Determination of chronic abuse of the anaesthetic agents midazolam and propofol as demonstrated by hair analysis

A 44-year-old female nurse in a department of anesthesiology was found dead at home. An empty bottle of Hypnovel (midazolam 5 mg/5 ml) and a hypodermic syringe were found near the corpse. The nurse was a known abuser of anaesthetic agents for many years. A complete screening for general unknown substances by FPIA, GC/MS, head space GC/MS and HPLC/DAD revealed the simultaneous presence of midazolam, propofol and ethanol in femoral blood. Segmental analysis of a 6-cm-long hair strand revealed the presence of midazolam and propofol in each 2-cm-long segment. Repetitive consumption of the two anaesthetic agents during the last 6 months before the death was therefore demonstrated. These compounds were also detected in pubic and axillary hairs. Self-administration of midazolam and propofol without respiratory assistance and medical control certainly contributed to the death. Received: 14 September 2000 / Accepted: 29 May 2001     

A case of abuse in which children were forced to take tablets containing scopolamine: segmental analysis of hair for scopolamine by ultra performance liquid chromatography-tandem mass spectrometry

Our laboratory received hair samples of three children after alleged exposure to Feminax tablets, which contain scopolamine as an ingredient; it was regarded as an offense by the police because a woman had repeatedly beaten her children and forced each of them to take four to ten Feminax tablets per day. Neither blood nor urine samples of the children had been obtained at the time of the alleged offense. Thus, hair strands were obtained from the children as specimens in acquiring evidence of the offense. We conducted segmental hair analysis of scopolamine using ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (MS-MS), which is highly sensitive and specific, and enabled the measurements of scopolamine at subpicogram-permilligram levels present in the hair segments. By our UPLC-MS-MS analysis, it was found that the concentrations in the hair segments ranged from 0.3 to 1.1 pg/mg and that exposure to scopolamine had continued for at least several months prior to the hair sampling for all children. Because of our scientific evidence, the mother pleaded guilty to the offense against her children despite her denial at the outset of the investigation.     

七氟烷或丙泊酚用于妇科腹腔镜手术的麻醉诱导

目的：研究吸入七氟烷和静脉靶控注射丙泊酚麻醉诱导对患者血液动力学和脑电双频指数（BIS）的影响。方法：择期手术患者60例,随机分为A组30例：逐渐使呼气末七氟烷浓度达到并维持2.8%~3.4%行吸入麻醉诱导;B组30例：设定丙泊酚血浆浓度3.0μg/ml行静脉靶控诱导。观察两组在麻醉诱导和气管插管前、后血液动力学和BIS值的变化。结果：两组在麻醉诱导和气管插管前、后BIS值均较基础值降低,达到理想的麻醉深度;两组血液动力学均有明显变化,A组变化更为显著。结论：控制呼气末七氟烷浓度及丙泊酚靶控输注全麻诱导均能提供足够的麻醉深度,但对循环抑制明显。在麻醉诱导期间应密切监测血液动力学变化。     

Hair testing in postmortem diagnosis of substance abuse: An unusual case of slow-release oral morphine abuse in an adolescent

Morphine sulfate misuse is essentially observed among regular heroin injectors. To our knowledge, primary addiction to morphine sulfate is exceptional, especially among young adolescents. A 13-year-old girl, with no history of addiction, was found dead with three empty blisters of Skenan^® LP 30 mg at her side. Opiates were detected in biological fluids and hair by chromatographic methods. Blood analyses confirmed morphine overdose (free morphine: 428 ng/mL; total morphine: 584 ng/mL) and segmental hair analysis confirmed regular exposure over several months (maximum morphine concentration 250 pg/mg). Suspecting the victim's mother of recreational use of Skenan^®, the magistrate ordered analysis of her hair, with negative results. From an epidemiological viewpoint, this case of oral morphine sulfate abuse in an adolescent with no previous history suggests the emergence of a new trend of morphine sulfate consumption. From a toxicological viewpoint, it demonstrates the value of hair testing, which documented the victim's regular exposure and made an important contribution to the police investigation.     

Severity and duration of mental deficiency symptoms after intravenous administration of propofol

The severity and duration of cognitive performance capacity deficits after intravenous administration of propofol were determined using the validated psychological test procedure syndrome short test (SKT), a simple reaction test and original driving licence exam questions. The test battery was performed before, immediately after, as well as 1 and 2 h after propofol administration in 23 persons. Immediately after propofol anaesthesia, six individuals had a slight performance loss, and four subjects showed mild deficits, consistent with medium organic neuropsychologic disorder or dementia. The status of the subjects rapidly changed for the better, and 2 h after propofol anaesthesia, only one person (4%) showed slight deficits of memory and attention. Therefore, it is suggested that patients refrain from any participation in road traffic for at least 2 h after propofol anaesthesia. Driving a car should not be admitted until an interval of 6 h has elapsed.     

异丙酚复合瑞芬太尼麻醉用于颅内手术的临床研究

目的依据异丙酚和瑞芬太尼药理特性用于颅内手术麻醉,评价其在颅内手术麻醉中的应用价值。方法选择需颅内手术的30名病人,随机分为异丙酚+瑞芬太尼静脉麻醉组(PR)和异丙酚+1%普鲁卡因静脉麻醉组(PP),每组15例。PR组麻醉诱导为静脉注射力月西、仙林、瑞芬太尼、异丙酚,麻醉维持为静脉滴注异丙酚2~4 mg/(kg.h)和瑞芬太尼2~4μg/(kg.h);PP组麻醉诱导为静脉注射力月西、仙林、芬太尼、异丙酚,麻醉维持为静脉滴注异丙酚2~4 mg/(kg.h)和1%普鲁卡因。记录平静、入室、插管、术中、术毕时的血压、心率和SpO2以及麻醉苏醒时间。结果PR组MAP与入室比插管时P<0.05,术中P<0.01,HR与入室比无明显变化P>0.05;PP组MAP与入室比插管时P<0.001,术中P<0.01,HR与入室比术毕P<0.01。PR与PP比MAP插管时P<0.01,HR术中和术毕P<0.05,术毕麻醉苏醒时间PR组短于PP组。结论PR组在颅内手术麻醉诱导、维持、术毕拔管期间血液动力学稳定,麻醉深浅可控性好,且苏醒平稳迅速,更适合颅脑外科手术的麻醉要求。     

A 10 year post-mortem analysis of keratin matrix in Perugia (Italy): focus on cocaine involvement in several types of death

The use of keratin matrix, in detecting drug consumption, offers compelling advantages compared to other conventional biological matrices used for these types of investigation, and provides important information to surveys which are characterised by a general underestimation, especially in Italy. In our study we collected and analysed 424 hair samples from corpses autopsied in Perugia from January 2001 to December 2011 in order to detect traces of drugs and especially of cocaine, and evaluate their involvement in several types of death. Hair samples were analysed by gas chromatography–mass spectrometry in the Laboratory of Forensic Toxicology of the Department of Legal Medicine of the University of Perugia: 232 samples derived from cases of overdose deaths; 192 were connected to different causes of death. The average concentration of cocaine in the keratin matrix samples was of 3.74 ng/mg in people who died from overdose, 3.09 ng/mg in people who died from other causes. In 232 cases of overdose deaths, 135 were positive for cocaine (accounting for 58.18% of total); in 192 deaths from other causes, 39 were positive for cocaine (accounting for 20.31% of the total). Our study demonstrated the crucial role of cocaine in overdose deaths and in other deaths, as is well known in other research.     

Cocaine found in a child’s hair due to environmental exposure?

We report a case of a 6-year-old boy who had been living with his parents, both cocaine smokers, and who was urgently admitted to hospital for general distress. Upon examination, cocaine and cocaine metabolites were detected in hair and urine samples. These toxicological findings most likely indicate that the child had passively consumed the drug when living in a heavily contaminated environment.     

Analysis of fentanyl and sufentanil in hair by GC/MS/MS

Fentanyl and sufentanil are potent narcotic analgesics used only in hospitals as anaesthetic agents. The dependence potential of fentanyl is known. As they are given in doses at the microgram level and their elimination half-life is in the order of a few hours, detection in body fluids is possible only for a short time after administration. Radioimmunological methods are the only ones capable of detecting fentanyl in hair, as normal GC/MS methods for hair analysis are not sensitive enough to detect the drugs after doses in the order of micrograms. We therefore chose GC/MS/MS to analyse fentanyl and sufentanil in two cases where the drugs were given under controlled conditions over several days. The concentration was in the order of less than 100 pg/mg hair.     

Y-STR analysis for detection and objective confirmation of child sexual abuse

We evaluated 26 child sexual assault cases for the incorporation of Y-STR screening in the routine detection and objective confirmation of sexual contact between the child victim and the perpetrator. Various samples, e.g. vaginal or anal swabs from patients aged 2–17 years old (25 females, 1 male), were collected 6–72 h after the incident. Due to the limited amounts of DNA in these samples, total DNA was extracted using a one-step procedure and screened with autosomal STRs to detect signs of a victim-assailant DNA mixture and with Y-STRs for assailant DNA. Autosomal STRs failed to give signs of victim-assailant DNA mixtures while Y-STRs were detected in 24 of the 26 cases corresponding to a success rate of 92.3%. With the possible presence of both male sperm and/or male epithelial cells in forensic evidence, Y-STR DNA markers were detected regardless of external ejaculation, microscopic detection of sperm and with post-coital intervals of up to 72 h. While only partial profiles were generated owing to low quantities of male DNA present, Y-STR screening results can serve as objective evidence of sexual contact in child sexual abuse cases involving victims who do not have any previous sexual history. This type of evidence can corroborate child victim testimony and spare the child victim from further trauma caused by prolonged forensic investigations and court proceedings. Alternatively, Y-STR screening can provide objective proof of non-involvement of an accused with the victim.     

Death of a female addict due to heroin and cocaine overdoses: a case report with multiparameter evaluation

This study undertook a multiparameter evaluation of the death of a 21-year-old woman known to be an abuser of heroin and cocaine. The toxicological analysis of multiple postmortem specimens such as blood and hair was carried out using liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS-MS). The blood specimens of the deceased showed the presence of opium components such as morphine and its glucuronides together with cocaine and benzoylecgonine. The detected xenobiotic levels probably explained the cause of her death resulting from combined action of unintentional illicit drug overdose. By analysis of four 2-cm long hair segments, a heroin-cocaine addiction for at least 8 months antemortem was able to be documented; the presence of 6-monoacetylmorphine (6-MAM), cocaine, and benzoylecgonine was demonstrated. The histopathological findings of lesions of the internal organs of the deceased were consistent with long heroin and cocaine abuse. The use of multiple parameters, such as blood and hair segments as matrices and drug metabolites such as 6-MAM, morphine, glucuronides, and benzoylecgonine as target compounds, gave a well-defined outline of her death.     

The significance of drug analysis of sweat in respect to rapid screening for drug abuse

Summary Morphine and methamphetamine, which are excreted in the sweat, are detected by the use of routine serological and physicochemical techniques for urinary examinations. Screening for drug abuse can be done with the same accuracy of that of urine. Rapid excretion of the drug via kidney (within one day) is followed by a slow but steady excretion of the sweat gland. Methamphetamine given orally in a dosis of 10 mg is excreted in the sweat at a constant rate (1.4 g/ml). No significant difference of the amount excreted by both systems is found. Alveolar lining seems to prevent the elimination of the volatile methamphetamine via respiration. Not only narcotics and stimulants, but also many alkaloids and barbiturates are excreted in the sweat and detected quantitatively by the same principles. The toxicological analysis of the sweat promises a new scope of forensic investigation.     

Patterns of abuse amongst Sri Lankan women returning home after working as domestic maids in the Middle East: An exploratory study of medico-legal referrals

ObjectiveMigrant worker abuse is well recognised, but poorly characterised within the scientific literature. This study aimed to explore patterns of abuse amongst Sri Lankan women returning home after working as domestic maids.MethodsSri Lanka has over 2 million of its citizens employed overseas as international labor migrants. A cross-sectional study was conducted on Sri Lankan female domestic maids returning from the Middle East region who were referred for medico-legal opinion.ResultsA total of 20 women were included in the study. Average length of their employment overseas was 14 months. Complaints of physical violence directed mainly through their employers were made by 60% of women. Upon physical examination, two-thirds had evidence of injuries, with a third being subjected to repetitive/systematic violence. Eighty percent suffered some form of psychological trauma. Personal identity papers and travel documents had been confiscated by the employer in 85% of cases, with two thirds indicating they were prevented and/or restricted from leaving their place of work/residence.ConclusionsOur study demonstrates that female domestic maid abuse manifests through multiple pathways. Violence against such workers span the full spectrum of physical, financial, verbal, emotional abuse and neglect, as defined by the World Health Organization. Findings from this exploratory study cannot be generalized to the large volume of migrant worker outflows. Further research is needed to determine incidence and define patterns in other migrant worker categories such as low-skilled male workers.     

创伤性脑损伤后脑组织抵抗素rstn基因的表达变化

目的 探讨创伤性脑损伤(TBI)大鼠脑组织抵抗素rstn基因表达的变化特征. 方法选择SD大鼠90只,按随机数字表法分成正常对照组(5只),假手术组(10只),轻、中和重度损伤组(每组25只).应用液压冲击法制作大鼠颅脑损伤模型,并应用RT-PGR方法检测各组大鼠伤后3,6,24,72 h和1,2,4周脑组织rstn基因表达的变化,同时监测损伤中度组大鼠外周血糖浓度变化,观察两者之间的关系. 结果重度损伤组大鼠于伤后24 h,中度损伤组大鼠于伤后72 h,轻度损伤组大鼠于伤后4周rstn基因的表达开始明显上升(P＜0.05).伤后4周时,所有损伤组海马、丘脑及皮质区域rstn基因表达均升高(P＜0.05),其中海马区域最高,丘脑区域最低(P＜0.05).不同区域均存在损伤侧rstn基因表达较高,对侧较低的现象(P＜0.05).重度损伤组大鼠rstn基因表达升高最明显(P＜0.05).脑组织rstn基因表达变化与外周血糖浓度呈线性正相关(R=5.32,P=0.03). 结论 TBI后rstn基因表达明显增加,rstn基因表达的时程变化可能与脑损伤严重程度相关.TBI后rstn基因存在同侧海马区域表达明显升高的组织分布特征.创伤后脑组织rstn基因表达变化与血糖代谢之间存在一定关系.     

Follow-up of pain processing recovery after ketamine in hyperalgesic fibromyalgia patients using brain perfusion ECD-SPECT

Purpose The aim of this study was to determine whether the follow-up of pain processing recovery in hyperalgesic fibromyalgia (FM) could be objectively evaluated with brain perfusion ethyl cysteinate dimer single photon computerized tomography (ECD-SPECT) after administration of ketamine. Materials and methods We enrolled 17 hyperalgesic FM women patients (48.5 ± 11 years, range 25–63). After treatment with subcutaneous ketamine, 11 patients were considered as “good responders”, with a decrease in pain intensity, evaluated by visual analog scale (VAS), greater than 50%. On the other hand, six patients were considered as “poor responders”. A voxel-based analysis of regional cerebral blood flow (rCBF) was conducted (p _voxel < 0.001uc), in the two subgroups of patients, before and after treatment, in comparison to a group of ten healthy subjects, matched for age and gender. Results In comparison to baseline brain SPECT, midbrain rCBF showed a greater increase after ketamine in the responder group than in the nonresponder group (p _cluster = 0.016c). In agreement with the clinical response, the change in midbrain rCBF after ketamine was highly correlated with the reduction of VAS pain score (r = 0.7182; p = 0.0041). Conclusion This prospective study suggests that blockade of facilitatory descending modulation of pain with ketamine can be evaluated in the periaqueductal grey with brain perfusion SPECT.     

Gait analysis after intake of increasing amounts of alcohol

Summary The ability to walk after intake of increasing amounts of alcohol was studied. Sixteen normal persons were tested on a computer-assisted treadmill. Ataxia or unsteadiness of gait was found to decrease during a blood alcohol concentration (BAC) of less than 0.4 mg/ml. Stride length was found to increase by increasing BAC.Supported by The Haand-I-Haand-Hafnia Insurance Jubilee Fund, The Jubilee Fund of the Nordic Mutual Insurance Ltd., and the Danish Medical Research Council, grant no. 512-154-15460.