methanol and solid phase extraction. High‐resolution MS only and targeted MS/MS modes are reported for the qualitative analysis and screening of other potential drugs of abuse in blood samples. All Ion MS mode was used for quantitative determination of colchicine afterward. The concentration of colchicine in the blood sample was approximately 41 ng/mL, and more than 200 μg/mL of the plant extract used for the suicide.     

Colchicine poisoning by accidental ingestion of meadow saffron (Colchicum autumnale): pathological and medicolegal aspects

Although intoxications with colchicine, the alkaloid of Colchicum autumnale (meadow saffron), are well known, in most cases the intoxications are evoked by oral or parenteral preparations traditionally used as medication against gout. The accidental ingestion of Colchicum autumnale, on the other hand, is a rare event and has to our knowledge only twice been described in detail. We report a further case in which two persons confused this highly poisonous plant with wild garlic (Allium ursinum), a popular spice in the Central European cuisine. While one person merely complained about a 3-day episode of nausea, vomiting and watery diarrhea, the second person died of multi-organ system derangements 48 h after the ingestion of the colchicum leaves. At autopsy hemorrhagic lung oedema, hypocellular bonemarrow, centrilobular fatty necrosis of the liver and necrosis of the proximal convoluted tubuli of the kidneys were observed. A colchicine concentration of 7.5 micrograms/ml was found in the bile whereas no substance was detected in the postmortem blood.     

秋水仙碱在急性中毒豚鼠体液和组织中的检测及分布

目的建立生物检材中秋水仙碱的液相色谱/串联质谱检测方法,研究秋水仙碱急性中毒在豚鼠体内的分布,为秋水仙碱中毒的法医学鉴定提供方法和评价依据。方法以4mg/kg剂量秋水仙碱给豚鼠灌胃染毒,2～8h死亡,用LC-MS/MS测定体液和组织中秋水仙碱的含量。结果秋水仙碱在豚鼠各体液和组织中含量从高到低依次为胆汁、尿液、胃、脾、肺、肾、心、胰、肝、肾上腺、睾丸,心血中秋水仙碱的含量最低。结论所建方法准确、灵敏,适用于体内痕量秋水仙碱的检测。胆汁和尿液是体内检测秋水仙碱的较佳检材。     

Epithelial cell mitotic arrest--a useful postmortem histologic marker in cases of possible colchicine toxicity

Following ingestion of 30 mg of presumed benztropine (Cogentin) a 39-year-old male developed nausea, vomiting and diarrhea. His admission to hospital was soon followed by collapse and death. Histological examination, however, revealed increased numbers of mitotic figures in otherwise normal epithelial cells of the esophagus and bronchioles, a feature characteristic of colchicine toxicity. Subsequent toxicological analyses confirmed the presence of colchicine in the urine, but not in the blood. A dispensing error had resulted in substitution of colchicine for Cogentin. Histological findings had, therefore, provided evidence of colchicine toxicity and had guided subsequent toxicological evaluation. In suspected cases of colchicine toxicity, histological samples should, therefore, be taken from multiple sites along the gastrointestinal and respiratory tract in addition to other organs and tissues so that diagnostic morphological changes can be looked for.     

尸体火化后鉴定秋水仙碱中毒一例

<正> 随着犯罪手段的现代化,某些药物中毒表现与疾病的相似之处,可被用来掩盖犯罪,必须引起重视。临床医师在遇到诊断不清,治疗无效时,应警惕药物中毒的可能。对鉴定临床死亡原因不明而又没有尸体的中毒案例,法医工作者可通过相应的动物实验和对死者生前一系列症状、体征及实验室检查结果的综合分析,仍可得出具有科学根据的结论。现报告一例。     

Fatal colchicine poisoning

In two cases, after i.v. injections of colchicine serum concentrations of 170 ng/ml and 240 ng/ml were found before death. Colchicine was extracted from serum with the aid of Extrelut extraction columns and analysed using HPLC. Urine was also analysed and the findings were confirmed by drawing a UV-curve for colchicine using the stop-flow method. In one case, colchicine was still detectable in urine 10 days after injection.     

Colchicine poisoning: case report of two suicides

Colchicine overdose is uncommon but potentially life threatening because of the high toxicity of the drug. Poisoning by colchicine may occur following ingestion of medication used in acute attacks of gout and inflammatory diseases. We describe two cases involving suicide by the ingestion of medications marketed in France. In case 1, only heart blood was taken after body external examination. In case 2 an autopsy was performed and heart blood, urine, gastric contents and bile were taken for toxicological analysis. Colchicine was assayed in biological specimens by an HPLC-DAD method, after extraction by dichloromethane at pH 8, adding prazepam as internal standard (IS). Analyses were performed on a Symetry C-8 column. Mobile phase was a gradient of acetonitrile/pH 3.8 phosphate buffer. Colchicine is eluted at 13.1 min and the method is linear for blood, urine and bile over the range 4-1000 ng/mL. LOQ is 4 ng/mL. The concentrations of colchicine detected are: case 1: heart blood 13 ng/mL; case 2: heart blood 66 ng/mL, urine 500 ng/mL, gastric content 12 ng/mL, bile 5632 ng/mL. Our findings are in the range of lethal concentrations previously described, but there is no correlation with the amount of ingested drug. Even after massive overdose, it could be impossible to detect colchicine in blood, and as there is a widespread enterohepatic recirculation before excretion in bile and feces, bile is the target sample to analyse. We conclude in both cases that the cause of death was suicide with colchicine. It appears very important to perform an autopsy in order to obtain bile, urine, heart blood and femoral blood.     

Fatal colchicine poisoning by accidental ingestion of meadow saffron-case report

A 62-year-old male died of colchicine poisoning after accidental ingestion of Colchicum autumnale (meadow saffron). He ate a salad of plant with green leaves regarded as wild garlic (Allium ursinum). A few hours later he developed symptoms of gastroenteritis and was admitted to hospital. In spite of gastric lavage, activated charcoal and supportive measures, multi-organ system failure developed over the next two days. Laboratory analysis showed highly elevated blood concentrations of hepatic enzymes, creatine kinase, lactate dehydrogenase and blood urea nitrogen, as well as leukocytopenia and thrombocytopenia. Mechanical ventilation, dopamine, noradrenaline, crystalloid solutions and fresh frozen plasma were applied but despite treatment the patient died five days after the ingestion. Post-mortem examination revealed hepatic centrilobular necrosis, nephrotoxic acute tubular necrosis, petechial bleeding in fatty tissue, blunt and shortened intestinal villi and cerebral toxic edema. Botanical identification of incriminated plant gave Colchicum autumnale which confirmed colchicine poisoning. Although the accidental ingestion of Colchicum autumnale is rare and to our knowledge only five such cases have been described in detail, this is the second fatal case in Croatia described in the last 3 years.     

液相色谱-串联质谱法测定血液和尿液中秋水仙碱

目的建立检测血液和尿液中秋水仙碱的液相色谱-串联质谱法。方法0.5mL血液或尿液以丁丙诺啡为内标,经pH9.2硼酸盐缓冲溶液碱化后,用乙酸乙酯进行提取,在ZORBAX SB-C18液相柱(150mm×2.1mm×5μm)上以V(甲醇)∶V(20mmol/L乙酸铵和0.1%甲酸缓冲溶液)=80∶20为流动相,流速为0.2mL/min,采用电喷雾正离子模式离子化、多反应监测模式检测秋水仙碱,内标法定量。结果血液、尿液中秋水仙碱与内标丁丙诺啡色谱分离良好,秋水仙碱在0.1~50 ng/mL内均具有良好的线性,相关系数>0.9990,最低检出限为0.05ng/mL,方法回收率为94%~116%,日内与日间精密度(RSD)均小于8.5%。结论所建LC-MS-MS方法灵敏度高、操作简便、快速、准确,适用于血液及尿液等生物检材中痕量秋水仙碱成分的检测。     

Colchicine poisoning resulting from accidental ingestion of meadow saffron (Colchicum autumnale)

A rare case of colchicine poisoning resulting from accidental ingestion of meadow saffron (Colchicun Autumnale) is reported. The plant can frequently be found in the woods of the Northern Hemisphere (1), also in Japan. A 48-year-old male was admitted to hospital complaining of vomiting, nausea and diarrhea following ingestion of the plant and died in four days. The most striking histological findings were metaphasic mitotic figures in the mucosa of the large intestine and the liver. Colchicine was detected in the bile with high-performance liquid chromatography/sonicspray ionization mass spectrometry (HPLC/SSI-MS).     

损伤经过时间的实验研究

作者在全身麻醉及无菌条件下,通过在大白鼠背部皮肤造成的切创创口,于伤后不同时间杀死.每组中1只于处死前8小时注射秋水仙碱以观察核分裂.取损伤处皮肤,经福尔马林固定、石蜡切片、HE染色、Gorden和Sweet染色(网状纤维)、Weigert染色(弹力纤维)、PTAH染色(纤维蛋白)和Van Gieson染色,于显微镜下观察.结果发现创口逐日缩小,但其中24小时创口较12小时创口有所扩大,伤后第6～7日创口呈突击式缩小.通过组织学变化观察,作者对创口收缩现象在判断损伤时间的意义及形成机理作了讨论.     

Mole gun--an unusual firearm, a case note

There are different kinds of types of firearms used worldwide and of different origin. This case note evaluates the mole gun, which cannot be found in the literature. This simple gun, which is usually used in the fields against moles, was used in an apartment as a trap against burglars. This instrument manufactured to be used as a trap against detrimental animals, and not to be used as a firearm, can create dangerous situations, if used for different purposes.     

Some samples of weapons and instruments used as weapon in criminal offenses in Turkey

The variety of instruments used for crime of violence is wide. Besides the manufactured legal weapons, there are comparable numbers of purchased instruments, which are used as lethal weapons and significant numbers of comprising home-made ones.The instruments used during the commission of a crime shows similarity throughout the countries. Nevertheless, there are small differences to be seen.The topic of this subject features the types of weapons used in criminal offenses in Turkey.     

Coming to terms with facial reproduction

The process of building human faces by applying clay to skulls to generate leads for identification of unknown human remains is plagued by the use of a number of terms which are already used for other purposes. Reconstitution, reconstruction, restoration, death mask, moulage, and sculpture have all been used, but each is used in another context in forensic science. "Facial reproduction" is suggested as a term which is not already in use in forensic science, which is precise, and which would thus be preferred over any of the other terms.     

The uniform crime reports revisited

Of all criminal justice statistics in the United States, the Uniform Crime Reports (UCR) are the most widely known, used, and criticized. While the criticisms leveled at the UCR have been many and varied, attempts to assess the effects of the shortcomings of the UCR have been rare. Unfortunately, national sources of data against which the UCR can be gauged are very limited. There are, however, two such sources which may be used—homicide statistics collected by the Center for Health Statistics and the 1967 National Opinion Research Center victimization survey. While only very crude comparisons can be made between the UCR and data from these two sources, the results suggest that for homicide trends and the geographic distribution of “index” offenses, UCR and non-UCR sources depict similar patterns.Finally, procedures which various researchers have proposed for constructing a “crime index” are compared to the simple-sum method used by the UCR. When counties are used as the unit of analysis, most of the weighting schemes examined are found to order the counties in similar fashion. The implications of these results are briefly discussed.     

关于利益衡量的两种知识——兼行比较德国、日本的民法解释学

德国的利益法学派所主张的作为补充法律漏洞方法的利益衡量和日本民法者所提出的利益衡量论有着很大的不同,属于两种不同的知识,但在我国却被不加区分地使用着。我国目前正展开对法学方法论的引入与讨论,究竟应该选择德国还是日本的进路,需要我们认真对待。     

The forensic taxonomic debate on Cannabis: semantic hokum.

It has been asserted that there are legal species of marihuana plants, and this contention has generated frequent court challenges of criminal prosecutions involving marihuana. Invariably the claim is made that the name C. sativa used in legislation is insufficiently comprehensive to proscribe all forms of marihuana. The maneuver being used, alarmingly, is potentially applicable to innumerable other materials, but its success is based on a failure to appreciate the subjective nature of taxonomy and the little-known but critical ambiguities which are inherent in scientific names. The complex principles and operational conventions of biological nomenclature are presented in elementary fashion. Despite important technical constraints on the use of scientific names, some facts are clear: these names are used subjectively, they may be highly ambiguous, the consensus on use of these names is liable to change with time and, most important, quite permissibly they may have substantially different meanings to different users. The claim that there are legal species of Cannabis merely amounts to a semantic ploy in which certain of the variants of Cannabis that have customarily been understood to be denoted by the species name C. sativa, and which are clearly understood to be proscribed, are simply arbitrarily redefined as different species. This ploy has proven unsuccessful in all cases where scientific evidence was adequately presented by the state and in all important court cases where the issue was critically examined.     

Migration of a Kirschner wire used in the fixation of a subcapital humeral fracture, causing cardiac tamponade: case report and review of literature

Metallic pins and wires are frequently used for fixation of fractures and dislocations. Migration is one of the potential complications of such fixation methods. Usually, migration of the pins causes only minor complications, but if the device migrates to a vital cavity, serious damage and even death may ensue. The shoulder girdle is one of the areas in which pins and wires are mostly used, the humeral neck fractures being one of them. We report a case in which a Kirschner wire migrated from a subcapital humeral fracture site into the aorta and pericardium, causing sudden cardiac tamponade and death.